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Search Results (491)

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Keywords = histomorphology

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20 pages, 647 KB  
Review
Posterior Pituitary and Hypothalamic Neuronal Tumors in the 5th WHO Classification: Molecular Insights, Diagnostic Markers, and Clinical Management
by Alexia Kesta, Omar Itani, Yahya Wehbeh and Dimitrios Kanakis
Int. J. Mol. Sci. 2026, 27(13), 6024; https://doi.org/10.3390/ijms27136024 (registering DOI) - 4 Jul 2026
Abstract
Posterior pituitary and hypothalamic neuronal tumors are uncommon sellar and suprasellar neoplasms that can mimic pituitary neuroendocrine tumors clinically and radiologically. The 5th edition World Health Organization classifications (Endocrine and Neuroendocrine Tumors) reinforce a lineage-based framework that separates anterior pituitary tumors from posterior [...] Read more.
Posterior pituitary and hypothalamic neuronal tumors are uncommon sellar and suprasellar neoplasms that can mimic pituitary neuroendocrine tumors clinically and radiologically. The 5th edition World Health Organization classifications (Endocrine and Neuroendocrine Tumors) reinforce a lineage-based framework that separates anterior pituitary tumors from posterior pituitary and hypothalamic neuronal lineages, which is particularly important in hormone-negative lesions and limited tissue samples. This narrative review provides a practical, pathology-centered approach to classification by integrating key anatomic and radiologic clues with histomorphology and targeted immunohistochemistry. We highlight the value and limitations of thyroid transcription factor 1, outline a stepwise workflow incorporating anterior pituitary transcription factors and neuronal differentiation markers, and discuss when vasopressin immunostaining is informative. We also summarize selected molecular insights and clinical management considerations relevant to surgical planning and follow-up. Full article
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20 pages, 9627 KB  
Review
Organic Acids in Rabbit Nutrition: Mechanisms, Advancements, and Potentials for Sustainable Production
by Tarek A. Ebeid, Mohamed Tharwat, Sohail Ahmad, Ahmed O. Abbas, Abdullah N. Alkhalaf and Fahad A. Alshanbari
Vet. Sci. 2026, 13(7), 620; https://doi.org/10.3390/vetsci13070620 - 26 Jun 2026
Viewed by 271
Abstract
Sustainable rabbit production requires effective nutritional strategies to enhance productivity, health status, and immune competence. Following the restriction of antibiotic growth promoters, organic acids (OAs) have gotten increasing attention as promising functional feed additives due to their multiple biological roles. This review aims [...] Read more.
Sustainable rabbit production requires effective nutritional strategies to enhance productivity, health status, and immune competence. Following the restriction of antibiotic growth promoters, organic acids (OAs) have gotten increasing attention as promising functional feed additives due to their multiple biological roles. This review aims to offer a comprehensive overview of the functional roles of OAs in rabbit nutrition, with a focus on their effects on gut morphology, nutrient digestibility, intestinal microbiota, antioxidative status, immunity, and growth performance in growing rabbits. The OAs may modulate gut microbiota balance through inhibition of pathogenic bacteria and promotion of beneficial microbial populations, thereby contributing to the establishment of a balanced intestinal ecosystem. This effect is particularly important during the post-weaning period, a critical stage characterized by increased susceptibility to enteric disorders and associated economic losses. The OAs may also enhance digestive enzyme activities, leading to improving nutrient digestibility, feed efficiency, and reducing feed wastage. In addition, OAs have been shown to improve intestinal histomorphology through coordinated effects on epithelial proliferation, mucosal renewal, and tight junction integrity. Furthermore, OAs have been shown to modulate antioxidative status and immune responses, which are essential for maintaining intestinal health and overall production sustainability. Collectively, OAs represent a promising and viable nutritional strategy to enhance the sustainability and efficiency of rabbit production systems through their beneficial effects on gut health, nutrient utilization, immune competence, and antioxidative status. Full article
(This article belongs to the Special Issue Nutritional Strategies to Improve Animal Health and Immunity)
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15 pages, 2133 KB  
Article
Transcriptomic and Meat Quality Differences in Longissimus Dorsi Muscle of Surgically Castrated Three-Year-Old Kazakh Horses
by Zexu Li, Wanlu Ren, Ran Wang, Luling Li, Shikun Ma, Yi Su, Dehaxi Shan, Qiuping Huang and Jianwen Wang
Biology 2026, 15(12), 959; https://doi.org/10.3390/biology15120959 - 18 Jun 2026
Viewed by 213
Abstract
Although the Kazakh horse is a dual-purpose breed renowned for both milk and meat production, the extent to which surgical castration alters gene expression in its muscles has not yet been fully elucidated. In this study, left longissimus dorsi muscle (LDM) samples were [...] Read more.
Although the Kazakh horse is a dual-purpose breed renowned for both milk and meat production, the extent to which surgical castration alters gene expression in its muscles has not yet been fully elucidated. In this study, left longissimus dorsi muscle (LDM) samples were obtained from six Kazakh stallions (W group) and six Kazakh geldings (S group) to comparatively evaluate meat quality parameters, examine histological characteristics in tissue sections, and apply transcriptomic profiling to comprehensively explore the principal regulatory pathways and candidate genes through which surgical castration modulates LDM growth. The results demonstrated that surgical castration did not induce significant alterations in meat color or pH-related parameters. However, cooking loss and shear force values were markedly diminished, accompanied by a marked decrease in muscle fiber cross-sectional area. Transcriptomic analysis identified 848 differentially expressed genes (DEGs) in total, comprising 415 upregulated and 433 markedly downregulated DEGs, which were predominantly enriched in key biological pathways, including actin cytoskeleton regulation. Moreover, eleven core candidate genes, including MYL2, MYL3, and TNNI1, were further screened and identified. Full article
(This article belongs to the Section Zoology)
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30 pages, 7790 KB  
Review
Advances in Diagnostic, Prognostic and Predictive Biomarker Testing for the Characterization of Uterine Mesenchymal Neoplasms
by Julia Dedda and Roman E. Zyla
Onco 2026, 6(2), 29; https://doi.org/10.3390/onco6020029 - 11 Jun 2026
Viewed by 334
Abstract
The family of uterine mesenchymal neoplasms is diverse in etiology and clinical impact. While histomorphology remains central to diagnostic classification, numerous biomarkers have been developed to aid in refining diagnoses and informing optimal treatment strategies. Indeed, a growing number of neoplasms are being [...] Read more.
The family of uterine mesenchymal neoplasms is diverse in etiology and clinical impact. While histomorphology remains central to diagnostic classification, numerous biomarkers have been developed to aid in refining diagnoses and informing optimal treatment strategies. Indeed, a growing number of neoplasms are being primarily classified on the basis of key pathognomonic genetic events, and this number is expected to continue expanding as access to next-generation sequencing rapidly democratizes. Moreover, several quantitative biomarker tests have been developed to aid in the prognostic stratification of tumours with ambiguous morphologic features, providing critical insights to clinicians seeking optimal oncologic management while minimizing unnecessary treatment morbidity. In this review, we discuss key advances in the utilization of biomarkers for diagnostic classification, prognostication, and the prediction of response to targeted therapeutics in uterine mesenchymal neoplasms, with the aim of highlighting the most clinically impactful biomarkers used by pathologists to enhance the clinical care of patients. Full article
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12 pages, 2706 KB  
Case Report
Beyond the Usual: Breast, Pituitary and Gastric Metastases from Clear Cell Renal Cell Carcinomas—A Case Series with Review of Literature
by Yin Ping Wong, Nur Liyana Khairuddin, Jegan Thanabalan and Geok Chin Tan
Diagnostics 2026, 16(12), 1773; https://doi.org/10.3390/diagnostics16121773 - 9 Jun 2026
Viewed by 351
Abstract
Background and Clinical Significance: Clear cell renal cell carcinoma (ccRCC) is notorious for its aggressiveness and great propensity to metastasize to virtually any organ, with a dismal five-year survival rate. While metastases from ccRCC typically occur in the lungs, lymph nodes, bones [...] Read more.
Background and Clinical Significance: Clear cell renal cell carcinoma (ccRCC) is notorious for its aggressiveness and great propensity to metastasize to virtually any organ, with a dismal five-year survival rate. While metastases from ccRCC typically occur in the lungs, lymph nodes, bones and liver, involvement of atypical locations such as the breast, pituitary gland and stomach is extremely rare. These unusual metastases can masquerade as primary tumours at their respective sites, posing significant diagnostic challenges. Case Presentation: Here, we describe three cases of metastatic ccRCC to unusual anatomical sites following nephrectomy: (1) a patient who presented with a suspicious left-sided breast mass and synchronous liver and lung metastases six months following the initial diagnosis of ccRCC; (2) a patient who presented with diplopia, found to have a pituitary lesion four months after nephrectomy; and (3) a patient with known pre-existing lung metastases who developed upper gastrointestinal bleeding one year post-nephrectomy, in whom oesophagogastroduodenoscopy (OGDS) revealed an 8 mm pedunculated gastric polyp. Histopathological examination following biopsies of these lesions showed compact nests and sheets of malignant cells with clear to eosinophilic cytoplasm and distinct membranes. Immunohistochemically, these malignant cells demonstrated CD10 immunopositivity, and were negative for CK7 and CK20, in keeping with the diagnosis of metastatic ccRCC. Conclusions: This case series illustrates the rare metastatic behaviour of ccRCC with its potential to spread to uncommon sites. Awareness of such presentations is crucial, particularly in patients with a known history of ccRCC, as these lesions may clinically and radiologically mimic primary tumours of the affected sites. Careful evaluation of its histomorphological features and judicious use of immunohistochemical panels, together with clinical and radiological correlations, is the key to arriving at an accurate diagnosis. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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13 pages, 708 KB  
Article
Effects of Dietary Phytobiotic Mixtures on Growth Performance, Nutrient Digestibility, Intestinal Histomorphology, Cecal Microbiota, and Antioxidant Status in Fattening Ducks
by Dimitrios Galamatis, Ioannis Panitsidis, Stella Dokou, Ioanna Stylianaki, Konstantina Vasilopoulou, Vasiliki Makri, Tilemachos Mantzios, Sumit Joshi, Shreya Gupta, Angelos Paroutoglou, Vangelis Economou, Panagiotis Sakkas, Vasileios Tsiouris and Ilias Giannenas
Poultry 2026, 5(3), 43; https://doi.org/10.3390/poultry5030043 - 8 Jun 2026
Viewed by 338
Abstract
This study aims to evaluate the effects of two phytobiotic mixtures on performance, nutrient digestibility, histomorphology, microbiota, and antioxidant status in fattening ducks. A total of 180 day-old male mixed-type ducks were randomly assigned to three dietary groups: a control group receiving a [...] Read more.
This study aims to evaluate the effects of two phytobiotic mixtures on performance, nutrient digestibility, histomorphology, microbiota, and antioxidant status in fattening ducks. A total of 180 day-old male mixed-type ducks were randomly assigned to three dietary groups: a control group receiving a basal diet, and two treatment groups (PM1: commercial phytobiotic formulation containing menthol, eucalyptus oil and turmeric leaf oil as key ingredients and PM2: commercial phytobiotic formulation containing garlic oil as a key ingredient) supplemented at 250 g/ton of feed. Ducks were reared for 49 days with six replicates of ten ducks. Performance parameters, including body weight (BW), body weight gain (BWG), and average feed intake (AFI), were significantly improved in phytobiotic groups (p ≤ 0.05). Apparent digestibility of dry matter, crude protein, ether extract, and starch remained unaffected (p > 0.05). Histological analysis showed no significant differences in villus height (VH) or crypt depth (CD). However, cecal microbiota culture-based analysis revealed increased total anerobic bacteria and Lactobacillus counts in PM1 and PM2 (p ≤ 0.05). Antioxidant status demonstrated reduced MDA levels and elevated total phenolic content (TPC) and total antioxidant capacity (TAC) in breast and thigh tissues of treated ducks. Overall, phytobiotic supplementation improved performance and microbiota balance, supporting the potential application of these phytobiotic formulations at the inclusion level of 250 g/ton in fattening ducks’ nutrition. Full article
(This article belongs to the Collection Poultry Nutrition)
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19 pages, 4142 KB  
Article
An Assessment of the Impacts of Feeding Four Fungal Extracts on the Lifespan and Midgut of Newly Emerged Carniolan Honey Bees (Apis mellifera carnica)
by Leticia S. Ansaloni, Caio E. C. Domingues, Marija Gregori, Andrej Gregori and Aleš Gregorc
Insects 2026, 17(6), 594; https://doi.org/10.3390/insects17060594 - 5 Jun 2026
Viewed by 296
Abstract
Given the current global agricultural system, honey bees are exposed to a complex network of stressors that can act simultaneously, making it challenging to maintain healthy colonies. Therefore, studies on natural products to improve colony health have increased in recent years. Among them, [...] Read more.
Given the current global agricultural system, honey bees are exposed to a complex network of stressors that can act simultaneously, making it challenging to maintain healthy colonies. Therefore, studies on natural products to improve colony health have increased in recent years. Among them, fungal extracts have been shown to be beneficial to honey bees. However, there remains a knowledge gap regarding lifespan and histomorphological studies in bees fed fungal extracts. Our current study aimed to assess the impacts of extracts from Ganoderma lucidum (GL), Hericium erinaceus (HE), Inonotus obliquus (IO), and Trametes versicolor (TV) on the lifespan and midgut of honey bees. Newly emerged Carniolan honey bees (Apis mellifera carnica) were fed 4% of each fungal extract until the death of the last individual to assess survival probability. For histomorphological analyses, bees were fed for 7, 14, and 21 days and sampled at these same time points. Then, the midguts were dissected and histologically processed for qualitative and semi-quantitative microscopic analyses. The results showed that the fungal extracts did not significantly affect honey bee survival, and that the histomorphology of the intestinal villi, digestive cells, and regenerative cells in bees treated with fungal extracts did not differ from that of untreated bees throughout the analyzed period. Similarly, no differences were observed in the midgut lesion index between bees treated with fungal extracts and the untreated group. Overall, the absence of harmful effects on lifespan and midgut suggests that feeding fungal extracts may be a potential alternative for supporting bee health. Full article
(This article belongs to the Special Issue Losses, Health and Wellbeing of Honey Bees Across the World)
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28 pages, 16095 KB  
Article
Chlorogenic Acid Improves Intestinal Health in Largemouth Bass (Micropterus salmoides) by Enhancing Antioxidant Defense, Reducing Inflammatory Responses, and Modulating the Gut Microbiota
by Qin Zhang, Lan Li, Dehong Lan, Miao Zhou, Ziyang Yuan, Tong Tong, Yongqiang Liu, Zhichang He, Zhongbao Guo and Weiguang Kong
Animals 2026, 16(11), 1668; https://doi.org/10.3390/ani16111668 - 29 May 2026
Viewed by 373
Abstract
Intestinal oxidative imbalance, inflammatory activation, and microbial dysbiosis are increasingly recognized as major factors affecting the health status of intensively cultured largemouth bass (Micropterus salmoides). Chlorogenic acid (CGA) is a plant-derived polyphenolic compound that is well known for its antioxidant and [...] Read more.
Intestinal oxidative imbalance, inflammatory activation, and microbial dysbiosis are increasingly recognized as major factors affecting the health status of intensively cultured largemouth bass (Micropterus salmoides). Chlorogenic acid (CGA) is a plant-derived polyphenolic compound that is well known for its antioxidant and anti-inflammatory properties. Although its inclusion as a dietary supplement in aquafeeds has garnered increasing interest, its effects on intestinal health in largemouth bass under normal rearing conditions remain largely unknown. Hence, the present investigation was designed to elucidate how incrementally elevated dietary CGA concentrations modulate oxidative capacity, inflammatory gene expression, mucosal histological features, and enteric microbiota structure in juvenile largemouth bass. In this study, largemouth bass were fed diets containing 0, 200, 400, or 600 mg/kg CGA for 70 days, and we evaluated intestinal antioxidant capacity, inflammation-related transcriptional responses, histomorphology, and gut microbiota were assessed. The results demonstrated that CGA supplementation significantly raised intestinal total antioxidant capacity as well as the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, while substantially decreasing malondialdehyde levels (p < 0.05). The transcription levels of cat, gsh-px, gst, sod, nrf2, and ucp2 were markedly upregulated, whereas keap1 expression was downregulated (p < 0.05). CGA supplementation also reduced the transcription levels of several proinflammatory genes, including il-1β, il-6, il-8, tnf-α, nf-κb, p50, map3k, jak2, as well as stat3, while significantly elevating il-10 expression, in the 200 and 400 mg/kg groups, tgf-β expression was also lowered (p < 0.05). Histological examination revealed that CGA supplementation influenced intestinal morphology in a dose-dependent manner; the most consistent improvements in villus length, villus width, and muscularis thickness occurred at the 400 mg/kg level, whereas the 600 mg/kg level showed weaker effects in several parameters compared with the control. Furthermore, 16S rRNA sequencing indicated that CGA altered microbial diversity, community structure, and predicted functional profiles in the intestine. In summary, dietary CGA supplementation was associated with enhanced intestinal antioxidant capacity, modified inflammation-related transcriptional responses, changes in intestinal morphology, and shifts in the gut microbial community of largemouth bass. Within the tested dose range, the 400 mg/kg group exhibited relatively favorable responses in several measured indicators under the present experimental conditions. Full article
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24 pages, 5837 KB  
Article
Effects of Compound Yeast Culture and Yeast Cell Wall Polysaccharide on Intestinal Barrier Function in Mongolian Ram Lambs
by Songjian Li, Pengxiang Bai, Shixiong Liu, Zixuan Xu, Majigsuren Zolzaya, Dorjgoo Purevtsogt, Hui Chen and Dacheng Liu
Animals 2026, 16(11), 1661; https://doi.org/10.3390/ani16111661 - 29 May 2026
Viewed by 663
Abstract
During the early growth stage, lambs are highly susceptible to pathogenic microbial invasion due to an underdeveloped intestinal structure, unstable microbial colonization, and immature mucosal immune function, leading to diarrhea, growth retardation, and elevated mortality factors that severely constrain the production efficiency and [...] Read more.
During the early growth stage, lambs are highly susceptible to pathogenic microbial invasion due to an underdeveloped intestinal structure, unstable microbial colonization, and immature mucosal immune function, leading to diarrhea, growth retardation, and elevated mortality factors that severely constrain the production efficiency and economic viability of the sheep industry. This study aimed to compare the regulatory effects of compound yeast culture (CYC) and yeast polysaccharides (YPs) on intestinal barrier function in Mongolian male lambs and clarify their underlying molecular mechanisms. Eighteen lambs were randomly assigned to three groups (n = 6/group): control group (basal diet), CYC group (40 g/kg), and YP group (3 g/kg). After a 30-day feeding trial, intestinal histomorphology, tight junction proteins, immune signaling pathways, and gut microbiota were analyzed. The results showed that both additives improved intestinal villus morphology, and CYC markedly increased the villus height/crypt depth ratio (p < 0.05). At the mechanical barrier level, CYC upregulated the protein expression of occludin, claudin-1, and ZO-1, whereas YPs increased occludin and ZO-1 expression (p < 0.05). Immunologically, CYC inhibited intestinal inflammation via the TLR4/TRAF6/MyD88/NF-κB pathway, increasing interleukin-10 (IL-10) and secretory immunoglobulin A (sIgA) while decreasing pro-inflammatory cytokines. YPs exerted similar anti-inflammatory effects through the TLR2/MyD88 pathway. Microbial analysis indicated that both additives increased the relative abundance of beneficial bacteria including Eubacterium, Bacillus, and Succinivibrio, while reducing the potential pathogen Mogibacterium. Spearman correlation analysis revealed that Mogibacterium was positively correlated with TNF-α and negatively correlated with occludin expression. In conclusion, CYC and YPs effectively enhance intestinal mechanical, immune, and biological barriers via different TLR-mediated pathways and microbial modulation. Both natural additives have great application potential for improving lamb health, reducing antibiotic dependence, and promoting sustainable green animal husbandry. Full article
(This article belongs to the Special Issue Feed Additives in Animal Nutrition: 2nd Edition)
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23 pages, 1178 KB  
Review
Age-Related Alterations in Swallowing in Healthy Aged Rodents: A Systematic Review
by Han-Na Kim and Ji-Youn Kim
Biology 2026, 15(11), 835; https://doi.org/10.3390/biology15110835 - 26 May 2026
Viewed by 393
Abstract
Age-related decline in swallowing function is increasingly recognized as a clinical concern in aging populations. To better understand the biological mechanisms underlying functional and structural changes associated with normal aging, rodent models provide a controlled experimental platform. This review systematically examined age-related changes [...] Read more.
Age-related decline in swallowing function is increasingly recognized as a clinical concern in aging populations. To better understand the biological mechanisms underlying functional and structural changes associated with normal aging, rodent models provide a controlled experimental platform. This review systematically examined age-related changes in swallowing function in healthy rodents, compared with that of young adults. A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Library. Twenty-nine articles were ultimately included in this review. Age-related alterations in swallowing function in healthy aged rodents were reported in the following categories: contraction properties of tongue muscles, histomorphological and biochemical changes in tongue muscles, swallowing-related cranial sensorimotor system, histological changes in pharyngeal muscles, and swallowing behavioral outcomes. The evidence summarized in this review provides insights into the functional, histological, and behavioral alterations in swallowing in healthy aged rodents compared with those of young adult rodents. These findings enhance the understanding of the biological basis of presbyphagia and support the translational value of rodent models in developing preventive and rehabilitative strategies for age-related dysphagia. Full article
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26 pages, 9939 KB  
Article
Early Metabolic and Oxidative Effects of Hop Extract, Alendronate, and Their Combination Across Tissues in an Estrogen-Deficient Rat Model: An Exploratory Study
by Edi Rođak, Nika Srb, Robert Grgac, Željko Debeljak, Ivana Ilić, Nada Oršolić and Nikola Bijelić
Nutrients 2026, 18(11), 1685; https://doi.org/10.3390/nu18111685 - 25 May 2026
Viewed by 293
Abstract
Background/Objectives: Postmenopausal osteoporosis is associated with systemic metabolic alterations related to estrogen deficiency. This exploratory study investigated the early metabolic, oxidative, and histomorphological effects of alendronate, a standardized hop extract, and their combination in ovariectomized (OV) rats. Methods: Female Wistar rats (n [...] Read more.
Background/Objectives: Postmenopausal osteoporosis is associated with systemic metabolic alterations related to estrogen deficiency. This exploratory study investigated the early metabolic, oxidative, and histomorphological effects of alendronate, a standardized hop extract, and their combination in ovariectomized (OV) rats. Methods: Female Wistar rats (n = 70) were randomly allocated to seven groups: six OV groups or a sham-operated control (n = 10 per group). Following a 30-day postoperative period for model development, animals received daily treatment for 2 weeks with vehicle (placebo), low- or high-dose alendronate (1 and 2 mg/kg, respectively), standardized hop extract (60 mg/kg), or both. Oxidative stress markers, liver and perigonadal adipose tissue histology, and tissue metabolism were assessed. Results: No evidence of adverse hepatic, renal, or systemic effects was observed. Oxidative damage markers remained largely unchanged, although ovariectomy was associated with reduced hepatic catalase activity, which was increased by high-dose alendronate. Treatment-related morphological changes in adipose tissue were observed. Serum triglyceride levels were unaffected, whereas total cholesterol was significantly increased in animals receiving hop extract. Hepatic triglyceride levels were influenced by alendronate treatment, modified by hop extract. MALDI-TOF MS suggested no OV-related alterations in amino acid, lipid, steroid, and redox-related metabolism in liver and adipose tissue. The subsequent treatments, especially in the high-dose alendronate group and hop-extract group, partially modified these metabolic signatures; however, these findings remain provisional pending MS/MS validation. Conclusions: Most outcomes were not significantly altered by OV. Alendronate and hop extract exert distinct short-term effects on selected metabolic and oxidative parameters in this exploratory model. Further studies are needed to investigate translational potential. Full article
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18 pages, 23876 KB  
Article
Exercise Alleviates Osteoporosis and Hyperglycemia in Type 1 Diabetes Mellitus Mice via Piezo1-Mediated Mechanotransduction
by Mengshu Cao, Fang Pang, Yanan Yu, Junzheng Yu, Sainan Ma, Lijun Sun, Xiushan Fan and Liang Tang
Biology 2026, 15(11), 819; https://doi.org/10.3390/biology15110819 - 22 May 2026
Viewed by 328
Abstract
Osteoporosis and hyperglycemia are increasingly recognized as dual public health concerns in T1DM. However, the precise molecular mechanisms by which exercise ameliorates these conditions, particularly the contribution of mechanosensitive channels such as Piezo1, remain incompletely elucidated. To explore these mechanisms, T1DM mice were [...] Read more.
Osteoporosis and hyperglycemia are increasingly recognized as dual public health concerns in T1DM. However, the precise molecular mechanisms by which exercise ameliorates these conditions, particularly the contribution of mechanosensitive channels such as Piezo1, remain incompletely elucidated. To explore these mechanisms, T1DM mice were subjected to a 6-week treadmill training protocol (15 m/min, 20 min/day, 6 days/week) to evaluate the functions of exercise on diabetic osteoporosis and hyperglycemia. Exercise intervention markedly improved bone quality in T1DM mice, alleviating osteoporotic manifestations, as evidenced by enhanced mechanical strength, restored bone microarchitecture, and normalized histomorphology. Concurrently, exercise significantly reduced hyperglycemia. To clarify the role of Piezo1, mechanical stretch was applied to Piezo1-knockout MC3T3-E1 (Piezo1−/−) cells in vitro, mimicking the mechanical stimulation induced by exercise. Consistent with the in vivo results, mechanical stimulation facilitated osteogenic differentiation and glucose metabolism through Piezo1-mediated mechanotransduction. Importantly, these beneficial effects were substantially abrogated in Piezo1−/− cells, highlighting the central role of Piezo1. Collectively, these findings demonstrate that Piezo1-mediated mechanotransduction constitutes a critical factor by which exercise mitigates osteoporosis and hyperglycemia in T1DM mice. This study provides a framework for the development of new therapeutic strategies targeting Piezo1-mediated mechanotransduction for T1DM management. Full article
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7 pages, 570 KB  
Case Report
Myxoid Lipoblastoma with New Fusion Transcript CHCHD7::PLAG1 in an 18-Month-Old Girl Diagnosed by Target RNA Sequencing: A Case Report
by Danijela Cvetković, Marina Gazdić Janković, Marina Miletić Kovačević, Amra Ramović Hamzagić, Irena Urošević, Vesna Rosić and Biljana Ljujić
Int. J. Mol. Sci. 2026, 27(10), 4312; https://doi.org/10.3390/ijms27104312 - 12 May 2026
Viewed by 244
Abstract
Lipoblastomas are rare, benign tumors arising from embryonic white fatty precursor cells that continue to proliferate in the postnatal period. We present a case of a minimally differentiated lipoblastoma with myxoid features. Our patient was an 18-month-old female with a painless solid tumefaction [...] Read more.
Lipoblastomas are rare, benign tumors arising from embryonic white fatty precursor cells that continue to proliferate in the postnatal period. We present a case of a minimally differentiated lipoblastoma with myxoid features. Our patient was an 18-month-old female with a painless solid tumefaction in the middle third of the right leg. Histopathologically, the nodular tumor mass consisted of lipoblasts embedded in a myxoid stroma. Immunohistochemistry showed strong diffuse positivity for S100, CD34, CD56, NSE and rare Ki67+ cells. FOXO1 polyploidy was detected in 30% of cells by FISH. Using target RNA sequencing, we detected a CHCHD7::PLAG1 fusion gene showing that the first exons of CHCHD7 were fused to either exon 2 or exon 3 of PLAG1. Our case demonstrates that due to the histomorphologic overlaps, the molecular diagnostics can be essential for the confirmation of the diagnosis of lipoblastoma. Full article
(This article belongs to the Special Issue Genes and Human Diseases: 3rd Edition)
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25 pages, 14607 KB  
Article
A Synaptogenesis-Associated Histomorphologic Signature from H&E Whole-Slide Images Predicts Glioma Prognosis and Identifies EFNB2-Positive Malignant Cells as a Candidate Neuro-Glioma Communication Hub
by Xiaolong Wu, Dong Liu, Haoming Geng, Binghan Zhang, Huantong Diao, Yiqiang Zhou, Gang Song, Ye Cheng and Jiantao Liang
Int. J. Mol. Sci. 2026, 27(10), 4300; https://doi.org/10.3390/ijms27104300 - 12 May 2026
Viewed by 422
Abstract
Synaptogenesis-related neuron–glioma interactions are increasingly recognized in glioma, yet it remains unclear whether routine H&E morphology can capture these programs and improve prognostic stratification. We integrated H&E whole-slide images, transcriptomes, and clinical data from 434 TCGA gliomas. Deep learning and quantitative pathology yielded [...] Read more.
Synaptogenesis-related neuron–glioma interactions are increasingly recognized in glioma, yet it remains unclear whether routine H&E morphology can capture these programs and improve prognostic stratification. We integrated H&E whole-slide images, transcriptomes, and clinical data from 434 TCGA gliomas. Deep learning and quantitative pathology yielded an integrated histomorphologic feature set of 2678 features. Synaptogenesis-related activity was quantified using ssGSEA for ninety-eight synaptogenesis-related genes. In the training cohort, Spearman analysis identified 149 correlated histomorphologic features, which were refined to thirty-five by elastic net regularization. Seventeen prognostic candidates were entered into the MIME1 framework, and the most parsimonious model, Enet[0.1], retained fourteen non-zero-coefficient features to define the synaptogenesis-associated histomorphologic signature and construct the pathology-derived risk score (PRS). Multi-omic analyses, Human Protein Atlas validation, and single-nucleus RNA-seq were used to investigate the hub gene and its cellular context. PRS robustly stratified survival in both training and validation cohorts and remained an independent prognostic factor after adjustment for age and 2021 WHO CNS grade. High-risk tumors showed increased stromal and immune scores and enrichment of immune, adhesion, and phagosome-related pathways. EFNB2 emerged as the hub gene and was enriched in glioblastoma, and EFNB2-positive malignant cells displayed prominent communication with neurons, including EFNB2-EPHB1 signaling. Exploratory re-analysis of the myeloid compartment further showed that glioblastoma was enriched for suppressive TAM-like states relative to astrocytoma grade 2, supporting a shift toward a more tumor-associated and potentially immunosuppressive microenvironment. Routine H&E histomorphology can capture synaptogenesis-related molecular programs in glioma. The resulting PRS provides clinically relevant prognostic stratification, while EFNB2-positive malignant cells may represent a candidate hub for neuron–tumor communication within a remodeled tumor ecosystem. Full article
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29 pages, 18861 KB  
Article
Experimental Models of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of a Choline-Deficient and Cholesterol-Enriched Diet in Rats
by Vladimir A. Shipelin, Nikita A. Petrov, Nikita V. Trusov, Yuliya S. Sidorova, Yulia M. Markova, Zakhar A. Chalyy, Anton D. Konev and Anastasiya S. Balakina
Int. J. Mol. Sci. 2026, 27(10), 4230; https://doi.org/10.3390/ijms27104230 - 9 May 2026
Viewed by 568
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread pathology requiring adequate preclinical models for studying pathogenesis and evaluating therapeutic and preventive agents. This study compared differential markers of MASLD pathogenesis in rats using two distinct dietary models: a choline-deficient high-fat diet (HFD-CD) [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread pathology requiring adequate preclinical models for studying pathogenesis and evaluating therapeutic and preventive agents. This study compared differential markers of MASLD pathogenesis in rats using two distinct dietary models: a choline-deficient high-fat diet (HFD-CD) and a cholesterol-enriched high-fat diet (HFD+CHOL). Male Wistar rats were fed either a control AIN93M diet, HFD-CD (40% fat, 20% fructose, and choline deficiency), or HFD+CHOL (40% fat, 20% fructose, and 1% cholesterol) for 56 days. Comprehensive assessment included phenotypic, biochemical, hematological, histomorphological parameters, oxidative stress markers, hepatocyte apoptosis, cytokine levels, and hepatic gene expression. HFD-CD induced steatosis with moderate insulin resistance, increased malondialdehyde levels, and suppressed Acaca, Scd and ChREBP gene expression. In contrast, HFD+CHOL caused macrovesicular steatosis, inflammation, early fibrosis, atherogenic dyslipidemia, intrahepatic cholesterol accumulation, hepatocyte apoptosis, upregulated Srebf1, Cyp7a1, and Nfkb1 expression, and activated Nrf2-dependent antioxidant responses. HFD-CD and HFD+CHOL induce two pathogenetically distinct MASLD phenotypes. The HFD-CD model, characterized by steatosis and oxidative stress without pronounced inflammation or fibrosis, is preferable for studying the preventive potential of bioactive food compounds. Conversely, the HFD+CHOL model with inflammatory and fibrotic components is more suitable for evaluating therapeutic agents aimed at mitigating inflammation, restoring cholesterol homeostasis, and attenuating fibrosis. Full article
(This article belongs to the Special Issue Molecular Insights into Chronic Liver Disease and Liver Failure)
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