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12 pages, 1369 KB  
Article
Establishment of an Indirect ELISA Detection Method for Porcine Reproductive and Respiratory Syndrome Virus NSP10
by Gan Li, Qipeng Zhang, Xiaojing Chen, Huawei Li, Ruining Wang, Keshan Zhang, Yaqiong Ye and Mengmeng Zhao
Vet. Sci. 2026, 13(8), 793; https://doi.org/10.3390/vetsci13080793 (registering DOI) - 8 Aug 2026
Abstract
As a highly contagious infectious disease in the swine industry, porcine reproductive and respiratory syndrome (PRRS) can cause reproductive disorders in sows and respiratory diseases in piglets, resulting in sustained economic losses. Nonstructural protein 10 (NSP 10), as one of the core components [...] Read more.
As a highly contagious infectious disease in the swine industry, porcine reproductive and respiratory syndrome (PRRS) can cause reproductive disorders in sows and respiratory diseases in piglets, resulting in sustained economic losses. Nonstructural protein 10 (NSP 10), as one of the core components of the replication and transcription complex of PRRS virus (PRRSV), has both helicase and adenosine triphosphatase activities, and has the potential as a diagnostic marker. In this study, NSP10 recombinant protein was used as coating antigen, and an indirect ELISA method for PRRSV NSP10 detection was established by square matrix titration. After optimizing the assay parameters, high specificity (no reactions with other pig viruses), high sensitivity (able to detect antibodies even when the positive blood sample was diluted 1280 times), and excellent reproducibility (less than 10% variation) were shown. Therefore, the NSP10 indirect enzyme-linked immunosorbent assay (ELISA) developed in this study provides an effective technical means for enhancing PRRSV surveillance in swine herds, thereby establishing a solid foundation for the clinical diagnosis and comprehensive prevention and control of PRRSV. Full article
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27 pages, 5072 KB  
Review
Enolase-1 and Inflammation
by Rafael Fernandez, Asha Jacob, Monowar Aziz and Ping Wang
Biomolecules 2026, 16(8), 1156; https://doi.org/10.3390/biom16081156 (registering DOI) - 8 Aug 2026
Abstract
Enolase-1 (ENO-1) is classically known as a highly conserved glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the final steps of glycolysis. This enzyme, however, is being increasingly implicated as a multifunctional moonlighting protein with compartment-specific roles in inflammation. Within [...] Read more.
Enolase-1 (ENO-1) is classically known as a highly conserved glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the final steps of glycolysis. This enzyme, however, is being increasingly implicated as a multifunctional moonlighting protein with compartment-specific roles in inflammation. Within the cytosol, ENO-1 regulates macrophage inflammation during sepsis; on the cell surface, it functions as a plasminogen receptor, and extracellularly, it can participate in innate immune signaling. Across innate and adaptive immunity, ENO-1 has been implicated in macrophage activation, neutrophil recruitment, endothelial cell dysfunction, fibroblast remodeling, and autoantigenicity. These functions have been linked to sepsis, acute respiratory distress syndrome, acute organ injury, hemorrhagic shock, rheumatoid arthritis, and cancer-associated inflammation in the tumor microenvironment. Therapeutic targeting of ENO-1 includes small-molecule inhibitors and monoclonal antibodies. ENO-1, with its compartment-specific functions in disease pathogenesis, serves as a significant therapeutic target for inflammatory diseases. In this review, we discuss the novel compartment-specific roles of ENO-1 in inflammatory diseases, defining its functions beyond its role in glycolysis. We conclude that both the metabolic and moonlighting functions of ENO-1 contribute to inflammation, and future studies should delineate its compartment-specific roles in inflammatory pathophysiology, as compartment-specific targeting may represent the future of ENO-1-directed therapy. Full article
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23 pages, 661 KB  
Article
Universal Tumor Screening in Colorectal Cancer: Role of MMR Immunohistochemistry for Lynch Syndrome and Early-Onset CRC
by Silvia Negro, Sara Lessio, Daniele Passeri, Andrea Baldo, Marco Scarpa, Angelo Paolo Dei Tos, Ganmaria Pennelli, Francesca Schiavi, Claudia Pinato, Matteo Fassan, Quoc Riccardo Bao, Francesca Bergamo, Sara Lonardi, Gaya Spolverato and Emanuele Damiano Luca Urso
Cancers 2026, 18(16), 2549; https://doi.org/10.3390/cancers18162549 (registering DOI) - 8 Aug 2026
Abstract
Background: Mismatch repair deficiency (MMRd) is a central molecular determinant of colorectal cancer (CRC) biology, prognosis, and treatment response, and Universal Tumour Screening (UTS) is advocated for Lynch syndrome (LS) detection; yet real-world performance across clinical subgroups remains limited. We evaluated MMRd [...] Read more.
Background: Mismatch repair deficiency (MMRd) is a central molecular determinant of colorectal cancer (CRC) biology, prognosis, and treatment response, and Universal Tumour Screening (UTS) is advocated for Lynch syndrome (LS) detection; yet real-world performance across clinical subgroups remains limited. We evaluated MMRd distribution and UTS-based LS detection in a large consecutive surgical cohort. Methods: We retrospectively analyzed 1022 consecutive CRC patients undergoing surgical resection at the University Hospital of Padua (2015–2023). MMR status was assessed by immunohistochemistry; MMRd cases underwent reflex BRAF mutation testing and, when available, MLH1 promoter methylation analysis, followed by germline multigene panel testing for suspected LS. Clinicopathological features were compared by MMR status, age at onset, and tumour location. Results: MMR testing was performed in 875 patients (85.6%), rising from 67.0% (2015–2017) to 97.4% (2021–2023). MMRd was identified in 139 tumors (15.9%) and was independently associated with age ≥ 70 years, colonic location, and stage 0–II. Of 22 patients with confirmed LS, 13 (59.1%) were newly identified through UTS; family history showed no significant univariate association with LS status and was not independently associated with MMRd after multivariable adjustment. MMRd prevalence was numerically higher in early- than late-onset CRC (20.0% vs. 15.4%), approaching significance after multivariable adjustment (OR 1.90, 95% CI 0.99–3.64; p = 0.054); hereditary syndromes were also more frequent in early-onset disease. MMRd was markedly rarer in rectal than colonic cancer (4.1% vs. 22.5%; p < 0.0001), though MMRd rectal cancers arose in younger patients. Conclusions: UTS identified a substantial proportion of LS carriers missed by age- or family-history criteria. The relationship between age and MMRd prevalence proved more nuanced than a simple comparison would suggest, reinforcing the value of universal over selective testing across the age spectrum, while MMRd rectal cancer shows a distinct younger profile relevant to immunotherapy-based organ preservation. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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26 pages, 2772 KB  
Review
Varicella–Zoster Virus Infection in Pregnancy: Maternal, Fetal, and Neonatal Implications in the Vaccination Era
by Isadora Rodrigues Almeida, Camila Silva Belo, Tammy Caram Sabatine, Thamy Cristina Campos, Annie Stefanelli, Liris Naomi Noguchi, Giuliana Augustinelli Sales, Gustavo Yano Callado, Angélica Lemos Debs Diniz, Roberta Granese, Edward Araujo Júnior and Antonio Braga
Microorganisms 2026, 14(8), 1745; https://doi.org/10.3390/microorganisms14081745 (registering DOI) - 8 Aug 2026
Abstract
Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more [...] Read more.
Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more severe forms of the disease, with pneumonia representing the main maternal complication and a leading cause of morbidity and mortality. Vertical transmission may result in congenital varicella syndrome, the most severe fetal consequence, whose risk is greatest between the 13th and 20th weeks of gestation, or in severe neonatal varicella when maternal infection occurs in the peripartum period. This article presents a narrative review of the literature. To enhance methodological transparency and reproducibility, key principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied to the literature search and study selection process. Searches were conducted in the PubMed/MEDLINE and SciELO databases, and 32 studies were included in the narrative synthesis. The review addresses the virology, pathophysiology, and epidemiology of VZV infection, including differences between temperate and tropical regions, as well as its clinical manifestations and maternal, fetal, and neonatal complications. Diagnosis is predominantly clinical, with the polymerase chain reaction being the most sensitive and specific confirmatory method and serology being useful mainly for the assessment of maternal immunity. Management encompasses the assessment of susceptibility, post-exposure prophylaxis according to current guideline recommendations, and early antiviral treatment of established infection. Preconception and postpartum vaccination remain the main preventive strategies. Despite recent advances, important gaps persist regarding prophylactic strategies and the long-term safety of antivirals during pregnancy. Full article
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33 pages, 1505 KB  
Article
Combined and Individual Effects of Chlorella sp. and Bacterial Probiotics in Biofloc Systems for White Shrimp (Penaeus vannamei)
by Tatiana Cascales-Martos, Jessica Brol, Silvia Martínez-Llorens, Ana Tomás-Vidal, M. Jover-Cerdá, F. J. Moyano and D. S. Peñaranda
Animals 2026, 16(16), 2469; https://doi.org/10.3390/ani16162469 (registering DOI) - 8 Aug 2026
Abstract
This study aimed to evaluate the effects of establishing a population of the green microalgae Chlorella sp. on different key aspects of a biofloc culture of Penaeus vannamei in comparison with those obtained with a commercial probiotic. The aspects evaluated were shrimp zootechnical [...] Read more.
This study aimed to evaluate the effects of establishing a population of the green microalgae Chlorella sp. on different key aspects of a biofloc culture of Penaeus vannamei in comparison with those obtained with a commercial probiotic. The aspects evaluated were shrimp zootechnical performance, nutritional composition of biofloc and microbial populations of shrimp intestinal microbiota and biofloc. Four treatments were tested: two of them included Chlorella sp. alone (M) or in combination to a bacterial probiotic (MP), while the other two included only the probiotic (P) or none of them (C). The presence of Chlorella sp. enhanced protein and phosphorus bioavailability in the biofloc and contributed to nutrient bioremediation within the system. However, shrimp growth performance and survival were significantly reduced, likely due to greater and more prolonged nitrate exposure following microalgae inoculation. Although overall nitrate and phosphate concentrations were higher in microalgae treatment, their accumulation over the experimental period was lower in the presence of Chlorella sp. In addition, microalgal supplementation reduced the abundance of bacterial groups associated with oligotrophic lifestyles, complex organic matter degradation, and nitrogen cycling in the intestinal microbiota. In contrast, probiotic supplementation increased protein content in shrimp and phosphorus bioavailability in the biofloc, while zootechnical performance remained comparable to the control and was higher than in microalgae treatments. Furthermore, probiotic addition reduced the abundance of Flavobacteriaceae, a bacterial family proposed as a bioindicator of White Feces Syndrome (WFS) in P. vannamei. Full article
36 pages, 17849 KB  
Review
Mechanisms of Obesity-Related Kidney Disease: From Adipose Depot Biology to the Chymase–Aldosterone and Ghrelin–Leptin Axes
by Hsuan-Chu Hsu, Li-Jane Shih, Yi-Chou Hou and Kuo-Cheng Lu
Biomolecules 2026, 16(8), 1155; https://doi.org/10.3390/biom16081155 (registering DOI) - 8 Aug 2026
Abstract
Obesity is an increasingly important and modifiable driver of chronic kidney disease (CKD), with effects that extend well beyond its associations with type 2 diabetes, hypertension, and dyslipidemia. To synthesize the evidence that excess adiposity is a causal and modifiable determinant of kidney [...] Read more.
Obesity is an increasingly important and modifiable driver of chronic kidney disease (CKD), with effects that extend well beyond its associations with type 2 diabetes, hypertension, and dyslipidemia. To synthesize the evidence that excess adiposity is a causal and modifiable determinant of kidney disease, and to examine how specific adipose depots injure the glomerulus and the tubulointerstitium, and then map these mechanisms onto established and emerging therapies. Throughout, obesity-related kidney disease (ORKD) denotes the full spectrum of diposity-driven renal injury, whereas obesity-related glomerulopathy (ORG) is reserved for the biopsy-defined glomerular lesion. Central, visceral, perirenal and renal-sinus adiposity act first through structural and haemodynamic mechanisms, promoting glomerular hyperfiltration, mechanical renal compression and activation of the adipose-derived renin–angiotensin–aldosterone system (RAAS). In parallel, these depots drive cellular and metabolic injury through lipotoxicity, adipokine imbalance, sterile inflammation, oxidative stress, gut dysbiosis, mitochondrial dysfunction, epigenetic remodelling and cellular senescence. Ectopic lipid accumulation within the renal parenchyma—fatty kidney—offers a unifying description of these changes and is most marked in type 2 diabetes mellitus. These interacting processes converge on podocyte stress, tubular metabolic failure, endothelial dysfunction and interstitial fibrosis, producing a phenotypic continuum that ranges from early albuminuria to obesity-related glomerulopathy and progressive CKD. Within the RAAS limb we highlight two comparatively underappreciated, adiposity-linked routes to injury: adipocyte-derived leptin directly upregulates adrenal aldosterone synthase (CYP11B2), and mast-cell chymase generates angiotensin II independently of angiotensin-converting enzyme, together reinforcing aldosterone- and angiotensin II–mediated damage that conventional RAAS blockade only partially interrupts. We further consider the counter-regulatory ghrelin–leptin axis, in which the suppression of ghrelin that accompanies obesity may withdraw an antioxidant, anti-inflammatory and podocyte-protective signal precisely as leptin-driven glomerular injury intensifies, positioning ghrelin as a plausible modulator and candidate biomarker of obesity-related kidney injury. We also examine how obesity complicates renal risk assessment, drug dosing, dialysis delivery and transplant access. Emerging, mechanism-matched therapies—SGLT2 inhibitors, GLP-1 receptor agonists, finerenone, structured lifestyle intervention, metabolic-bariatric surgery and, most recently, aldosterone synthase inhibitors that suppress the chymase- and leptin-driven aldosterone escaping receptor blockade—now enable a precision cardiovascular-kidney-metabolic framework that aligns adipose-depot biology, biomarkers, histology and treatment response to guide mechanism-based care in ORKD. Full article
(This article belongs to the Section Molecular Medicine)
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11 pages, 4611 KB  
Case Report
Tildrakizumab in the Treatment of Complex and Severe Psoriasis: A Case Series
by Claudio Marasca, Domenico D’Amico, Claudia Giofrè and Viviana Lora
J. Clin. Med. 2026, 15(16), 6161; https://doi.org/10.3390/jcm15166161 (registering DOI) - 8 Aug 2026
Abstract
Background/Objectives: Patients with a clinical diagnosis of severe psoriasis complicated by comorbidities such as cardiovascular disease, obesity, metabolic syndrome and/or with the involvement of high-impact areas constitute a clinical challenge. Tildrakizumab is a monoclonal antibody targeting the IL-23/Th17 axis with a proven [...] Read more.
Background/Objectives: Patients with a clinical diagnosis of severe psoriasis complicated by comorbidities such as cardiovascular disease, obesity, metabolic syndrome and/or with the involvement of high-impact areas constitute a clinical challenge. Tildrakizumab is a monoclonal antibody targeting the IL-23/Th17 axis with a proven record of efficacy and safety in these patients. Methods: Here we present four cases of patients with severe psoriasis and comorbidities including cardiovascular disease (Case 1), obesity (Cases 2 and 3), metabolic syndrome (Case 3), and/or high-impact areas (Cases 2–4). Three patients (Cases 1–3) had previously received biologics but developed secondary failure or loss of efficacy; one patient was bio-naïve (Case 4). Results: The treatment with tildrakizumab in all four patients led to a quick onset (by Week 4 in all cases) of complete and lasting (1 year in Case 1, 4 years in Case 2 and 2 years in Cases 3 and 4) remission with no adverse events reported. Conclusions: Tildrakizumab is a valuable therapeutic option for patients with psoriasis and complex clinical situations, and in particular, in cases with obesity and difficult-to-treat lesion locations such as hands, scalp and genitals. Therapeutic success is often linked to an improvement in patients’ quality of life. Full article
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12 pages, 361 KB  
Article
Incidence and Associated Risk Factors in the Development of Carfilzomib-Induced Cardiovascular Toxicity
by Noor Lad, Jayda Esplund, Dennis Grauer, Shebli Atrash, Prerna Mewawalla, Tejaswi Gadela, Charles Porter, Muhammad Mushtaq, Jeries Kort, Donald C. Moore, Al-Ola Abdallah, Zahra Mahmoudjafari and Jordan Snyder
Curr. Oncol. 2026, 33(8), 471; https://doi.org/10.3390/curroncol33080471 (registering DOI) - 8 Aug 2026
Abstract
Background: Carfilzomib, a second-generation proteasome inhibitor, is widely used in multiple myeloma (MM) treatment but has been associated with cardiovascular adverse events (CVAEs). Real-world data evaluating the incidence and risk factors are limited. Methods: We conducted a multicenter retrospective cohort study of 385 [...] Read more.
Background: Carfilzomib, a second-generation proteasome inhibitor, is widely used in multiple myeloma (MM) treatment but has been associated with cardiovascular adverse events (CVAEs). Real-world data evaluating the incidence and risk factors are limited. Methods: We conducted a multicenter retrospective cohort study of 385 adult MM patients treated with carfilzomib between January 2020 and August 2024 at three U.S. institutions. The primary objective of this study was to determine the incidence of carfilzomib-associated CVAEs. The secondary objectives included the identification of risk factors, characterization of cardiovascular events, and time-to-onset analysis. Results: Carfilzomib-associated CVAEs occurred in 25 patients (6.5%). The median time to event was 114 days. Heart failure was the most common manifestation (86%), followed by arrhythmias (32%) and acute coronary syndromes (8%). Patients with baseline heart failure had a significantly increased risk of CVAEs (HR 1.61, p = 0.042), whereas arrhythmias showed a trend toward significance. Traditional cardiovascular risk factors were not independently associated with an increased risk. CVAEs were associated with numerically inferior overall survival (45.7 vs. 97.3 months; HR 1.316, 95% CI 0.728–2.377, p = 0.361). Partial recovery of the left ventricular ejection fraction was observed following treatment discontinuation. Conclusion: Carfilzomib-associated CVAEs were infrequent but clinically meaningful in this multicenter cohort. These findings support consideration of a risk-adapted cardio-oncology approach, particularly in patients with pre-existing cardiac dysfunction, where closer surveillance and early intervention may help mitigate clinically significant cardiotoxicity. Full article
(This article belongs to the Special Issue U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection)
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17 pages, 738 KB  
Article
Perceived Knowledge of the Use of Probiotics in Irritable Bowel Syndrome: A Cross-Sectional Survey
by Emanuele Sinagra, Dario Raimondo, Marcello Maida, Francesco Vito Mandarino, Ernesto Fasulo, Giovanni Marasco, Daniele Costanzo, Viviana Cimino, Guido Manfredi, Francesca Rossi, Rita Alloro, Giuseppe Rizzo, Giuseppe Conoscenti, Arianna Sferruzza, Roberto Ajovalasit, Sandro Sferrazza, Giulio Calabrese, Roberta Burlon, Emanuela Fertitta, Simona Di Ganci, Silvana Leanza, Danilo Coco, Francesco Pugliese, Mariangela Cosentino, Andrea Costantino, Roberto Vassallo, Rossella D’Anna and Endrit Shahiniadd Show full author list remove Hide full author list
Gastroenterol. Insights 2026, 17(3), 43; https://doi.org/10.3390/gastroent17030043 (registering DOI) - 8 Aug 2026
Abstract
Background and Objectives: This study aimed to characterize physicians’ knowledge and practice patterns regarding the use of probiotics in the management of irritable bowel syndrome (IBS). By examining clinical experiences and barriers to adoption, this research sought to identify critical gaps in practice [...] Read more.
Background and Objectives: This study aimed to characterize physicians’ knowledge and practice patterns regarding the use of probiotics in the management of irritable bowel syndrome (IBS). By examining clinical experiences and barriers to adoption, this research sought to identify critical gaps in practice and establish a foundation for evidence-based improvements in patient care. Materials and Methods: The survey was conducted in accordance with the CROSS (Consensus-based Checklist for Reporting of Survey Studies) guidelines. Attendees of a medical congress, specifically general practitioners, gastroenterologists, surgeons, and internists with an interest in the clinical significance and therapeutic modulation of the human microbiome, were invited to participate. Participants completed a 38-item, paper-based questionnaire. The instrument assessed respondents’ self-perceived knowledge of probiotics, their understanding of probiotic definitions and specific strains, and their current clinical practice patterns—particularly regarding the management of irritable bowel syndrome (IBS). Additionally, the survey explored information sources, the frequency of self-prescription, and the perceived need for further education, with a specific focus on safety profiles and clinical concerns. Results: Of the 70 invited attendees, 68 completed the survey, yielding a response rate of 97.1%. The respondent cohort included 40 general practitioners (GPs), 20 gastroenterologists (GEs), four surgeons (SSs), and four internists (SIMs). More than half of the respondents were female (n = 37, 54.4%), with a median age of 43 years (range: 28–70). Exactly half of the respondents (n = 34, 50.0%) agreed that probiotics always have a role in the management of irritable bowel syndrome (IBS); however, only 44.1% (n = 30) reported familiarity with the relevant scientific literature on probiotics. Furthermore, respondents more frequently recognized bacterial species associated with single-strain probiotic formulations compared to those in multi-strain mixtures. The primary concern regarding the administration of probiotics for IBS was this lack of familiarity with the scientific literature, cited by 23.5% of respondents. Notably, 100% of the surveyed cohort expressed a need for further education on the topic. Conclusions: The emergence of scientific and clinical evidence results in a clinical practice characterized by high prescribing habits, despite the lack of formal approval. These findings highlight evidence showing the effectiveness of certain probiotic strains in managing IBS symptoms, suggesting the need for standardized guidelines. Given the demonstrated need for further education among the surveyed cohort, integrating probiotic-specific training into both undergraduate medical curricula and continuing professional development programs could significantly enhance the clinical knowledge and awareness of both current and future practitioners. Full article
(This article belongs to the Section Gastrointestinal Disease)
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19 pages, 3804 KB  
Article
The Laron Syndrome Mouse Model Reveals a Potential Contribution of Methylglyoxal-Derived Glycative Stress to IGF-1-Driven Prostate Cancer Progression
by Dominga Manfredelli, Camilla Torcoli, Cinzia Lilli, Catia Bellucci, Vincenzo N. Talesa, Francesca Mancuso, Tiziano Baroni and Cinzia Antognelli
Biology 2026, 15(16), 1342; https://doi.org/10.3390/biology15161342 (registering DOI) - 8 Aug 2026
Abstract
Individuals with Laron syndrome, a rare condition characterized by congenital insulin-like growth factor 1 (IGF-1) deficiency, display a remarkably low incidence of cancer, suggesting the existence of protective mechanisms linking reduced IGF-1 signaling to decreased cancer susceptibility. Consistent with this observation, IGF-1 is [...] Read more.
Individuals with Laron syndrome, a rare condition characterized by congenital insulin-like growth factor 1 (IGF-1) deficiency, display a remarkably low incidence of cancer, suggesting the existence of protective mechanisms linking reduced IGF-1 signaling to decreased cancer susceptibility. Consistent with this observation, IGF-1 is a recognized promoter of prostate cancer (PCa) progression, although the underlying mechanisms remain incompletely understood. Methylglyoxal (MG)-derived glycative stress, reflected by the accumulation of MG-derived hydroimidazolone 1 (MG-H1), has been implicated in PCa progression but has never been investigated in Laron syndrome. We found that liver tissues from Laron mice exhibited lower MG-H1 levels, suggesting reduced MG-derived glycative stress associated with low IGF-1 signaling. These findings prompted us to investigate whether MG-derived glycative stress contributes to IGF-1-driven PCa progression. Compared with the less aggressive LNCaP cells, PC3 cells displayed higher basal IGF-1 and MG-H1 levels, consistent with a potential association between IGF-1 and MG-derived glycative stress in PCa progression. Moreover, IGF-1 stimulation of LNCaP cells increased MG-H1 accumulation, proliferation, colony formation, invasiveness, and gene expression of matrix metalloproteinase (MMP)-1, MMP-7, MMP-9, receptor for advanced glycation end-products (RAGE), and Osteopontin (OPN), all of which were markedly attenuated by the MG scavenger aminoguanidine (AG). Collectively, these findings support a potential contribution of MG-derived glycative stress to IGF-1-driven PCa progression. Full article
(This article belongs to the Section Developmental and Reproductive Biology)
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26 pages, 2067 KB  
Review
Vitamin D and Metabolic Syndrome: Molecular Mechanisms and Clinical Implications: A Narrative Review
by Héctor Fuentes-Barría, Raúl Aguilera-Eguía, Miguel Alarcón-Rivera and Cherie Flores-Fernández
Int. J. Mol. Sci. 2026, 27(16), 7101; https://doi.org/10.3390/ijms27167101 (registering DOI) - 7 Aug 2026
Abstract
Metabolic syndrome (MetS) is a complex multisystem disorder characterized by insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which substantially increase the risk of type 2 diabetes mellitus and cardiovascular disease. The aim of this narrative review is to [...] Read more.
Metabolic syndrome (MetS) is a complex multisystem disorder characterized by insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which substantially increase the risk of type 2 diabetes mellitus and cardiovascular disease. The aim of this narrative review is to examine the role of vitamin D in the pathophysiology of MetS from a multisystem perspective. Specifically, it synthesizes current evidence on the molecular mechanisms through which vitamin D may influence inter-organ communication, insulin resistance, adipose tissue dysfunction, hepatic metabolism, skeletal muscle function, chronic inflammation, oxidative stress, and mitochondrial homeostasis, highlighting its potential contribution to the prevention and management of MetS. Current evidence indicates that MetS should not be regarded merely as a cluster of isolated metabolic abnormalities but rather as a disorder characterized by disrupted molecular signaling and impaired communication among metabolically active organs. In this context, experimental and preclinical evidence suggests that vitamin D, through activation of the vitamin D receptor (VDR), modulates key signaling pathways, including AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor gamma (PPAR-γ), thereby influencing insulin sensitivity, inflammation, oxidative stress, mitochondrial function, and metabolic homeostasis. Nevertheless, clinical evidence remains heterogeneous due, in part, to the lack of consensus regarding serum 25-hydroxyvitamin D thresholds for defining vitamin D status, as well as differences in baseline vitamin D concentrations, supplementation regimens, study populations, and methodological designs. Overall, the available evidence suggests that vitamin D should be considered an adjunct to lifestyle-based interventions rather than a stand-alone therapeutic strategy. Future research is warranted to clarify its clinical utility in the prevention and management of MetS. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases, 5th Edition)
20 pages, 2516 KB  
Review
Capsaicin for Orofacial Pain Management: Systematic Review and Meta-Analysis
by Ana Claudia de Macedo Andrade, Fernanda Aragão Felix, Sebastián Brauchi and Bruna Benso
Int. J. Mol. Sci. 2026, 27(16), 7099; https://doi.org/10.3390/ijms27167099 - 7 Aug 2026
Abstract
Orofacial pain is a multifactorial condition that severely impacts basic functions and overall quality of life in patients, underscoring the need for non-opioid therapeutic strategies. Targeting the Transient Receptor Potential Vanilloid 1 (TRPV1) pathway has emerged as a biologically plausible approach, given its [...] Read more.
Orofacial pain is a multifactorial condition that severely impacts basic functions and overall quality of life in patients, underscoring the need for non-opioid therapeutic strategies. Targeting the Transient Receptor Potential Vanilloid 1 (TRPV1) pathway has emerged as a biologically plausible approach, given its central role in nociceptive transduction and peripheral sensitization. Capsaicin, a selective TRPV1 agonist, induces receptor desensitization and has shown potential in chronic pain modulation; however, its efficacy in orofacial conditions remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of capsaicin in managing orofacial pain, compared to placebo or other pharmacological interventions. Following PRISMA guidelines, a comprehensive search of five databases (PubMed, Scopus, Web of Science, CDSR, and LILACS) was conducted without language or date restrictions. Studies involving human participants with orofacial pain treated with capsaicin were included. The protocol was registered in PROSPERO (CRD420251004538). Risk of bias was assessed using the RoB2, RoB2 crossover trial and ROBINS-I checklist, and meta-analyses were performed using random-effects models. Nine studies enrolling a total of 164 participants met the eligibility criteria and encompassed temporomandibular disorders, burning mouth syndrome, oral mucositis, trigeminal neuralgia, and neuropathic facial pain. Although placebo-controlled comparisons showed a trend toward pain reduction that did not reach statistical significance (MD = –1.87; [95% CI: –3.94, 0.19]; p = 0.08; I2 = 86%), and no significant difference was found between capsaicin concentrations (MD = 0.46; [95% CI: –2.67, 3.60]; p = 0.77, I2 = 66%), pre–post analyses of uncontrolled (single-arm) studies demonstrated a significant and clinically meaningful reduction in pain following capsaicin treatment (MD = –6.39; [95% CI: –7.40, –5.38; p < 0.001, I2 = 0%). Capsaicin also showed an acceptable safety profile: although adverse events were significantly more frequent than with control (OR = 19.84; [95% CI: 4.32–91.21]; p < 0.001, I2 = 0%), these were mild, localized, and self-limited. Capsaicin may provide clinically meaningful pain relief in selected orofacial conditions, particularly burning mouth syndrome, where uncontrolled evidence was most consistent (I2 = 0%); evidence for temporomandibular disorders was more heterogeneous and did not reach significance in pooled placebo-controlled analyses. Full article
(This article belongs to the Special Issue TRP Channels: Mechanisms, Functions, and Therapeutic Implications)
20 pages, 29894 KB  
Review
Multiparametric Ultrasound for Characterisation of Testicular Lesions: Beyond Orchiectomy
by Michele Bertolotto, Irene Campo, Rosaria Perrone, Alberto Zucconi, Andrea Piasentin and Roberto Stramare
Diagnostics 2026, 16(16), 2501; https://doi.org/10.3390/diagnostics16162501 - 7 Aug 2026
Abstract
The increasing detection of small, non-palpable testicular lesions has challenged the traditional paradigm that every solid intratesticular mass should be managed by radical orchiectomy. Many incidental lesions, particularly in infertile men and in patients with negative tumour markers, are benign or non-neoplastic, making [...] Read more.
The increasing detection of small, non-palpable testicular lesions has challenged the traditional paradigm that every solid intratesticular mass should be managed by radical orchiectomy. Many incidental lesions, particularly in infertile men and in patients with negative tumour markers, are benign or non-neoplastic, making overtreatment a clinically relevant concern. In this setting, ultrasound has become central to a more conservative and individualised diagnostic strategy. By combining high-resolution grey-scale imaging with Doppler, microvascular imaging, CEUS and elastography, multiparametric ultrasound provides complementary information on lesion morphology, vascularity, stiffness and interval change. When integrated with clinical presentation, tumour markers, fertility status, syndromic background and patient history, these features can help characterise lesions and estimate the likelihood of malignancy in the appropriate clinical context. Although imaging cannot replace histology, it can refine pre-test probability, support active surveillance in selected low-risk lesions, guide testis-sparing surgery, and improve assessment of the operated testis. This review examines the role of multiparametric ultrasound in characterisation of focal testicular lesions across different clinical settings, including incidentalomas, acute scrotal pain, trauma, bilateral disease, heterogeneous parenchyma, genetic and endocrine syndromes, and the postoperative testis. A structured, context-sensitive imaging approach may help reduce unnecessary orchiectomy while preserving timely detection of malignant, persistent, recurrent or metachronous disease. Full article
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32 pages, 1066 KB  
Review
Growth Differentiation Factor-15 in Acute Coronary Syndromes: Prognostic Value and Barriers to Clinical Implementation
by Michal Pruc, Maciej Maslyk, Andrzej Bielski, Milosz J. Jaguszewski and Lukasz Szarpak
Int. J. Mol. Sci. 2026, 27(16), 7093; https://doi.org/10.3390/ijms27167093 - 7 Aug 2026
Abstract
High-sensitivity cardiac troponin has made the diagnosis of myocardial infarction (MI) faster and more precise, but it does not measure the broader biological vulnerability that often determines the outcome after an acute coronary syndrome (ACS). Growth differentiation factor-15 (GDF-15) is induced by ischemic [...] Read more.
High-sensitivity cardiac troponin has made the diagnosis of myocardial infarction (MI) faster and more precise, but it does not measure the broader biological vulnerability that often determines the outcome after an acute coronary syndrome (ACS). Growth differentiation factor-15 (GDF-15) is induced by ischemic stress, inflammation, oxidative injury, renal dysfunction, metabolic disease, and ageing. This biology explains its appeal in ACS, but also its diagnostic limitation: GDF-15 is not cardiac-specific and should not be used as an alternative to electrocardiography and high-sensitivity troponin algorithms for early MI diagnosis. Its better supported role is prognostic. Across emergency department chest pain cohorts, non-ST elevation MI, ST elevation MI, post-ACS trial populations, and serial biomarker studies, higher GDF-15 concentrations are most consistently associated with all-cause mortality, cardiovascular mortality, heart failure, and major bleeding, while associations with recurrent ischemic events alone are less specific. The key unresolved issue is incremental clinical value. GDF-15 may improve discrimination and reclassification beyond clinical predictors, troponin, natriuretic peptides, renal function and GRACE or GRACE 2.0 in selected settings, but statistical association is not equivalent to clinical utility. Its possible role in bleeding risk estimation and antithrombotic benefit–risk assessment is clinically important, especially after the PLATO biomarker analyses, yet routine GDF-15-guided dual antiplatelet therapy decisions remain unsupported. Future implementation requires validated thresholds, calibration, decision curve evidence, health economic evaluation, and trials in which GDF-15-guided management changes care and improves outcomes. Full article
70 pages, 3883 KB  
Review
Sulforaphane and Broccoli-Derived Preparations in Obesity and Obesity-Related Metabolic Dysfunction: Mechanistic Insights, Preclinical Evidence, and Clinical Perspectives
by Efthymios Poulios, Sousana K. Papadopoulou, Evmorfia Psara, Dimitrios Tasoulas and Constantinos Giaginis
Pharmaceuticals 2026, 19(8), 1244; https://doi.org/10.3390/ph19081244 - 7 Aug 2026
Abstract
Background/Objectives: Obesity is a major global health challenge characterized by adipose tissue dysfunction, insulin resistance, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and increased cardiometabolic risk. Despite substantial therapeutic advances, limitations related to cost, adverse effects, and long-term adherence have stimulated interest in [...] Read more.
Background/Objectives: Obesity is a major global health challenge characterized by adipose tissue dysfunction, insulin resistance, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and increased cardiometabolic risk. Despite substantial therapeutic advances, limitations related to cost, adverse effects, and long-term adherence have stimulated interest in complementary nutritional approaches. Sulforaphane, a bioactive isothiocyanate derived primarily from broccoli and other cruciferous vegetables, has attracted considerable attention because of its antioxidant, anti-inflammatory, and metabolic regulatory properties. This narrative review critically evaluates the current evidence regarding the role of sulforaphane and broccoli-derived preparations in obesity and obesity-associated metabolic dysfunction. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Eligible publications included in vitro, animal, clinical, observational, and relevant review studies investigating sulforaphane, glucoraphanin, or broccoli-derived preparations in relation to obesity, adiposity, insulin resistance, metabolic syndrome, inflammation, oxidative stress, energy metabolism, and related metabolic abnormalities. Results: In vitro studies consistently demonstrate inhibition of adipocyte differentiation and lipid accumulation, attenuation of oxidative stress and inflammatory signaling, and enhancement of cellular energy metabolism. Animal studies further report reductions in adiposity, insulin resistance, hepatic steatosis, oxidative stress, and chronic inflammation, together with improvements in energy expenditure, metabolic flexibility, and obesity-associated metabolic abnormalities. Mechanistic evidence indicates that sulforaphane exerts pleiotropic metabolic effects through activation of the Nrf2 and AMPK pathways, suppression of NF-κB-mediated inflammation, improvement of mitochondrial function, promotion of thermogenesis and adipose tissue browning, regulation of lipid metabolism, and modulation of gut microbiota composition. Human studies, although limited and heterogeneous, suggest possible improvements in glycemic control, insulin sensitivity, endothelial function, and other surrogate metabolic biomarkers associated with obesity. However, evidence demonstrating clinically meaningful reductions in body weight, adiposity, or body composition remains limited and inconsistent, and improvements in these surrogate biomarkers should not be interpreted as evidence of reduced obesity-related morbidity or clinically meaningful adiposity reduction. Bioavailability, myrosinase activity, food processing, gut microbiota composition, and interindividual variability remain important determinants of efficacy and key translational challenges. Conclusions: Current evidence provides strong mechanistic and preclinical support for sulforaphane as a promising candidate adjunctive nutritional intervention for improving obesity-associated metabolic dysfunction. Nevertheless, current human evidence suggests possible metabolic benefits but does not establish sulforaphane as an effective weight-loss intervention or an evidence-based treatment for obesity. Large, long-term randomized controlled trials employing standardized sulforaphane preparations and comprehensive assessments of body weight, adiposity, body composition, metabolic health, pharmacokinetics, and gut microbiota composition are required to establish its clinical efficacy and define its role within precision nutrition strategies for obesity and obesity-associated metabolic dysfunction. Full article
(This article belongs to the Section Natural Products)
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