Pub Date : 2025-01-10DOI: 10.1016/j.tice.2025.102730
Khalid J. Alzahrani , Mahmoud El Safadi , Khalaf F. Alsharif , Fuad M. Alzahrani , Muhammad Faisal Hayat
Endosulfan (ESN) is an organophosphate insecticidal agent that is documented to induce various organ toxicities. Genistein (GEN) is a plant derived polyphenolic compound with excellent biological as well as pharmacological properties. This research was planned to assess the palliative potential of GEN to avert ENS prompted colonic toxicity. Albino rats (n = 36) were involved in this experiment that were divided into the control, ESN (5 mg/kg), ESN (5 mg/kg) + GEN (10 mg/kg), and GEN (10 mg/kg) alone treated group. We found that ENS intoxication upregulated the gene expression of STAT3, JAK1, TRAF6, MyD88, NF-κB, IL- IL-1β, TLR4, TNF-α, and IL-6 while reducing the gene expression of IκB. Moreover, ENS intoxication elevated the levelss of malondialdehyde (MDA) & reactive oxygen species (ROS) while decreasing the activties of glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), and glutathione S-transferase (GST). Furthermore, ESN administration notably escalated the concentrations of fecal calprotectin whereas reduced the concentrations of fecal elastase, lactase and sucrase. Besides, ESN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while diminishing the levels of Bcl-2. Colonic histology was distorted after ESN provision. Nonetheless, GEN treatment remarkably protected the colonic tissues via regulating abovementioned irregularities owing to its marvelous anti-inflammatory, anti-apoptotic as well as antioxidant potential.
{"title":"Palliative potential of genistein to counteract endosulfan instigated colon toxicity via regulating TLR4/MyD88, JAK1/STAT3 and NF-κB pathway: A biochemical and histological approach","authors":"Khalid J. Alzahrani , Mahmoud El Safadi , Khalaf F. Alsharif , Fuad M. Alzahrani , Muhammad Faisal Hayat","doi":"10.1016/j.tice.2025.102730","DOIUrl":"10.1016/j.tice.2025.102730","url":null,"abstract":"<div><div>Endosulfan (ESN) is an organophosphate insecticidal agent that is documented to induce various organ toxicities. Genistein (GEN) is a plant derived polyphenolic compound with excellent biological as well as pharmacological properties. This research was planned to assess the palliative potential of GEN to avert ENS prompted colonic toxicity. Albino rats (n = 36) were involved in this experiment that were divided into the control, ESN (5 mg/kg), ESN (5 mg/kg) + GEN (10 mg/kg), and GEN (10 mg/kg) alone treated group. We found that ENS intoxication upregulated the gene expression of STAT3, JAK1, TRAF6, MyD88, NF-κB, IL- IL-1β, TLR4, TNF-α, and IL-6 while reducing the gene expression of IκB. Moreover, ENS intoxication elevated the levelss of malondialdehyde (MDA) & reactive oxygen species (ROS) while decreasing the activties of glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), and glutathione S-transferase (GST). Furthermore, ESN administration notably escalated the concentrations of fecal calprotectin whereas reduced the concentrations of fecal elastase, lactase and sucrase. Besides, ESN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while diminishing the levels of Bcl-2. Colonic histology was distorted after ESN provision. Nonetheless, GEN treatment remarkably protected the colonic tissues via regulating abovementioned irregularities owing to its marvelous anti-inflammatory, anti-apoptotic as well as antioxidant potential.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102730"},"PeriodicalIF":2.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012282","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 : 2025-01-10DOI: 10.1016/j.tice.2025.102735
Khalid J. Alzahrani , Mahmoud El Safadi , Fuad M. Alzahrani , Ali Akbar , Naif O. alsiwiehri
Bromoxynil (BML) is a toxic herbicide that is reported to cause various organ toxicities. However, there is not a single investigation conducted to elucidate the adverse impacts of BML on hepatic tissues at different dose concentrations. Therefore, the current investigation was planned to assess the deleterious effects of BML on liver against different dose concentrations. Thirty-six albino rats (Sprague Dawley) were divided into four groups including the control, BML (10 mg/kg), BML (20 mg/kg) and BML (40 mg/kg). Gene expressions were assessed by qRT-PCR while other biochemical parameters were evaluated through ELISA as well as standard assays. The histological procedure was conducted as per the standard protocols of histomorphology. It is revealed that BML intoxication at all tested doses showed notable elevation in the gene expression of tumor necrosis factor-alpha (TNF-α), toll-like receptors-4 (TLR-4), interleukin-1beta (IL-1β), myeloid differentiation primary response protein-88 (MyD88), interleukin-6 (IL-6), tumor necrosis factor receptor-associated factor-6 (TRAF-6), cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB), Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) while reducing the gene expression of inhibitor of kappa-B (I-κB). Moreover, BML exposure (10 mg/kg, 20 mg/kg, 40 mg/kg) reduced the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH), glutathione S- transferase (GST), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). However, an elevation was observed in the levels of alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) while a reduction in the levels of total proteins and albumin was observed after high dose (20 mg/kg, 40 mg/kg) of BML. There was insignificant elevation among the values of these biomarkers at 10 mg/kg administration of BML. Besides, BML exposure at 10 mg/kg, 20 mg/kg and 40 mg/kg escalated the levels of Bcl-2–associated X protein (Bax), cysteine–aspartic acid protease-9 (Caspase-9) and cysteine–aspartic acid protease-3 (Caspase-3) while reducing the levels of B-cell lymphoma 2 (Bcl-2) in hepatic tissues. Similarly, BML at all tested concentrations showed adverse impacts on hepatic histology. These findings validated the deleterious impacts of BML on hepatic tissues owing to its pro-oxidative, pro-inflammatory and pro-apoptotic potential.
{"title":"Bromoxynil induced hepatic toxicity via dysregulating TLR4/MyD88, JAK1/STAT3 and NF-κB signaling pathways: A dose-dependent investigation","authors":"Khalid J. Alzahrani , Mahmoud El Safadi , Fuad M. Alzahrani , Ali Akbar , Naif O. alsiwiehri","doi":"10.1016/j.tice.2025.102735","DOIUrl":"10.1016/j.tice.2025.102735","url":null,"abstract":"<div><div>Bromoxynil (BML) is a toxic herbicide that is reported to cause various organ toxicities. However, there is not a single investigation conducted to elucidate the adverse impacts of BML on hepatic tissues at different dose concentrations. Therefore, the current investigation was planned to assess the deleterious effects of BML on liver against different dose concentrations. Thirty-six albino rats (Sprague Dawley) were divided into four groups including the control, BML (10 mg/kg), BML (20 mg/kg) and BML (40 mg/kg). Gene expressions were assessed by qRT-PCR while other biochemical parameters were evaluated through ELISA as well as standard assays. The histological procedure was conducted as per the standard protocols of histomorphology. It is revealed that BML intoxication at all tested doses showed notable elevation in the gene expression of tumor necrosis factor-alpha (TNF-α), <em>toll-like receptors-4 (TLR-4), interleukin-1beta (IL-1β), myeloid differentiation primary response protein-88 (M</em>y<em>D88), interleukin-6 (IL-6), tumor necrosis factor receptor-associated factor-6 (TRAF-6), cyclooxygenase-2 (COX-2),</em> nuclear <em>factor kappa-B (NF-κB), Janus kinase 1 (JAK1)</em> and <em>signal transducer and activator of transcription 3 (STAT3)</em> while reducing the gene expression of <em>inhibitor of kappa-B</em> (<em>I-κB</em>). Moreover, BML exposure (10 mg/kg, 20 mg/kg, 40 mg/kg) reduced the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH), glutathione S- transferase (GST), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). However, an elevation was observed in the levels of alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) while a reduction in the levels of total proteins and albumin was observed after high dose (20 mg/kg, 40 mg/kg) of BML. There was insignificant elevation among the values of these biomarkers at 10 mg/kg administration of BML. Besides, BML exposure at 10 mg/kg, 20 mg/kg and 40 mg/kg escalated the levels of Bcl-2–associated X protein (Bax), cysteine–aspartic acid protease-9 (Caspase-9) and cysteine–aspartic acid protease-3 (Caspase-3) while reducing the levels of B-cell lymphoma 2 (Bcl-2) in hepatic tissues. Similarly, BML at all tested concentrations showed adverse impacts on hepatic histology. These findings validated the deleterious impacts of BML on hepatic tissues owing to its pro-oxidative, pro-inflammatory and pro-apoptotic potential.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102735"},"PeriodicalIF":2.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012203","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 : 2025-01-09DOI: 10.1016/j.tice.2025.102723
Sanaz Keshavarz Shahbaz , Aida Mokhlesi , Roghaye Keshavarz Sadegh , Kimia Rahimi , Tannaz Jamialahmadi , Alexandra E. Butler , Prashant Kesharwani , Amirhossein Sahebkar
Mobility disability is a common condition affecting older adults, making walking and the performance of activities of daily living difficult. Frailty, cachexia and sarcopenia are related conditions that occur with advancing age and are characterized by a decline in muscle mass, strength, and functionality that negatively impacts health. Chronic low-grade inflammation is a significant factor in the onset and progression of these conditions. The toll-like receptors (TLRs) and the NLRP3 inflammasome are the pathways of signaling that regulate inflammation. These pathways can potentially be targeted therapeutically for frailty, cachexia and sarcopenia as research has shown that dysregulation of the TLR/NLRP3 inflammasome signaling pathways is linked to these conditions. Activation of TLRs with pathogen-associated molecular patterns (PAMPs or DAMPs) results in chronic inflammation and tissue damage by releasing pro-inflammatory cytokines. Additionally, NLRP3 inflammasome activation enhances the inflammatory response by promoting the production and release of interleukins (ILs), thus exacerbating the underlying inflammatory mechanisms. These pathways are activated in the advancement of disease in frail and sarcopenic individuals. Targeting these pathways may offer therapeutic options to reduce frailty, improve musculoskeletal resilience and prevent or reverse cachexia-associated muscle wasting. Modulating TLR/NLRP3 inflammasome pathways may also hold promise in slowing down the progression of sarcopenia, preserving muscle mass and enhancing overall functional ability in elderly people. The aim of this review is to investigate the signaling pathways of the TLR/NLRP3 inflammasome as a main target in frailty, cachexia and sarcopenia.
{"title":"TLR/NLRP3 inflammasome signaling pathways as a main target in frailty, cachexia and sarcopenia","authors":"Sanaz Keshavarz Shahbaz , Aida Mokhlesi , Roghaye Keshavarz Sadegh , Kimia Rahimi , Tannaz Jamialahmadi , Alexandra E. Butler , Prashant Kesharwani , Amirhossein Sahebkar","doi":"10.1016/j.tice.2025.102723","DOIUrl":"10.1016/j.tice.2025.102723","url":null,"abstract":"<div><div>Mobility disability is a common condition affecting older adults, making walking and the performance of activities of daily living difficult. Frailty, cachexia and sarcopenia are related conditions that occur with advancing age and are characterized by a decline in muscle mass, strength, and functionality that negatively impacts health. Chronic low-grade inflammation is a significant factor in the onset and progression of these conditions. The toll-like receptors (TLRs) and the NLRP3 inflammasome are the pathways of signaling that regulate inflammation. These pathways can potentially be targeted therapeutically for frailty, cachexia and sarcopenia as research has shown that dysregulation of the TLR/NLRP3 inflammasome signaling pathways is linked to these conditions. Activation of TLRs with pathogen-associated molecular patterns (PAMPs or DAMPs) results in chronic inflammation and tissue damage by releasing pro-inflammatory cytokines. Additionally, NLRP3 inflammasome activation enhances the inflammatory response by promoting the production and release of interleukins (ILs), thus exacerbating the underlying inflammatory mechanisms. These pathways are activated in the advancement of disease in frail and sarcopenic individuals. Targeting these pathways may offer therapeutic options to reduce frailty, improve musculoskeletal resilience and prevent or reverse cachexia-associated muscle wasting. Modulating TLR/NLRP3 inflammasome pathways may also hold promise in slowing down the progression of sarcopenia, preserving muscle mass and enhancing overall functional ability in elderly people. The aim of this review is to investigate the signaling pathways of the TLR/NLRP3 inflammasome as a main target in frailty, cachexia and sarcopenia.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102723"},"PeriodicalIF":2.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012290","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}
Parkinson's disease (PD) is a type of chronic neurodegenerative disorder. There is an ongoing need for the development of new medications to address this illness. Loureirin C is known to have a protective impact on neurological disorders. Nonetheless, its specific function in Parkinson's Disease (PD) has yet to be fully understood. In this study, we examined the effects of Loureirin C in a cellular model of PD. The PD cell model was established by treating PC-12 cells with 6-hydroxydopamine (6-OHDA). We revealed that Loureirin C promoted the growth of 6-OHDA-treated PC-12 cells. In addition, Loureirin C suppressed the apoptosis of 6-OHDA-treated PC-12 cells and alleviated ferroptosis. Further, Loureirin C improved mitochondrial membrane potential in 6-OHDA-treated PC-12 cells. Mechanically, Loureirin C mediated Nrf2 pathway. Accordingly, Loureirin C not only inhibits ferroptosis but also apoptosis in the 6-OHDA-induced PD cell model, leading us to consider the potential value of Loureirin C in the treatment of PD.
{"title":"Loureirin C inhibits ferroptosis and apoptosis in 6-OHDA-induced Parkinson's model","authors":"Zhongmei Chen , Ruimin Hou , Yuping Zhang , Mingjian Xiong , Dongping Zhang , Chawen Ding","doi":"10.1016/j.tice.2025.102721","DOIUrl":"10.1016/j.tice.2025.102721","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a type of chronic neurodegenerative disorder. There is an ongoing need for the development of new medications to address this illness. Loureirin C is known to have a protective impact on neurological disorders. Nonetheless, its specific function in Parkinson's Disease (PD) has yet to be fully understood. In this study, we examined the effects of Loureirin C in a cellular model of PD. The PD cell model was established by treating PC-12 cells with 6-hydroxydopamine (6-OHDA). We revealed that Loureirin C promoted the growth of 6-OHDA-treated PC-12 cells. In addition, Loureirin C suppressed the apoptosis of 6-OHDA-treated PC-12 cells and alleviated ferroptosis. Further, Loureirin C improved mitochondrial membrane potential in 6-OHDA-treated PC-12 cells. Mechanically, Loureirin C mediated Nrf2 pathway. Accordingly, Loureirin C not only inhibits ferroptosis but also apoptosis in the 6-OHDA-induced PD cell model, leading us to consider the potential value of Loureirin C in the treatment of PD.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102721"},"PeriodicalIF":2.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972100","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 : 2025-01-08DOI: 10.1016/j.tice.2025.102727
Ruzanna A. Shushanyan , Hasmik M. Karapetyan , Edita E. Nadiryan , Nikolay V. Avtandilyan , Anna V. Grigoryan , Anna F. Karapetyan
High altitude characterized by the low partial pressure of the oxygen is a life-threatening condition that contributes to the development of acute pulmonary edema and hypoxic lung injury. In this study, we aimed to investigate the contribution of some inflammatory and oxidative stress markers along with antioxidant system enzymes in the pathogenesis of HAPE (high-altitude pulmonary edema) formation. We incorporated the study on 42 male rats to unravel the role of mast cells (MCs) and TNF-α in the lung after the effect of acute hypobaric hypoxia. The HAPE model was mimicked with a decompression chamber at the altitude of 7620 m for a duration of 24 h. The study reveals various histological changes in the rat’s lung exposed to hypoxia that was accompanied by immense inflammatory cell infiltration, edema, hemorrhages, and fibrosis. Moreover, the wet weight of the lungs and the arginase level was also increased (p < 0.05). While the NO level was shown to be diminished (p < 0.01). Acute hypobaric hypoxia also caused MC degranulation and increased TNF-α-expression in the lung, which considerably promoted inflammation after hypoxic damage. However, the antioxidant system was weakened following the decreased activity of SOD and catalase. Moreover, the cell energy metabolism was also altered accompanied by an elevated level of LDH. Our findings suggest that the NO and arginase and antioxidant system enzymes along with TNF-α and MCs may play a role in HAPE pathogenesis and contribute to the alveolar-capillary barrier disruption that leads to edema formation. Uncovering the pathological mechanisms of this disease would provide valuable information about the molecular basis of pulmonary edema development and therefore used for further preventive tools to manage the risks posed by high altitude-induced lung damage.
{"title":"Tissue remodeling during high-altitude pulmonary edema in rats: Biochemical and histomorphological analysis","authors":"Ruzanna A. Shushanyan , Hasmik M. Karapetyan , Edita E. Nadiryan , Nikolay V. Avtandilyan , Anna V. Grigoryan , Anna F. Karapetyan","doi":"10.1016/j.tice.2025.102727","DOIUrl":"10.1016/j.tice.2025.102727","url":null,"abstract":"<div><div>High altitude characterized by the low partial pressure of the oxygen is a life-threatening condition that contributes to the development of acute pulmonary edema and hypoxic lung injury. In this study, we aimed to investigate the contribution of some inflammatory and oxidative stress markers along with antioxidant system enzymes in the pathogenesis of HAPE (high-altitude pulmonary edema) formation. We incorporated the study on 42 male rats to unravel the role of mast cells (MCs) and TNF-α in the lung after the effect of acute hypobaric hypoxia. The HAPE model was mimicked with a decompression chamber at the altitude of 7620 m for a duration of 24 h. The study reveals various histological changes in the rat’s lung exposed to hypoxia that was accompanied by immense inflammatory cell infiltration, edema, hemorrhages, and fibrosis. Moreover, the wet weight of the lungs and the arginase level was also increased (p < 0.05). While the NO level was shown to be diminished (p < 0.01). Acute hypobaric hypoxia also caused MC degranulation and increased TNF-α-expression in the lung, which considerably promoted inflammation after hypoxic damage. However, the antioxidant system was weakened following the decreased activity of SOD and catalase. Moreover, the cell energy metabolism was also altered accompanied by an elevated level of LDH. Our findings suggest that the NO and arginase and antioxidant system enzymes along with TNF-α and MCs may play a role in HAPE pathogenesis and contribute to the alveolar-capillary barrier disruption that leads to edema formation. Uncovering the pathological mechanisms of this disease would provide valuable information about the molecular basis of pulmonary edema development and therefore used for further preventive tools to manage the risks posed by high altitude-induced lung damage.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102727"},"PeriodicalIF":2.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012288","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}
Research and tools are necessary for understanding prostate cancer biology. 3D cell culture models have been created to overcome the limitations of animal models and 2D cell culture. The amniotic membrane (AM), a natural biomaterial, emerges as an ideal scaffold for 3D cultures due to its accessibility and incorporation of the extracellular matrix (ECM) in both solid and liquid forms.
Methods
In this study, decellularized human amniotic membranes (DAM) and AM hydrogel were obtained and characterized. The solid DAM scaffold was employed to analyse cell proliferation, cell cycle, migration, apoptosis, and the content of epithelial-mesenchymal transition (EMT) proteins in prostate cancer cells in comparison to traditional 2D culture conditions under androgen deprivation treatment. Additionally, the liquid form of AM was assessed for its potential for 3D cultures of prostate cancer cells such as cells embedded in ECM, spheroid encapsulation, and invasion, with a parallel comparison to collagen.
Results
The 3D DAM scaffold significantly impacted cancer cell migration, morphology, proliferation, and EMT protein expression compared to 2D models. AM hydrogel effectively preserved the structural integrity of spheroids and led to lower proliferated cells embedded in AM hydrogel compared to 2D culture. AM hydrogel, like collagen, has the potential to be utilized for simulating in vitro cellular invasion from the ECM.
Conclusion
In summary, the potential of the biomaterial of DAM and AM hydrogel in creating 3D culture models, combined with the brief duration required for decellularizing the AM, suggests that these materials offer an ideal tool for in vitro prostate cancer research.
{"title":"Exploring the potential of solid and liquid amniotic membrane biomaterial in 3D models for prostate cancer research: A comparative analysis with 2D models","authors":"Keykavos Gholami , Mehrnaz Izadi , Ramin Heshmat , Seyed Mohammad Kazem Aghamir","doi":"10.1016/j.tice.2025.102726","DOIUrl":"10.1016/j.tice.2025.102726","url":null,"abstract":"<div><h3>Objective</h3><div>Research and tools are necessary for understanding prostate cancer biology. 3D cell culture models have been created to overcome the limitations of animal models and 2D cell culture. The amniotic membrane (AM), a natural biomaterial, emerges as an ideal scaffold for 3D cultures due to its accessibility and incorporation of the extracellular matrix (ECM) in both solid and liquid forms.</div></div><div><h3>Methods</h3><div>In this study, decellularized human amniotic membranes (DAM) and AM hydrogel were obtained and characterized. The solid DAM scaffold was employed to analyse cell proliferation, cell cycle, migration, apoptosis, and the content of epithelial-mesenchymal transition (EMT) proteins in prostate cancer cells in comparison to traditional 2D culture conditions under androgen deprivation treatment. Additionally, the liquid form of AM was assessed for its potential for 3D cultures of prostate cancer cells such as cells embedded in ECM, spheroid encapsulation, and invasion, with a parallel comparison to collagen.</div></div><div><h3>Results</h3><div>The 3D DAM scaffold significantly impacted cancer cell migration, morphology, proliferation, and EMT protein expression compared to 2D models. AM hydrogel effectively preserved the structural integrity of spheroids and led to lower proliferated cells embedded in AM hydrogel compared to 2D culture. AM hydrogel, like collagen, has the potential to be utilized for simulating in vitro cellular invasion from the ECM.</div></div><div><h3>Conclusion</h3><div>In summary, the potential of the biomaterial of DAM and AM hydrogel in creating 3D culture models, combined with the brief duration required for decellularizing the AM, suggests that these materials offer an ideal tool for in vitro prostate cancer research.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102726"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984854","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 : 2025-01-07DOI: 10.1016/j.tice.2025.102722
Bingjie Fan, Lili Yin, A.’ni Wang, Fei Li, Shuguang Han
Background
Diabetes mellitus (DM), a chronic metabolic disease, is characterized by long-term hyperglycemia resulting from the defect of insulin production and insulin resistance. The damage and dysfunction of pancreatic β-cells is a main link in DM development.
Methods
In this work, pancreatic β-cell line INS-1E cells were exposed to 30 mM glucose for 48 h to construct an in vitro DM model. For gain-of-function experiments, HG-treated INS-1E cells were transfected with Oe-PIM1 to thoroughly discuss the biological role of PIM1 in HG-injured pancreatic β-cells. Furthermore, to probe into whether JNK/p38 signaling involved in the protective role of PIM1 in HG-injured pancreatic β-cells, HG-treated INS-1E cells were pre-treated with a JNK activator anisomycin (0.01 μM) for 1 h for rescue experiments.
Results
It was verified that HG treatment obviously downregulated PIM1 expression in INS-1E cells. PIM1 overexpression enhanced insulin secretion, inhibited ferroptosis and strengthened PINK1/Parkin-mediated mitophagy of HG-treated INS-1E cells. PIM1 overexpression inactivated JNK/p38 signaling pathway in HG-treated INS-1E cells. Activation of JNK/p38 signaling pathway partially abolished the strengthening effects of PIM1 overexpression on PINK1/Parkin-mediated mitophagy in HG-treated INS-1E cells. Upregulation of PIM1 strengthened PINK1/Parkin-mediated mitophagy in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway. Besides, activation of JNK/p38 signaling pathway partially abolished the enhancing effects of PIM1 overexpression on insulin secretion and the suppressive effects of PIM1 overexpression on ferroptosis in HG-treated INS-1E cells. Upregulation of PIM1 enhanced insulin secretion and inhibited ferroptosis in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway.
Conclusion
In a word, upregulation of PIM1 may alleviate HG-induced pancreatic β-cell injury through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.
{"title":"PIM1 enhances insulin secretion and inhibits ferroptosis of high glucose-induced pancreatic β-cells through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway","authors":"Bingjie Fan, Lili Yin, A.’ni Wang, Fei Li, Shuguang Han","doi":"10.1016/j.tice.2025.102722","DOIUrl":"10.1016/j.tice.2025.102722","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM), a chronic metabolic disease, is characterized by long-term hyperglycemia resulting from the defect of insulin production and insulin resistance. The damage and dysfunction of pancreatic β-cells is a main link in DM development.</div></div><div><h3>Methods</h3><div>In this work, pancreatic β-cell line INS-1E cells were exposed to 30 mM glucose for 48 h to construct an <em>in vitro</em> DM model. For gain-of-function experiments, HG-treated INS-1E cells were transfected with Oe-PIM1 to thoroughly discuss the biological role of PIM1 in HG-injured pancreatic β-cells. Furthermore, to probe into whether JNK/p38 signaling involved in the protective role of PIM1 in HG-injured pancreatic β-cells, HG-treated INS-1E cells were pre-treated with a JNK activator anisomycin (0.01 μM) for 1 h for rescue experiments.</div></div><div><h3>Results</h3><div>It was verified that HG treatment obviously downregulated PIM1 expression in INS-1E cells. PIM1 overexpression enhanced insulin secretion, inhibited ferroptosis and strengthened PINK1/Parkin-mediated mitophagy of HG-treated INS-1E cells. PIM1 overexpression inactivated JNK/p38 signaling pathway in HG-treated INS-1E cells. Activation of JNK/p38 signaling pathway partially abolished the strengthening effects of PIM1 overexpression on PINK1/Parkin-mediated mitophagy in HG-treated INS-1E cells. Upregulation of PIM1 strengthened PINK1/Parkin-mediated mitophagy in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway. Besides, activation of JNK/p38 signaling pathway partially abolished the enhancing effects of PIM1 overexpression on insulin secretion and the suppressive effects of PIM1 overexpression on ferroptosis in HG-treated INS-1E cells. Upregulation of PIM1 enhanced insulin secretion and inhibited ferroptosis in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway.</div></div><div><h3>Conclusion</h3><div>In a word, upregulation of PIM1 may alleviate HG-induced pancreatic β-cell injury through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102722"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012286","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 : 2025-01-07DOI: 10.1016/j.tice.2025.102724
Sherein F. El-sayed , Samar Mortada Mahmoud , Walaa Samy , Reham M. Wahid , Aliaa Talaat , Sara G. Seada
Background
The prevalence of gastric ulcers has grown significantly in the modern era affecting 10 % of global population. Aspirin downregulates gastrokines 1(GKN1) expression in gastric mucosa and GKN1 down-regulation results in gastric cancer. Vitamin D3 (Vit.D3) has anti-inflammatory and antioxidant effects.
Aim
Study the gastroprotective impact of Vit.D3 following aspirin-induced gastric injury in relation to gastrokines and investigate the possible underlying mechanisms.
Materials and methods
24 rats were divided into 4 groups: control, Vit.D3 supplemented normal, aspirin-induced gastric injury, and Vit.D3 supplemented gastric injury groups. Some oxidative stress markers with gene expression of GKN1&2, mucin 5AC (Muc5ac) and NLR family pyrin domain containing 3 (NLRP3) in the gastric tissue were done. Histopathological and immunohistochemical study of E-Cadherin, nuclear factor kappa beta (NFκB), and metalloproteinase-9 (MMP-9) in the stomach mucosa were identified.
Results
Vit.D3 supplementation significantly upregulated E-Cadherin, GSH, GKN1 and Muc5ac in the gastric tissue. Also, it improved the morphology, histology of gastric tissue, by alleviating oxidative stress and NFκB, MMP-9 and down regulation of inflammasome (NLRP3).
Conclusion
Vitamin D3 has a potential protective effect against aspirin -induced gastric injury via upregulating gastrokine1 and E-cadherin and down regulation of NFKB/MMP-9 signaling pathway and NLRP3 inflammasome.
{"title":"Vitamin D3 mitigates aspirin-induced gastric injury by modulating gastrokines, E-cadherin, and inhibiting NLRP3 and NF-κB/MMP-9 signaling pathway","authors":"Sherein F. El-sayed , Samar Mortada Mahmoud , Walaa Samy , Reham M. Wahid , Aliaa Talaat , Sara G. Seada","doi":"10.1016/j.tice.2025.102724","DOIUrl":"10.1016/j.tice.2025.102724","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of gastric ulcers has grown significantly in the modern era affecting 10 % of global population. Aspirin downregulates gastrokines 1(GKN1) expression in gastric mucosa and GKN1 down-regulation results in gastric cancer. Vitamin D3 (Vit.D3) has anti-inflammatory and antioxidant effects.</div></div><div><h3>Aim</h3><div>Study the gastroprotective impact of Vit.D3 following aspirin-induced gastric injury in relation to gastrokines and investigate the possible underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>24 rats were divided into 4 groups: control, Vit.D3 supplemented normal, aspirin-induced gastric injury, and Vit.D3 supplemented gastric injury groups. Some oxidative stress markers with gene expression of GKN1&2, mucin 5AC (Muc5ac) and NLR family pyrin domain containing 3 (NLRP3) in the gastric tissue were done. Histopathological and immunohistochemical study of E-Cadherin, nuclear factor kappa beta (NFκB), and metalloproteinase-9 (MMP-9) in the stomach mucosa were identified.</div></div><div><h3>Results</h3><div>Vit.D3 supplementation significantly upregulated E-Cadherin, GSH, GKN1 and Muc5ac in the gastric tissue. Also, it improved the morphology, histology of gastric tissue, by alleviating oxidative stress and NFκB, MMP-9 and down regulation of inflammasome (NLRP3).</div></div><div><h3>Conclusion</h3><div>Vitamin D3 has a potential protective effect against aspirin -induced gastric injury via upregulating gastrokine1 and E-cadherin and down regulation of NFKB/MMP-9 signaling pathway and NLRP3 inflammasome.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102724"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012292","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 : 2025-01-07DOI: 10.1016/j.tice.2025.102728
Mohammed A. Alshehri, Mohammed Alissa , Abdullah Alghamdi
Cyclophosphamide (CP) is an alkylating chemotherapy agent that induces liver toxicity by cross-linking DNA, causing cell apoptosis. While CP is effective in cancer treatment, its side effects on the liver are significant. Recent studies have indicated that antioxidants, such as resveratrol, may reduce these toxic effects. In this study, we aimed to investigate the role of resveratrol in mitigating CP-induced hepatic apoptosis, oxidative stress, and inflammation in rats. Twenty male mature Sprague-Dawley rats were divided into 4 groups of equal size: control group, Resveratrol group which received resveratrol (20 mg/kg) for 15 consecutive days, CP group which received CP as a single dose (150 mg/kg) on day 16, and CP+Resveratrol group which was similar of the resveratrol and CP groups. Tissue samples were obtained for the histological, immunohistochemical, biochemical, and molecular evaluations. Findings showed that treatment with CP significantly decreased the total liver volume, numerical density of hepatocytes, length density of sinusoidals, and concentrations of antioxidative biomarkers (GSH and SOD). However, the CP+Resveratrol group exhibited notably greater values in these parameters compared to the CP group. Additionally, CP treatment resulted in a significant increase in serum levels of AST and ALT, higher numerical density of Kupffer cells, increased densities of apoptotic cells (increased Bax and caspase-3, and decreased Bcl-2 expression levels), elevated levels of MDA, and upregulated inflammatory genes (IL-1β and TNF-α). In contrast, co-treatment with resveratrol significantly reduced these parameters, suggesting its protective effects against CP-induced liver toxicity. We conclude that giving resveratrol can attenuate apoptosis, oxidative stress, inflammation, and histological alterations in the liver induced by CP toxicity.
{"title":"Resveratrol attenuates cyclophosphamide-induced hepatic apoptosis in association with the inhibition of oxidative stress and inflammation in a rat model of acute liver injury","authors":"Mohammed A. Alshehri, Mohammed Alissa , Abdullah Alghamdi","doi":"10.1016/j.tice.2025.102728","DOIUrl":"10.1016/j.tice.2025.102728","url":null,"abstract":"<div><div>Cyclophosphamide (CP) is an alkylating chemotherapy agent that induces liver toxicity by cross-linking DNA, causing cell apoptosis. While CP is effective in cancer treatment, its side effects on the liver are significant. Recent studies have indicated that antioxidants, such as resveratrol, may reduce these toxic effects. In this study, we aimed to investigate the role of resveratrol in mitigating CP-induced hepatic apoptosis, oxidative stress, and inflammation in rats. Twenty male mature Sprague-Dawley rats were divided into 4 groups of equal size: control group, Resveratrol group which received resveratrol (20 mg/kg) for 15 consecutive days, CP group which received CP as a single dose (150 mg/kg) on day 16, and CP+Resveratrol group which was similar of the resveratrol and CP groups. Tissue samples were obtained for the histological, immunohistochemical, biochemical, and molecular evaluations. Findings showed that treatment with CP significantly decreased the total liver volume, numerical density of hepatocytes, length density of sinusoidals, and concentrations of antioxidative biomarkers (GSH and SOD). However, the CP+Resveratrol group exhibited notably greater values in these parameters compared to the CP group. Additionally, CP treatment resulted in a significant increase in serum levels of AST and ALT, higher numerical density of Kupffer cells, increased densities of apoptotic cells (increased Bax and caspase-3, and decreased Bcl-2 expression levels), elevated levels of MDA, and upregulated inflammatory genes (IL-1β and TNF-α). In contrast, co-treatment with resveratrol significantly reduced these parameters, suggesting its protective effects against CP-induced liver toxicity. We conclude that giving resveratrol can attenuate apoptosis, oxidative stress, inflammation, and histological alterations in the liver induced by CP toxicity.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102728"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984855","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 : 2025-01-06DOI: 10.1016/j.tice.2024.102719
Ludmila M. Sencha, Maria A. Karpova, Olga E. Dobrynina, Irina V. Balalaeva
The extracellular matrix (ECM) and its primary chemical components, including collagen, play a pivotal role in carcinogenesis and tumor progression. The ECM actively regulates cell proliferation, migration, and, importantly, resistance to various adverse factors. It is widely recognized as a key factor in modifying the resistance of tumor cells to various treatment modalities and cytotoxic compounds. However, the role of the ECM in tumor cell adaptation to nutritional deficiencies and hypoxic conditions remains significantly less studied. Since it is generally accepted that tumor cells resistance increases when cultured in a three-dimensional matrix, we sought to experimentally test the universality of this statement. In this work, we analyzed the responses of tumor cells with varying origins and proliferative activities, including human bladder carcinoma, epidermoid carcinoma, and ovarian carcinoma, to deprivation of serum, glucose and oxygen. We compared cell resistance to suboptimal conditions when cultured in a monolayer on tissue culture (TC)-treated polystyrene, on collagen-coated surfaces, or within a three-dimensional hydrogel composed of collagen type I. All three cell lines were stably transfected with fluorescent protein genes. To register the cell growth dynamics, we used a fluorescence-based technique that allows long-term quantitative observations without disrupting the hydrogel. The analyzed cell lines demonstrated different patterns of relative sensitivity to suboptimal conditions. We revealed that the direction and intensity of the collagen matrix effect depend on the cell type. Slowly proliferating ovarian carcinoma cells showed no noticeable changes in their behavior when cultured in a gel compared to a monolayer. In the case of bladder carcinoma, we registered predominantly resistance-stimulating effect of the collagen matrix, but it was significant only under serum deprivation. The most pronounced effect of collagen was registered for epidermoid carcinoma. Importantly, this effect was ambivalent: gel-embedded cells demonstrated significantly enhanced resistance to serum deprivation, but, at the same time, they were more responsive to glucose starvation and hypoxic conditions. We attribute the registered phenomenon to the individual characteristics of tumor cells with different origins and metabolic activities.
{"title":"Cell-type dependent effect of 3D collagen matrix on cancer cell resistance to suboptimal conditions: the case of serum deprivation, glucose starvation, and hypoxia","authors":"Ludmila M. Sencha, Maria A. Karpova, Olga E. Dobrynina, Irina V. Balalaeva","doi":"10.1016/j.tice.2024.102719","DOIUrl":"10.1016/j.tice.2024.102719","url":null,"abstract":"<div><div>The extracellular matrix (ECM) and its primary chemical components, including collagen, play a pivotal role in carcinogenesis and tumor progression. The ECM actively regulates cell proliferation, migration, and, importantly, resistance to various adverse factors. It is widely recognized as a key factor in modifying the resistance of tumor cells to various treatment modalities and cytotoxic compounds. However, the role of the ECM in tumor cell adaptation to nutritional deficiencies and hypoxic conditions remains significantly less studied. Since it is generally accepted that tumor cells resistance increases when cultured in a three-dimensional matrix, we sought to experimentally test the universality of this statement. In this work, we analyzed the responses of tumor cells with varying origins and proliferative activities, including human bladder carcinoma, epidermoid carcinoma, and ovarian carcinoma, to deprivation of serum, glucose and oxygen. We compared cell resistance to suboptimal conditions when cultured in a monolayer on tissue culture (TC)-treated polystyrene, on collagen-coated surfaces, or within a three-dimensional hydrogel composed of collagen type I. All three cell lines were stably transfected with fluorescent protein genes. To register the cell growth dynamics, we used a fluorescence-based technique that allows long-term quantitative observations without disrupting the hydrogel. The analyzed cell lines demonstrated different patterns of relative sensitivity to suboptimal conditions. We revealed that the direction and intensity of the collagen matrix effect depend on the cell type. Slowly proliferating ovarian carcinoma cells showed no noticeable changes in their behavior when cultured in a gel compared to a monolayer. In the case of bladder carcinoma, we registered predominantly resistance-stimulating effect of the collagen matrix, but it was significant only under serum deprivation. The most pronounced effect of collagen was registered for epidermoid carcinoma. Importantly, this effect was ambivalent: gel-embedded cells demonstrated significantly enhanced resistance to serum deprivation, but, at the same time, they were more responsive to glucose starvation and hypoxic conditions. We attribute the registered phenomenon to the individual characteristics of tumor cells with different origins and metabolic activities.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102719"},"PeriodicalIF":2.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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