Tissue & cell最新文献

{"title":"Lycopene alleviates cognitive dysfunctions in an Alzheimer's disease rat model via suppressing the oxidative and neuroinflammatory signaling","authors":"Sara El-Sayed El-kazaz ,&nbsp;Mona Hafez Hafez ,&nbsp;Ahmed E. Noreldin ,&nbsp;Asmaa F. Khafaga","doi":"10.1016/j.tice.2025.102975","DOIUrl":"10.1016/j.tice.2025.102975","url":null,"abstract":"<div><div>Oxidative stress and neuroinflammation are key contributors to the development of neurodegenerative disorders, including Alzheimer's disease (AD). Lycopene (LYC) has demonstrated effectiveness in inhibiting inflammatory and oxidative stress markers and appears to exert a modulatory impact on several physiological pathways, behavioral manifestations, and cognitive symptoms associated with AD in animal models. In the present study, an AD model was established in male Wistar albino rats through daily oral administration of hydrated aluminum chloride (AlCl₃·6H₂O) at a dose of 75 mg/kg for six weeks. A Morris water maze (MWM) behavioral test was conducted to confirm memory impairment and cognitive deterioration in the treated rats. Animals exhibiting cognitive dysfunction were subsequently treated with LYC (5 mg/kg orally) for an additional six weeks, followed by a second MWM test before sacrifice. The findings revealed that LYC significantly enhanced performance and cognitive function in the AD model rats and markedly (p &lt; 0.001) reduced the accumulation of amyloid β1–42, proinflammatory mediators [interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α)], malondialdehyde (MDA), and nitrite levels. Furthermore, LYC significantly (p &lt; 0.001) decreased the acetylcholine (ACh) concentration, monoamine oxidase (MAO), creatine kinase (CK), and lactate dehydrogenase (LDH) activites. Additionally, LYC significantly (p &lt; 0.001) increased the acetylcholinesterase (AChE) activity, nuclear factor erythroid-2-related factor 2 (Nrf2), serotonin, anti-inflammatory mediators [transforming growth factor beta-1 (TGF-β1) and interleukin-10 (IL-10)] levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. The therapeutic efficacy of LYC was further supported by improvements in the histopathological appearance of brain tissues, significant (p &lt; 0.001) enhancement of synaptophysin immunohistochemical expression, and suppression of the immunohistochemical expression of cell cycle-related proteins (Ki67 and proliferating cell nuclear antigen [PCNA]). In conclusion, LYC may represent a promising therapeutic agent for AD by targeting multiple pathogenic mechanisms.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102975"},"PeriodicalIF":2.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic effect of Astaxanthin on drill-induced closed femoral fracture model in male Wistar rats","authors":"Hasan Yousefi-Manesh ,&nbsp;Laleh Foroutani ,&nbsp;Armita Yousefi ,&nbsp;Khazar Adibmoradi Langroudi ,&nbsp;Sahand Adib Moradi ,&nbsp;Pasha Reza Shams Azar ,&nbsp;Seyed Mohammad Tavangar ,&nbsp;Alireza Hadizadeh ,&nbsp;Mojdeh Sarzaeim ,&nbsp;Shiva Hadizadeh ,&nbsp;Yasaman Kheirandish ,&nbsp;Azadeh Manayi","doi":"10.1016/j.tice.2025.102917","DOIUrl":"10.1016/j.tice.2025.102917","url":null,"abstract":"<div><h3>Purpose</h3><div>Bone fracture is one of the most significant injuries of the body, which is usually caused by trauma. Astaxanthin (AST) showed beneficial effects on inflammation and oxidative stress, indicating protective effects on bone tissue. This study was performed with the aim of evaluating the effect of AST on the improvement of behavioral changes and the ossification process in the defect created in the femur of the rats.</div></div><div><h3>Methods</h3><div>Animals were randomly divided into 3 groups, sham (healthy), control (bone fracture), and treatment. The sham group received water and normal food. In the control group, the fracture of the femur (3 holes) was done through a dental drill. A group of animals was treated daily with AST (1 mg/kg) by intraperitoneal injection (i.p.) 24 h after surgery for 3 weeks.</div></div><div><h3>Results</h3><div>Behavioral tests (open field test and grid walk test) showed increased movement inconsistency and balance in the control group compared to the sham group. At the same time, treatment with AST for 3 weeks improved movement disorders in behavioral tests. The results of histological analysis and radiography showed that the treatment with AST led to decreased inflammation and necrosis and increased bone optical density. Fracture caused elevation in the levels of oxidative stress marker (MDA) as well as the pro-inflammatory cytokine (TNF-α and (IL-1β). However, treatment with AST reversed it.</div></div><div><h3>Conclusions</h3><div>Based on the results from this study, AST, as an anti-inflammatory, and an antioxidant therapeutic agent, has therapeutic effects on bone fractures.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102917"},"PeriodicalIF":2.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inorganic nitrate attenuates neuroinflammation after traumatic brain injury via Sialin","authors":"Zanxu Liu ,&nbsp;Liang Hu ,&nbsp;Qiaochu Wang ,&nbsp;Xiang Zhao ,&nbsp;Weiming Liu ,&nbsp;Bin Zhang ,&nbsp;Wen Pan ,&nbsp;Wenpeng Song ,&nbsp;Xi Chen ,&nbsp;Chunmei Zhang ,&nbsp;Jinsong Wang ,&nbsp;Songlin Wang ,&nbsp;Jian Zhou","doi":"10.1016/j.tice.2025.102955","DOIUrl":"10.1016/j.tice.2025.102955","url":null,"abstract":"<div><h3>Background</h3><div>Traumatic brain injury (TBI) is a significant concern in neurosurgery due to its severe consequences. Neuroinflammation is a critical response following the initial brain insult, leading to cumulative neuronal damage and chronic neurodegeneration, with limited effective treatments available. Inorganic nitrate, an essential nutrient known for its anti-inflammatory properties, is widely utilized in disease prevention and treatment. This study investigated the short-term effects of inorganic nitrate on neuroinflammation and explored the role of Sialin in neuroprotection during the early phase post-TBI.</div></div><div><h3>Methods</h3><div>Male C57BL/6 mice underwent TBI using an electrically controlled cortical impactor (eCCI) model. Animals were administered nitrate or sterile saline intragastrically twice daily for 1,3 or 7 days post-injury (dpi) until sacrifice. Neurobehavioral function was evaluated, and brain tissues were collected for morphological, histopathological, and molecular analyses.</div></div><div><h3>Results</h3><div>Nitrate enhanced neurobehavioral function recovery and improved neurological outcomes at 3 dpi. While nitrate did not significantly reduce structural damage, it did decrease neuronal loss and apoptosis in the early stages of TBI. RNA-seq of injured brains at 3 dpi revealed more genes and signaling pathways linked to immune processes following early nitrate treatment compared to the vehicle, indicating inflammation inhibition. This was further confirmed at the mRNA and protein levels. Specifically, key gene markers of inflammatory mediators were notably suppressed by early nitrate compared to the corresponding TBI vehicle groups. However, the knockdown of <em>Slc17a5</em> reduced the effectiveness of nitrate on short-term neurobehavior in TBI mice and nullified its anti-inflammatory effects.</div></div><div><h3>Conclusion</h3><div>Inorganic nitrate can improve neurological outcomes and attenuate neuroinflammation following TBI, attributed in part to the normalisation of the inflammatory response mediated by Sialin. The discovery lays a promising groundwork for the protective effects of nitrate in TBI conditions.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102955"},"PeriodicalIF":2.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenomethionine suppresses lung tumor growth without hepatorenal toxicity in mice via the induction of apoptosis-ferroptosis and angiogenesis inhibition","authors":"Houru Liu ,&nbsp;Caiyun Zhang ,&nbsp;Lei Zhang ,&nbsp;Jie Shen ,&nbsp;Kan He ,&nbsp;Bei Huang","doi":"10.1016/j.tice.2025.102956","DOIUrl":"10.1016/j.tice.2025.102956","url":null,"abstract":"<div><div>The high global mortality rate of lung cancer underscores the urgent need for novel therapeutic strategies. Selenium (Se), an essential trace element, exhibits tumor-suppressive properties across malignancies. This study systematically evaluated the antitumor efficacy of selenomethionine (SeMet) compared with that of selenocysteine (SeCys) in Lewis lung carcinoma (LLC) cells <em>in vitro</em> and in tumor-bearing mice <em>in vivo</em>. Compared with SeCys (IC₅₀ = 45.89 μM), SeMet demonstrated superior cytotoxicity against LLC cells (IC₅₀ = 30.19 μM) and significantly inhibited proliferation and migration by inducing apoptosis and ferroptosis. <em>In vivo</em>, SeMet treatment inhibited tumour growth by 50.87 % through the suppression of angiogenesis, outperforming SeCys (27.3 %). Transcriptomic analysis revealed the downregulation of proangiogenic chemokines (<em>Cxcl1</em>, <em>Cxcl2</em>, <em>Cxcl3</em>, <em>Cxcl5</em>) and the upregulation of antitumor chemokines (<em>Cxcl9</em>, <em>Cxcl16</em>) in SeMet-treated tumors. Additionally, SeMet enhanced the activity of antioxidant enzymes (T-SOD and GSH-PX) and reduced the levels of proinflammatory cytokines (IL-6 and TNF-α) without hepatorenal toxicity. These findings establish SeMet as a multifaceted therapeutic candidate for lung cancer through dual induction of apoptosis-ferroptosis and angiogenesis inhibition.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102956"},"PeriodicalIF":2.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the ovariole structure and oogenesis between Bittacus cirratus Tjeder and Bittacus planus Cheng (Mecoptera: Bittacidae)","authors":"Yan-Chun Yang,&nbsp;Qiu-Yue Qin,&nbsp;Bao-Zhen Hua","doi":"10.1016/j.tice.2025.102950","DOIUrl":"10.1016/j.tice.2025.102950","url":null,"abstract":"<div><div>The eggs are subspherical in some species of Bittacidae, but are cuboidal in others. However, the formation mechanism of cuboidal eggs remains unclear so far. Here, we compared the ovariole structure and oogenesis between the hangingflies <em>Bittacus cirratus</em> Tjeder, 1956 with cuboidal eggs and <em>Bittacus planus</em> Cheng, 1949 with subspherical eggs using light and transmission electron microscopy. The results show that the ovariole is of the meroistic-polytrophic type, consisting of a terminal filament, a germarium, a vitellarium, and an ovarian pedicel. During the oogenesis, each follicle has one oocyte and three nurse cells surrounded by follicle cells. The difference occurs between <em>B. planus</em> and <em>B. cirratus</em> during the choriogenesis. In <em>B. cirratus</em>, the follicle is in an elliptical shape along the anterior-posterior axis during the late previtellogenesis, but transforms into a cuboidal shape during the choriogenesis. The formation mechanism of the cuboidal eggs is briefly discussed for hangingflies.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102950"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the morphological, cellular, biochemical, and molecular modifications in the BG01V human embryonic stem cell-derived neuronal cells","authors":"Venkanna Bhanothu","doi":"10.1016/j.tice.2025.102965","DOIUrl":"10.1016/j.tice.2025.102965","url":null,"abstract":"<div><div>Changes in the morphology, metabolic activity, intracellular calcium (Ca^2 +) transients, expression of topoisomerase-2β (Topo-2β), and senescence of human embryonic stem cells (hESCs)-derived neuronal cells on basic hESC culture media and neuronal differentiation medium at different time intervals is not clear. Hence, we aimed to investigate the morphological, cellular, biochemical, and molecular alterations in the BG01V hESC-derived neuronal cells on basic hESC culture media and neuronal differentiation media at different time intervals.</div></div><div><h3>Materials and methods</h3><div>BG01V hESC-derived neuronal cells grown on basic hESC culture media and neuronal differentiation media were evaluated for morphological changes by microscopy, metabolic activity by MTT assay, cell viability by Trypan Blue exclusion assay, cellular activity by estimating the Ca²⁺ deposits, cellular senescence by senescence-associated beta-galactosidase (SA-β-gal) activity, and level of Topo-2β using Western blotting at different time intervals.</div></div><div><h3>Results</h3><div>Contrasting to the BG01V hESCs grown on basic hESC culture media, a notable increase in the neuronal cell-like structures, neuritic outgrowth, and expression of nestin protein on neural induction was observed. Higher levels of Ca²⁺ deposits, metabolic activity, SA-β-gal activity, and Topo-2β expression in BG01V hESC-derived neuronal cells grown on neuronal differentiation media on day 12 compared to hESCs grown on basic hESC culture media including other days were noted.</div></div><div><h3>Conclusion</h3><div>This study suggests the increase of calcium salts reflecting the calcium activity at distinct phases of neuronal differentiation, ranging from neural induction to neurite extension. The metabolic and SA-β-gal activity of BG01V hESC-derived neuronal cells may suggest the ongoing biological aging process. Upregulation and activation of Topo-2β upon differentiation induction at the mid-phase suggest the activation of inducible gene loci and downregulation of Topo-2β at a later stage.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102965"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved uterine conditions following ovarian transplantation of adipose-derived mesenchymal stem cell conditioned media in rats with letrozole-induced polycystic ovary syndrome: Histomorphometrical, biochemical, and molecular analysis","authors":"Reyhane Naghibzade ,&nbsp;Golnaz Shafiei ,&nbsp;Seyed Noureddin Nematollahi‑Mahani ,&nbsp;Somayeh Solhjoo ,&nbsp;Tahereh Haghpanah","doi":"10.1016/j.tice.2025.102971","DOIUrl":"10.1016/j.tice.2025.102971","url":null,"abstract":"<div><div>Regenerative medicine is a new hope for the treatment of diseases such as polycystic ovarian syndrome (PCOS). Due to the beneficial effects of adipose stem cell-derived conditioned media transplantation (ASC-CM) on polycystic ovary phenotypes and also considering the relationship between uterine function and ovarian hormone level, this study, for the first time, evaluates the transplantation of ASC-CM in compared to ASC on the altered state of the uterus, estrogen level as well as its receptors expression in PCOS model. Animals were divided randomly into two groups, including the CMC group and the PCOS group. After PCOS confirmation, the PCOS rats were allocated into four subgroups, including PCOS-Vehicle, PCOS-Media, PCOS-ASC, and PCOS-ASC-CM. After four weeks, the uterus tissues were removed for weighing, histomorphometrical evaluation, and immunoblotting assessments of estrogen receptors (ERα and ERβ). The sera were obtained for estrogen hormone level evaluation. Uterine histopathological conditions, such as marked reductions of the heights of the luminal and glandular epithelial cells as well as altered lining epithelial cells of the lumen and glands, alongside diminished uterine weight and thickness, were observed in the PCOS-V and PCOS-Media groups when compared to those of the CMC group. Additionally, their estrogen levels and ERα and ERβ expression levels decreased. However, ASC-CM administration, compared to ASCs alone, more effectively improved these altered uterine conditions of PCOS rats, resulting in enhanced uterine and endometrial wall thickness, luminal and glandular epithelial cell heights, estrogen levels, and also ESRα and ESRβ mRNA transcripts expression compared to those of the PCOS-V and PCOS-Media groups. So, the transplantation of ASC-CM, compared to ASC, could induce more estrogenic histological changes in the PCOS uterine alterations, which suggests a helpful strategy for improving forgotten uterine status in PCOS phenotypes.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102971"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the NLR pathway alleviates MAPK1 mutation-driven proliferation and differentiation deficits and enhanced apoptosis in P19 cells","authors":"Tingying Lei ,&nbsp;Lei Liu ,&nbsp;Fei Guo ,&nbsp;Ru Li ,&nbsp;Li Zhen ,&nbsp;Fang Fu ,&nbsp;Min Pan ,&nbsp;Jin Han ,&nbsp;Hang Zhou ,&nbsp;Chunling Ma ,&nbsp;Ruibin Huang ,&nbsp;Xinyi Zhao ,&nbsp;Dongzhi Li ,&nbsp;Can Liao","doi":"10.1016/j.tice.2025.102973","DOIUrl":"10.1016/j.tice.2025.102973","url":null,"abstract":"<div><h3>Background</h3><div>Congenital heart disease (CHD) is the leading cause of birth defect-related mortality. Genetic mutations, including those in the MAPK1 gene, play a critical role in the development of CHD. However, the exact mechanisms by which MAPK1 mutations contribute to CHD remain unclear.</div></div><div><h3>Methods</h3><div>The MAPK1 mutation (c.1061 T &gt; G, p.F354C) was introduced into P19 murine embryonal carcinoma cells using CRISPR/Cas9 technology. Differentiation was induced with 1 % dimethyl sulfoxide (DMSO), and cell proliferation and apoptosis were assessed using the Cell Counting Kit-8, flow cytometry, and Hoechst staining assays, respectively. Transcriptome sequencing was conducted to explore downstream targets associated with the MAPK1 mutation, and the effects of NOD-like receptor (NLR) pathway inhibition on the phenotype of MAPK1-mutant cells were examined using NOD-IN-1.</div></div><div><h3>Results</h3><div>MAPK1 mutation notably reduced cell viability, promoted apoptosis, and impaired cardiomyocyte differentiation in P19 cells. Western blot analyses revealed decreased protein levels of Bcl-2 and cilium formation markers (p-GSK3βand DZIP1), alongside elevated levels of Bax in MAPK1-mutant cells. Additionally, the mRNA expression of cardiomyocyte differentiation markers, including cTnT, GATA4, MEF2C, and αMHC, was reduced in P19 cells with the MAPK1 mutation. Cells harboring the MAPK1 mutation exhibited clear chromatin condensation and formed fewer and smaller embryoid bodies. Mechanistically, MAPK1 mutation upregulated the protein expression of NOD1 and NOD2 and increased the phosphorylation of RIP2. Treatment with the NLR pathway inhibitor NOD-IN-1 significantly alleviated the detrimental effects of the MAPK1 mutation.</div></div><div><h3>Conclusion</h3><div>MAPK1 gene mutation promotes the NLR signaling pathway and affects CHD development, providing new insights into the treatment of CHD.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102973"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BDNF alleviates senescence and enhances osteogenic differentiation in bone marrow mesenchymal stem cells via the TrkB/PI3K/AKT pathway","authors":"Jimei Zhang ,&nbsp;Ling Zhu ,&nbsp;Jianping Zhou ,&nbsp;Qunying Yu ,&nbsp;Guangyuan Yang ,&nbsp;Chaoli Luo ,&nbsp;Jianguo Meng ,&nbsp;Shan Xing ,&nbsp;Jing Liu ,&nbsp;Donggang Mou ,&nbsp;Xuming Yang","doi":"10.1016/j.tice.2025.102972","DOIUrl":"10.1016/j.tice.2025.102972","url":null,"abstract":"<div><h3>Background</h3><div>Bone marrow mesenchymal stem cells (BMSCs) are stem cells that reside in bone marrow and have multidirectional differentiation potential. BMSCs have been used to treat bone injury. However, long-term passage leads to the aging of BMSCs and the weakening of osteogenic differentiation. Furthermore, brain-derived neurotrophic factor (BDNF) may enhance the antiaging ability of BMSCs. The purpose of this study was to investigate the role of BDNF in the senescence and osteogenic differentiation of human BMSCs (hBMSCs).</div></div><div><h3>Methods</h3><div>The senescence of hBMSCs was induced by successive passages. The mRNA and protein expression levels were measured using RT<img>qPCR and Western blotting. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining were used to identify osteogenic differentiation in the cells.</div></div><div><h3>Results</h3><div>After long-term passage, the hBMSCs morphologically gradually expanded and appeared flat, cell viability decreased, the number of fibroblast-like colony-forming units (CFU-Fs) decreased, and the number of β-galactosidase (SA-β-gal)-positive cells and the mRNA expression levels of the senescence-related genes p53, p21 and p16 increased. The activity of ALP, the level of calcium salt deposition and the protein levels of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN) and BDNF were significantly decreased. Subsequent research indicated that the senescence and inhibition of the osteogenic differentiation of hBMSCs induced by long-term culture were caused by low expression of BDNF. From a mechanistic standpoint, BDNF can activate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway by upregulating the expression of tropomyosin receptor kinase B (TrkB), thereby improving the senescence and inhibition of the osteogenic differentiation of hBMSCs caused by long-term passage.</div></div><div><h3>Conclusion</h3><div>BDNF improves the senescence and inhibition of the osteogenic differentiation of hBMSCs caused by long-term passage via regulation of the TrkB/PI3K/AKT signaling axis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102972"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the p38MAPK/STAT3/NF-κB65 pathway modulates the hepatoprotective effect of pentoxifylline against sodium valproate-induced liver injury in rats; A study based on integrating network pharmacology and experiment validation","authors":"Gellan Alaa Mohamed Kamel ,&nbsp;Shaimaa Hussein","doi":"10.1016/j.tice.2025.102942","DOIUrl":"10.1016/j.tice.2025.102942","url":null,"abstract":"<div><div>Sodium valproate (SVP) is frequently utilized in the treatment of epilepsy. Extended administration of SVP elevates the likelihood of hepatotoxicity. Pentoxifylline (PTX) functions as a nonselective phosphodiesterase inhibitor and is commonly utilized in the treatment of vascular conditions, exhibiting extensive antioxidant and anti-inflammatory properties. This research examined PTX's protective role in mitigating SVP-induced liver injury, clarifying the potential molecular mechanisms involved. SVP and PTX intersection targets were identified through network pharmacology. In addition, we conducted an in vivo experiment utilizing the SVP-induced liver injury model. Eighteen adult male rats were allocated to three groups, with the control group receiving oral normal saline. The SVP group was administered SVP (dissolved in normal saline) daily for 2 weeks. The PTX + SVP group was administered SVP in conjunction with PTX daily for two weeks. PTX hepatoprotective effect against SVP could include apoptosis, anti-inflammatory mechanisms, and various signaling pathways, such as NF-κB, STAT3, and MAPK, as indicated by the KEGG and GO enrichment analysis of the 272 common targets. We identified BCL2, IL6, and TNF as potential hub targets of PTX for liver injury treatment based on the construction of the PPI network. In vivo experiments demonstrated that PTX hindered MAPK P38/STAT3/NF-κB-related pathways' activation, diminished oxidative stress, apoptosis, and inflammatory response, and substantially ameliorated SVP-induced liver injury. The network pharmacology study concluded that the MAPK P38/STAT3/NF-κB pathway plays a role in PTX protective effect against SVP-induced liver injuries, as demonstrated by the <em>in vivo</em> experiment results.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102942"},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929616","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}