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21 pages, 3028 KB  
Article
Mechanism of Terpene Formation in Pogostemon cablin cv. Jing Huoxiang Revealed by Metabolome and Transcriptome Analysis
by Wei Ma, Xiukun Wan, Ge Yao, Fuli Wang and Hui Jiang
Int. J. Mol. Sci. 2026, 27(15), 6836; https://doi.org/10.3390/ijms27156836 - 30 Jul 2026
Viewed by 52
Abstract
Pogostemon cablin (Blanco) Benth. cv. ‘Jing Huoxiang’, is a valuable medicinal plant widely studied for its aboveground tissues, which are rich in bioactive compounds such as patchouli alcohol. However, systematic investigations into the biosynthesis of sesquiterpenes in its underground parts (roots) remain limited, [...] Read more.
Pogostemon cablin (Blanco) Benth. cv. ‘Jing Huoxiang’, is a valuable medicinal plant widely studied for its aboveground tissues, which are rich in bioactive compounds such as patchouli alcohol. However, systematic investigations into the biosynthesis of sesquiterpenes in its underground parts (roots) remain limited, with several critical knowledge gaps: (1) the metabolic basis of root-specific accumulation of polycyclic sesquiterpenes is unclear; (2) key terpene synthase (TPS) gene resources remain underexplored; and (3) the regulatory network of terpenoid biosynthesis is poorly understood. Addressing these questions is essential for the rational design and efficient production of terpene synthases. In this study, we integrated metabolomic and transcriptomic approaches to systematically characterize terpenoid profiles across different tissues of P. cablin and elucidate their biosynthetic regulation. Using GC-MS analysis, we identified distinct terpenoid compositions in roots, stems, leaves, flowers, and glandular trichomes. Notably, patchouli alcohol and pogostone accounted for over 60% of the total volatile oil content, while roots specifically accumulated polycyclic sesquiterpenes such as β-caryophyllene and α-humulene. Through transcriptome sequencing and bioinformatic analysis, we comprehensively annotated the TPS gene family, revealing that the TPS-a subfamily (34 genes) was the most abundant in P. cablin, with several members exhibiting root-predominant expression. Co-expression network analysis further identified candidate genes encoding potential high-efficiency polycyclic sesquiterpene synthases and uncovered a β-caryophyllene/α-humulene-regulated tertiary metabolic pathway. Our findings not only fill a critical gap in understanding sesquiterpene biosynthesis in the underground tissues of P. cablin but also provide a foundation for synthetic biology-based optimization of terpenoid production. This research paves the way for the efficient biosynthesis of sesquiterpenes to meet industrial demands in pharmaceuticals, fragrances, and biofuels. Full article
(This article belongs to the Special Issue Plant Molecular Ecology and Genomic Perspectives)
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18 pages, 3050 KB  
Article
Adaptive Structural and Transcriptional Responses Contribute to Cold Tolerance Variation in Xinluzhong 61 and Tahe 2 Cotton Cultivars
by Hemeng Wang, Yuhao Hu, Fengjiao Wang, Mengmeng Jia, Ziyi Yang, Zhijie Wang, Fuling Wang and Yanqin Wang
Int. J. Mol. Sci. 2026, 27(14), 6401; https://doi.org/10.3390/ijms27146401 - 18 Jul 2026
Viewed by 237
Abstract
This study elucidated the molecular, morphological and anatomical mechanisms underlying differential cold tolerance between two cotton cultivars, cold-tolerant Xinluzhong 61 (C61) and cold-sensitive Tahe 2 (C2). Seedlings were subjected to 0 °C cold stress for 12 and 24 h, followed by comparative transcriptomic [...] Read more.
This study elucidated the molecular, morphological and anatomical mechanisms underlying differential cold tolerance between two cotton cultivars, cold-tolerant Xinluzhong 61 (C61) and cold-sensitive Tahe 2 (C2). Seedlings were subjected to 0 °C cold stress for 12 and 24 h, followed by comparative transcriptomic (RNA-Seq) and comprehensive anatomical analyses of cotyledons, true leaves and stems. Transcriptomic profiling identified 8834 and 14,664 differentially expressed genes (DEGs) in C2 and C61 at 12 h, and 14,399 and 16,791 DEGs at 24 h, respectively. KEGG enrichment revealed prominent involvement of phenylpropanoid biosynthesis, photosynthesis, and cutin/suberin/wax biosynthesis at 12 h, shifting to phagosome, cysteine and methionine metabolism at 24 h. Phenotypic and anatomical observations confirmed that C61 developed dense stem glandular trichomes absent in C2, maintained significantly greater leaf thickness, palisade tissue thickness and palisade-to-spongy ratio in true leaves after 24 h stress, and exhibited thicker stem xylem. These findings highlight core adaptive traits and provide valuable genetic targets for improving cold tolerance in cotton. Full article
(This article belongs to the Special Issue Plant Stress Biology)
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23 pages, 1821 KB  
Review
Epigenome Editing for Cannabinoid Yield: Targets, Tools, and Priorities in Cannabis sativa
by S. M. Ahsan, Sanjida Sultana Keya, Md. Injamum-Ul-Hoque, Nayan Chandra Howlader, Md. Rakib Hasan, Md Azizul Haque, Hossain Uddin Shekhar, Hyong Woo Choi and Md. Mezanur Rahman
Int. J. Mol. Sci. 2026, 27(14), 6299; https://doi.org/10.3390/ijms27146299 - 15 Jul 2026
Viewed by 541
Abstract
Cannabinoid content can vary several-fold across Cannabis sativa L. cultivars that carry functional, closely related CBDA synthase (CBDAS) and THCA synthase (THCAS) alleles, a difference that coding-sequence variation among functional alleles does not fully explain. Structural and copy-number variation [...] Read more.
Cannabinoid content can vary several-fold across Cannabis sativa L. cultivars that carry functional, closely related CBDA synthase (CBDAS) and THCA synthase (THCAS) alleles, a difference that coding-sequence variation among functional alleles does not fully explain. Structural and copy-number variation at the synthase loci, the functional or pseudogenised state of synthase alleles, and linkage at the B locus account for much of the qualitative drug-versus-hemp chemotype; however, these genetic factors do not fully explain the quantitative, several-fold variation in cannabinoid content among cultivars that carry functional, near-identical synthase alleles. Three independent lines of evidence now indicate that chromatin-level regulation contributes to this variation. H3K4me3 and H3K56ac co-occupy the promoters and gene bodies of THCAS, CBDAS, OLS, and OAC exclusively in glandular trichome tissue while H3K27me3 marks the identical loci in vegetative tissues, indicating that a Polycomb-to-Trithorax chromatin switch is associated with trichome-specific cannabinoid gene expression, potentially independently of transcription factor availability. Progressive DNA hypomethylation accumulates during micropropagation in a cultivar-specific manner, with promoter-region differentially methylated positions reaching up to 22% by twenty subcultures, identifying DNA methylation maintenance as a candidate determinant of epigenetic stability in clonally propagated material, although the functional consequences for cannabinoid pathway gene expression and yield remain to be quantitatively established. In Cannabis indica cell suspension cultures, UV irradiation increases genome-wide DNA methylation (detected by MSAP, which does not resolve locus-specific changes) and elevates CBDAS transcript levels approximately 4-fold relative to non-irradiated controls. This coupling of an environmentally triggered methylation change to cannabinoid pathway gene expression in the Cannabis genus is suggestive, but the genome-wide MSAP signal and the use of C. indica cell cultures mean the locus-specific methylation change at the CBDAS promoter remains to be demonstrated. These findings identify specific, experimentally documented chromatin states as candidate targets for dCas9-effector intervention, including the H3K27me3 repressive state at cannabinoid loci that could be addressed by dCas9-KDM6A and the propagation-induced CG hypomethylation that could be addressed by dCas9-DNMT3A; these editing strategies remain hypotheses that have not yet been tested in Cannabis. We synthesize functional evidence from Catharanthus roseus, Papaver somniferum, and Artemisia annua demonstrating that equivalent chromatin switches control secondary metabolite yield in medicinal plants, evaluate which dCas9-effector architectures are most appropriate for each Cannabis chromatin target, and identify the critical mechanistic gaps that must be closed before epigenome editing can be rationally deployed for cannabinoid yield enhancement in Cannabis. Full article
(This article belongs to the Special Issue Plant Epigenetic Memory Under Abiotic Stress)
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16 pages, 5625 KB  
Article
A Comprehensive Evaluation of 3D-Printed Breast Phantoms: Impacts of Printing Technology and STL Processing on Multimodal Fidelity
by Nikolay Dukov, Vencislav Nastev, Viktoria Petkova, Ivan Buliev, Zhivko Bliznakov, Valentina Dobreva and Kristina Bliznakova
Technologies 2026, 14(7), 426; https://doi.org/10.3390/technologies14070426 - 12 Jul 2026
Viewed by 272
Abstract
Anthropomorphic breast phantoms are increasingly used for the development and evaluation of breast imaging technologies. The aim of this study is to evaluate the impacts of the material combination and stereolithography or Standard Tessellation Language (STL) export methodology on the multimodal imaging performance [...] Read more.
Anthropomorphic breast phantoms are increasingly used for the development and evaluation of breast imaging technologies. The aim of this study is to evaluate the impacts of the material combination and stereolithography or Standard Tessellation Language (STL) export methodology on the multimodal imaging performance of patient-derived breast phantoms. A breast model derived from segmented magnetic resonance imaging (MRI) data was used to fabricate four multi-material phantom sections representing adipose- and glandular-equivalent regions. Two material combinations—acrylic styrene acrylonitrile and high-impact polystyrene (ASA-HIPS) and acrylic styrene acrylonitrile and acrylonitrile butadiene styrene (ASA-ABS)—and two STL export procedures were evaluated, including a conventional mesh-based workflow and an in-house voxel-preserving approach designed to eliminate interface gaps. The phantoms were imaged using clinical computed tomography (CT), mammography, and digital breast tomosynthesis systems. Quantitative evaluation included contrast-based image characteristics and region of interest-based intensity distribution analysis. The results showed that ASA-HIPS phantoms demonstrated higher inter-material contrast and greater attenuation separation than ASA-ABS across all imaging modalities. The voxel-preserving STL export procedure improved physical interface integrity and eliminated visible inter-material gaps, while producing only minor differences in global radiological metrics compared with the conventional workflow. CT imaging of the breast samples acquired at 70 kVp showed attenuation characteristics consistent with clinically reported Hounsfield unit ranges for low-density breast tissues observed in clinical CT examinations. Full article
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12 pages, 24260 KB  
Case Report
Desmoid-Type Fibromatosis of the Male Breast Associated with Bilateral Gynecomastia: Diagnostic Challenges and Surgical Management
by Tevfik Satir, Uzay Cambaz and Ibrahim Güler
J. Clin. Med. 2026, 15(14), 5377; https://doi.org/10.3390/jcm15145377 - 9 Jul 2026
Viewed by 319
Abstract
Background/Objectives: Breast fibromatosis (desmoid-type fibromatosis) is a rare, locally aggressive neoplasm that may closely mimic breast carcinoma on imaging. Occurrence in male patients is exceptionally uncommon, particularly in association with gynecomastia. We report a rare case of male breast fibromatosis and discuss the [...] Read more.
Background/Objectives: Breast fibromatosis (desmoid-type fibromatosis) is a rare, locally aggressive neoplasm that may closely mimic breast carcinoma on imaging. Occurrence in male patients is exceptionally uncommon, particularly in association with gynecomastia. We report a rare case of male breast fibromatosis and discuss the diagnostic challenges, surgical decision-making, and reconstructive management. Methods: A 35-year-old male presented with a palpable right breast mass and bilateral grade II gynecomastia. Histopathological and immunohistochemical analyses were performed. Following multidisciplinary evaluation, the patient underwent wide local excision of the lesion with immediate glandular-adipose tissue rearrangement and simultaneous contralateral gynecomastia correction. Results: Ultrasonography demonstrated a hypoechoic lesion of 12 × 11 mm, whereas mammography revealed an irregular mass measuring up to 34 mm. Core needle biopsy showed a fibroblast-rich spindle-cell proliferation with nuclear β-catenin positivity, consistent with desmoid-type fibromatosis. Final histopathology confirmed a 2.5 cm lesion with negative resection margins (minimum margin 5 mm). Immediate reconstruction achieved a satisfactory chest contour and symmetry. No evidence of recurrence was observed during 18 months of follow-up. Conclusions: Breast fibromatosis should be considered in the differential diagnosis of suspicious male breast lesions because radiological findings may closely resemble breast carcinoma. Histopathological confirmation remains essential for appropriate management. In selected patients, immediate glandular-adipose tissue rearrangement may facilitate single-stage defect reconstruction and preservation of chest contour following oncologic excision. Full article
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17 pages, 1900 KB  
Article
Optimization of In Vitro Propagation of Artemisia pontica Through Integrated Morphophysiological, Biochemical, and SEM Analysis Under GA3 and MeJA
by Mariateresa Cardarelli, Alessandra Trinchera and Alessandra Vitali
Horticulturae 2026, 12(7), 828; https://doi.org/10.3390/horticulturae12070828 - 6 Jul 2026
Viewed by 525
Abstract
Efficient micropropagation systems are essential for the large-scale production of uniform and high-quality plant material in aromatic species. In this study, the effects of gibberellic acid (GA3; 1.4, 2.8, and 5.6 μM) and methyl jasmonate (MeJA; 2.2, 4.4, and 8.8 [...] Read more.
Efficient micropropagation systems are essential for the large-scale production of uniform and high-quality plant material in aromatic species. In this study, the effects of gibberellic acid (GA3; 1.4, 2.8, and 5.6 μM) and methyl jasmonate (MeJA; 2.2, 4.4, and 8.8 μM) were evaluated on the in vitro performance of Artemisia pontica across two successive subcultures. Morphological, physiological, and biochemical parameters were assessed, and the most effective treatment was further investigated through scanning electron microscopy (SEM) to evaluate leaf trichome characteristics. GA3 treatments significantly enhanced shoot growth, shoot number, and relative growth rate, with the strongest response observed at 2.8 μM. This concentration also promoted higher chlorophyll content and antioxidant activity, indicating improved physiological status and metabolic performance of plantlets. In contrast, MeJA treatments, particularly at 8.8 μM, reduced growth performance and pigment accumulation, suggesting a less favorable physiological status for micropropagation. Multivariate analysis (PCA and hierarchical clustering) revealed a clear separation among treatments, with GA3 at 2.8 μM associated with a coordinated increase in growth-related and antioxidant traits. SEM analysis showed that GA3 influenced leaf epidermal structure, increasing the density of T-shaped, non-glandular trichomes and the diameter of glandular secreting trichomes, suggesting structural adjustments linked to metabolic activity. Overall, the results indicate that GA3 at 2.8 μM represents the most effective supplementation under the tested conditions, promoting a balanced improvement in shoot proliferation, physiological performance, antioxidant activity, and selected structural traits. Full article
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23 pages, 34498 KB  
Article
Mechanism of Lian-Huo-Hua-Zhuo Formula in Alleviating Gastric Mucosal Inflammation in a Mouse Model of Chronic Atrophic Gastritis by Inhibiting the IL-17 Signaling Pathway
by Xiaoxuan Mo, Fan Gao, Jiaye Tian, Fengyue Xu, Zeyang Xie, Hongyan Wei, Jinhu Yang, Jianming Jiang, Guoxing Deng and Qiuhong Guo
Pharmaceuticals 2026, 19(7), 1043; https://doi.org/10.3390/ph19071043 - 5 Jul 2026
Viewed by 474
Abstract
Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory [...] Read more.
Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG. Full article
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12 pages, 26678 KB  
Article
Secretory Cavity Development and Epidermal Exudation Pathways in Fruits of Ruta graveolens L. (Rutaceae)
by Silvia Rodrigues Machado, Aline Rodrigues de Almeida, Karla Bianca de Deus Bento, Sabrina Lemes Dias and Tatiane Maria Rodrigues
Plants 2026, 15(13), 2084; https://doi.org/10.3390/plants15132084 - 3 Jul 2026
Viewed by 372
Abstract
Ruta graveolens L. fruits are densely covered with translucent dots corresponding to secretory cavities that accumulate bioactive metabolites, primarily essential oils. Immature fruits present an aromatic surface exudate, indicating the active release of secretory products despite the internal location of the cavities. This [...] Read more.
Ruta graveolens L. fruits are densely covered with translucent dots corresponding to secretory cavities that accumulate bioactive metabolites, primarily essential oils. Immature fruits present an aromatic surface exudate, indicating the active release of secretory products despite the internal location of the cavities. This study investigated the origin, development, ultrastructure, and secretion-release mechanisms of fruit secretory cavities using light, scanning, and transmission electron microscopy. Secretory cavities originated from clusters of ground meristem cells associated with phloem strands. Lumen formation began with the collapse of central cells, while surrounding cells differentiated into a metabolically active secretory epithelium rich in polymorphic plastids, smooth endoplasmic reticulum, mitochondria, vesicles, and lipid bodies. Mature cavities consisted of a multilayered epithelium surrounding a large lumen and enclosed by a parenchymatous sheath. Progressive lysis of inner epithelial cells contributed to lumen expansion and secretion accumulation. As cavities enlarged, they became positioned immediately beneath the epidermis, whose cells became compressed and flattened. Secretion was released through the rupture of glandular and epidermal cells and through stomata located in epicarp depressions. Ultrastructural evidence indicates the combined operation of eccrine, granulocrine, and holocrine secretion mechanisms. Pectin–cellulosic wall thickenings likely function as apoplastic barriers, directing secretion toward the lumen and protecting adjacent tissues. Full article
(This article belongs to the Section Plant Development and Morphogenesis)
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20 pages, 753 KB  
Review
Cell and Gene Therapy for Patients Suffering from Xerostomia (Dry Mouth): Positioning Extracellular Vesicles as the Bridge Between Biomarker Discovery and Regenerative Therapy in Xerostomia—A Scoping Review
by Kumud Gogna, Hiba Mohammed Ali, Albert Leung and Shahnawaz Khijmatgar
Int. J. Mol. Sci. 2026, 27(13), 5926; https://doi.org/10.3390/ijms27135926 - 30 Jun 2026
Viewed by 701
Abstract
Xerostomia is a common and debilitating condition caused by salivary gland dysfunction, frequently associated with primary Sjögren’s syndrome and head and neck radiotherapy. Current management is largely symptomatic and does not address underlying glandular injury. Extracellular vesicles (EVs), including exosomes, have emerged as [...] Read more.
Xerostomia is a common and debilitating condition caused by salivary gland dysfunction, frequently associated with primary Sjögren’s syndrome and head and neck radiotherapy. Current management is largely symptomatic and does not address underlying glandular injury. Extracellular vesicles (EVs), including exosomes, have emerged as candidate mediators of intercellular communication that have been proposed for diagnostic and therapeutic applications; however, their translational relevance to xerostomia remains uncertain and is currently supported only by exploratory evidence. This scoping review aimed to map and interpret current evidence on EV-based approaches in xerostomia and salivary gland dysfunction. A scoping review was conducted in accordance with “Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR)” checklist. Twenty-five articles were included, comprising 14 primary studies and 11 review articles. Studies were analysed based on application focus, methodological characteristics, reported outcomes, and translational readiness. Most primary studies focused on EVs as diagnostic biomarkers or their roles in immune–epithelial signalling. Therapeutic research was limited and largely confined to human-relevant translational models, namely human peripheral blood mononuclear cell (PBMC) assays and freshly resected human salivary gland tissue-maintained ex vivo. Outcomes were predominantly molecular and cellular, with minimal assessment of salivary flow or patient-reported symptoms. The current evidence base, although biologically plausible, remains exploratory: most included studies are mechanistic, and no clinical efficacy studies in xerostomia were identified. A substantial gap therefore persists between molecular findings and clinically meaningful outcomes, and further translational research is required before any conclusions can be drawn regarding the clinical utility of EV-based approaches. Full article
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12 pages, 88898 KB  
Case Report
Feline Lower-Lip Apocrine Sweat Gland Adenocarcinoma with Mandibular Nodal Metastasis: A Case Report
by Yongwon Park, Ajin Lee, Jeonghoon Jang and Hwi-Yool Kim
Vet. Sci. 2026, 13(7), 606; https://doi.org/10.3390/vetsci13070606 - 23 Jun 2026
Viewed by 364
Abstract
Apocrine sweat gland adenocarcinoma is an uncommon feline adnexal neoplasm, and lower-lip involvement is rarely documented. A 14-year-old spayed female Siamese cat was evaluated for a firm 1.3 cm right lower-lip mass at a documented hemorrhagic lesion site. Approximately 1 year earlier, the [...] Read more.
Apocrine sweat gland adenocarcinoma is an uncommon feline adnexal neoplasm, and lower-lip involvement is rarely documented. A 14-year-old spayed female Siamese cat was evaluated for a firm 1.3 cm right lower-lip mass at a documented hemorrhagic lesion site. Approximately 1 year earlier, the lesion was fluctuant and superficially erosive to ulcerative; fine-needle aspiration yielded bloody fluid with cytologically nondiagnostic material. The lesion reportedly subsided after empirical treatment, but reassessment, tissue diagnosis, and objective confirmation of resolution were not performed. Cytology of the later same-site mass supported malignant epithelial neoplasia. Contrast-enhanced computed tomography (CT) identified a 12.5 × 13.2 × 16.6 mm rim-enhancing mass without mandibular invasion or distant metastasis; the ipsilateral mandibular lymph node was mildly thickened. Histopathology supported a diagnosis of lower-lip apocrine sweat gland adenocarcinoma with lymphovascular tumor emboli, lymphatic invasion, and nodal metastasis. The diagnosis was supported by superficial dermal/subcutaneous location, adjacent adnexal structures, skeletal-muscle separation from nearby minor salivary glands, epithelial immunoreactivity, periodic acid-chiff (PAS) and Alcian blue findings without distinct intratumoral mucin/mucopolysaccharide-rich material. The cat died without necropsy on postoperative day 87. This case supports tissue-based diagnosis and regional lymph node assessment for suspicious feline lower-lip glandular epithelial lesions. Full article
(This article belongs to the Special Issue Focus on Tumours in Pet Animals: 3rd Edition)
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2 pages, 147 KB  
Abstract
Venom Biology of the Lesser Weever Fish: Intraspecific Variability, Bioactivity, and Biotechnological Potential
by Ricardo Estevens, Telma Luís, Samuel Ramos Pereira, Vera M. Mendes, Bruno Manadas, Carolina Madeira and Pedro M. Costa
Proceedings 2026, 146(1), 32; https://doi.org/10.3390/proceedings2026146032 - 17 Jun 2026
Viewed by 294
Abstract
Fish venom biology reaches far beyond addressing risks of human envenomation. The critical understanding of venom composition and the drivers that modulate it will enable scientists to deliver a span of novel bioresources with multiple potential biotechnological applications. The lesser weever fish ( [...] Read more.
Fish venom biology reaches far beyond addressing risks of human envenomation. The critical understanding of venom composition and the drivers that modulate it will enable scientists to deliver a span of novel bioresources with multiple potential biotechnological applications. The lesser weever fish (Echiichtys vipera), common in the surf of sandy beaches in Portugal, is a noteworthy case study due to frequent envenomation episodes during summer, albeit the lack of information regarding its venom system and the composition of its venom. We collected about one hundred animals from Costa da Caparica (W Portugal) as beach trawl (arte xávega) by-catch. Histology showed a similar essential microanatomical structure of glands in both venomous spines (dorsal and opercular) and no obvious gender differences. Transversal sections across the spines showed a T-shaped supportive bone structure that harbor masses of large, glandular cells that bear large sacculi. The structure is surrounded by a retractable layer of skin, thicker in the opercular spines comparatively to dorsal. The lack of muscular tissue near the glands and missing venom delivery ducts in the spines suggest that venom secretion in this species is holocrine, i.e., that venom is delivered through rupture of the skin and underlying glandular tissue upon mechanical pressure. Proteomics of the venomous spines (dorsal and opercular) showed a different proteomic signature between males and females, pointing to intersexual variation and suggesting that other biotic and abiotic factors might influence venom composition (maturation stage or geographic distribution). Additionally, protein homology matches performed against known toxins from marine venomous fishes indicated the presence of novel unexplored toxins in this species besides expected cytolysins. Our focus in the future is to identify, isolate and characterize the individual components of this venom. We anticipate new insights on the intraspecific adaptation of fish venom systems to specific ecological needs and advocate for sustainable bioprospecting for novel proteins with high biotechnological potential. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
19 pages, 14700 KB  
Review
Salivary Hyalinizing Clear Cell Carcinoma and Odontogenic Clear Cell Carcinoma: A Case Series and a Scoping Review Comparing Clinicopathological Presentations
by Primali Rukmal Jayasooriya, Sumedha Madhavie Range, Ayodya Methmini Fernando, Balapuwaduge Ranjit Rigobert Nihal Mendis and Tommaso Lombardi
Diagnostics 2026, 16(12), 1846; https://doi.org/10.3390/diagnostics16121846 - 15 Jun 2026
Viewed by 335
Abstract
Background/Objectives: Hyalinizing clear cell carcinoma (HCCC) and clear cell odontogenic carcinoma (CCOC) are rare clear cell neoplasms with overlapping histopathological features. This study aimed to compare their clinicopathological characteristics, particularly in anatomically challenging sites such as the palate and maxilla. Methods: Three [...] Read more.
Background/Objectives: Hyalinizing clear cell carcinoma (HCCC) and clear cell odontogenic carcinoma (CCOC) are rare clear cell neoplasms with overlapping histopathological features. This study aimed to compare their clinicopathological characteristics, particularly in anatomically challenging sites such as the palate and maxilla. Methods: Three analyses were performed. First, an unpublished series of five HCCC and three CCOC cases was evaluated for diagnostic histopathological features. Second, a PRISMA-ScR-guided literature review of 58 HCCCs and 45 CCOCs restricted to tumours arising in intraoral minor salivary glands, major salivary glands and gnathic bones published between 2000 and 2025 was conducted using PubMed. Third, a sub-analysis compared palatal HCCC and maxillary CCOC (25 vs. 14 cases), integrating literature and unpublished cases. Results: The case series and overall literature review showed that HCCC and CCOC predominantly occurred in adults (mean age, case series: 50.8 years; literature: 56.33 years for HCCC and 61 vs. 54.11 years for CCOC) with a female predilection (case series: 60%; literature: 68%) and generally exhibited clinically indolent behaviour. The site of occurrence, soft tissue (HCCC) versus intraosseous location (CCOC), was the principal distinguishing feature. No marked differences were observed between the two tumours in either the overall literature analysis or the site-specific sub-analysis. However, CCOC at maxillary/palatal sites presented with a higher number of larger lesions and higher number of cases with nodal metastasis compared with HCCC, most probably indicating delayed clinical detection rather than intrinsic aggressiveness of CCOC. Histopathological overlap was considerable; however, diffuse dense hyalinization (4/5), focal glandular differentiation (2/5), mucous-secreting cells (4/5) and salivary gland association (5/5) favoured HCCC, whereas patchy hyalinization (3/3), larger tumour lobules (3/3) and peripheral palisading (2/3) favoured CCOC. Conclusions: HCCC and CCOC demonstrate clinicopathological similarities and shared EWSR1 rearrangement, supporting a close biological relationship. The considerable overlap between these tumours support the hypothesis that CCOC may represent the intraosseous counterpart of HCCC and highlight the importance of integrated clinicopathological assessment and further clarification in future WHO classifications. Full article
(This article belongs to the Special Issue Advances in Oral Pathology of Basic and Clinical Cancer Research)
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16 pages, 2221 KB  
Article
Dual Actions of Butyrate on Immunoepithelial Remodeling in Ex Vivo Intestinal Biopsies from Patients with Inflammatory Bowel Disease
by Sara Troisi, Cesare Pane, Letizia Masi, Filippo Biamonte, Domenico Scannone, Antonio Cappa Spina, Miriam Di Mattia, Valeria Emoli, Ivan Capobianco, Sonia Distante, Barbara Rondinone, Valentina Petito, Antonio Gasbarrini, Loris Riccardo Lopetuso and Franco Scaldaferri
Metabolites 2026, 16(6), 395; https://doi.org/10.3390/metabo16060395 - 6 Jun 2026
Viewed by 1421
Abstract
Background/Objectives: Butyrate, a microbiota-derived short-chain fatty acid, plays a central role in intestinal homeostasis, yet its concentration-dependent effects on human inflamed mucosa remain poorly defined. This study investigates the dose-dependent impact of butyrate on inflammatory signaling and epithelial architecture in ex vivo intestinal [...] Read more.
Background/Objectives: Butyrate, a microbiota-derived short-chain fatty acid, plays a central role in intestinal homeostasis, yet its concentration-dependent effects on human inflamed mucosa remain poorly defined. This study investigates the dose-dependent impact of butyrate on inflammatory signaling and epithelial architecture in ex vivo intestinal biopsies from patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Intestinal biopsies from six IBD patients (four UC, two CD) were cultured ex vivo for 24 h with calcium butyrate (5, 10, 100 mM). Cytokine secretion was analyzed by multiplex immunoassay, total protein release was quantified, and glandular morphology was assessed by stereological analysis. Results: Butyrate was associated with a dose-dependent reduction in pro-inflammatory cytokines-including TNF-α, IFN-γ, IL-6, and IL-17-in both inflamed and non-inflamed tissue. Non-linear responses were observed for specific mediators, such as IP-10, which displayed a biphasic pattern in inflamed UC biopsies. Notably, UC and CD biopsies exhibited distinct response profiles: UC samples showed marked cytokine modulation, including reduction in IL-15, whereas CD samples, evaluated at 5 and 10 mM, showed limited modulation across conditions. A trend toward reduced total protein secretion was observed in diseased UC biopsies following butyrate exposure. Stereological analysis revealed preservation of glandular area at 5 mM, reduction at 10 mM, and extensive tissue disruption at 100 mM precluding structural evaluation. Conclusions: In this pilot study, butyrate exerts dose-dependent and disease-specific effects in human IBD mucosa within a narrow therapeutic window. These exploratory findings suggest that dose-optimized strategies for butyrate-based interventions may be particularly relevant in UC, although larger confirmatory studies are needed. Full article
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20 pages, 40900 KB  
Article
TICAM1-Mediated TLR3/TLR4 Signaling Promotes Endometrial Stromal Cell Proliferation, Migration, and Invasion in Endometriosis via IRF3/IFN-β Axis
by HaLiSai MuDanLiFu, Suming Huang, Yamei Li, Yan Liang, Xiaoya Zhao, Qian Zhu, Sifan Ji, Jie Zhou, Chuqing He, Shunna Ge and Jian Zhang
Int. J. Mol. Sci. 2026, 27(11), 5089; https://doi.org/10.3390/ijms27115089 - 4 Jun 2026
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Abstract
Endometriosis (EMs) is an estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, yet its precise pathogenesis remains incompletely elucidated. TICAM1, a key adaptor protein in the Toll-like receptor (TLR) signaling pathway, is known to be involved in [...] Read more.
Endometriosis (EMs) is an estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, yet its precise pathogenesis remains incompletely elucidated. TICAM1, a key adaptor protein in the Toll-like receptor (TLR) signaling pathway, is known to be involved in inflammatory responses; however, its specific role in EMs has not been defined. This study integrated evidence from clinical tissue samples of patients with ovarian endometriomas, in vitro studies, and in vivo models to explore the role of TICAM1 in EMs. TICAM1 expression was significantly upregulated in both eutopic and ectopic endometrium, with the highest levels observed in ectopic lesions, where it was primarily localized to stromal and glandular epithelial cells. Functional experiments showed that TICAM1 overexpression promoted the proliferation, migration, and invasion of human endometrial stromal cells (hESCs), while TICAM1 knockdown suppressed these activities. Concurrently, TLR3 and TLR4 were also upregulated in EMs tissues, and their activation increased TICAM1 expression. Knockdown of TICAM1 attenuated the enhanced cellular activities induced by TLR3/TLR4 activation. Mechanistically, IRF3 and IFN-β levels were elevated in both EMs tissues and TICAM1-overexpressing hESCs, while TICAM1 knockdown inhibited TLR3/TLR4-induced IRF3 phosphorylation and subsequent IFN-β production. These findings were further corroborated in a mouse model of EMs. Together, our findings suggest that TICAM1 may enhance the proliferation, migration, and invasion of hESCs by mediating TLR3/TLR4 signaling and promoting IRF3 phosphorylation and subsequent IFN-β production, thereby potentially contributing to EMs progression. Therefore, targeting TICAM1 may represent a potential therapeutic direction for ovarian endometrioma-associated EMs, while its relevance to superficial peritoneal and deep infiltrating EMs requires further investigation. Full article
(This article belongs to the Section Molecular Oncology)
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26 pages, 36567 KB  
Article
A Reactive Oxygen Species-Responsive Biomimetic Adhesive Hydrogel Mediates Immunoregulation to Effectively Prevent Intrauterine Adhesions
by Wanzhen Li, Chenyu Liao, Yuzhen Li, Zijun Lin, Danni Xiao, Gengsheng Ye, Yanjuan Huang, Chunshun Zhao and Shengmiao Cui
Pharmaceutics 2026, 18(6), 685; https://doi.org/10.3390/pharmaceutics18060685 - 30 May 2026
Viewed by 887
Abstract
Background: Intrauterine adhesions, a leading cause of female infertility, frequently recur in 30–62.5% of patients despite hysteroscopic adhesiolysis and adjuvant therapies. Current intrauterine barriers, including injectable hydrogels, often lack sufficient bioactivity and tissue retention, failing to address the underlying pathological inflammation and oxidative [...] Read more.
Background: Intrauterine adhesions, a leading cause of female infertility, frequently recur in 30–62.5% of patients despite hysteroscopic adhesiolysis and adjuvant therapies. Current intrauterine barriers, including injectable hydrogels, often lack sufficient bioactivity and tissue retention, failing to address the underlying pathological inflammation and oxidative stress driving abnormal fibrosis. Methods: Herein, we tailored a reactive oxygen species (ROS)-responsive, mussel-inspired adhesive injectable hydrogel (OHA-CP@TA) to intelligently modulate the inflammatory niche and promote normal endometrial regeneration. OHA-CP@TA was fabricated through Schiff base bonds between oxidized hyaluronic acid (OHA) and phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA), and boronate ester bonds between CMCS-PBA and tannic acid (TA). Results: OHA-CP@TA exhibited good mechanical strength, injectability, self-healing, and shear-thinning properties, and importantly, robust and stable adhesion to uterine tissue, overcoming endometrial mucus clearance. It also showed favorable in vivo uterine cavity retention for at least 7 days that covered the critical endometrial repair period. Within the postoperative inflammatory milieu, OHA-CP@TA intelligently released TA in a ROS-dependent manner, which effectively scavenged various ROS and significantly alleviated inflammation, and promoted M1 macrophage polarization into M2 phenotype. This targeted ROS scavenging and immunoregulation inhibited endometrium fibrosis progression, evidenced by downregulation of α-SMA and Col-1, and actively promoted endometrial repair and regeneration, demonstrated by enhanced angiogenesis, increased endometrial thickness, and restoration of glandular numbers. Furthermore, OHA-CP@TA exhibited good biocompatibility, in vivo biodegradability and safety. Conclusions: Therefore, OHA-CP@TA represents a promising, clinically translatable strategy for overcoming the limitations of current IUA management. Full article
(This article belongs to the Section Biopharmaceutics)
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