Acta histochemica最新文献

{"title":"Autophagy markers expression pattern in developing liver of the yotari (dab1 -/-) mice and humans","authors":"Edita Dražić Maras ,&nbsp;Nela Kelam ,&nbsp;Anita Racetin ,&nbsp;Ejazul Haque ,&nbsp;Maja Dražić ,&nbsp;Katarina Vukojević ,&nbsp;Yu Katsuyama ,&nbsp;Mirna Saraga-Babić ,&nbsp;Natalija Filipović","doi":"10.1016/j.acthis.2024.152224","DOIUrl":"10.1016/j.acthis.2024.152224","url":null,"abstract":"<div><div>Autophagy plays an important role in the physiology and pathology of the liver. Several negative autophagy regulators have been discovered, including epidermal growth factor receptor (EGFR), mediated by activation of the PI3K/Akt/mTOR signaling pathway. Disabled-1 (Dab1) is one of the mediating adaptor factors of PI3K/Akt/mTOR signaling pathways. We investigated the potential impact of Dab1 on autophagy-related markers (LC3B, LAMP2A, HSC70, and GRP78) in the developing liver by using a model of yotari mice and compared it with autophagy marker expression in human liver development. Mouse embryos were obtained at gestation days 13.5 and 15.5 (E13.5 and E15.5), and a total of 5 normal human conceptuses were obtained between gestation days 5 and 10. Histological sections were analyzed by immunohistochemistry. The highest expression of the early endosome-forming factor LC3B and the microautophagy factor LAMP2a was observed at the transition from embryonic to early fetal phase, whereas the expression of the chaperones HSC 70 and GRP78 was highest at embryonic phase. The expression patterns of three of these factors in mouse liver were different from those in human liver: the expression of LC3B was high at E13.5, that of HSC 70 at 15.5, whereas the expression of GRP78 did not change significantly. On the other hand, the expression pattern of LAMP2a was similar to that in human development and was higher at E15.5 than at E13.5. Moreover, knockout of Dab1 resulted in significantly lower expression of LC3B and LAMP2a in mouse embryo livers (at E13.5), indicating a possible role of Dab1 in regulating autophagy during embryonic development in the liver.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152224"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794218","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}

{"title":"Normal dermal mesenchymal stem cells improve the functions of psoriatic keratinocytes by inducing autophagy","authors":"Nannan Liang,&nbsp;Yue Cao,&nbsp;Junqin Li,&nbsp;Kaiming Zhang","doi":"10.1016/j.acthis.2025.152229","DOIUrl":"10.1016/j.acthis.2025.152229","url":null,"abstract":"<div><h3>Objective</h3><div>Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Although stem cell-based therapies have shown promise in treating psoriasis, the underlying mechanisms remain unclear. This study aimed to established a psoriatic cell model to investigate the effect of normal dermal mesenchymal stem cell (DMSCs) on keratinocyte proliferation, inflammation responses and the associated mechanism.</div></div><div><h3>Methods</h3><div>To create an <em>in vitro</em> model of psoriasis, HaCaT cells were stimulated with a mixture of five inflammatory cytokines including IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5). A transwell co-culture system was employed to assess the influence of normal DMSCs on proliferation and inflammation response of HaCaT cells. Cell viability was assessed using the CCK-8 assay and EDU incorporation assay. The expression levels of mRNA for inflammatory cytokines (IL-8, IL-17A and TNF-α) in HaCaT cells co-cultured with either normal or psoriatic DMSCs were quantified by qRT-PCR. Apoptosis was evaluated by annexin V-FITC/PI double staining and TUNEL/DAPI staining assay. Autophagy was detected by immunostaining, RT-PCR and western blotting. Additionally, the expression levels of mRNA and protein of both Akt and mammalin target of rapamycin(mTOR) were also determined.</div></div><div><h3>Results</h3><div>Normal DMSCs were found to decrease the viability and promote apoptosis of HaCaT cells treated with M5. Furthermore, DMSCs reduced the secretion of proinflammatory cytokines, such as IL-8, IL-17A and TNF-α. Importantly, normal DMSCs were shown to induced autophagy in HaCaT cell. Pretreatment of HaCaT cells with autophagy inhibitor 3-methyladenine (3-MA) reversed the anti-psoriatic effect of normal DMSCs. Notably, DMSCs promote autophagy in M5-treated HaCaT cells by inhibition of p-Akt/Akt and p-mTOR/mTOR ratio.</div></div><div><h3>Conclusion</h3><div>Normal mesenchymal stem cells promote autophagy through the inhibition of Akt/mTOR signaling pathway, leading to the alleviation of psoriasis in vitro. These findings provide insights into the potential mechanisms by which DMSCs may exert therapeutic effects in psoriasis and support further investigation into their clinical applications.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152229"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045266","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}

{"title":"Molecular signature-based labeling techniques for vascular endothelial cells","authors":"Krutika H. Dobariya,&nbsp;Divya Goyal,&nbsp;Hemant Kumar","doi":"10.1016/j.acthis.2024.152222","DOIUrl":"10.1016/j.acthis.2024.152222","url":null,"abstract":"<div><div>Vascular endothelial cells (VECs) play a crucial role in the development and maintenance of vascular biology specific to the tissue types. Molecular signature-based labeling and imaging of VECs help researchers understand potential mechanisms linking VECs to disease pathology, serving as valuable biomarkers in clinical settings and trials. Labeling techniques involve selectively tagging or marking VECs for visualization. Immunolabeled employs antibodies that specifically bind to VECs markers, while fluorescent tracers or dyes can directly label VECs for imaging. Some techniques use specific carbohydrate residues on cell surface, while others employ endothelial-specific promoters to express fluorescent proteins. Additionally, VEC can be labeled with contrast agents, radiolabeled tracers, and nanoparticles. The choice of labeling technique depends on study context, including whether it involves animal models, in vitro cell cultures, or clinical applications. Herein, we discussed the various labeling methods utilized to label VECs and the techniques to visualize them.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152222"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790877","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}

{"title":"Acridine orange fluorescence in chromosome cytochemistry: Molecular modeling rationale for understanding the differential fluorescence on double- and single-stranded nucleic acids","authors":"Alfonso Blázquez-Castro ,&nbsp;Juan C. Stockert","doi":"10.1016/j.acthis.2024.152225","DOIUrl":"10.1016/j.acthis.2024.152225","url":null,"abstract":"<div><div>Many fluorophores display interesting features that make them useful biological labels and dyes, particularly in Cell Biology and Cytogenetics. Changes in the absorption-emission spectra (ortho- and metachromasia) are accounted among them. Acridine orange (AO) is one of such fluorochromes with an exemplary orthochromatic <em>vs.</em> metachromatic emission, which depends on its concentration and binding mode to different cell substrates. Here, we revisit the differential AO fluorescence that occurs in selected biological materials, which allows the identification of single-stranded or double-stranded nucleic acids. Although known for a long time, the ultimate reason for this differential phenomenon has not been properly addressed. We propose a potential molecular mechanism that adequately accounts for the distinct AO emission when bound either to denatured or denatured-reassociated DNA. This mechanism, based on theoretical molecular modelling, implies a difference in the degree of overlap of excited state orbitals whenever AO molecules are interacting with bases from single- or double-stranded nucleic acids. In the first case, massive orbital overlapping leads to a metachromatic red AO emission. Otherwise, no excited-state orbital overlapping occurs, due to excessive distance between intercalated AO molecules, which manifests as orthochromatic green fluorescence. Our molecular modelling supports this interplay between orbital overlap/not overlap and metachromatic/orthochromatic fluorescence.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152225"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiopoietins/Tie2 signaling axis and its role in angiogenesis of psoriasis","authors":"Jiao Li,&nbsp;Hui Hou,&nbsp;Junqin Li,&nbsp;Kaiming Zhang","doi":"10.1016/j.acthis.2024.152228","DOIUrl":"10.1016/j.acthis.2024.152228","url":null,"abstract":"<div><div>Hyperplasia of microvessels in the superficial dermis is the main pathological feature of psoriasis, and is linked to the pathogenesis of psoriasis. Thus, anti-angiogenic therapy may be effective for psoriasis. Angiopoietins (Angs) are crucial angiogenic factors. Ang1 supports a static mature vascular phenotype, while Ang2 is associated with the formation of abnormal vascular structure, vascular leakage and inflammation. The Ang/Tie2 axis and its signal transduction play an important role in regulation of vascular stability, angiogenesis and inflammation. Targeting the Ang/Tie2 signal axis can normalize microvessels in psoriatic lesions. This paper reviews Ang/Tie2 signal axis and its role in angiogenesis of psoriasis, aiming to provide new ideas and strategies for anti-angiogenic therapy of psoriasis.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152228"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926185","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}

{"title":"3D examination reveals increased destruction of alpha-actin-positive structures in advanced follicular lymphoma stages","authors":"Katharina Geib ,&nbsp;Sonja Scharf ,&nbsp;Hendrik Schäfer ,&nbsp;Sylvia Hartmann ,&nbsp;Martin-Leo Hansmann ,&nbsp;Patrick Wurzel","doi":"10.1016/j.acthis.2025.152232","DOIUrl":"10.1016/j.acthis.2025.152232","url":null,"abstract":"<div><div>Follicular lymphoma (FL) represents the most prevalent subtype of non-Hodgkin’s-lymphoma in Western Europe and the United States. While the examination of two-dimensional histological slides remains the gold standard method for diagnosing FL stages, three-dimensional analysis provides additional insights, particularly regarding cellular morphology, spatial relationships and network connectivity. This investigation assessed the tumor-related morphological destruction of fibroreticular cell (FRC) networks bordering germinal centres in FL. A confocal laser scanning technology and a digital three-dimensional analysis system were used. Quantitive measurements included the length of fibroblastic reticular walls surrounding the germinal centres as well as the size of the gaps and holes within these structures. Three-dimensional analysis revealed progressive structural degradation and a reduction in mechanical barrier integrity, with differences observed between low- and high-grade FL. High-grade FL exhibited greater network destruction. Fibroblastic reticular cell networks’ wall length demonstrated a consistent decline across all grades. The lengths of these walls and wall-like structures in FL grades 1 or 2 were similar to reactive germinal centres seen in lymphadenitis, as well as the gap size. The gaps are thought to be responsible for B- and T-cell exchange. This work demonstrated the massive destruction of neoplastic germinal centres in grades 3a and 3b FL. In grade 3b, this was accompanied by a likely dysfunctional mechanical border of the germinal centre and the near-complete loss of structural integrity. Under physiological conditions, gaps and holes regulate lymphoid traffic. Under reactive conditions, only a few specific T-cells can access the germinal centre. Under neoplastic conditions, the diameter of these gaps increases as grades increase, culminating in complete structural disruption in grade 3b. The mechanical destruction was found to begin at one pole of the germinal centre, as evidenced by localized decay and fragmentation of FRC walls on one side. Fibroblastic reticular cell networks are critical for maintaining chemokine gradients to ensure compartmentalisation of lymphoid structures. Their ongoing degradation in FL of the networks leads to a morphological loss of function. This is due to the blurring of various lymph node zones.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152232"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063085","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}

{"title":"Effect of chloroquine on autophagy and the severity of caerulein-induced acute pancreatitis in mice","authors":"Manish Kumar Sharma ,&nbsp;Kumari Priyam ,&nbsp;Punit Kumar ,&nbsp;Pramod Kumar Garg ,&nbsp;Tara Sankar Roy ,&nbsp;Tony George Jacob","doi":"10.1016/j.acthis.2025.152234","DOIUrl":"10.1016/j.acthis.2025.152234","url":null,"abstract":"<div><div>Impaired autophagy is implicated in the pathogenesis of caerulein-induced model of acute pancreatitis (AP). Chloroquine blocks the fusion of autophagosome and lysosome and affects completion of the cellular autophagic flux. Adult, male, Swiss albino mice (20–25 g) were divided into four groups- 1, 2, 3 and 4 of 6 mice each. Mice in Group1 were given 8, hourly intraperitoneal injections of normal saline. Group 2 was also given intraperitoneal injections of chloroquine (60 mg/Kg) at 14 h and 30-min prior to first injection of normal saline. Mice in Groups 3 and 4 given 8, hourly intraperitoneal injections of caerulein (50 µg /Kg/dose). Group 4 also received chloroquine as Group 2. After sacrifice at the 9th hour in CO₂-chamber, blood was drawn for amylase activity and cytokines estimation (IL-6, TNF-α, GM-CSF, IL-1β and IL-10) and pancreas was harvested for histopathology, transmission electron microscopy (TEM) and immunoblotting (LC3II, Beclin 1, SQSTM1, RIPK1, P65, Caspase-3, RIPK3, HMGB1). The relative expression of SQSTM1 and the autophagic vacuole area was higher in groups 2, 3 and 4 (p &lt; 0.05), suggestive of increased impairment of autophagic flux. Autolysosome count was significantly increased in group 3 in comparison to group 1 (p = 0.0049). Autolysosome area was also increased in group 4 in comparison to group 3 (p = 0.031), which suggested impairment of autophagy. Total histopathological score and amylase activity were equivalent in groups 3 and 4. RIPK1 in pancreas and TNF-α level in plasma were more in group 4 than 3 (p = 0.014, 0.02, respectively). Expression of Caspase-3, was lesser in group 4 than 3 (p &lt; 0.001). Expression of HMGB1was more in group 4 than 3 (p = 0.046). Chloroquine enhances necrosis and inflammation in caerulein-induced pancreatitis.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152234"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132646","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}

{"title":"Aberration of CA3 functionally mediates the pathogenesis of Cardiomyocyte hypertrophy in a miR-138–5p dependent manner","authors":"Tingting Chu ,&nbsp;Qinghua Han ,&nbsp;Hongtao Shi ,&nbsp;Chao Li ,&nbsp;Qi Ma ,&nbsp;Peng Li ,&nbsp;Fang Wang ,&nbsp;Jing Zhang","doi":"10.1016/j.acthis.2025.152233","DOIUrl":"10.1016/j.acthis.2025.152233","url":null,"abstract":"<div><div>Cardiomyocyte hypertrophy (CDH) is a critical factor in heart disease, leading to heart failure and increased mortality. Despite extensive research, the precise molecular mechanisms underlying CDH remain unclear. In our study, we conducted total RNA sequencing on blood-derived exosomes from 11 CDH patients and 8 healthy donors. This analysis identified differentially expressed genes (DEGs), which we further validated using real-time qPCR and ROC analysis to demonstrate their diagnostic potential in clinical samples. To explore the functional role of CA3 in CDH, we manipulated its expression using the AAV9 vector in TAC (transverse aortic constriction) rat models(N = 6). We observed a significant increase in CA3 expression in both the blood of CDH patients and TAC rat models. Knockdown of Ca3 using the AAV9 vector resulted in improved cardiac function in TAC rats (N = 6), as evidenced by a ∼30 % reduction in LVEF% (left ventricular ejection fraction) and LVFS% (left ventricular fractional shortening) compared to Sham-operated controls. Additionally, LV (left ventricular) mass and the HW/BW (heart weight to body weight ratio) were significantly higher in the TAC groups. Mechanistically, we identified miR-138–5p as a direct regulator of CA3 through the StarBase bioinformatics tool. This interaction was experimentally validated using a dual-luciferase reporter assay and real-time qPCR. We found that miR-138–5p expression was down-regulated in both CDH patients and TAC rat models. Restoration of miR-138–5p expression mitigated the phenotypes induced by Ca3 overexpression. Our findings reveal a novel miR-138–5p/CA3 axis involved in the pathogenesis of CDH, suggesting potential therapeutic avenues for this heart disease.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152233"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349664","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}

{"title":"Targeting TEAD would be a potential strategy for scarless wound repair: A preliminary study","authors":"Ming-Yan Yang ,&nbsp;Hong-Yuan Quan ,&nbsp;Da-Lei Li ,&nbsp;Jian Ruan ,&nbsp;Hua-Ying Fan","doi":"10.1016/j.acthis.2024.152223","DOIUrl":"10.1016/j.acthis.2024.152223","url":null,"abstract":"<div><div>Despite of decades of efforts, novel approaches are still limited to attenuate or prevent skin scarring. A previous report published in <em>Science</em> demonstrated that inhibition of YAP promotes scarless wound repair by regeneration. Due to the difficult drugability of targeting YAP, we speculated that inhibition of TEAD, a partner molecule of YAP, might exist similar therapeutic potential. Therefore, the aim of the study was to evaluate therapeutical effect of a novel inhibitor of TEAD auto-palmitoylation, VT107, on scar formation in a cutaneous wound healing model. Our findings confirmed VT107 exhibited favorable effect on preventing scarring, manifesting as reducing fibroblast proliferation and collagen denaturation, decreasing TGF-β1 and collagen deposition, as well as connective tissue growth factor (CTGF) expression. These findings provide a novel insight for the development of anti-scarring strategies. TEAD would become an ideal target for the treatment of scars.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152223"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816992","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}

{"title":"Introducing the “hypotheses in cell biology” section","authors":"Jesus Espada","doi":"10.1016/j.acthis.2024.152227","DOIUrl":"10.1016/j.acthis.2024.152227","url":null,"abstract":"","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152227"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}