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14 pages, 3165 KB  
Article
MIT-001, a Mitochondria-Targeted ROS Scavenger, Ameliorates DSS-Induced Colitis and Is Associated with Reduced HMGB1 and IL-1β Expression
by Dongwoo Kim, Soon Ha Kim, Jung Wan Choe, Seung Young Kim, Jong Jin Hyun, Sung Woo Jung, Young Kul Jung, Hyung Joon Yim and Ja Seol Koo
Int. J. Mol. Sci. 2026, 27(13), 6051; https://doi.org/10.3390/ijms27136051 - 6 Jul 2026
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation in which excessive cell death and the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1) amplify mucosal injury. Although necrosis—particularly regulated forms including necroptosis and ferroptosis—has emerged as [...] Read more.
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation in which excessive cell death and the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1) amplify mucosal injury. Although necrosis—particularly regulated forms including necroptosis and ferroptosis—has emerged as a contributor to IBD pathogenesis, the therapeutic potential of targeting necrotic cell death remains incompletely explored. We investigated whether MIT-001 (previously known as NecroX-7), a mitochondria-targeted reactive oxygen species (ROS) scavenger with anti-necrotic activity, ameliorates intestinal inflammation in an acute dextran sulfate sodium (DSS)-induced colitis model. In vitro, MIT-001 reduced hydrogen peroxide-induced necrotic cell death in IEC-18 intestinal epithelial cells and was associated with a qualitative reduction in the 55-kDa cleaved poly(ADP-ribose) polymerase-1 (PARP-1) fragment (a marker of necrosis), with no apparent change in the apoptosis-related 89-kDa fragment. In vivo, oral administration of MIT-001 to C57BL/6 mice with DSS-induced colitis was associated with preservation of colon length, reduced histological injury, and a marked decrease in HMGB1-positive cells in colonic tissue. Among pro-inflammatory cytokines, IL-1β expression was significantly reduced, while IL-12, monocyte chemoattractant protein-1 (MCP-1), and TNF-α showed non-significant downward trends. These findings indicate that MIT-001 ameliorates DSS-induced colitis in association with reduced HMGB1 and IL-1β expression, supporting further investigation of mitochondria-targeted anti-necrotic strategies as a potential adjunctive approach in IBD. Full article
(This article belongs to the Section Molecular Biology)
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11 pages, 2702 KB  
Case Report
A Diagnostic Challenge in Regional Australia: Concurrent Mycobacterium avium Complex Lymphadenitis and Hairy Cell Leukemia
by Magnus Hanbin Liew, Branavan Sivagnanam, Andrea Chui Rong Chieng, Mohammad Ashraful Islam, Chih-Chiang Hu and Surender Juneja
J. Clin. Med. 2026, 15(13), 5174; https://doi.org/10.3390/jcm15135174 - 2 Jul 2026
Viewed by 102
Abstract
Introduction: Hairy cell leukemia is a rare, indolent chronic B cell lymphoproliferative disorder characterized by cytopenia, splenomegaly and profound immune dysfunction, predisposing affected individuals to opportunistic infections including non-tuberculous mycobacteria. Concurrent presentation with disseminated mycobacterial infection is un-common and may pose significant diagnostic [...] Read more.
Introduction: Hairy cell leukemia is a rare, indolent chronic B cell lymphoproliferative disorder characterized by cytopenia, splenomegaly and profound immune dysfunction, predisposing affected individuals to opportunistic infections including non-tuberculous mycobacteria. Concurrent presentation with disseminated mycobacterial infection is un-common and may pose significant diagnostic challenges. Case Presentation: We report the case of a 68-year-old Caucasian man with a history of splenectomy who presented with fever, lymphadenopathy, leukopenia and a generalized rash. Initial investigations including infectious, hematological and vasculitis workups were inconclusive. Lymph node histology demonstrated necrotizing lymphadenitis, which in the context of an otherwise negative investigations was initially suggestive of Kikuchi–Fujimoto disease. Subsequently, cultures from lymph node tissue and blood yielded Mycobacterium avium complex, establishing a diagnosis of disseminated infection. Further bone marrow evaluation with flow cytometry ultimately confirmed underlying hairy cell leukemia. Conclusions: This case highlights how an impaired immune milieu may obscure classic clinical and histopathological features, contributing to diagnostic delay and potentially inappropriate immunosuppressive treatment. Clinicians should maintain a high index of suspicion for underlying hematological malignancy in patients presenting with unexplained cytopenia in association with atypical infections. Early consideration of bone marrow evaluation can be crucial. Full article
(This article belongs to the Section Hematology)
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26 pages, 5755 KB  
Review
Spatial-Niche Perspective on the Heterogeneity and Functional Reprogramming of Tumor-Associated Macrophages in Digestive System Tumors
by Jingcheng Zhang, Yi Huang, Mingsi Zhang, Jiaheng Lou, Shuo Zhang, Sicheng Zhao, Zhiyuan Song, Kaiyuan Zhang, Tao Jiang and Guangji Zhang
Cells 2026, 15(13), 1198; https://doi.org/10.3390/cells15131198 - 1 Jul 2026
Viewed by 288
Abstract
Tumor-associated macrophages (TAMs) are among the most important myeloid cell populations in the tumor microenvironment of digestive system tumors and are characterized by marked plasticity, heterogeneity, and context dependence. This review focuses on gastric, colorectal, liver, and pancreatic cancers as representative digestive system [...] Read more.
Tumor-associated macrophages (TAMs) are among the most important myeloid cell populations in the tumor microenvironment of digestive system tumors and are characterized by marked plasticity, heterogeneity, and context dependence. This review focuses on gastric, colorectal, liver, and pancreatic cancers as representative digestive system solid tumors in which TAM spatial organization has been increasingly characterized by single-cell and spatial omics studies. Traditional M1/M2 polarization or fixed subtype-based classification is insufficient to capture the continuous state transitions of TAMs across tumor types, disease stages, and tissue regions. Recent evidence suggests that TAM heterogeneity reflects dynamic functional states shaped within distinct spatial niches by local oxygen supply, metabolic stress, stromal architecture, vascular status, and interactions with neighboring cells. From a spatial-niche perspective, this review synthesizes current evidence on TAM distribution patterns, phenotypic changes, and functional biases across six recurrent spatial contexts: the hypoxic core, invasive front, fibrotic septa, perivascular regions, tertiary lymphoid structure (TLS)-adjacent regions, and necrotic borders. By linking these niches with cross-niche functional axes and evidence-supported molecular programs, we provide a structured niche-to-function framework for comparing TAM spatial heterogeneity and its major functional dimensions, including metabolic adaptation, tissue remodeling, and immune-inflammatory regulation. This context-sensitive framework may help guide future studies of niche-specific TAM reprogramming and rational combinations with immunotherapy and other treatment strategies. Full article
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13 pages, 5554 KB  
Article
Correlation Between IVIM-DWI and DCE-MRI Parameters in Soft Tissue Tumors: A Comparative Analysis of Benign and Malignant Lesions
by Ahmet Peker, Yunus Emre Senturk, Enes Muhammed Canturk and Mohammed Salman Shazeeb
Tomography 2026, 12(7), 99; https://doi.org/10.3390/tomography12070099 - 1 Jul 2026
Viewed by 101
Abstract
Objective: The objective of this study was to investigate the relationship between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced MRI (DCE-MRI) parameters in soft tissue tumors (STTs). Methods: This retrospective study included patients with histopathologically confirmed STTs who underwent [...] Read more.
Objective: The objective of this study was to investigate the relationship between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced MRI (DCE-MRI) parameters in soft tissue tumors (STTs). Methods: This retrospective study included patients with histopathologically confirmed STTs who underwent both DCE-MRI and IVIM-DWI between March 2022 and February 2024. Patients with prior therapy and lipomatous tumors were excluded. DCE-MRI parameters (Ktrans, Kep, Ve, iAUC) were obtained from pharmacokinetic maps using manually placed regions of interest (ROIs) in the most perfused tumor areas, avoiding necrotic and cystic regions. Corresponding ROIs were applied to IVIM-DWI maps. IVIM parameters (D, D*, f) were calculated using 11 b-values. Results: Twenty-nine patients (mean age, 56 ± 18 years; 14 malignant, 15 benign) were included. Interobserver agreement was excellent for DCE-MRI parameters, whereas IVIM-DWI parameters showed moderate-to-good agreement, with D showing the lowest reproducibility. In malignant tumors, f demonstrated strong positive correlations with Ktrans (r = 0.81, p < 0.001) and iAUC (r = 0.79, p < 0.001), both of which remained significant after correction for multiple comparisons. fD* was higher in malignant than in benign lesions in the unadjusted group comparison; however, diagnostic performance was not evaluated in the present study. No significant differences were observed for DCE-MRI parameters between benign and malignant tumors. Conclusions: IVIM-DWI parameters demonstrated associations with DCE-MRI metrics in malignant STTs and may provide complementary information regarding tumor perfusion. However, the findings should be interpreted cautiously because ROI analysis was limited to a single representative slice. Further validation using larger cohorts and volumetric tumor assessment is required. Full article
(This article belongs to the Section Cancer Imaging)
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23 pages, 1302 KB  
Article
Confidence-Aware Decision-Level Fusion of Unpaired Radiographic and Histopathological Images for Osteosarcoma Classification
by Mehmet Akif Çifçi
Appl. Sci. 2026, 16(13), 6512; https://doi.org/10.3390/app16136512 - 30 Jun 2026
Viewed by 174
Abstract
Reliable osteosarcoma tissue characterization combines radiographic evidence of bone-level structural change with histopathological assessment of cellular morphology. In rare cancers, however, patient-matched multimodal datasets are rarely available because radiology and pathology follow separate clinical workflows and cohort sizes are small. This study examines [...] Read more.
Reliable osteosarcoma tissue characterization combines radiographic evidence of bone-level structural change with histopathological assessment of cellular morphology. In rare cancers, however, patient-matched multimodal datasets are rarely available because radiology and pathology follow separate clinical workflows and cohort sizes are small. This study examines whether decision-level fusion can integrate radiographs and histopathology images originating from independent, unpaired patient cohorts, and reports the results as a methodological proof of concept rather than as a clinically validated diagnostic system. Two EfficientNet-B0 encoders were trained separately using osteosarcoma-positive radiographs from the Kaggle Bone Tumor Classification dataset (180 images) and H&E-stained histopathology tiles from the TCIA Osteosarcoma Tumor Assessment collection (1144 tiles from four patients). Histopathology tiles carry three labels: non-tumor, viable tumor, and necrotic tumor. Because radiographs do not provide tissue-viability labels and cannot directly distinguish viable from necrotic tumor, the radiographic branch was used as a weak radiograph-derived probability prior mapped into the shared three-class decision space during fusion. Fusion operates only on modality-specific probability vectors; no case-level or patient-level pairing is assumed or required. The adaptive gating network estimates a per-sample radiograph-prior weight, α, from the concatenated vector, [Pr, Ph], where Pr denotes the radiograph-derived probability prior, Ph denotes the histopathology probability vector, and 1 − α denotes the histopathology weight. To limit leakage in the small histopathology cohort, the four patients were assigned to fixed training (P001 and P002), calibration (P003), and test (P004) partitions with strict patient-level separation. On the single held-out test patient (171 tiles), adaptive gating fusion classified 166 of 171 tiles correctly (97.08% accuracy, macro-F1 of 0.97, and macro-AUC of 0.99), compared with 161 of 171 tiles (94.15%) for fixed-α fusion at α = 0.25. McNemar’s test for this comparison gave χ2 = 3.20, p = 0.074, so the improvement was numerically higher but not statistically significant at the 0.05 level. Simpler classifiers on the same three-dimensional fused vector reached comparable accuracy (95.91–96.49%), and none differed significantly from adaptive gating. These results indicate that confidence-aware decision-level fusion is feasible under unpaired, data-constrained conditions, and that its present value lies in interpretable per-sample modality weighting rather than in a demonstrated accuracy advantage. The single-patient histopathology test set precludes any claim of clinical generalizability; validation on larger, multi-institutional, patient-level cohorts remains necessary. Full article
(This article belongs to the Section Materials Science and Engineering)
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22 pages, 4961 KB  
Review
Spatial Heterogeneity of Intratumoral Microbiota and Its Roles in Tumor–Microbiota Interactions and Therapeutic Implications
by Li Li, Xiaoqian Shi, Mingyang Liu, Tongzhen Xu, Yinan Chen, Ranjiaxi Wang, Qiyue Zhang and Dan Li
Pathogens 2026, 15(7), 687; https://doi.org/10.3390/pathogens15070687 - 30 Jun 2026
Viewed by 301
Abstract
The intratumoral microbiota has emerged as a critical component of the tumor microenvironment (TME), with accumulating evidence indicating that its biological functions are influenced not only by microbial composition but also by their spatial organization within tumor tissues. This review summarizes the historical [...] Read more.
The intratumoral microbiota has emerged as a critical component of the tumor microenvironment (TME), with accumulating evidence indicating that its biological functions are influenced not only by microbial composition but also by their spatial organization within tumor tissues. This review summarizes the historical development and potential origins of intratumoral microbiota, and elaborates on the concept and biological significance of spatial heterogeneity. Based on recurrent spatial distribution patterns reported across different tumor types, we propose a conceptual framework comprising several putative spatial niches, including hypoxic/necrotic, immune-enriched, stromal-associated, invasive/metastatic, and intracellular niches. We further discuss the potential mechanisms contributing to the establishment and maintenance of spatial heterogeneity. The clinical significance of spatial microbial signatures is critically evaluated, alongside a comprehensive overview of spatial analytical methodologies, ranging from in situ hybridization and immunology-based approaches to emerging spatial omics and multi-omics integration strategies. Finally, we address key challenges and limitations, including contamination control, causal inference, barriers to clinical translation, and the underexplored spatial dimensions of the intratumoral mycobiome and virome. By synthesizing current knowledge and identifying critical gaps, this review aims to provide a conceptual and methodological framework for advancing spatially resolved investigations of intratumoral microbiota and facilitating their potential translational applications in precision oncology. Full article
(This article belongs to the Section Bacterial Pathogens)
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13 pages, 2189 KB  
Article
First Record of Hepatospora eriocheir Infection in the Chinese Mitten Crab Eriocheir sinensis in the Baltic Sea
by Magdalena Stachnik, Monika Normant-Saremba and Anna Kycko
Pathogens 2026, 15(7), 681; https://doi.org/10.3390/pathogens15070681 - 26 Jun 2026
Viewed by 182
Abstract
Hepatospora eriocheir is a microsporidian parasite of the Chinese mitten crab Eriocheir sinensis, an invasive decapod now widely distributed in European inland and coastal waters. Although the host is common across much of Europe, confirmed European records of H. eriocheir have remained [...] Read more.
Hepatospora eriocheir is a microsporidian parasite of the Chinese mitten crab Eriocheir sinensis, an invasive decapod now widely distributed in European inland and coastal waters. Although the host is common across much of Europe, confirmed European records of H. eriocheir have remained scarce and, until now, have not included the Baltic Sea region. In this study, 15 adult E. sinensis collected from the Vistula Lagoon, southern Baltic Sea, were examined using gross pathological assessment, wet-mount microscopy, histopathology, PCR amplification, Sanger sequencing, and phylogenetic analyses of parasite SSU rRNA and host COI sequences. Hepatopancreatic alterations were observed in several individuals, ranging from pale discolouration and friability to loss of normal tissue organisation. Spores were detected in fresh squash preparations from affected tissue, and histology revealed epithelial disruption, intratubular spore accumulation, and necrotic changes consistent with progressive microsporidian infection. Molecular screening confirmed H. eriocheir in 60.0% of crabs, with positive cases occurring in both females and males. The parasite sequences formed a single, well-supported clade and were highly similar to previously reported H. eriocheir sequences from the United Kingdom and China. Host COI sequences represented three mitochondrial haplotypes, indicating that the infection occurred across more than one host mitochondrial haplotype background. These findings constitute the first record of H. eriocheir in E. sinensis from the Baltic Sea and support the hypothesis that infected crabs reaching the Vistula Lagoon are connected with the wider North Sea invasion system rather than an isolated Baltic lineage. Full article
(This article belongs to the Special Issue Pathogens of Fish and Shellfish)
10 pages, 7401 KB  
Case Report
Diagnostic Pitfall in Cardiac Angiosarcoma: Initial Misdiagnosis as Masson Tumor Due to Sampling of Necrotic Tissue
by Hasan Obeidat, Mahyar Toofantabrizi, Katie Li, Sarah J. Silva and Hibba Tul Rehman
Reports 2026, 9(3), 201; https://doi.org/10.3390/reports9030201 - 25 Jun 2026
Viewed by 189
Abstract
Background and Clinical Significance: Cardiac and mediastinal angiosarcomas are rare, aggressive malignancies that often present with nonspecific symptoms and pose significant diagnostic challenges. Tumor heterogeneity and necrosis may lead to false-negative biopsy results; Case Presentation: We report a 64-year-old man who initially presented [...] Read more.
Background and Clinical Significance: Cardiac and mediastinal angiosarcomas are rare, aggressive malignancies that often present with nonspecific symptoms and pose significant diagnostic challenges. Tumor heterogeneity and necrosis may lead to false-negative biopsy results; Case Presentation: We report a 64-year-old man who initially presented with cardiac tamponade of unclear etiology. Despite an extensive workup, the patient remained asymptomatic for five months before re-presenting with dyspnea and a large mediastinal mass compressing the right heart, along with a lytic rib lesion. Initial ultrasound-guided biopsy of the rib lesion demonstrated a benign vascular proliferation consistent with Masson tumor (intravascular papillary endothelial hyperplasia), which was discordant with aggressive imaging findings. Further evaluation with positron emission tomography–computed tomography (PET-CT) revealed peripheral metabolic activity, and cardiac magnetic resonance imaging (MRI) demonstrated a heterogeneous mass with central necrosis and peripheral enhancement. A repeat CT-guided biopsy targeting the metabolically active region confirmed angiosarcoma, with immunohistochemical staining demonstrating diffuse positivity for ERG, CD31, and CD34. The patient was treated with palliative radiation and paclitaxel-based chemotherapy but experienced rapid clinical decline and transitioned to comfort-focused care; Conclusions: This case highlights the importance of correlating imaging with pathology and emphasizes the risk of sampling error in necrotic tumors. PET-guided biopsy targeting viable tumor regions is essential in cases with discordant findings. Full article
(This article belongs to the Section Oncology)
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17 pages, 968 KB  
Review
Unraveling CARD9 Mutations in Deep Dermatophytosis: A Genetic Gateway to Fungal Invasion and Immune Dysfunction
by Dipika Shaw, Gargi Mudey, Sunil Dogra and Hitaishi Mehta
J. Fungi 2026, 12(6), 451; https://doi.org/10.3390/jof12060451 - 21 Jun 2026
Viewed by 475
Abstract
Deep dermatophytosis is a rare, life-threatening fungal infection characterised by the invasion of dermatophytes beyond the superficial layers of keratinised tissue into the dermis and subcutaneous tissues. The present review aimed to identify the current knowledge on the role of Caspase Recruitment Domain-containing [...] Read more.
Deep dermatophytosis is a rare, life-threatening fungal infection characterised by the invasion of dermatophytes beyond the superficial layers of keratinised tissue into the dermis and subcutaneous tissues. The present review aimed to identify the current knowledge on the role of Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in the pathogenesis, clinical spectrum, diagnosis, and management of deep dermatophytosis. For innate immune activation, CARD9 acts as an adaptor molecule. Basically, CARD9 helps mediate the connection between the fungal pattern recognition receptor (Dectin-1) and the NF-κB and MAPK signalling pathways, and it mediates cytokine production, thereby activating phagocytic activities. Thereby, any change or mutation in the CARD9 gene may disrupt these pathways, leading to dysfunctional neutrophils and impaired Th17-mediated antifungal immunity. Clinically, patients with CARD9 deficiency are immunocompetent but susceptible to recurrent and/or severe fungal infections [Candida, dermatophytes (Trichophyton spp.), and phaeohyphomycetes]. Deep dermatophytosis in these patients is usually chronic, treatment-resistant, and characterized by erythematous papules, nodules, plaques, ulcers, or necrotic lesions, most of which occur on the lower limbs. It usually occurs in adulthood and is more common in males. There have been instances of geographic clustering of CARD9 deficiency in Asia, North Africa, and the Middle East. Early recognition and genetic diagnosis of CARD9 mutations in patients with recurrent or atypical deep dermatophytosis. Although antifungal therapy is essential, hematopoietic stem cell transplantation can be a definitive treatment for selected patients with CARD9 deficiency. Thus, CARD9 deficiency is a critical factor in the better management of patients but remains an underrecognized cause of severe, treatment-resistant deep dermatophytosis, and early genetic diagnosis is essential for guiding targeted management and improving patient outcomes. This review emphasises the importance of CARD9 in antifungal immunity and underscores the need for greater clinical awareness and the incorporation of genetic evaluation into the management of deep dermatophytosis. Full article
(This article belongs to the Special Issue Dermatophytes and Cutaneous Fungal Infections)
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21 pages, 15281 KB  
Article
Comparative Cytotoxicity and Inflammatory Profiles of CeraSeal Versus AH Plus in Periodontal Tissue Repair: An In Vitro and In Vivo Study
by Gulnihol Sharipova, Jasur Rizaev, Shuxrat Boymuradov, Mirzaakbar Kamolov, Adolat Mamadiyorova, Latipov Javdat, Umarov Doniyor and Nozimjon Ibrokhimov
J. Mol. Pathol. 2026, 7(2), 24; https://doi.org/10.3390/jmp7020024 - 15 Jun 2026
Viewed by 439
Abstract
Background/Objectives: Endodontic perforation repair requires biomaterials that balance sealing ability with minimal cellular injury. AH Plus (epoxy resin-based) remains widely used despite cytotoxicity concerns. CeraSeal (calcium silicate-based bioceramic) is a potentially more biocompatible alternative. However, comparative data on sealer-induced cytotoxicity and inflammatory [...] Read more.
Background/Objectives: Endodontic perforation repair requires biomaterials that balance sealing ability with minimal cellular injury. AH Plus (epoxy resin-based) remains widely used despite cytotoxicity concerns. CeraSeal (calcium silicate-based bioceramic) is a potentially more biocompatible alternative. However, comparative data on sealer-induced cytotoxicity and inflammatory responses remain limited. This study compared the cytotoxicity and inflammatory profiles of CeraSeal and AH Plus using in vitro and in vivo approaches. Methods: Human periodontal ligament stem cells (hPDLSCs) were exposed to sealer extracts (1:4 AH Plus, 1:8 CeraSeal) for 120 h. Cell death was assessed by MTT, Live/Dead, LDH release, and Annexin V/PI flow cytometry. Oxidative stress was quantified via ROS generation (DCFH-DA). In a rat furcation perforation model (n = 8 teeth/group), inflammatory markers (TNF-α, IL-1β, CD68), osteogenic activity (ALP), and osteoclasts (TRAP) were evaluated. Results: AH Plus was associated with significantly greater necrotic cell death (357.6 ± 47.6% LDH release vs. CeraSeal 128.8 ± 37.5%; p = 0.0079) and reduced hPDLSC viability at all time points (p < 0.0001). ROS generation was comparable between sealers (~32–35%, p > 0.05). In vivo, IL-1β was higher in AH Plus-treated tissues (52.25 vs. 24.88 cells/mm2; p = 0.0002), while TNF-α and CD68 were greater in CeraSeal (p ≤ 0.0011). ALP was higher in AH Plus (median 6.15 vs. 3.68; p = 0.0002), with no difference in TRAP-positive osteoclasts. Morphometric analysis showed superior cellular preservation with CeraSeal (p = 0.0079), while inflammatory infiltration was higher in CeraSeal (p = 0.0002). Conclusions: AH Plus was associated with a necrotic-inflammatory profile with elevated IL-1β and higher ALP expression. CeraSeal demonstrated better cellular preservation, lower LDH release, and a distinct inflammatory signature (higher TNF-α and CD68). These findings establish comparative response profiles for the two sealers and support CeraSeal as a potentially biocompatible alternative, though further mechanistic studies are warranted. Full article
(This article belongs to the Collection Feature Papers in Journal of Molecular Pathology)
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13 pages, 40558 KB  
Case Report
Perioperative Challenges in Oral Cavity Cancer Reconstruction in a Patient with Behçet’s Disease: A Case Report
by Joon-Hyuk Lee, Il-Kug Kim and Sung-Eun Kim
J. Clin. Med. 2026, 15(12), 4562; https://doi.org/10.3390/jcm15124562 - 12 Jun 2026
Viewed by 196
Abstract
Background/Objectives: Behçet’s disease is a chronic relapsing multisystem inflammatory disorder characterized by recurrent mucocutaneous ulceration, vasculitis, and exaggerated inflammatory responses to minor trauma. These features may adversely affect wound healing after major head and neck oncologic reconstruction. This case report describes repeated wound [...] Read more.
Background/Objectives: Behçet’s disease is a chronic relapsing multisystem inflammatory disorder characterized by recurrent mucocutaneous ulceration, vasculitis, and exaggerated inflammatory responses to minor trauma. These features may adversely affect wound healing after major head and neck oncologic reconstruction. This case report describes repeated wound breakdown after oral cavity reconstruction in a patient with Behçet’s disease and advanced floor-of-mouth squamous cell carcinoma. Methods: A 51-year-old woman with Behçet’s disease and T4N2bM0 squamous cell carcinoma involving the floor of the mouth and tongue underwent tumor resection followed by reconstruction of the oral cavity defect using a right anterolateral thigh perforator free flap. Subsequent surgical procedures included debridement of necrotic tissue, negative-pressure wound therapy, split-thickness skin grafting of the thigh donor site, and salvage tumor resection with pectoralis major myocutaneous flap reconstruction after tumor recurrence. Results: After the initial anterolateral thigh free flap reconstruction, flap perfusion was satisfactory in the immediate postoperative period; however, delayed marginal necrosis developed from the distal tongue-side flap margin, whereas the floor-of-mouth portion remained relatively stable. The right thigh donor site also developed progressive suture-line necrosis and wound dehiscence, requiring operative debridement, negative-pressure wound therapy, and split-thickness skin grafting. Although skin grafting achieved eventual donor-site coverage, partial graft necrosis and delayed secondary healing occurred. Persistent fistula and wound instability delayed postoperative radiotherapy, and recurrent floor-of-mouth squamous cell carcinoma subsequently developed approximately 6 months after the initial surgery. After salvage resection and pectoralis major myocutaneous flap reconstruction, the flap appeared viable at inset, but marginal ecchymosis, partial necrosis, and wound dehiscence again developed, requiring additional debridement, quilting sutures, and negative-pressure wound therapy. The wound gradually stabilized with staged wound management. Conclusions: This case illustrates a multifactorial pattern of repeated marginal wound breakdown after technically successful flap reconstruction in a patient with Behçet’s disease. Behçet-related pathergy-like inflammation, vasculitis, and microcirculatory dysfunction may represent possible contributing mechanisms, but they were not directly proven in this patient. In oral cavity reconstruction, such wound instability may delay adjuvant therapy and adversely affect oncologic outcomes. Careful perioperative planning, close multidisciplinary coordination, meticulous tension-free closure, early recognition of wound compromise, and readiness for staged wound management are essential in patients with Behçet’s disease undergoing major head and neck oncologic reconstruction. Full article
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22 pages, 8658 KB  
Review
Imaging and Non-Imaging Approaches for the Diagnosis and Monitoring of Necrotizing Enterocolitis—What Lies Ahead?
by Indrani Bhattacharjee, Catalina Le Cacheux, Eric B. Ortigoza, Jonathan Dillman, Sherwin S. Chan and Alain Cuna
Children 2026, 13(6), 787; https://doi.org/10.3390/children13060787 - 5 Jun 2026
Viewed by 407
Abstract
Necrotizing enterocolitis (NEC) remains one of the most serious gastrointestinal emergencies in preterm infants, and imaging plays a central role in diagnosis and clinical management. Historically, evaluation has relied primarily on abdominal radiography, which remains widely available and embedded in established diagnostic frameworks. [...] Read more.
Necrotizing enterocolitis (NEC) remains one of the most serious gastrointestinal emergencies in preterm infants, and imaging plays a central role in diagnosis and clinical management. Historically, evaluation has relied primarily on abdominal radiography, which remains widely available and embedded in established diagnostic frameworks. However, the hallmark radiographic signs of NEC (i.e., pneumatosis intestinalis, portal venous gas, and free air) reflect relatively advanced manifestations of intestinal injury that indicate established mucosal disruption or transmural necrosis. Bowel ultrasound has increasingly complemented radiography by enabling real-time assessment of bowel wall integrity, perfusion, motility, and intra-abdominal fluid, providing physiologic information that may refine clinical interpretation and monitoring of disease progression. Expanding use of neonatologist-performed bowel ultrasound may further improve access to bedside intestinal imaging and facilitate more timely evaluation in neonatal intensive care settings. In parallel, emerging imaging technologies seek to extend the capabilities of conventional imaging by interrogating biologic processes that underlie intestinal injury. Modalities such as contrast-enhanced ultrasound, ultra-high-frequency ultrasound, and photoacoustic imaging offer the potential to characterize bowel microvascular perfusion, tissue oxygenation, and microstructural changes that may precede overt radiographic abnormalities. Complementary physiologic monitoring approaches are also being explored to identify infants at risk before clinical disease develops. Techniques including superior mesenteric artery Doppler, near-infrared spectroscopy, bowel acoustic monitoring, and electrogastrography aim to detect early alterations in intestinal perfusion, oxygenation, and motility. In addition, artificial intelligence applied to imaging and physiologic data may enhance pattern recognition, risk stratification, and clinical decision support. Together, these advances suggest that NEC evaluation is evolving from a paradigm focused on detecting late structural injury toward integrated approaches capable of identifying intestinal vulnerability earlier and monitoring disease more precisely. Full article
(This article belongs to the Special Issue Necrotizing Enterocolitis in Newborns)
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10 pages, 2008 KB  
Case Report
First Report of Mycobacterium bovis and Nocardia spp. Co-Infection in a Roan Antelope
by Luca Botta, Matteo Cuccato, Neva Cormio, Veronica Crocchianti, Maria Goria, Emanuelle Bergeron, Delphine Mouniée, Veronica Rodriguez Nava and Frine Eleonora Scaglione
Animals 2026, 16(11), 1721; https://doi.org/10.3390/ani16111721 - 4 Jun 2026
Viewed by 672
Abstract
Nocardia spp. and Mycobacterium spp. are known etiological agents of granulomatous pulmonary infections in humans and animals; however, co-infections involving these pathogens have not previously been reported in veterinary medicine. This paper describes the first documented case of co-infection with Mycobacterium bovis and [...] Read more.
Nocardia spp. and Mycobacterium spp. are known etiological agents of granulomatous pulmonary infections in humans and animals; however, co-infections involving these pathogens have not previously been reported in veterinary medicine. This paper describes the first documented case of co-infection with Mycobacterium bovis and Nocardia spp. in a captive roan antelope (Hippotragus equinus). The animal was a 9-year-old female roan antelope from a safari park in northern Italy that died suddenly with a one-month history of weight loss. Post-mortem examination revealed severe, diffuse, chronic granulomatous pneumonia associated with fibrino-granulomatous pleuritis and granulomatous pericarditis. Histologically, multifocal to coalescing necrotizing granulomas were observed, with intralesional acid-fast bacteria. Microbiological culture and biomolecular analyses allowed the identification of M. bovis and Nocardia spp. in lung tissue samples. The Nocardia genome sequence was 98.5% similar to N. tengchongensis, a recently discovered species. The findings emphasize the importance of comprehensive diagnostic approaches in animal granulomatous lung disease. Mixed infections in captive wildlife represent a One Health concern, as the potential for zoonotic adaptation and transmission to humans cannot be excluded. Therefore, pathogen surveillance is of particular importance within zoological collections. Full article
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12 pages, 1271 KB  
Case Report
Fatal Systemic Infection Caused by Multidrug-Resistant Clostridioides difficile in a Domestic Rabbit: A Comprehensive Case Analysis
by Vlad Iorgoni, Livia Stanga, Paula Nistor, Ioan Cristian Dreghiciu, Alexandru Gligor, Bogdan Florea, Janos Degi, Ionica Iancu, Horia Iorgoni, Cosmin Horatiu Maris, Florin Vlad and Viorel Herman
Antibiotics 2026, 15(6), 572; https://doi.org/10.3390/antibiotics15060572 - 3 Jun 2026
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Abstract
Background/Objectives: Rabbit farming in Romania is increasingly important for providing high-quality meat, yet productivity is frequently threatened by enteric diseases, particularly in young animals. Among bacterial etiologies, Clostridioides difficile (C. difficile) has emerged as a significant gastrointestinal pathogen, with findings [...] Read more.
Background/Objectives: Rabbit farming in Romania is increasingly important for providing high-quality meat, yet productivity is frequently threatened by enteric diseases, particularly in young animals. Among bacterial etiologies, Clostridioides difficile (C. difficile) has emerged as a significant gastrointestinal pathogen, with findings suggestive of systemic dissemination and public health implications. This study aimed to investigate a fatal case of C. difficile infection in a farmed rabbit and to characterize the pathogen’s microbiological, toxigenic, and antimicrobial profile. Methods: An 11-month-old male German Giant Spotted rabbit presenting acute diarrhea, anorexia, and rapid deterioration after unsupervised administration of enrofloxacin and sulfaquinoxaline was submitted postmortem. Necropsy was performed, and samples from cecum, colon, liver, spleen, mesenteric lymph nodes, lungs, and femoral bone marrow were collected. Microbiological analysis included selective culture on CCFA medium, ELISA for toxin A and B detection, MALDI-TOF MS identification, PCR confirmation, and antimicrobial susceptibility testing with the VITEK 2 system. Histopathological examination was conducted on intestinal and parenchymal tissues. Results: Necropsy revealed severe congestion and necrosis of the cecal and colonic mucosa, hepatomegaly, splenic congestion, and petechial hemorrhages. C. difficile was isolated from intestinal sites, confirmed as toxigenic by ELISA and PCR. Histopathology showed necrotizing colitis with epithelial desquamation, fibrin deposition, and heterophilic infiltration. The strain exhibited resistance to clindamycin, ampicillin, and tetracycline, with susceptibility to vancomycin, linezolid, and tigecycline. Conclusions: This case demonstrates that C. difficile can cause severe disease in rabbits, particularly following antimicrobial-induced dysbiosis. The findings underscore the importance of prudent antibiotic use, monitoring of toxigenic strains in rabbit populations, and implementation of preventive strategies to mitigate health risks in both animals and potentially humans. Full article
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25 pages, 560 KB  
Review
What Does Bacteria Have to Do with Cancer? The Influence of the Body’s Microbiota on Cancer in Cats and Dogs
by Patrycja Kasperska, Iga Horodyska, Julia Mateja, Aleksandra Sobierajewicz, Marta Miszczak, Karolina Bierowiec and Joanna Bubak
Int. J. Mol. Sci. 2026, 27(11), 5005; https://doi.org/10.3390/ijms27115005 - 1 Jun 2026
Viewed by 664
Abstract
The body’s microbiota plays a fundamental role in maintaining homeostasis and influences immune function, metabolism, and tissue integrity. A growing body of research suggests that fluctuations in the composition and abundance of individual microbiota populations may influence cancer development and the effectiveness of [...] Read more.
The body’s microbiota plays a fundamental role in maintaining homeostasis and influences immune function, metabolism, and tissue integrity. A growing body of research suggests that fluctuations in the composition and abundance of individual microbiota populations may influence cancer development and the effectiveness of therapy. The condition of microbiota dysbiosis has been demonstrated to induce chronic inflammation, immune system dysregulation, and, most significantly, modulation of molecular pathways that promote tumorigenesis. The efficacy and toxicity of cancer treatment can be influenced by the composition of the microbiota. Bacteria can modify the effectiveness and toxicity of chemotherapy and immunotherapy by affecting drug metabolism and the body’s immune response. In contrast, the development of anticancer therapies that utilize bacteria is gaining increasing interest. This alternative to conventional treatment utilizes the natural ability of certain bacterial species to selectively colonize hypoxic and necrotic environments. The exploration of natural and genetically modified bacteria as vectors for the delivery of cytotoxins, immunomodulators, or therapeutic genes in the combat of cancer is a current area of research. In addition, their capacity to stimulate an antitumor immune response is also exploited. Preclinical investigations in animals have demonstrated the efficacy of this therapeutic approach, underscoring the promise of bacterial therapies as either an adjunct to conventional treatment or as a standalone strategy for combating cancer. This article synthesizes the current knowledge regarding the role of microbiota in carcinogenesis in animals and discusses recent developments in the field of bacterial therapies. The text also addresses the challenges, safety considerations, and future perspectives associated with translating microbiota-targeted and bacterial therapies into veterinary and comparative oncology. Full article
(This article belongs to the Section Molecular Oncology)
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