Pub Date : 2025-02-19DOI: 10.1016/j.tice.2025.102784
Paula Bertin de Morais , Gerson Santos de Almeida , Amanda Fantini de Camargo Andrade , Ricardo de Oliveira Orsi , Willian Fernando Zambuzzi , Célio Jr. Da Costa Fernandes
Numerous studies have demonstrated the significant role of propolis in various biological processes, including inflammation and the repair of endothelial and bone tissues. The cascade of inflammation, proliferation, and tissue remodeling characterizes the injury site. Remarkable progress has been made in the field of alternative medicine with the utilization of propolis. In this study, we specifically investigated the effects of alcoholic extract of propolis on cell adhesion, survival, remodeling, and differentiation pathways in osteoblasts. Our findings revealed the activation of survival proteins such as AKT, ERK, and phosphorylated ERK during the adhesion phase, while interleukins, specifically IL-6 and TNF, exhibited increased expression during cell differentiation. Furthermore, treatment with propolis extract led to enhanced activity of metalloproteinases (MMP9 and MMP2) and HIF-1α, a crucial activator of angiogenesis and bone remodeling. It was observed that the alcoholic propolis extract stimulated cell proliferation, differentiation, and repair, with key molecules involved in these processes including pro-inflammatory factors IL-6 and TNFα, as well as HIF-1, MMP2, and BMP7 proteins. Collectively, these factors induced an initial state of proliferation followed by differentiation and repair. Therefore, the alcoholic extract of propolis holds promise as a potential therapeutic agent, particularly in cases involving tissue repair. Nevertheless, further comprehensive in vitro and in vivo studies targeting this area are necessary to advance our understanding.
{"title":"Modulation of HIF-1α and TNF-α in pre-osteoblasts treated with alcohol extract of propolis: Implications for cellular response and signaling pathways","authors":"Paula Bertin de Morais , Gerson Santos de Almeida , Amanda Fantini de Camargo Andrade , Ricardo de Oliveira Orsi , Willian Fernando Zambuzzi , Célio Jr. Da Costa Fernandes","doi":"10.1016/j.tice.2025.102784","DOIUrl":"10.1016/j.tice.2025.102784","url":null,"abstract":"<div><div>Numerous studies have demonstrated the significant role of propolis in various biological processes, including inflammation and the repair of endothelial and bone tissues. The cascade of inflammation, proliferation, and tissue remodeling characterizes the injury site. Remarkable progress has been made in the field of alternative medicine with the utilization of propolis. In this study, we specifically investigated the effects of alcoholic extract of propolis on cell adhesion, survival, remodeling, and differentiation pathways in osteoblasts. Our findings revealed the activation of survival proteins such as AKT, ERK, and phosphorylated ERK during the adhesion phase, while interleukins, specifically IL-6 and TNF, exhibited increased expression during cell differentiation. Furthermore, treatment with propolis extract led to enhanced activity of metalloproteinases (MMP9 and MMP2) and HIF-1α, a crucial activator of angiogenesis and bone remodeling. It was observed that the alcoholic propolis extract stimulated cell proliferation, differentiation, and repair, with key molecules involved in these processes including pro-inflammatory factors IL-6 and TNFα, as well as HIF-1, MMP2, and BMP7 proteins. Collectively, these factors induced an initial state of proliferation followed by differentiation and repair. Therefore, the alcoholic extract of propolis holds promise as a potential therapeutic agent, particularly in cases involving tissue repair. Nevertheless, further comprehensive in vitro and in vivo studies targeting this area are necessary to advance our understanding.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102784"},"PeriodicalIF":2.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471141","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 : 2025-02-18DOI: 10.1016/j.tice.2025.102801
Juan Li , Keqi Jia , Wenjie Wang , Yingxue Pang , Hui Wang , Jun Hao , Dong Zhao , Fan Li
F-box and WD repeat domain-containing 7 (FBXW7) protein is known as one of the crucial components of the E3 ubiquitin ligase called the Skp1-Cullin1-F-box (SCF) complex, which regulates the degradation of a network of proteins via the ubiquitin-proteasome system. In our study, we investigated the latent impact of FBXW7 on renal tubular cells injury and its molecular mechanism in diabetic kidney disease (DKD). FBXW7 was upregulated in kidneys of diabetic mice and human renal proximal tubular cells exposed to high glucose. Again, the function of experiment found that overexpression of FBXW7 led to epithelial-mesenchymal transition (EMT) of HK2 cells, as indicated by decreased E-cadherin and increased α-smooth muscle actin (α-SMA). Knockdown of FBXW7 ameliorated high glucose-induced EMT of HK2 cells via downregulation of TGF-β1. Then, FBXW7 overexpression downregulated the stability of the KLF5 protein and promoted protein ubiquitination in normal glucose-cultured HK2 cells, which was significantly reversed by the addition of MG132, a specific proteasome inhibitor. Furthermore, overexpression of KLF5 effectively prevented FBXW7 upregulation-induced EMT in HK2 cells. Finally, chemical inhibitors or mTOR kinase dead vector to interfere the activity of mTOR effectively suppressed FBXW7 expression in HK2 cells treated with high glucose. Taken together, these above data suggest that mTOR signaling pathway-regulated FBXW7 mediates high glucose-induced EMT of renal tubular cells by affecting the stability of KLF5.
{"title":"FBXW7 mediates high glucose-induced epithelial to mesenchymal transition via KLF5 in renal tubular cells of diabetic kidney disease","authors":"Juan Li , Keqi Jia , Wenjie Wang , Yingxue Pang , Hui Wang , Jun Hao , Dong Zhao , Fan Li","doi":"10.1016/j.tice.2025.102801","DOIUrl":"10.1016/j.tice.2025.102801","url":null,"abstract":"<div><div>F-box and WD repeat domain-containing 7 (FBXW7) protein is known as one of the crucial components of the E3 ubiquitin ligase called the Skp1-Cullin1-F-box (SCF) complex, which regulates the degradation of a network of proteins via the ubiquitin-proteasome system. In our study, we investigated the latent impact of FBXW7 on renal tubular cells injury and its molecular mechanism in diabetic kidney disease (DKD). FBXW7 was upregulated in kidneys of diabetic mice and human renal proximal tubular cells exposed to high glucose. Again, the function of experiment found that overexpression of FBXW7 led to epithelial-mesenchymal transition (EMT) of HK2 cells, as indicated by decreased E-cadherin and increased α-smooth muscle actin (α-SMA). Knockdown of FBXW7 ameliorated high glucose-induced EMT of HK2 cells via downregulation of TGF-β1. Then, FBXW7 overexpression downregulated the stability of the KLF5 protein and promoted protein ubiquitination in normal glucose-cultured HK2 cells, which was significantly reversed by the addition of MG132, a specific proteasome inhibitor. Furthermore, overexpression of KLF5 effectively prevented FBXW7 upregulation-induced EMT in HK2 cells. Finally, chemical inhibitors or mTOR kinase dead vector to interfere the activity of mTOR effectively suppressed FBXW7 expression in HK2 cells treated with high glucose. Taken together, these above data suggest that mTOR signaling pathway-regulated FBXW7 mediates high glucose-induced EMT of renal tubular cells by affecting the stability of KLF5.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102801"},"PeriodicalIF":2.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487869","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 : 2025-02-17DOI: 10.1016/j.tice.2025.102800
Twinkle Mishra, Sarika Wairkar
Keloid is an outcome of abnormal cellular response in the wound healing process with excessive fibroblast and collagen deposition in the dermal layer of the skin. It is characterized by a scar showing fibrous outgrowth that grows beyond the original boundaries of the wound. Thus, it is cosmetically and functionally disturbing to the patient. Keloidal development depends on various patient and environmental factors, possibly initiating abnormal wound healing. Due to abnormal wound healing, various aberrant cellular responses are observed during keloid development, like delayed inflammatory response, increased growth factors, varied cytokine level, decreased apoptosis, increased angiogenesis, and imbalanced proteinases. Bacteria and the immune system also play a role in keloid development. Advancements like single-cell RNA sequencing and transcriptomics studies have led to a better understanding of pathogenesis. In line with the complex pathogenesis, the later part of the review covers a detailed analysis of various treatment options employed for keloid, which includes silicone-based topical therapy, drug-based therapy, invasive approach (surgery), and minimally invasive therapies (radiation, laser therapy, and cryotherapy). The advantages and limitations of individual and combination therapies are also discussed. Keloids tend to re-occur after treatment; hence, follow-up is very important, making keloid treatment a complex procedure. Novel therapeutics in keloid have advantages like better efficacy of drugs, less pain, self-administration, and fewer side effects. A few nanotherapeutics advancements, such as microneedles, nanoparticles, liposomes, and exosomes, are discussed in the review.
{"title":"Pathogenesis, attenuation, and treatment strategies for keloid management","authors":"Twinkle Mishra, Sarika Wairkar","doi":"10.1016/j.tice.2025.102800","DOIUrl":"10.1016/j.tice.2025.102800","url":null,"abstract":"<div><div>Keloid is an outcome of abnormal cellular response in the wound healing process with excessive fibroblast and collagen deposition in the dermal layer of the skin. It is characterized by a scar showing fibrous outgrowth that grows beyond the original boundaries of the wound. Thus, it is cosmetically and functionally disturbing to the patient. Keloidal development depends on various patient and environmental factors, possibly initiating abnormal wound healing. Due to abnormal wound healing, various aberrant cellular responses are observed during keloid development, like delayed inflammatory response, increased growth factors, varied cytokine level, decreased apoptosis, increased angiogenesis, and imbalanced proteinases. Bacteria and the immune system also play a role in keloid development. Advancements like single-cell RNA sequencing and transcriptomics studies have led to a better understanding of pathogenesis. In line with the complex pathogenesis, the later part of the review covers a detailed analysis of various treatment options employed for keloid, which includes silicone-based topical therapy, drug-based therapy, invasive approach (surgery), and minimally invasive therapies (radiation, laser therapy, and cryotherapy). The advantages and limitations of individual and combination therapies are also discussed. Keloids tend to re-occur after treatment; hence, follow-up is very important, making keloid treatment a complex procedure. Novel therapeutics in keloid have advantages like better efficacy of drugs, less pain, self-administration, and fewer side effects. A few nanotherapeutics advancements, such as microneedles, nanoparticles, liposomes, and exosomes, are discussed in the review.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102800"},"PeriodicalIF":2.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479593","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 : 2025-02-17DOI: 10.1016/j.tice.2025.102797
Jie Pi , Yangxin Tang , Ying Fu , Xu Wang , Linwei Liu , Xinhua Liu , Jianguo Xiang , Deliang Li
A histological and ultrastructural examination of spermatogenesis and spermatozoa in diploid, triploid and tetraploid Corbicula fluminea was conducted. In the Yangtze River estuary, the spermatozoa of C. flumiena exhibited a primitive uniflagellate structure, whereas a modified biflagellate morphology was observed in inland freshwater habitats. This study presents the initial observation of sperm morula in spermatogenesis in C. fluminea. The mature spermatozoa were released as single cells and as spermatozeugmata. It was observed that uniflagellate spermatozoa undergo two meiotic divisions during it formation, whereas biflagellate spermatozoa undergo only one. The uniflagellate and biflagellate spermatozoa were observed to comprise of three distinct parts: the head, middle piece and tail. The longest and shortest spermatozoa (69.24 μm ± 1.70 vs 54.11 μm ± 1.26) were both biflagellate spermatozoa, originating from tetraploid and diploid individuals, respectively. The number of mitochondria was observed to increase in accordance with ploidy. In the uniflagellate spermatozoa, the two centrioles were observed to be oriented perpendicular to each other. In contrast, the two centrioles were oriented in parallel with each other in biflagellate spermatozoa, with each centriole attaching a flagellum. The undulating membrane of the tail contains a substantial number of glycogen granules. The differences in spermiogenesis, sperm morphology and structure between C. flumiena from estuarine (amphogenesis and in vitro development) and inland freshwater habitats (androgenesis and brooding larvae in the inner demibranch) result in better adaptations to the respective reproduction modes.
{"title":"Spermatogenesis and ultrastructure of the spermatozoa at three ploidy levels in the bivalve species, Corbicula fluminea","authors":"Jie Pi , Yangxin Tang , Ying Fu , Xu Wang , Linwei Liu , Xinhua Liu , Jianguo Xiang , Deliang Li","doi":"10.1016/j.tice.2025.102797","DOIUrl":"10.1016/j.tice.2025.102797","url":null,"abstract":"<div><div>A histological and ultrastructural examination of spermatogenesis and spermatozoa in diploid, triploid and tetraploid <em>Corbicula fluminea</em> was conducted. In the Yangtze River estuary, the spermatozoa of <em>C. flumiena</em> exhibited a primitive uniflagellate structure, whereas a modified biflagellate morphology was observed in inland freshwater habitats. This study presents the initial observation of sperm morula in spermatogenesis in <em>C. fluminea</em>. The mature spermatozoa were released as single cells and as spermatozeugmata. It was observed that uniflagellate spermatozoa undergo two meiotic divisions during it formation, whereas biflagellate spermatozoa undergo only one. The uniflagellate and biflagellate spermatozoa were observed to comprise of three distinct parts: the head, middle piece and tail. The longest and shortest spermatozoa (69.24 μm ± 1.70 <em>vs</em> 54.11 μm ± 1.26) were both biflagellate spermatozoa, originating from tetraploid and diploid individuals, respectively. The number of mitochondria was observed to increase in accordance with ploidy. In the uniflagellate spermatozoa, the two centrioles were observed to be oriented perpendicular to each other. In contrast, the two centrioles were oriented in parallel with each other in biflagellate spermatozoa, with each centriole attaching a flagellum. The undulating membrane of the tail contains a substantial number of glycogen granules. The differences in spermiogenesis, sperm morphology and structure between <em>C. flumiena</em> from estuarine (amphogenesis and in vitro development) and inland freshwater habitats (androgenesis and brooding larvae in the inner demibranch) result in better adaptations to the respective reproduction modes.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102797"},"PeriodicalIF":2.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471182","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 : 2025-02-16DOI: 10.1016/j.tice.2025.102795
Fen Wang , Jianwei Li , Zhixuan Zhang , Guangyi Huang , Xiaodong Zhang , Qian Liu , Wang Xiao , Fengqi Liu , Jialong Sun , Yankui Liu , Yiyi Ma , Ruijuan Zhuang , Yingqiang Du , Xiaoyan Wang , Changzheng Gao , Xin Gu
Baicalin has garnered attention for its potential therapeutic effects on various cardiovascular conditions, including drug-induced cardiac injury. In this study, we utilized a murine model to explore the protective role of baicalin against cardiac dysfunction induced by vandetanib. Our findings indicate that baicalin administration effectively ameliorated vandetanib-induced cardiac injury. Echocardiographic assessments revealed significant improvements in the myocardial contraction in mice treated with baicalin compared with those receiving vandetanib alone. Histological analysis revealed reduced myocardial inflammation and fibrosis in baicalin-treated mice. Specifically, baicalin suppressed proinflammatory factors such as IL-6, IL-1β, and TNF-α, thereby attenuating the inflammatory response triggered by vandetanib. Moreover, baicalin inhibited myocardial apoptosis, as evidenced by decreased levels of Caspase-3, Bax, and p53, while concurrently elevated expression of the antiapoptotic protein Bcl-2. Mechanistically, baicalin-mediated inhibition of the NLRP3 inflammasome pathway has emerged as a crucial aspect of its cardioprotective action and promotes redox balance in myocardial cells under vandetanib-induced oxidative stress. It upregulated the expression of the antioxidant enzymes SOD1 and SOD2, thereby mitigating intracellular ROS accumulation and preserving cardiomyocyte viability. In conclusion, our study highlights baicalin as a promising therapeutic agent for mitigating vandetanib-induced cardiac injury through multiple mechanisms, including anti-inflammatory, antiapoptotic, antioxidant, and NLRP3 inflammasome inhibitory actions. Our findings will be further validated in clinical trials and explore the translational potential of baicalin in treating drug-induced cardiotoxicity in humans.
{"title":"Baicalin reduced vandetanib induced myocardial injury by regulating redox balance and NLRP3 inflammasome pathway","authors":"Fen Wang , Jianwei Li , Zhixuan Zhang , Guangyi Huang , Xiaodong Zhang , Qian Liu , Wang Xiao , Fengqi Liu , Jialong Sun , Yankui Liu , Yiyi Ma , Ruijuan Zhuang , Yingqiang Du , Xiaoyan Wang , Changzheng Gao , Xin Gu","doi":"10.1016/j.tice.2025.102795","DOIUrl":"10.1016/j.tice.2025.102795","url":null,"abstract":"<div><div>Baicalin has garnered attention for its potential therapeutic effects on various cardiovascular conditions, including drug-induced cardiac injury. In this study, we utilized a murine model to explore the protective role of baicalin against cardiac dysfunction induced by vandetanib. Our findings indicate that baicalin administration effectively ameliorated vandetanib-induced cardiac injury. Echocardiographic assessments revealed significant improvements in the myocardial contraction in mice treated with baicalin compared with those receiving vandetanib alone. Histological analysis revealed reduced myocardial inflammation and fibrosis in baicalin-treated mice. Specifically, baicalin suppressed proinflammatory factors such as IL-6, IL-1β, and TNF-α, thereby attenuating the inflammatory response triggered by vandetanib. Moreover, baicalin inhibited myocardial apoptosis, as evidenced by decreased levels of Caspase-3, Bax, and p53, while concurrently elevated expression of the antiapoptotic protein Bcl-2. Mechanistically, baicalin-mediated inhibition of the NLRP3 inflammasome pathway has emerged as a crucial aspect of its cardioprotective action and promotes redox balance in myocardial cells under vandetanib-induced oxidative stress. It upregulated the expression of the antioxidant enzymes SOD1 and SOD2, thereby mitigating intracellular ROS accumulation and preserving cardiomyocyte viability. In conclusion, our study highlights baicalin as a promising therapeutic agent for mitigating vandetanib-induced cardiac injury through multiple mechanisms, including anti-inflammatory, antiapoptotic, antioxidant, and NLRP3 inflammasome inhibitory actions. Our findings will be further validated in clinical trials and explore the translational potential of baicalin in treating drug-induced cardiotoxicity in humans.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102795"},"PeriodicalIF":2.7,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471131","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 : 2025-02-15DOI: 10.1016/j.tice.2025.102791
Mamdouh Eldesoqui , Lashin S. Ali , Omnia S. Erfan , Amal F. Dawood , Abdelnaser A. Badawy , Sahar K. Ali , Zeinab A. Mohammed , Alia Mohamed Mahmoud , Eman M. Embaby , Eman Mohamad El Nashar , Majed Aldehri , Hind Zafrah , Norah Saeed Al-Zahrani , Rania Hassan Mohamed Soliman
Background
Ulcerative colitis (UC) is an inflammatory bowel disease characterized by the overproduction of reactive oxygen species (ROS) and the release of inflammatory mediators. Dihydroartemisinin (DHA) is a semi-synthetic active metabolite of artemisinin that has anti-inflammatory, antioxidant, and anti-fibrotic properties.
Objective
This study aimed to assess the therapeutic benefits of DHA on acetic acid(AA) -induced UC in rats, with particular emphasis on its anti-inflammatory effects and its influence on NFκB/TNF-α/RIPK1 necroptotic pathways.
Methods
Eighteen rats were allocated into control, acetic acid-induced colitis (AA), and DHA-treated (AA+DHA) groups. Colitis was caused by rectal instillation of 5 % acetic acid. DHA was supplied via intraperitoneal injection. Histological, biochemical studies of oxidative stress, inflammatory and anti-inflammatory mediators, Western blotting for TNF-α, RIPK1, and caspase 3, and immunohistochemical assessment of NFκB, TNF-α, and RIPK1, were conducted.
Results
DHA treatment markedly diminished macroscopic damage, disease activity index, histopathology scores, and malondialdehyde (MDA) levels, enhancing glutathione (GSH) levels. Additionally, DHA decreased serum TNF-α and IL-6 and increased IL-10. Western blotting and immunohistochemistry investigations validated the reduced expression of TNF-α, RIPK1, and caspase 3 in DHA-treated rats.
Conclusion
DHA demonstrates protective properties against acetic acid-induced UC by decreasing oxidative stress and inflammation, modifying TNF-α activity to regulate apoptotic and necroptotic pathways. So, DHA may be a favorable therapeutic alternative for the management of ulcerative colitis.
{"title":"Dihydroartemisinin attenuates acetic acid-induced ulcerative colitis in rats: Suppression of inflammation and modulation of NFκβ/TNF-α/RIPK1-mediated necroptosis and apoptosis","authors":"Mamdouh Eldesoqui , Lashin S. Ali , Omnia S. Erfan , Amal F. Dawood , Abdelnaser A. Badawy , Sahar K. Ali , Zeinab A. Mohammed , Alia Mohamed Mahmoud , Eman M. Embaby , Eman Mohamad El Nashar , Majed Aldehri , Hind Zafrah , Norah Saeed Al-Zahrani , Rania Hassan Mohamed Soliman","doi":"10.1016/j.tice.2025.102791","DOIUrl":"10.1016/j.tice.2025.102791","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is an inflammatory bowel disease characterized by the overproduction of reactive oxygen species (ROS) and the release of inflammatory mediators. Dihydroartemisinin (DHA) is a semi-synthetic active metabolite of artemisinin that has anti-inflammatory, antioxidant, and anti-fibrotic properties.</div></div><div><h3>Objective</h3><div>This study aimed to assess the therapeutic benefits of DHA on acetic acid(AA) -induced UC in rats, with particular emphasis on its anti-inflammatory effects and its influence on NFκB/TNF-α/RIPK1 necroptotic pathways.</div></div><div><h3>Methods</h3><div>Eighteen rats were allocated into control, acetic acid-induced colitis (AA), and DHA-treated (AA+DHA) groups. Colitis was caused by rectal instillation of 5 % acetic acid. DHA was supplied via intraperitoneal injection. Histological, biochemical studies of oxidative stress, inflammatory and anti-inflammatory mediators, Western blotting for TNF-α, RIPK1, and caspase 3, and immunohistochemical assessment of NFκB, TNF-α, and RIPK1, were conducted.</div></div><div><h3>Results</h3><div>DHA treatment markedly diminished macroscopic damage, disease activity index, histopathology scores, and malondialdehyde (MDA) levels, enhancing glutathione (GSH) levels. Additionally, DHA decreased serum TNF-α and IL-6 and increased IL-10. Western blotting and immunohistochemistry investigations validated the reduced expression of TNF-α, RIPK1, and caspase 3 in DHA-treated rats.</div></div><div><h3>Conclusion</h3><div>DHA demonstrates protective properties against acetic acid-induced UC by decreasing oxidative stress and inflammation, modifying TNF-α activity to regulate apoptotic and necroptotic pathways. So, DHA may be a favorable therapeutic alternative for the management of ulcerative colitis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102791"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436430","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}
This review examines the molecular mechanisms driving structural damage in Spondyloarthritis (SpA), a chronic inflammatory condition characterized by new bone formation that can lead to partial or complete spinal ankylosis. We explore the complex interplay between inflammation, mechanical stress, and bone metabolism in SpA, focusing on key signaling pathways and cytokines that contribute to disease progression. The review analyzes both structural and inflammatory aspects, particularly the role of enthesis biology and the impact of mechanical factors. Additionally, we assess how current therapeutic approaches, including biologic treatments targeting specific inflammatory pathways such as tumor necrosis factor inhibitors, affect disease progression. While these treatments can reduce inflammation and manage clinical symptoms, their limited ability to completely prevent new bone formation highlights the complexity of the underlying pathological processes. We also evaluate emerging therapeutic strategies targeting specific molecular pathways involved in bone formation. Understanding these intricate molecular mechanisms and their interactions is crucial for developing more effective targeted therapies that could potentially not only manage symptoms but also prevent or reverse structural damage in SpA patients.
{"title":"Mechanisms of ossification of the entheses in spondyloarthritis physiopathogenic aspects and possible therapeutic implication","authors":"Barile Raffaele, Maruotti Nicola, Rotondo Cinzia, Rella Valeria, Cantatore Francesco Paolo, Corrado Addolorata","doi":"10.1016/j.tice.2025.102803","DOIUrl":"10.1016/j.tice.2025.102803","url":null,"abstract":"<div><div>This review examines the molecular mechanisms driving structural damage in Spondyloarthritis (SpA), a chronic inflammatory condition characterized by new bone formation that can lead to partial or complete spinal ankylosis. We explore the complex interplay between inflammation, mechanical stress, and bone metabolism in SpA, focusing on key signaling pathways and cytokines that contribute to disease progression. The review analyzes both structural and inflammatory aspects, particularly the role of enthesis biology and the impact of mechanical factors. Additionally, we assess how current therapeutic approaches, including biologic treatments targeting specific inflammatory pathways such as tumor necrosis factor inhibitors, affect disease progression. While these treatments can reduce inflammation and manage clinical symptoms, their limited ability to completely prevent new bone formation highlights the complexity of the underlying pathological processes. We also evaluate emerging therapeutic strategies targeting specific molecular pathways involved in bone formation. Understanding these intricate molecular mechanisms and their interactions is crucial for developing more effective targeted therapies that could potentially not only manage symptoms but also prevent or reverse structural damage in SpA patients.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102803"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446064","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 : 2025-02-14DOI: 10.1016/j.tice.2025.102796
Ling Lin , Ying Zou , Di Zhang
Background
Human RRS1 gene is abnormally expressed in many cancers, and RRS1 can inhibit the level of p53. Ferroptosis mediated by p53 pathway may be a potential therapeutic strategy for cancer. However, the specific role of RRS1 in lung cancer is not clear.
Methods
The correlation between the expression level of RRS1 and the overall survival of lung cancer patients was explored through UALCAN and Kaplan-Meier plotter. A549 cells and drug-resistant A549/DDP cells were used in vitro. Wound healing, Transwell and tubule formation experiment were used to detect the abilities of cell invasion, migration and tube formation. Detecting the level of lipid ROS by BODIPY(581/591) C11 staining, the expression level of total iron and ferroptosis-related proteins were detected, so as to judge the ferroptosis in cells. Detecting the apoptosis by flow cytometry and the expression of apoptosis-related proteins by western blot, so as to observe the effect of interfering with RRS1 on cisplatin resistance of cells.
Results
The expression of RRS1 was up-regulated, and its level was negatively correlated with the overall survival time of lung cancer patients. In vitro experiments showed that RRS1 interference reduced the invasion and migration of lung cancer cells, inhibited the expressions of MMP2 and MMP9 proteins and decreased the tube-forming ability of cells. After interfering with RRS1, the level of p53, lipid ROS and the total iron content in cells increased, the expression of SLC7A11 and GPX4 decreased while the expression of ACSL4 increased, which indicated that ferroptosis was enhanced. Interference with RRS1 increased the apoptosis of drug-resistant cells, decreased the expression of Bcl2 while increased the expression of Bax and caspase3(cleaved), which decreased the cisplatin resistance of lung cancer cell A549. However, after silencing p53, these effects were reversed.
Conclusion
RRS1 inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway.
{"title":"Silencing ribosome biogenesis regulator 1 homolog (RRS1) inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway","authors":"Ling Lin , Ying Zou , Di Zhang","doi":"10.1016/j.tice.2025.102796","DOIUrl":"10.1016/j.tice.2025.102796","url":null,"abstract":"<div><h3>Background</h3><div>Human RRS1 gene is abnormally expressed in many cancers, and RRS1 can inhibit the level of p53. Ferroptosis mediated by p53 pathway may be a potential therapeutic strategy for cancer. However, the specific role of RRS1 in lung cancer is not clear.</div></div><div><h3>Methods</h3><div>The correlation between the expression level of RRS1 and the overall survival of lung cancer patients was explored through UALCAN and Kaplan-Meier plotter. A549 cells and drug-resistant A549/DDP cells were used in vitro. Wound healing, Transwell and tubule formation experiment were used to detect the abilities of cell invasion, migration and tube formation. Detecting the level of lipid ROS by BODIPY(581/591) C11 staining, the expression level of total iron and ferroptosis-related proteins were detected, so as to judge the ferroptosis in cells. Detecting the apoptosis by flow cytometry and the expression of apoptosis-related proteins by western blot, so as to observe the effect of interfering with RRS1 on cisplatin resistance of cells.</div></div><div><h3>Results</h3><div>The expression of RRS1 was up-regulated, and its level was negatively correlated with the overall survival time of lung cancer patients. In vitro experiments showed that RRS1 interference reduced the invasion and migration of lung cancer cells, inhibited the expressions of MMP2 and MMP9 proteins and decreased the tube-forming ability of cells. After interfering with RRS1, the level of p53, lipid ROS and the total iron content in cells increased, the expression of SLC7A11 and GPX4 decreased while the expression of ACSL4 increased, which indicated that ferroptosis was enhanced. Interference with RRS1 increased the apoptosis of drug-resistant cells, decreased the expression of Bcl2 while increased the expression of Bax and caspase3(cleaved), which decreased the cisplatin resistance of lung cancer cell A549. However, after silencing p53, these effects were reversed.</div></div><div><h3>Conclusion</h3><div>RRS1 inhibits angiogenesis and cisplatin resistance of lung cancer cells by activating ferroptosis mediated by p53 pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102796"},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453474","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 : 2025-02-14DOI: 10.1016/j.tice.2025.102794
Chen-Hsun Ho , Chia-Kwung Fan , Yi-Chen Chu , Shih-Ping Liu , Po-Ching Cheng
Bladder cancer is the most common type of urinary tumor. Current research has focused on alternative therapies that protect the bladder. Some studies suggested that cancer can be treated by inducing apoptosis. Therefore, finding new drugs for related or adjuvant treatments has become important. PT is a natural derivative of resveratrol. The antioxidant effects of PT include the scavenging of extracellular ROS and the induction of apoptosis. PT has been shown to induce several types of tumor cell death; however, the detailed mechanism of action remains unclear. The present examined PT's cytotoxicity and apoptosis-inducing abilities as an anti-bladder cancer drug in normal bladder epithelial and bladder cancer cells. Under PT treatment, bladder cancer HTB-9 cells showed a significant apoptotic effect compared to normal bladder epithelial SV-HUC-1 cells in a dose- and time-dependent manner. Fluorescence microscopy, flow cytometry, and western blotting showed a positive correlation with the expression of apoptotic proteins, especially caspase-3. PT promoted the apoptosis of bladder cancer cells in a time- and dose-dependent manner and had no significant effect on normal bladder epithelial cells involved in internal and external apoptotic pathways, especially the internal ones. The results demonstrate the potential of PT to promote apoptotic death in bladder cancer cells, suggesting its possible use as a drug to treat bladder cancer.
{"title":"Effects of pterostilbene on inducing apoptosis in normal bladder and bladder cancer cells","authors":"Chen-Hsun Ho , Chia-Kwung Fan , Yi-Chen Chu , Shih-Ping Liu , Po-Ching Cheng","doi":"10.1016/j.tice.2025.102794","DOIUrl":"10.1016/j.tice.2025.102794","url":null,"abstract":"<div><div>Bladder cancer is the most common type of urinary tumor. Current research has focused on alternative therapies that protect the bladder. Some studies suggested that cancer can be treated by inducing apoptosis. Therefore, finding new drugs for related or adjuvant treatments has become important. PT is a natural derivative of resveratrol. The antioxidant effects of PT include the scavenging of extracellular ROS and the induction of apoptosis. PT has been shown to induce several types of tumor cell death; however, the detailed mechanism of action remains unclear. The present examined PT's cytotoxicity and apoptosis-inducing abilities as an anti-bladder cancer drug in normal bladder epithelial and bladder cancer cells. Under PT treatment, bladder cancer HTB-9 cells showed a significant apoptotic effect compared to normal bladder epithelial SV-HUC-1 cells in a dose- and time-dependent manner. Fluorescence microscopy, flow cytometry, and western blotting showed a positive correlation with the expression of apoptotic proteins, especially caspase-3. PT promoted the apoptosis of bladder cancer cells in a time- and dose-dependent manner and had no significant effect on normal bladder epithelial cells involved in internal and external apoptotic pathways, especially the internal ones. The results demonstrate the potential of PT to promote apoptotic death in bladder cancer cells, suggesting its possible use as a drug to treat bladder cancer.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102794"},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436428","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 : 2025-02-13DOI: 10.1016/j.tice.2025.102792
Dina Y. Hegab , Nabela I. El-Sharkawy , Gihan G. Moustafa , Yasmina M. Abd-Elhakim , Enas N. Said , Mohamed M.M. Metwally , Taghred M. Saber
Colchicine (CHC), a poisonous plant alkaloid, has been widely utilized for decades in the treatment of gout, but has a rather low therapeutic index, which causes oxidative stress leading to cognitive impairment, brain damage, apoptosis, and hitopathological alterations in humans and experimental animals. The present investigation evaluated the potential palliative effect of the pumpkin seeds oil (PSO) at a dose of 4 ml/kg b.wt against CHC (0.6 mg/kg b.wt) -induced neurotoxic and neurobehavioral effects in rats. Forty male rats weighing 245–260 g were assigned to four groups. The results displayed that CHC exposure induced neurobehavioral disorders and a remarkable decline in the serotonin and dopamine levels and the immunoexpression of BDNF and GFAP in the brain. Besides, CHC treatment evoked brain oxidative stress, as manifested by depleted antioxidant enzyme activities and elevated malondialdehyde (MDA) and protein carbonyl (PC) levels. Also, CHC triggered brain DNA damage, as indicated by a marked increment in the brain 8-Hydroxyguanosine (8-OHdG) level. However, concurrent treatment with the PSO effectively attenuated the CHC-induced toxic effects as evidenced by a noticeable increase in the serotonin (33 ± 3.05) and dopamine (2.48 ± 0.40) concentrations, and the BDNF and GFAP immunoexpression in the brain. Moreover, PSO mitigated CHC-induced brain oxidative stress and DNA damage as shown by elevated antioxidant enzyme activities (164 ± 3.46 SOD and 7.55 ± 0.43 CAT) and reduced MDA (1.62 ± 0.23), PC (1.35 ± 0.23), and 8-OHdG (3.02 ± 0.33) levels. These results concluded that PSO could serve as a therapeutic strategy to ameliorate the neurotoxic and neurobehavioral impacts of CHC.
{"title":"Pumpkin seeds oil rescues colchicine-induced neurotoxicity in rats via modifying oxidative stress, DNA damage, and immunoexpression of BDNF and GFAP","authors":"Dina Y. Hegab , Nabela I. El-Sharkawy , Gihan G. Moustafa , Yasmina M. Abd-Elhakim , Enas N. Said , Mohamed M.M. Metwally , Taghred M. Saber","doi":"10.1016/j.tice.2025.102792","DOIUrl":"10.1016/j.tice.2025.102792","url":null,"abstract":"<div><div>Colchicine (CHC), a poisonous plant alkaloid, has been widely utilized for decades in the treatment of gout, but has a rather low therapeutic index, which causes oxidative stress leading to cognitive impairment, brain damage, apoptosis, and hitopathological alterations in humans and experimental animals. The present investigation evaluated the potential palliative effect of the pumpkin seeds oil (PSO) at a dose of 4 ml/kg b.wt against CHC (0.6 mg/kg b.wt) -induced neurotoxic and neurobehavioral effects in rats. Forty male rats weighing 245–260 g were assigned to four groups. The results displayed that CHC exposure induced neurobehavioral disorders and a remarkable decline in the serotonin and dopamine levels and the immunoexpression of BDNF and GFAP in the brain. Besides, CHC treatment evoked brain oxidative stress, as manifested by depleted antioxidant enzyme activities and elevated malondialdehyde (MDA) and protein carbonyl (PC) levels. Also, CHC triggered brain DNA damage, as indicated by a marked increment in the brain 8-Hydroxyguanosine (8-OHdG) level. However, concurrent treatment with the PSO effectively attenuated the CHC-induced toxic effects as evidenced by a noticeable increase in the serotonin (33 ± 3.05) and dopamine (2.48 ± 0.40) concentrations, and the BDNF and GFAP immunoexpression in the brain. Moreover, PSO mitigated CHC-induced brain oxidative stress and DNA damage as shown by elevated antioxidant enzyme activities (164 ± 3.46 SOD and 7.55 ± 0.43 CAT) and reduced MDA (1.62 ± 0.23), PC (1.35 ± 0.23), and 8-OHdG (3.02 ± 0.33) levels. These results concluded that PSO could serve as a therapeutic strategy to ameliorate the neurotoxic and neurobehavioral impacts of CHC.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102792"},"PeriodicalIF":2.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419129","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号