Pub Date : 2025-03-01Epub Date: 2025-01-02DOI: 10.1016/j.acthis.2024.152228
Jiao Li, Hui Hou, Junqin Li, Kaiming Zhang
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.
{"title":"Angiopoietins/Tie2 signaling axis and its role in angiogenesis of psoriasis","authors":"Jiao Li, Hui Hou, Junqin Li, 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}
Pub Date : 2025-03-01Epub Date: 2025-01-29DOI: 10.1016/j.acthis.2025.152232
Katharina Geib , Sonja Scharf , Hendrik Schäfer , Sylvia Hartmann , Martin-Leo Hansmann , Patrick Wurzel
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.
{"title":"3D examination reveals increased destruction of alpha-actin-positive structures in advanced follicular lymphoma stages","authors":"Katharina Geib , Sonja Scharf , Hendrik Schäfer , Sylvia Hartmann , Martin-Leo Hansmann , 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}
Pub Date : 2025-03-01Epub Date: 2025-02-05DOI: 10.1016/j.acthis.2025.152234
Manish Kumar Sharma , Kumari Priyam , Punit Kumar , Pramod Kumar Garg , Tara Sankar Roy , Tony George Jacob
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 < 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 < 0.001). Expression of HMGB1was more in group 4 than 3 (p = 0.046). Chloroquine enhances necrosis and inflammation in caerulein-induced pancreatitis.
{"title":"Effect of chloroquine on autophagy and the severity of caerulein-induced acute pancreatitis in mice","authors":"Manish Kumar Sharma , Kumari Priyam , Punit Kumar , Pramod Kumar Garg , Tara Sankar Roy , 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 CO<sub>2</sub>-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 < 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 < 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}
Pub Date : 2025-03-01Epub Date: 2025-02-08DOI: 10.1016/j.acthis.2025.152233
Tingting Chu , Qinghua Han , Hongtao Shi , Chao Li , Qi Ma , Peng Li , Fang Wang , Jing Zhang
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.
{"title":"Aberration of CA3 functionally mediates the pathogenesis of Cardiomyocyte hypertrophy in a miR-138–5p dependent manner","authors":"Tingting Chu , Qinghua Han , Hongtao Shi , Chao Li , Qi Ma , Peng Li , Fang Wang , 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}
Pub Date : 2025-03-01Epub Date: 2024-12-12DOI: 10.1016/j.acthis.2024.152223
Ming-Yan Yang , Hong-Yuan Quan , Da-Lei Li , Jian Ruan , Hua-Ying Fan
Despite of decades of efforts, novel approaches are still limited to attenuate or prevent skin scarring. A previous report published in Science 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.
{"title":"Targeting TEAD would be a potential strategy for scarless wound repair: A preliminary study","authors":"Ming-Yan Yang , Hong-Yuan Quan , Da-Lei Li , Jian Ruan , 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}
Pub Date : 2025-03-01Epub Date: 2025-01-08DOI: 10.1016/j.acthis.2024.152226
Juan C. Stockert , Richard W. Horobin
In recent years, a great interest has been focused on the prebiotic origin of nucleic acids and life on Earth. An attractive idea is that life was initially based on an autocatalytic and autoreplicative RNA (the RNA-world). RNA duplexes are right-handed helical chains with antiparallel orientation, but the rationale for these features is not yet known. An antiparallel (inverted) stacking of purine nucleosides was reported in crystallographic studies. Molecular modeling also supports the inverted orientation of nucleosides. This preferential stacking can also appear when nucleosides are included in a montmorillonite clay matrix. Free-energy values and geometrical parameters show that D-ribose chirality is preferred for the formation of right-handed RNA molecules. Thus, a “zipper” model with antiparallel and auto-intercalated nucleosides linked by phosphate groups can be proposed to form single RNA chains. Unstacking with strand separation and base pairing by H-bonding, results in shortening and inclination of ribose-phosphate chains, leading to right-handed helicity and antiparallel duplexes. Incorporation of complementary precursors on the major groove template by a self-assembly mechanism provides a prebiotic (non-enzymatic) “tetris” replication model by formation of a transient RNA tetrad and tetraplex. Original hairpin motifs appear as simple building units that form typical RNA structures such as hammerheads, cloverleaves and dumbbells. They occur today in the circular viroids and virusoids, as well as in highly branched and complex rRNA molecules.
{"title":"Prebiotic RNA self-assembling and the origin of life: Mechanistic and molecular modeling rationale for explaining the prebiotic origin and replication of RNA","authors":"Juan C. Stockert , Richard W. Horobin","doi":"10.1016/j.acthis.2024.152226","DOIUrl":"10.1016/j.acthis.2024.152226","url":null,"abstract":"<div><div>In recent years, a great interest has been focused on the prebiotic origin of nucleic acids and life on Earth. An attractive idea is that life was initially based on an autocatalytic and autoreplicative RNA (the RNA-world). RNA duplexes are right-handed helical chains with antiparallel orientation, but the rationale for these features is not yet known. An antiparallel (inverted) stacking of purine nucleosides was reported in crystallographic studies. Molecular modeling also supports the inverted orientation of nucleosides. This preferential stacking can also appear when nucleosides are included in a montmorillonite clay matrix. Free-energy values and geometrical parameters show that <span>D</span>-ribose chirality is preferred for the formation of right-handed RNA molecules. Thus, a “zipper” model with antiparallel and auto-intercalated nucleosides linked by phosphate groups can be proposed to form single RNA chains. Unstacking with strand separation and base pairing by H-bonding, results in shortening and inclination of ribose-phosphate chains, leading to right-handed helicity and antiparallel duplexes. Incorporation of complementary precursors on the major groove template by a self-assembly mechanism provides a prebiotic (non-enzymatic) “tetris” replication model by formation of a transient RNA tetrad and tetraplex. Original hairpin motifs appear as simple building units that form typical RNA structures such as hammerheads, cloverleaves and dumbbells. They occur today in the circular viroids and virusoids, as well as in highly branched and complex rRNA molecules.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152226"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942444","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 : 2025-03-01Epub Date: 2025-01-16DOI: 10.1016/j.acthis.2025.152230
Ting Wang, Ruoan Jiang, Xueling Tang, Yingsha Yao, Peiyue Jiang
Background
Cervical cancer is a major health burden in females worldwide, available studies indicated that sex-determining region Y-box 2 (SOX2) is closely related to the malignant phenotypes of multiple cancers including cervical cancer. However, the underlying mechanisms were blurred.
Experimental Procedures
A bioinformatics analysis was conducted to investigate the clinical correlation between SOX2 and cervical cancer. Transient transfection and lentivirus infection were utilized to achieve overexpression and knockdown of SOX2, respectively. The role of SOX2 in cervical cancer was confirmed by transwell and colony-forming assays. Immunoblot, dual-luciferase reporter, chromatin immunoprecipitation (ChIP), and biochemical experiments were employed. In addition, the xenograft models and immunohistochemistry (IHC) experiments were performed to validate the findings in vivo.
Results
The expression of SOX2 was significantly positively associated with the cell migration, invasion, and colony-forming abilities of cervical cancer cells. The following immunoblots revealed that the SOX2-induced malignant phenotypes might be related to the glycolysis process, since overexpressing SOX2 significantly promoted the hexokinase 2 (HK2) and glucose transporter-1 (GLUT1) expression, and increased the content of glucose and lactic acid. The further dual-luciferase reporter and ChIP experiments confirmed a binding relationship between SOX2 and HK2 promoter. More importantly, overexpressing SOX2 promoted tumor growth concomitant with a hyper-expression of HK2 and GLUT1 in xenograft tumor tissues, yet the treatment of glycolysis inhibitor significantly reversed those outcomes.
Conclusion
SOX2 promotes the malignant progression of cervical cancer by facilitating glycolysis.
{"title":"SOX2 promotes the glycolysis process to accelerate cervical cancer progression by regulating the expression of HK2","authors":"Ting Wang, Ruoan Jiang, Xueling Tang, Yingsha Yao, Peiyue Jiang","doi":"10.1016/j.acthis.2025.152230","DOIUrl":"10.1016/j.acthis.2025.152230","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer is a major health burden in females worldwide, available studies indicated that sex-determining region Y-box 2 (SOX2) is closely related to the malignant phenotypes of multiple cancers including cervical cancer. However, the underlying mechanisms were blurred.</div></div><div><h3>Experimental Procedures</h3><div>A bioinformatics analysis was conducted to investigate the clinical correlation between SOX2 and cervical cancer. Transient transfection and lentivirus infection were utilized to achieve overexpression and knockdown of SOX2, respectively. The role of SOX2 in cervical cancer was confirmed by transwell and colony-forming assays. Immunoblot, dual-luciferase reporter, chromatin immunoprecipitation (ChIP), and biochemical experiments were employed. In addition, the xenograft models and immunohistochemistry (IHC) experiments were performed to validate the findings <em>in vivo</em>.</div></div><div><h3>Results</h3><div>The expression of SOX2 was significantly positively associated with the cell migration, invasion, and colony-forming abilities of cervical cancer cells. The following immunoblots revealed that the SOX2-induced malignant phenotypes might be related to the glycolysis process, since overexpressing SOX2 significantly promoted the hexokinase 2 (HK2) and glucose transporter-1 (GLUT1) expression, and increased the content of glucose and lactic acid. The further dual-luciferase reporter and ChIP experiments confirmed a binding relationship between SOX2 and HK2 promoter. More importantly, overexpressing SOX2 promoted tumor growth concomitant with a hyper-expression of HK2 and GLUT1 in xenograft tumor tissues, yet the treatment of glycolysis inhibitor significantly reversed those outcomes.</div></div><div><h3>Conclusion</h3><div>SOX2 promotes the malignant progression of cervical cancer by facilitating glycolysis.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152230"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998285","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}
Pub Date : 2025-03-01Epub Date: 2025-02-04DOI: 10.1016/j.acthis.2025.152235
Ilija Perutina , Nela Kelam , Mirko Maglica , Anita Racetin , Azer Rizikalo , Natalija Filipović , Ivana Kuzmić Prusac , Marko Bošnjak , Josip Mišković , Boris Kablar , Nasrollah Ghahrani , Katarina Vukojević
This study aimed to investigate the spatiotemporal expression patterns of key markers involved in regulating the canonical and non-canonical Wnt pathway during human fetal kidney development, comparing healthy (CTRL) and congenital anomalies of the kidney and urinary tract (CAKUT) affected kidneys. Human fetal kidneys, ranging from the 18th to the 38th developmental weeks, including various CAKUT phenotypes (horseshoe, dysplastic, duplex and hypoplastic), underwent double immunofluorescence microscopy analysis following antibody staining. Immunoreactivity levels were quantified in different kidney structures, and expression dynamics were assessed using linear and nonlinear regression modeling techniques. The study revealed a decrease in the overall protein expression of acetylated α-tubulin during normal kidney development, while the highest percentage of positive cells was observed in the horseshoe kidney (HK), thus disturbing microtubule composition in normal cell division and differentiation. Additionally, a continuous decrease of inversin-positive cells in hypoplastic (HYP) and duplex kidneys (UD), but the exponential growth of DVL-1 expression score in dysplastic kidneys (DYS) with developmental age, result in suppression of final kidney differentiation by continuous canonical Wnt signaling activation, thus supporting the essential role of the switch from canonical to non-canonical Wnt pathway in nephrogenesis. Furthermore β-catenin-positive cells in dysplastic and hypoplastic kidney exhibited the highest percentage of positive signal, with a decline in β-catenin positive cells over time in the control group, indicating disturbances in transition from canonical to non-canonical Wnt pathway in CAKUT-affected kidneys. The findings suggest that the crosstalk between canonical and non-canonical Wnt signaling pathways is crucial for normal nephrogenesis, highlighting their potential roles in normal and dysfunctional kidney development.
{"title":"Spatiotemporal distribution of Wnt signaling pathway markers in human congenital anomalies of kidney and urinary tract","authors":"Ilija Perutina , Nela Kelam , Mirko Maglica , Anita Racetin , Azer Rizikalo , Natalija Filipović , Ivana Kuzmić Prusac , Marko Bošnjak , Josip Mišković , Boris Kablar , Nasrollah Ghahrani , Katarina Vukojević","doi":"10.1016/j.acthis.2025.152235","DOIUrl":"10.1016/j.acthis.2025.152235","url":null,"abstract":"<div><div>This study aimed to investigate the spatiotemporal expression patterns of key markers involved in regulating the canonical and non-canonical Wnt pathway during human fetal kidney development, comparing healthy (CTRL) and congenital anomalies of the kidney and urinary tract (CAKUT) affected kidneys. Human fetal kidneys, ranging from the 18th to the 38th developmental weeks, including various CAKUT phenotypes (horseshoe, dysplastic, duplex and hypoplastic), underwent double immunofluorescence microscopy analysis following antibody staining. Immunoreactivity levels were quantified in different kidney structures, and expression dynamics were assessed using linear and nonlinear regression modeling techniques. The study revealed a decrease in the overall protein expression of acetylated α-tubulin during normal kidney development, while the highest percentage of positive cells was observed in the horseshoe kidney (HK), thus disturbing microtubule composition in normal cell division and differentiation. Additionally, a continuous decrease of inversin-positive cells in hypoplastic (HYP) and duplex kidneys (UD), but the exponential growth of DVL-1 expression score in dysplastic kidneys (DYS) with developmental age, result in suppression of final kidney differentiation by continuous canonical Wnt signaling activation, thus supporting the essential role of the switch from canonical to non-canonical Wnt pathway in nephrogenesis. Furthermore β-catenin-positive cells in dysplastic and hypoplastic kidney exhibited the highest percentage of positive signal, with a decline in β-catenin positive cells over time in the control group, indicating disturbances in transition from canonical to non-canonical Wnt pathway in CAKUT-affected kidneys. The findings suggest that the crosstalk between canonical and non-canonical Wnt signaling pathways is crucial for normal nephrogenesis, highlighting their potential roles in normal and dysfunctional kidney development.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152235"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132647","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}
Epidemic keratoconjunctivitis (EKC) is one of the most severe clinical manifestations of human adenovirus ocular surface infection, which may lead to the formation of subepithelial infiltrates (SEIs) in the anterior corneal stroma in 20–50 % of cases. SEIs may be asymptomatic or give rise to corneal aberrations and visual impairment for months or years after acute infection, despite treatments. Here, we describe the ultrastructural and immunophenotypic features of the anterior corneal stroma of a patient who underwent superficial anterior lamellar keratoplasty (SALK) surgery to remove corneal opacities related to clinically significant and steroid-unresponsive, long-lasting SEIs after adenoviral EKC. Before femtosecond laser-assisted SALK surgical intervention, the patient underwent in vivo confocal microscopy that showed a cluster of hyperreflective inflammatory cells within the basal epithelium, associated to an abnormal sub-basal nerve plexus with a fragmented nervous component appearance. The areas corresponding to the SEIs appeared as roundish hyperreflective spots with undefined borders. Transmission electron microscopy analysis of the excised anterior corneal button revealed the presence of giant stromal cells displaying myofibroblast-like features immediately beneath the Bowman’s layer. Such abnormal cells exhibited ultrastructural signs of endoplasmic reticulum stress and autophagy, and were positive for markers of activated fibroblasts/myofibroblasts at immunofluorescence analysis. The deeper stroma was instead populated by normal stromal cells (i.e., keratocytes). This case report provides the first morphological evidence that persistent SEIs could be the macroscopic expression of subepithelial giant stromal cells with myofibroblast-like characteristics. Such a novel observation might pave the way toward a better targeted therapeutic management of SEIs.
{"title":"New insights into persistent corneal subepithelial infiltrates following epidemic keratoconjunctivitis: The first case report with ultrastructural and immunohistochemical investigations","authors":"Rita Mencucci , Michela Cennamo , Irene Rosa , Daniele Guasti , Matilde Buzzi , Eleonora Sgambati , Mirca Marini , Mirko Manetti","doi":"10.1016/j.acthis.2025.152231","DOIUrl":"10.1016/j.acthis.2025.152231","url":null,"abstract":"<div><div>Epidemic keratoconjunctivitis (EKC) is one of the most severe clinical manifestations of human adenovirus ocular surface infection, which may lead to the formation of subepithelial infiltrates (SEIs) in the anterior corneal stroma in 20–50 % of cases. SEIs may be asymptomatic or give rise to corneal aberrations and visual impairment for months or years after acute infection, despite treatments. Here, we describe the ultrastructural and immunophenotypic features of the anterior corneal stroma of a patient who underwent superficial anterior lamellar keratoplasty (SALK) surgery to remove corneal opacities related to clinically significant and steroid-unresponsive, long-lasting SEIs after adenoviral EKC. Before femtosecond laser-assisted SALK surgical intervention, the patient underwent in vivo confocal microscopy that showed a cluster of hyperreflective inflammatory cells within the basal epithelium, associated to an abnormal sub-basal nerve plexus with a fragmented nervous component appearance. The areas corresponding to the SEIs appeared as roundish hyperreflective spots with undefined borders. Transmission electron microscopy analysis of the excised anterior corneal button revealed the presence of giant stromal cells displaying myofibroblast-like features immediately beneath the Bowman’s layer. Such abnormal cells exhibited ultrastructural signs of endoplasmic reticulum stress and autophagy, and were positive for markers of activated fibroblasts/myofibroblasts at immunofluorescence analysis. The deeper stroma was instead populated by normal stromal cells (i.e., keratocytes). This case report provides the first morphological evidence that persistent SEIs could be the macroscopic expression of subepithelial giant stromal cells with myofibroblast-like characteristics. Such a novel observation might pave the way toward a better targeted therapeutic management of SEIs.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 1","pages":"Article 152231"},"PeriodicalIF":2.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057765","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}
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