Pub Date : 2026-01-24DOI: 10.1016/j.tice.2026.103346
Youssef Elsabbgh , Ashraf El Sharaby , Asmaa Aboelnour , Mohamed M.A. Abumandour , Ahmed G. Nomir
The adult White Pekin duck’s small intestine is anatomically adapted for rapid growth, high-fat diet digestion, and strong immunity, essential for its physiological needs. This study analyzes the adaptive anatomical features of the small intestine—duodenum, jejunum, and ileum—through gross examination, light microscopy (LM), histochemical techniques, scanning electron microscopy (SEM), and morphometric analysis. To achieve this objective, sixteen ducks were examined. Gross examination revealed a U-shaped duodenum, a coiled jejunum with Meckel’s diverticulum, and a straight ileum attached to paired ceca. Histologically, the duodenum displayed finger-like villi with the deepest crypts, while the jejunum had the tallest villi and the highest villus/crypt ratio. The ileum showed compact villi and the highest goblet cell (GC) density. GCs were quantified and differentiated using PAS, AB, and PAS-AB combination staining. PAS-positive (neutral mucins) cells predominated in villi, especially in the jejunum, while AB-positive (acidic mucins) cells were most abundant in ileal crypts, indicating regional specialization in mucosal protection. SEM revealed ultrastructural features including dense microvilli, epithelial exfoliation, and GC secretory vesicles. Enterocytes exhibited organelles such as mitochondria and rough endoplasmic reticulum, as well as junctional complexes including tight junctions and desmosomes. These findings highlight the segmental specialization of the Pekin duck’s small intestine, with the jejunum optimized for nutrient absorption and the ileum for immune defense. The detailed mucin profile and ultrastructural features provide insight into the digestive efficiency and adaptive physiology of this fast-growing avian species.
{"title":"Integrated Morphological Analysis Of The Small Intestine In The Pekin Duck's (Anas platyrhynchos) Using Gross Anatomical, Histological, Histochemical, and Scanning Electron Microscopic Techniques","authors":"Youssef Elsabbgh , Ashraf El Sharaby , Asmaa Aboelnour , Mohamed M.A. Abumandour , Ahmed G. Nomir","doi":"10.1016/j.tice.2026.103346","DOIUrl":"10.1016/j.tice.2026.103346","url":null,"abstract":"<div><div>The adult White Pekin duck’s small intestine is anatomically adapted for rapid growth, high-fat diet digestion, and strong immunity, essential for its physiological needs. This study analyzes the adaptive anatomical features of the small intestine—duodenum, jejunum, and ileum—through gross examination, light microscopy (LM), histochemical techniques, scanning electron microscopy (SEM), and morphometric analysis. To achieve this objective, sixteen ducks were examined. Gross examination revealed a U-shaped duodenum, a coiled jejunum with Meckel’s diverticulum, and a straight ileum attached to paired ceca. Histologically, the duodenum displayed finger-like villi with the deepest crypts, while the jejunum had the tallest villi and the highest villus/crypt ratio. The ileum showed compact villi and the highest goblet cell (GC) density. GCs were quantified and differentiated using PAS, AB, and PAS-AB combination staining. PAS-positive (neutral mucins) cells predominated in villi, especially in the jejunum, while AB-positive (acidic mucins) cells were most abundant in ileal crypts, indicating regional specialization in mucosal protection. SEM revealed ultrastructural features including dense microvilli, epithelial exfoliation, and GC secretory vesicles. Enterocytes exhibited organelles such as mitochondria and rough endoplasmic reticulum, as well as junctional complexes including tight junctions and desmosomes. These findings highlight the segmental specialization of the Pekin duck’s small intestine, with the jejunum optimized for nutrient absorption and the ileum for immune defense. The detailed mucin profile and ultrastructural features provide insight into the digestive efficiency and adaptive physiology of this fast-growing avian species.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103346"},"PeriodicalIF":2.5,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vitro models of oral dysplasia fail to recapitulate physiologically relevant tissue-tissue interfaces and other microenvironmental cues. This study aimed to present a preliminary organ-on-a-chip (OoC) model of a precancerous oral cavity lesion (OD-OoC). The objective was to reproduce in a two-channel microfluidic device an in vitro tridimensional (3D) model characterized by an organized interaction between endothelial cells, fibroblasts, and dysplastic oral keratinocytes on a collagen I-coated membrane. On day 1, human umbilical vein endothelial cells (ECs) were introduced in the bottom channel, and the chip was inverted to allow cell adhesion to the lower side of the membrane. The chip was then inverted back to the original position, and human gingival fibroblasts (hGFs) were introduced into the top channel. On day 2, the laminar flow was activated, while uniform layers of hGFs and ECs were forming in the respective channels. On day 3, dysplastic oral keratinocytes (DOKs) were inoculated in the top channel above the hGFs layer. On day 5, the chip was fixed with 4 % paraformaldehyde and stained with antibodies targeting podoplanin, Trop2, and VE-cadherin for staining of hGFS, ECs, and DOKs, respectively. Confocal microscopy confirmed the presence of all cell types, showing fibroblast migration from the top channel to the bottom channel of the chip, where they localized between the membrane and the ECs. DOKs confined to the top channel showed slight and uneven E-cadherin and EpCAM (Epithelial Cell Adhesion Molecule) positivity, but evident positivity for Trop-2, confirming that their phenotype differed from that of healthy epithelial cells. The presented OD-OoC could enable in vitro monitoring of epithelial cell phenotype changes and cell migration across the membrane, suggesting its potential applicability in future oral cancer research.
{"title":"A preliminary model of an oral dysplastic lesion on a chip","authors":"Roberto Plebani , Tania Vanessa Pierfelice , Emira D’Amico , Mario Romano , Simonetta D’Ercole , Giovanna Iezzi , Morena Petrini","doi":"10.1016/j.tice.2026.103347","DOIUrl":"10.1016/j.tice.2026.103347","url":null,"abstract":"<div><div><em>In vitro</em> models of oral dysplasia fail to recapitulate physiologically relevant tissue-tissue interfaces and other microenvironmental cues. This study aimed to present a preliminary organ-on-a-chip (OoC) model of a precancerous oral cavity lesion (OD-OoC). The objective was to reproduce in a two-channel microfluidic device an <em>in vitro</em> tridimensional (3D) model characterized by an organized interaction between endothelial cells, fibroblasts, and dysplastic oral keratinocytes on a collagen I-coated membrane. On day 1, human umbilical vein endothelial cells (ECs) were introduced in the bottom channel, and the chip was inverted to allow cell adhesion to the lower side of the membrane. The chip was then inverted back to the original position, and human gingival fibroblasts (hGFs) were introduced into the top channel. On day 2, the laminar flow was activated, while uniform layers of hGFs and ECs were forming in the respective channels. On day 3, dysplastic oral keratinocytes (DOKs) were inoculated in the top channel above the hGFs layer. On day 5, the chip was fixed with 4 % paraformaldehyde and stained with antibodies targeting podoplanin, Trop2, and VE-cadherin for staining of hGFS, ECs, and DOKs, respectively. Confocal microscopy confirmed the presence of all cell types, showing fibroblast migration from the top channel to the bottom channel of the chip, where they localized between the membrane and the ECs. DOKs confined to the top channel showed slight and uneven E-cadherin and EpCAM (Epithelial Cell Adhesion Molecule) positivity, but evident positivity for Trop-2, confirming that their phenotype differed from that of healthy epithelial cells. The presented OD-OoC could enable in vitro monitoring of epithelial cell phenotype changes and cell migration across the membrane, suggesting its potential applicability in future oral cancer research.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103347"},"PeriodicalIF":2.5,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.tice.2026.103344
Fatma Abdelhakeem , Elsayed S.I. Mohammed , Mohammed Al-Rasheed , Fatma A. Madkour
Organogenesis of the avian pancreas is a critical developmental process that ensures proper digestive and metabolic functions in birds. This study investigated the morphogenesis and ultrastructural differentiation of the quail pancreas. Fifty-eight quail embryos from day 5 to day 17 of incubation were used for this study. The developing pancreas consistently composed of exocrine and endocrine portions. On day 5, primitive pancreatic tubules (duct-like structures) appeared within the duodenal mesenchyme, lined with pseudostratified and simple columnar epithelium, and associated with early endocrine clusters representing the islets of Langerhans. By day 6, the pancreas was enclosed by a delicate capsule, and the pancreatic cells became cuboidal to pyramidal with prominent basally located nuclei. Progressive lobulation occurred from days 8 and 9, forming dorsal, ventral, third, and splenic lobes with increased vascularization and telocytes distribution. On 10th day of incubation, four distinct lobes were established, and each lobe had its own capsule on 14th day. By day 17, mature serous acini exhibited basophilic basal cytoplasm and apical zymogen granules, indicating functional secretory activity. Ultrastructurally, exocrine acinar cells displayed abundant rough endoplasmic reticulum, prominent nuclei, and diverse zymogen granules. Centroacinar and intercalated ductal cells formed the initial ductal network. Telocytes appeared in perivascular and interacinar regions, suggesting a regulatory role in tissue organization. Endocrine islets were made of α-, β-, and δ-cells, each possessing distinct secretory granules corresponding to glucagon, insulin, and somatostatin secretion, respectively. Grossly, the pancreas developed progressively between the duodenal limbs and attained distinct lobular organization by hatching. These findings elucidate the prehatching structural maturation of the quail pancreas, establishing a foundation for understanding avian pancreatic development and function.
{"title":"Morphological architecture of the developing pancreas in quail embryos: A histological and ultrastructural perspective","authors":"Fatma Abdelhakeem , Elsayed S.I. Mohammed , Mohammed Al-Rasheed , Fatma A. Madkour","doi":"10.1016/j.tice.2026.103344","DOIUrl":"10.1016/j.tice.2026.103344","url":null,"abstract":"<div><div>Organogenesis of the avian pancreas is a critical developmental process that ensures proper digestive and metabolic functions in birds. This study investigated the morphogenesis and ultrastructural differentiation of the quail pancreas. Fifty-eight quail embryos from day 5 to day 17 of incubation were used for this study. The developing pancreas consistently composed of exocrine and endocrine portions. On day 5, primitive pancreatic tubules (duct-like structures) appeared within the duodenal mesenchyme, lined with pseudostratified and simple columnar epithelium, and associated with early endocrine clusters representing the islets of Langerhans. By day 6, the pancreas was enclosed by a delicate capsule, and the pancreatic cells became cuboidal to pyramidal with prominent basally located nuclei. Progressive lobulation occurred from days 8 and 9, forming dorsal, ventral, third, and splenic lobes with increased vascularization and telocytes distribution. On 10th day of incubation, four distinct lobes were established, and each lobe had its own capsule on 14th day. By day 17, mature serous acini exhibited basophilic basal cytoplasm and apical zymogen granules, indicating functional secretory activity. Ultrastructurally, exocrine acinar cells displayed abundant rough endoplasmic reticulum, prominent nuclei, and diverse zymogen granules. Centroacinar and intercalated ductal cells formed the initial ductal network. Telocytes appeared in perivascular and interacinar regions, suggesting a regulatory role in tissue organization. Endocrine islets were made of α-, β-, and δ-cells, each possessing distinct secretory granules corresponding to glucagon, insulin, and somatostatin secretion, respectively. Grossly, the pancreas developed progressively between the duodenal limbs and attained distinct lobular organization by hatching. These findings elucidate the prehatching structural maturation of the quail pancreas, establishing a foundation for understanding avian pancreatic development and function.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103344"},"PeriodicalIF":2.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.tice.2026.103333
Ramadan Kandyel , Saeed Alasmari , Salem H. Alharethi , Abdulrhman A. Almadiy , Bader Albogami , Diaa Massoud , Basma G. Hanafy , Ahmed G. Nomir , Mohamed Abumandour
The morphological structure of the oropharyngeal cavity roof of the Black-tailed Native-Hen (Tribonyx ventralis) had not been previously researched. The study aimed to provide a comprehensive morphological description of the oropharyngeal cavity roofs of the Black-tailed Native-Hen using gross, SEM, and histological techniques. The oropharyngeal roof was categorized into three regions: pre-conchal, middle conchal, and infundibular. The dorsal palatine surface carried twelve papillary rows: eleven longitudinal and one transverse. These rows were presented in a manner such that one median longitudinal row was on the pre-choanal region, eight longitudinal rows were on the choanal field on each side of the choanal opening, two longitudinal rows bordered the rostral portion of the choanal opening, and one transverse row separated the rostral and caudal portions. Papillae are arranged in twelve rows on the palatine surface, with free distribution in specific lateral areas, while the caudal choanal and infundibular regions lack papillae. The choanal opening was located in the caudal palatine half, which was divided into two parts: the rostral long papillary and the caudal wide non-papillary portions. Histologically, the salivary glands were classified into five types based on their position: rostral, median, caudal, intraepithelial, and infundibular. The oropharyngeal roof, influenced by various lifestyles and environments, significantly influences food handling and direction toward the esophagus.
{"title":"Oropharyngeal cavity roof adaptations of the migratory black-tailed native-hen (Tribonyx ventralis): Gross, scanning electron microscopic, and histological features","authors":"Ramadan Kandyel , Saeed Alasmari , Salem H. Alharethi , Abdulrhman A. Almadiy , Bader Albogami , Diaa Massoud , Basma G. Hanafy , Ahmed G. Nomir , Mohamed Abumandour","doi":"10.1016/j.tice.2026.103333","DOIUrl":"10.1016/j.tice.2026.103333","url":null,"abstract":"<div><div>The morphological structure of the oropharyngeal cavity roof of the Black-tailed Native-Hen (<em>Tribonyx ventralis</em>) had not been previously researched. The study aimed to provide a comprehensive morphological description of the oropharyngeal cavity roofs of the Black-tailed Native-Hen using gross, SEM, and histological techniques. The oropharyngeal roof was categorized into three regions: pre-conchal, middle conchal, and infundibular. The dorsal palatine surface carried twelve papillary rows: eleven longitudinal and one transverse. These rows were presented in a manner such that one median longitudinal row was on the pre-choanal region, eight longitudinal rows were on the choanal field on each side of the choanal opening, two longitudinal rows bordered the rostral portion of the choanal opening, and one transverse row separated the rostral and caudal portions. Papillae are arranged in twelve rows on the palatine surface, with free distribution in specific lateral areas, while the caudal choanal and infundibular regions lack papillae. The choanal opening was located in the caudal palatine half, which was divided into two parts: the rostral long papillary and the caudal wide non-papillary portions. Histologically, the salivary glands were classified into five types based on their position: rostral, median, caudal, intraepithelial, and infundibular. The oropharyngeal roof, influenced by various lifestyles and environments, significantly influences food handling and direction toward the esophagus.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103333"},"PeriodicalIF":2.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.tice.2026.103329
Narindra H. Roopnarine , Tom A. Aire , Antoinette V. Lensink , Sunil K. Gupta , Curtis.E. Hopkins , Matthew B. Charles
The structure and functions of components of the excurrent ducts of the testis of birds are still poorly understood. Most of the few reports on these ducts are on domesticated avian species. This report on the cattle egret is one of the very few studies on wild birds. Tissues from the ducts of five sexually mature and active male birds were routinely prepared and stained for light and transmission electron microscopy. The epididymis and ductus deferens of the cattle egret are generally similar structurally to those reported for domestic birds, with a number of cellular differences. The epithelium of certain segments of the egret’s rete testis displayed numerous, large intercellular spaces, not usually observed in most domestic avian species. As in the domestic species of birds, the proximal efferent ducts in the cattle egret displayed a robust endocytic apparatus as well as abundant lysosomes, but there were very few heterolysosomes and telolysosomes, which were common in domestic species. The border between the proximal and distal efferent ducts also demonstrated active spermiophagy. In addition to evidence of moderate secretary activities, the presence of extremely large heterolysosomes and telolysosomes also demonstrated the endocytic and digestive ability of cells lining the ductus deferens.
{"title":"Ultrastructural features of the excurrent ducts of the testis of a wild bird, the cattle egret (Bubulcus ibis)","authors":"Narindra H. Roopnarine , Tom A. Aire , Antoinette V. Lensink , Sunil K. Gupta , Curtis.E. Hopkins , Matthew B. Charles","doi":"10.1016/j.tice.2026.103329","DOIUrl":"10.1016/j.tice.2026.103329","url":null,"abstract":"<div><div>The structure and functions of components of the excurrent ducts of the testis of birds are still poorly understood. Most of the few reports on these ducts are on domesticated avian species. This report on the cattle egret is one of the very few studies on wild birds. Tissues from the ducts of five sexually mature and active male birds were routinely prepared and stained for light and transmission electron microscopy. The epididymis and ductus deferens of the cattle egret are generally similar structurally to those reported for domestic birds, with a number of cellular differences. The epithelium of certain segments of the egret’s rete testis displayed numerous, large intercellular spaces, not usually observed in most domestic avian species. As in the domestic species of birds, the proximal efferent ducts in the cattle egret displayed a robust endocytic apparatus as well as abundant lysosomes, but there were very few heterolysosomes and telolysosomes, which were common in domestic species. The border between the proximal and distal efferent ducts also demonstrated active spermiophagy. In addition to evidence of moderate secretary activities, the presence of extremely large heterolysosomes and telolysosomes also demonstrated the endocytic and digestive ability of cells lining the ductus deferens.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103329"},"PeriodicalIF":2.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The present study investigated a promising strategy for scaling up the expansion of high-quality human limbal stem cells (LSCs) in vitro. The LSCs isolated from human cornea biopsies were cultured with Mitomycin-C (MMC)-treated Swiss-3T3 feeder layers using three different methods: LSCs with MMC-treated Swiss-3T3 (L with MS), LSCs on MMC-treated Swiss-3T3 (L on MS), and LSCs on reverse MMC-treated Swiss-3T3 (L on RMS). Cell morphology, purity, and differentiation during culture were examined through light microscopy, flow cytometry, immunofluorescence staining, and reverse transcription-polymerase chain reaction (RT-PCR). Results showed that the LSCs continued to grow and exhibited the highest expression of p63 + cells (99.5 ± 0.5 %) in the L on RMS method. After 7 days of culture, the L on RMS method exhibited a significantly higher cell expansion rate than the L with MS method (**p < 0.01). Moreover, RT-PCR demonstrated that the cultured LSCs could naturally differentiate into epithelial cells, indicated by K3 expression. The cells could also efficiently form colonies while maintaining their stem cell markers. Therefore, the L on RMS method is promising for rapidly expanding high-quality LSCs and preserving their growth and stemness for corneal tissue engineering and reconstructive surgery.
本研究探讨了一种在体外扩大高质量人角膜缘干细胞（LSCs）的有希望的策略。将从人角膜活检中分离的LSCs用丝裂霉素c （MMC）处理过的Swiss-3T3饲养层进行培养，采用三种不同的方法：MMC处理过的Swiss-3T3 （L与MS结合）、MMC处理过的Swiss-3T3 （L与MS结合）和反向MMC处理过的Swiss-3T3 （L与RMS结合）的LSCs。通过光镜、流式细胞术、免疫荧光染色和逆转录聚合酶链反应（RT-PCR）检测细胞形态、纯度和培养过程中的分化情况。结果显示，LSCs继续生长，在L on RMS法中p63 + 细胞的表达量最高（99.5 ± 0.5 %）。培养7 d后，RMS法的细胞扩增率显著高于MS法（**p <； 0.01）。RT-PCR结果表明，培养的LSCs可以自然分化为上皮细胞，K3表达表明。这些细胞还可以有效地形成集落，同时保持它们的干细胞标记。因此，L on RMS方法有望快速扩增高质量的LSCs，并保持其生长和干性，用于角膜组织工程和重建手术。
{"title":"A promising strategy to rapidly expand high-quality human limbal stem cells for tissue engineering and cornea reconstruction","authors":"Keng-Liang Ou , Hsieh-Tsung Shen , Chi-Hsun Tsai , Takashi Saito , Chia-Yu Wu","doi":"10.1016/j.tice.2026.103343","DOIUrl":"10.1016/j.tice.2026.103343","url":null,"abstract":"<div><div>The present study investigated a promising strategy for scaling up the expansion of high-quality human limbal stem cells (LSCs) <em>in vitro</em>. The LSCs isolated from human cornea biopsies were cultured with Mitomycin-C (MMC)-treated Swiss-3T3 feeder layers using three different methods: LSCs with MMC-treated Swiss-3T3 (L with MS), LSCs on MMC-treated Swiss-3T3 (L on MS), and LSCs on reverse MMC-treated Swiss-3T3 (L on RMS). Cell morphology, purity, and differentiation during culture were examined through light microscopy, flow cytometry, immunofluorescence staining, and reverse transcription-polymerase chain reaction (RT-PCR). Results showed that the LSCs continued to grow and exhibited the highest expression of p63 + cells (99.5 ± 0.5 %) in the L on RMS method. After 7 days of culture, the L on RMS method exhibited a significantly higher cell expansion rate than the L with MS method (**<em>p</em> < 0.01). Moreover, RT-PCR demonstrated that the cultured LSCs could naturally differentiate into epithelial cells, indicated by K3 expression. The cells could also efficiently form colonies while maintaining their stem cell markers. Therefore, the L on RMS method is promising for rapidly expanding high-quality LSCs and preserving their growth and stemness for corneal tissue engineering and reconstructive surgery.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103343"},"PeriodicalIF":2.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.tice.2026.103340
Mohammed Alissa , Suad A. Alghamdi , Abdulkarim S. Binshaya , Tawfiq N. Juraybi , Awaji Y. Safhi , Amal A. Albati , Adil Abalkhail , Adel M. Alqarni
Brexpiprazole (BPZ) is a third-generation atypical antipsychotic drug that is reported to induce various organ toxicity in non-target organisms. The current investigation was conducted to explore the dose-dependent toxicity of BPZ on cardiac tissues. Thirty-six rats were divided into four groups including control, BPZ (3 mg/kg), BPZ (10 mg/kg), and BPZ (30 mg/kg) treated group. BPZ intoxication compromised mRNA expressions of Calcineurin/NFAT and Calcium Signaling Pathway as evidenced by increased expression of protein phosphatase 3 catalytic subunit alpha (PPP3CA), nuclear factor of activated T cells, cytoplasmic 3 (NFATC3), regulator of calcineurin 1 (RCAN1), and phospholamban (PLN) while downregulating the expression of Ryanodine receptor 2 (RYR2), calcium voltage-gated channel subunit alpha c (CACNA1C), ATPase sarcoplasmic/endoplasmic reticulum Ca2 + transporting 2 (SERCA2). Oxidative stress was clearly observed given the level of reactive oxygen species (ROS) and malondialdehyde (MDA) was markedly elevated coupled with significant inhibition of endogenous antioxidant enzymes including, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GSR), reduced glutathione (GSH) and glutathione S-transferase (GST) after BPZ intoxication. Functional cardiac impairment was further corroborated by significant changes occurring in echocardiographic parameters of myocardial impairment and ventricular dysfunction following the exposure of BPZ. Consistently, BPZ administration provoked the levels of creatine phosphokinase (CPK), B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT). Higher BPZ doses (10 and 30 mg/kg) triggered apoptotic imbalance, i.e., an increase in Cysteine-aspartic acid protease-3 (Caspase-3), Cysteine-aspartic acid protease-9 (Caspase-9), Bcl-2–associated X protein (Bax), while a significant reduction in the levels of B cell lymphoma-2 (Bcl-2). Histopathological evaluation showed severe myocardial damage in cardiac morphology following the intoxication of BPZ. In silico analyses supported these results showing binding affinity of BPZ with important key regulatory proteins. Collectively, the obtained data suggest that long-term exposure to BPZ results in cardiotoxicity mediated by oxidative stress, inflammation, apoptosis, and functional cardiac dysfunction.
{"title":"Brexpiprazole induces acute cardiotoxicity via disrupting calcineurin/NFAT and calcium signaling pathway: A validation from biochemical, echocardiographic, histological, and computational analysis","authors":"Mohammed Alissa , Suad A. Alghamdi , Abdulkarim S. Binshaya , Tawfiq N. Juraybi , Awaji Y. Safhi , Amal A. Albati , Adil Abalkhail , Adel M. Alqarni","doi":"10.1016/j.tice.2026.103340","DOIUrl":"10.1016/j.tice.2026.103340","url":null,"abstract":"<div><div>Brexpiprazole (BPZ) is a third-generation atypical antipsychotic drug that is reported to induce various organ toxicity in non-target organisms. The current investigation was conducted to explore the dose-dependent toxicity of BPZ on cardiac tissues. Thirty-six rats were divided into four groups including control, BPZ (3 mg/kg), BPZ (10 mg/kg), and BPZ (30 mg/kg) treated group. BPZ intoxication compromised mRNA expressions of Calcineurin/NFAT and Calcium Signaling Pathway as evidenced by increased expression of protein phosphatase 3 catalytic subunit alpha (PPP3CA), nuclear factor of activated T cells, cytoplasmic 3 (NFATC3), regulator of calcineurin 1 (RCAN1), and phospholamban (PLN) while downregulating the expression of Ryanodine receptor 2 (RYR2), calcium voltage-gated channel subunit alpha c (CACNA1C), ATPase sarcoplasmic/endoplasmic reticulum Ca<sup>2 +</sup> transporting 2 (SERCA2). Oxidative stress was clearly observed given the level of reactive oxygen species (ROS) and malondialdehyde (MDA) was markedly elevated coupled with significant inhibition of endogenous antioxidant enzymes including, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GSR), reduced glutathione (GSH) and glutathione S-transferase (GST) after BPZ intoxication. Functional cardiac impairment was further corroborated by significant changes occurring in echocardiographic parameters of myocardial impairment and ventricular dysfunction following the exposure of BPZ. Consistently, BPZ administration provoked the levels of creatine phosphokinase (CPK), B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT). Higher BPZ doses (10 and 30 mg/kg) triggered apoptotic imbalance, i.e., an increase in Cysteine-aspartic acid protease-3 (Caspase-3), Cysteine-aspartic acid protease-9 (Caspase-9), Bcl-2–associated X protein (Bax), while a significant reduction in the levels of B cell lymphoma-2 (Bcl-2). Histopathological evaluation showed severe myocardial damage in cardiac morphology following the intoxication of BPZ. In silico analyses supported these results showing binding affinity of BPZ with important key regulatory proteins. Collectively, the obtained data suggest that long-term exposure to BPZ results in cardiotoxicity mediated by oxidative stress, inflammation, apoptosis, and functional cardiac dysfunction.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103340"},"PeriodicalIF":2.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.tice.2026.103345
Yagang Ding , Bangde Xue , Mingkui Gao , Sibin Guan , Qinchuan Li , Jun Liu
Adipose-derived stem cells are widely used in aging field because of their extensive sources, low immunogenicity and strong secretory function. In particular, the exosomes of adipose-derived stem cells are rich in small molecules of RNA and protein. Studies have shown that exosomes also play a role in regulation of ER stress. Therefore, we hypothesized that exosomes of adipose-derived stem cells could regulate ER stress and delay fibroblasts senescence. In this study, we use H2O2 to promote cellular senescence and treat with adipose-derived stem cell exosomes. The function of cell proliferation and apoptosis were compared, and the levels of validating factor and collagen were detected. Then we explored the mechanism of action of exosomes derived from adipose-derived stem cells. We found adipose-derived stem cell exosomes could inhibit fibroblast senescence, including promoting cell proliferation, inhibiting apoptosis and regulating collagen secretion, by regulating ER stress through SIRT1. To further validate the relevance of this mechanism at the population level, public human skin transcriptomic data were analyzed, revealing coordinated downregulation of SIRT1 expression and unfolded protein response (UPR) signaling during physiological skin aging, with a strong positive correlation between SIRT1 expression and UPR pathway activity. This study suggests that adipose-derived stem cell exosomes attenuate stress-induced senescence-like changes in fibroblasts, highlighting their potential relevance in the modulation of cellular aging.
{"title":"Adipose-derived stem cell exosomes attenuated fibroblast senescence by regulating endoplasmic reticulum stress through SIRT1","authors":"Yagang Ding , Bangde Xue , Mingkui Gao , Sibin Guan , Qinchuan Li , Jun Liu","doi":"10.1016/j.tice.2026.103345","DOIUrl":"10.1016/j.tice.2026.103345","url":null,"abstract":"<div><div>Adipose-derived stem cells are widely used in aging field because of their extensive sources, low immunogenicity and strong secretory function. In particular, the exosomes of adipose-derived stem cells are rich in small molecules of RNA and protein. Studies have shown that exosomes also play a role in regulation of ER stress. Therefore, we hypothesized that exosomes of adipose-derived stem cells could regulate ER stress and delay fibroblasts senescence. In this study, we use H<sub>2</sub>O<sub>2</sub> to promote cellular senescence and treat with adipose-derived stem cell exosomes. The function of cell proliferation and apoptosis were compared, and the levels of validating factor and collagen were detected. Then we explored the mechanism of action of exosomes derived from adipose-derived stem cells. We found adipose-derived stem cell exosomes could inhibit fibroblast senescence, including promoting cell proliferation, inhibiting apoptosis and regulating collagen secretion, by regulating ER stress through SIRT1. To further validate the relevance of this mechanism at the population level, public human skin transcriptomic data were analyzed, revealing coordinated downregulation of SIRT1 expression and unfolded protein response (UPR) signaling during physiological skin aging, with a strong positive correlation between SIRT1 expression and UPR pathway activity. This study suggests that adipose-derived stem cell exosomes attenuate stress-induced senescence-like changes in fibroblasts, highlighting their potential relevance in the modulation of cellular aging.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103345"},"PeriodicalIF":2.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1016/j.tice.2026.103332
Ahmad A. Obaid , Mazen M. Ghaith , Ahmad Najem Alshammari , Ekramy M. Elmorsy , Manal S. Fawzy , Neven A. Ebrahim , Hamada S. Salem , Nashwa Mostafa Hussein
Background
Chlorpyrifos was shown to cause oxidative, inflammatory, and apoptotic renal damage. The natural Astaxanthin (ASX) exhibits nephroprotective effects, however its limited bioavailability hinders its therapeutic potential. Chitosan nanoparticles were shown to enhance bioavailability and therapeutic delivery of the natural compounds.
Objective
This study investigated the renoprotective effects of astaxanthin-loaded chitosan nanoparticles (ASX-CNPs) compared with crude astaxanthin (ASX) against chlorpyrifos (CPF)-induced nephrotoxicity in male Wistar rats.
Methods
Ninety rats (235 g) were randomly assigned into six groups (n = 15) and orally treated for 60 days with saline, ASX (40 mg/kg), ASX-CNPs (40 mg/kg), CPF (10 mg/kg), or combinations of CPF with ASX or ASX-CNPs. ASX-CNPs were characterized by transmission electron microscopy and dynamic light scattering, revealing uniform spherical nanoparticles with high stability and an encapsulation efficiency of 84.72 %. Oxidative, inflammatory, and apoptotic pathways were evaluated via different assays
Results
CPF exposure significantly impaired renal function, elevating blood urea, creatinine, uric acid, cystatin C, and NGAL levels, while promoting oxidative stress, lipid peroxidation, and DNA damage. CPF also suppressed the Nrf2/HO-1 antioxidant pathway, triggered inflammation and nitrosative stress, and disrupted apoptotic balance by increasing Bax and Caspase-3 while decreasing Bcl-2 expression. Histopathological and ultra-structural analysis confirmed severe renal alterations, including glomerular contraction, structurally disrupted mitochondria, vascular congestion, and tubular degeneration. Co-treatment with ASX-CNPs markedly ameliorated biochemical, oxidative, inflammatory, nitrosative, and apoptotic disturbances, restoring renal morphology close to normal. In contrast, crude ASX provided partial protection, with less pronounced effects on antioxidant enzyme activities, cytokine levels, and tissue architecture. The superior efficacy of ASX-CNPs highlights the advantages of nanoparticle delivery in enhancing bioavailability, stability, and cellular uptake compared with the conventional form.
Conclusion
These findings indicate that ASX-CNPs represent a promising nanotherapeutic strategy for preventing CPF-induced kidney injury and demonstrate the enhanced protective potential of nanoformulations over their crude counterparts
{"title":"Astaxanthin-loaded chitosan nanoparticles attenuate chlorpyrifos-induced nephrotoxicity via activation of the Nrf2/HO-1 axis and suppression of oxidative, inflammatory, and apoptotic pathways","authors":"Ahmad A. Obaid , Mazen M. Ghaith , Ahmad Najem Alshammari , Ekramy M. Elmorsy , Manal S. Fawzy , Neven A. Ebrahim , Hamada S. Salem , Nashwa Mostafa Hussein","doi":"10.1016/j.tice.2026.103332","DOIUrl":"10.1016/j.tice.2026.103332","url":null,"abstract":"<div><h3>Background</h3><div>Chlorpyrifos was shown to cause oxidative, inflammatory, and apoptotic renal damage. The natural Astaxanthin (ASX) exhibits nephroprotective effects, however its limited bioavailability hinders its therapeutic potential. Chitosan nanoparticles were shown to enhance bioavailability and therapeutic delivery of the natural compounds.</div></div><div><h3>Objective</h3><div>This study investigated the renoprotective effects of astaxanthin-loaded chitosan nanoparticles (ASX-CNPs) compared with crude astaxanthin (ASX) against chlorpyrifos (CPF)-induced nephrotoxicity in male Wistar rats.</div></div><div><h3>Methods</h3><div>Ninety rats (235 g) were randomly assigned into six groups (n = 15) and orally treated for 60 days with saline, ASX (40 mg/kg), ASX-CNPs (40 mg/kg), CPF (10 mg/kg), or combinations of CPF with ASX or ASX-CNPs. ASX-CNPs were characterized by transmission electron microscopy and dynamic light scattering, revealing uniform spherical nanoparticles with high stability and an encapsulation efficiency of 84.72 %. Oxidative, inflammatory, and apoptotic pathways were evaluated via different assays</div></div><div><h3>Results</h3><div>CPF exposure significantly impaired renal function, elevating blood urea, creatinine, uric acid, cystatin C, and NGAL levels, while promoting oxidative stress, lipid peroxidation, and DNA damage. CPF also suppressed the Nrf2/HO-1 antioxidant pathway, triggered inflammation and nitrosative stress, and disrupted apoptotic balance by increasing Bax and Caspase-3 while decreasing Bcl-2 expression. Histopathological and ultra-structural analysis confirmed severe renal alterations, including glomerular contraction, structurally disrupted mitochondria, vascular congestion, and tubular degeneration. Co-treatment with ASX-CNPs markedly ameliorated biochemical, oxidative, inflammatory, nitrosative, and apoptotic disturbances, restoring renal morphology close to normal. In contrast, crude ASX provided partial protection, with less pronounced effects on antioxidant enzyme activities, cytokine levels, and tissue architecture. The superior efficacy of ASX-CNPs highlights the advantages of nanoparticle delivery in enhancing bioavailability, stability, and cellular uptake compared with the conventional form.</div></div><div><h3>Conclusion</h3><div>These findings indicate that ASX-CNPs represent a promising nanotherapeutic strategy for preventing CPF-induced kidney injury and demonstrate the enhanced protective potential of nanoformulations over their crude counterparts</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103332"},"PeriodicalIF":2.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-17DOI: 10.1016/j.tice.2026.103331
Peng Yi, Bo Peng, Ying Cao, Xianghong Fu
Background
Male infertility represents a major global health challenge. Heat shock protein A1A (HSPA1A), a stress-inducible molecular chaperone, shows potential importance in spermatogenesis, though its precise mechanistic role remains undefined.
Methods
Analysis of human sperm transcriptome data (GSE6969) revealed HSPA1A expression in fertile versus infertile samples. Functional characterization involved the overexpression of HSPA1A in spermatogonia (GC-1 spg) and its knockdown in spermatocytes (GC-2 spd(ts)), assessing apoptosis, proliferation, and cell cycle progression. HSPA1A-interacting proteins were identified through immunoprecipitation-mass spectrometry and validated by co-immunoprecipitation. Downstream targets were investigated via bioinformatic analysis and proteomics. In vivo validation employed a mouse model of chronic HSP70 inhibition (VER-155008).
Results
HSPA1A is highly expressed in fertile sperm, and its overexpression significantly inhibited apoptosis, enhanced proliferation, and induced S/G2 phase arrest, while HSPA1A knockdown produced opposite effects. BAG5 was identified as a primary HSPA1A interactor. Mechanistically, the HSPA1A-BAG5 complex promoted ubiquitination-mediated degradation of ATF2, subsequently downregulating apoptotic signaling. In vivo HSPA1A inhibition induced testicular atrophy, reduced sperm count, impaired sperm morphology and acrosome reaction, disrupted seminiferous tubule architecture, and elevated germ cell apoptosis. Concurrent upregulation of ATF2, p53, and reduced testosterone levels were observed.
Conclusion
The HSPA1A-BAG5 complex maintains spermatogenic cell survival and proliferation through ubiquitination-dependent ATF2 degradation. These findings elucidate a novel regulatory axis essential for spermatogenesis and position HSPA1A as a promising therapeutic target for male infertility.
{"title":"HSPA1A-BAG5 chaperone complex promotes spermatogenesis by driving ubiquitination-mediated degradation of ATF2","authors":"Peng Yi, Bo Peng, Ying Cao, Xianghong Fu","doi":"10.1016/j.tice.2026.103331","DOIUrl":"10.1016/j.tice.2026.103331","url":null,"abstract":"<div><h3>Background</h3><div>Male infertility represents a major global health challenge. Heat shock protein A1A (HSPA1A), a stress-inducible molecular chaperone, shows potential importance in spermatogenesis, though its precise mechanistic role remains undefined.</div></div><div><h3>Methods</h3><div>Analysis of human sperm transcriptome data (GSE6969) revealed HSPA1A expression in fertile versus infertile samples. Functional characterization involved the overexpression of HSPA1A in spermatogonia (GC-1 spg) and its knockdown in spermatocytes (GC-2 spd(ts)), assessing apoptosis, proliferation, and cell cycle progression. HSPA1A-interacting proteins were identified through immunoprecipitation-mass spectrometry and validated by co-immunoprecipitation. Downstream targets were investigated via bioinformatic analysis and proteomics. <em>In vivo</em> validation employed a mouse model of chronic HSP70 inhibition (VER-155008).</div></div><div><h3>Results</h3><div>HSPA1A is highly expressed in fertile sperm, and its overexpression significantly inhibited apoptosis, enhanced proliferation, and induced S/G2 phase arrest, while HSPA1A knockdown produced opposite effects. BAG5 was identified as a primary HSPA1A interactor. Mechanistically, the HSPA1A-BAG5 complex promoted ubiquitination-mediated degradation of ATF2, subsequently downregulating apoptotic signaling. <em>In vivo</em> HSPA1A inhibition induced testicular atrophy, reduced sperm count, impaired sperm morphology and acrosome reaction, disrupted seminiferous tubule architecture, and elevated germ cell apoptosis. Concurrent upregulation of ATF2, p53, and reduced testosterone levels were observed.</div></div><div><h3>Conclusion</h3><div>The HSPA1A-BAG5 complex maintains spermatogenic cell survival and proliferation through ubiquitination-dependent ATF2 degradation. These findings elucidate a novel regulatory axis essential for spermatogenesis and position HSPA1A as a promising therapeutic target for male infertility.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"100 ","pages":"Article 103331"},"PeriodicalIF":2.5,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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