Tissue & cell最新文献

{"title":"Mechanisms of mitochondrial autophagy-mediated crosstalk between ferroptosis and cuproptosis in lung cancer","authors":"Lang Jiang ,&nbsp;Zhijun Shen","doi":"10.1016/j.tice.2025.103148","DOIUrl":"10.1016/j.tice.2025.103148","url":null,"abstract":"<div><div>Globally, lung cancer has an extremely high morbidity and fatality rate among malignant tumors. Studies on the mechanisms of cell death have yielded fresh concepts and treatment approaches for lung cancer in recent years. As a crucial mitochondrial quality control mechanism, mitochondrial autophagy is strongly related to new forms of cell death, ferroptosis and cuproptosis, and it is crucial for the development, progression, management, and outcomes of lung cancer. In order to provide a theoretical foundation and possible therapeutic targets for precision lung cancer treatment, this review provides an overview of the molecular mechanisms of mitochondrial autophagy, ferroptosis, and cuproptosis as well as how these mechanisms of action interact with one another in lung cancer.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103148"},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103001","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 potential protective role of L-citrulline against cadmium-induced renal dysfunction in male albino rats: The implications of the Nrf2/HO-1 antioxidant signaling pathway","authors":"Mamdouh Eldesoqui ,&nbsp;Hagar M. Mohamed ,&nbsp;Aya Megahed ,&nbsp;Rania A. Fouad ,&nbsp;Samar Sakr ,&nbsp;Samir A.A. El-Gendy ,&nbsp;Ahmed M. Rashwan ,&nbsp;Ahmed A. El-Mansi ,&nbsp;Amal F. Dawood ,&nbsp;Mohamed A.M. Alsafy ,&nbsp;Valentina Kubale ,&nbsp;Eman M. Embaby","doi":"10.1016/j.tice.2025.103149","DOIUrl":"10.1016/j.tice.2025.103149","url":null,"abstract":"<div><div>Cadmium (Cd), a prevalent ecological and occupational pollutant from industrial discharge that poses serious health hazards, is known to be harmful to the kidneys. L-citrulline (L-Cit), a non-essential amino acid that has shown potential in lowering oxidative stress and improving organ function, is a good candidate for achieving renal protection against Cd-induced impaired antioxidant defenses in albino rats. Four groups of thirty-two adult male albino rats each were randomly assigned: control, L-Cit, CdCl₂, and L-Cit + CdCl₂. The L-Cit + CdCl₂ group received 900 mg/kg L-Cit 120 min before Cd exposure, while the CdCl₂ group received 5 mg/kg Cd for 30 days. Biochemical assays evaluated kidney functions, oxidative stress markers, and quantitative RT-PCR gene expression analysis for nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Tissue damage and apoptosis were assessed using histopathological analyses and immunohistochemistry labeling for Nrf2, HO-1, and caspase-3. Exposure to Cd significantly increased blood creatinine, urea, and uric acid levels, suggesting impaired renal function. Concurrent delivery of L-Cit significantly ameliorated these changes, further improving markers of kidney function beyond those of the control groups. Furthermore, elevated MDA levels, decreased GSH content, reduced SOD and CAT activities, and decreased serum nitric oxide (NO) indicated oxidative stress due to Cd exposure. L-Cit treatment successfully lowered MDA levels and restored antioxidant enzyme abilities. Histopathological studies found that L-Cit administration significantly reduced the Cd-induced renal damage in rats. L-Cit also upregulates the HO-1 and Nrf2 expression, which report its protective antioxidant properties. The current study shows that L-Cit showed protective effects against Cd-induced nephrotoxicity by modulating the NO and Nrf2/HO-1 signaling pathways, offering promising therapeutic insights for managing heavy metal-induced renal damage. Its mechanics and therapeutic applications merit further investigation.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103149"},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109140","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":"Formononetin enhances angiogenesis in diabetic wounds by inhibiting ferroptosis through suppression of mtROS-mediated xCT/GPX4 upregulation","authors":"Xinying Li ,&nbsp;Ding Zhu ,&nbsp;Yanguo Wang,&nbsp;Chuanqi Zhao,&nbsp;Yuangang Lu","doi":"10.1016/j.tice.2025.103141","DOIUrl":"10.1016/j.tice.2025.103141","url":null,"abstract":"<div><h3>Background</h3><div>Impaired angiogenesis critically contributes to delayed wound healing in diabetic patients. Mitochondrial damage in endothelial cells worsens this vascular dysfunction. Formononetin (FMN), a phytoestrogen from <em>Astragalus</em> roots, is traditionally used to enhance blood function and microcirculation; however, its mechanism remains unclear. This study investigates whether FMN protects human umbilical vein endothelial cells (HUVECs) from high glucose (HG)-induced ferroptosis, and we also evaluated its potential to enhance vascular repair and accelerate diabetic wound healing.</div></div><div><h3>Methods</h3><div>We used Western Blotting to measure ferroptosis markers including the cystine/gluta-mate antiporter system (xCT) and glutathione peroxidase 4 (GPX4) in both HUVECs and diabetic mouse wound tissue. To assess oxidative stress, we measured glutathione content (GSH), malondialdehyde production (MDA), and intracellular iron accumulation. Mitochondrial changes were evaluated through MitoSOX, TOMM20 protein expression, and JC-1 fluorescence. Wound tissue sections were processed for H&amp;E staining to examine healing stages, and CD31 immunofluorescence was performed to visualize angiogenesis in the wound tissue.</div></div><div><h3>Results</h3><div>FMN effectively reduced ferroptosis markers in HG-treated HUVECs, and Erastin treatment abolished this protective effect. The compound appeared to block ferroptosis through two mechanisms: restoration of mitochondrial integrity and reactivation of the xCT/GPX4 antioxidant system. When we tested FMN in diabetic mice, wound closure rates improved substantially, the expression of xCT and GPX4 was increased, and CD31 expression in wound vessels increased, which matched what we observed in vitro.</div></div><div><h3>Conclusion</h3><div>Ferroptosis is critically involved in the pathogenesis of diabetic wounds. FMN exerts protective effects against HG-induced ferroptosis in HUVECs via restoration of mitochondrial function and mitigation of mitochondrial reactive oxygen species (mtROS) accumulation through xCT/GPX4 activation. This evidence suggests FMN could serve as a promising natural therapeutic agent for diabetic wound treatment.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103141"},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118659","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":"Tirzepatide enhances liver structural integrity by promoting mitochondrial dynamics and mitophagy via PINK1/PRKN and SIRT3/NRF2 pathways in an obese-diabetic-menopausal mouse model","authors":"Ilitch A. Marcondes-de-Castro ,&nbsp;Thatiany S. Marinho ,&nbsp;Marcia B. Aguila ,&nbsp;Carlos A. Mandarim-de-Lacerda","doi":"10.1016/j.tice.2025.103146","DOIUrl":"10.1016/j.tice.2025.103146","url":null,"abstract":"<div><div>The effects on hepatic mitochondrial structure, mitophagy, and cellular homeostasis were investigated when treated with Tirzepatide (Tzp), a dual GIP/GLP-1 receptor agonist, in a mouse model combining obesity, type 2 diabetes, and menopause—conditions that collectively exacerbate metabolic dysfunction-associated steatotic liver disease (MASLD). Female C57BL/6 mice were fed either a control or high-fat, high-sucrose diet for 12 weeks, and half underwent bilateral ovariectomy to simulate menopause. Tzp was administered daily for four weeks. Liver tissue was evaluated for ultrastructural alterations, gene expression, and protein profiles. Untreated obese-diabetic and obese-diabetic-ovariectomized mice exhibited hepatocellular fat accumulation, mitochondrial swelling, and disorganized cristae, indicative of metabolic and oxidative stress. In contrast, Tzp-treated mice displayed preserved hepatic architecture and intact mitochondrial morphology. Tzp significantly downregulated autophagy genes (Ulk3, Atg5, Atg7) and key mitophagy regulators (PINK1, PRKN), reestablishing mitochondrial balance, primarily through the modulation of mitophagy and enhanced organelle stability. Simultaneously, it upregulated mitochondrial biogenesis markers (Ppargc1a, Tfam), antioxidant enzymes (SOD2, GR, GPX, CAT), and redox modulators (Sirt3, Nrf2), while normalizing oxidative stress-related genes (Nos1, Nox1). Tzp also mitigated endoplasmic reticulum (ER) stress by downregulating Atf4, Ddit3, and Gadd45 and rebalanced mitochondrial dynamics through the suppression of fission markers (Dnml1, Fis1) and the restoration of fusion mediators (Mfn1, Mfn2). Three-way ANOVA confirmed Tzp's broad regulatory effects on hepatic gene expression, while principal component analysis revealed clear transcriptional separation between treated and untreated groups. In conclusion, these findings demonstrate that Tzp preserves liver ultrastructure and restores mitochondrial dynamics, supporting its therapeutic potential in MASLD and hormone-related metabolic disorders.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103146"},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102965","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":"Asiatic acid reverses cisplatin resistance in A549/DDP cells by activating the P38 MAPK/Slug pathway","authors":"Min Yu ,&nbsp;Qian Zhang ,&nbsp;Wenli Shang ,&nbsp;Shenghong Wei ,&nbsp;Hongxia Wen ,&nbsp;Shufen Huo ,&nbsp;Xiang Li ,&nbsp;Xuan Li ,&nbsp;Heng Zhang ,&nbsp;Yingxuan Tian","doi":"10.1016/j.tice.2025.103145","DOIUrl":"10.1016/j.tice.2025.103145","url":null,"abstract":"<div><h3>Background</h3><div>Drug resistance has become a major challenge in the treatment of non-small cell lung cancer (NSCLC). A promising therapeutic approach involves the identification of potent resistance modulators and their combined application with conventional chemotherapeutic agents. Asiatic acid (AA), a bioactive pentacyclic triterpenoid derived from the medicinal plant <em>Centella asiatica</em>, has shown significant anticancer properties in various studies. This study aims to evaluate the molecular mechanisms by which AA affects cisplatin (DDP)-resistant lung cancer A549/DDP cells.</div></div><div><h3>Methods</h3><div>The optimal concentrations of AA and DDP for A549 and A549/DDP cells were initially identified using the CCK-8. Following this, AA's impact on A549/DDP cells was evaluated in vitro, while resistance mechanisms were investigated via molecular docking and verified using pathway inhibitors. Furthermore, a nude mice lung cancer xenograft model was established to investigate the impact of AA on tumor growth in vivo.</div></div><div><h3>Results</h3><div>AA may enhance the sensitivity of A549/DDP cells to DDP by inhibiting the levels of P-gp, MVP, and Bcl-2, while promoting the levels of Bax and Caspase-3. Molecular docking and in vitro experiments demonstrated that AA forms stable interactions with p-p38 MAPK, P-gp, and Slug, and reduces Slug-mediated resistance pathways by inhibiting the phosphorylation of p38 MAPK. This ultimately increases the sensitivity of NSCLC cells to DDP. The p38 MAPK inhibitor Doramapimod partially reversed this effect. In vivo experiments further showed that Doramapimod weakened the AA-mediated DDP-sensitizing effect, promoting tumor growth.</div></div><div><h3>Conclusion</h3><div>AA reverses cisplatin resistance in A549/DDP cells by activating the P38 MAPK/Slug pathway. The p38 MAPK inhibitor Doramapimod partially reverses this effect.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103145"},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158514","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":"Immunomodulatory effects of hexanoic extract of Narcissus tazetta flowers after subacute exposure to BALB/c mice through a phased approach immunotoxicity assessment","authors":"Seyed Mostafa Moshirian-Farahi ,&nbsp;Fatemeh Forouzanfar ,&nbsp;Hassan Rakhshandeh ,&nbsp;Bahram Memar ,&nbsp;Roghayeh Rashidi ,&nbsp;Saeide Mansoori ,&nbsp;Bamdad Riahi-Zanjani ,&nbsp;Mahmood Sadeghi","doi":"10.1016/j.tice.2025.103147","DOIUrl":"10.1016/j.tice.2025.103147","url":null,"abstract":"<div><div><em>Narcissus tazetta</em>, a perennial herbaceous and medicinal plant, exhibits various pharmacological properties. The current study investigates the immunomodulatory effects of hexanoic extract of <em>N. tazetta</em> flowers (HENTF) in BALB/c mice immune system. Over a 14-day period, HENTF was administered orally at doses of 25 and 50 mg/kg. Evaluations of the immune system included histopathological examination of spleen and bone marrow, spleen cellularity, delayed type hypersensitivity (DTH) response, lymphocyte proliferation assay, hemagglutination titer (HA), and cytokines production. These findings suggest that HENTF exhibits immunostimulatory properties. The results demonstrated that higher dose of 50 mg/kg might enhance the immune responses on both cellular and humoral levels, with significant effects in the proliferation of lymphocytes. Mechanistic studies are necessary to precisely explore how HENTF exerts its immunostimulatory properties. Future investigations are recommended to evaluate the efficacy of HENTF as a co-adjuvant or immunostimulant in therapeutic applications for immune dysfunction.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103147"},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102955","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":"Curcumin attenuates malathion-induced lung injury in rats by modulating oxidative stress, inflammation, and fibrosis via Nrf2/HO-1, NF-κB/TNF-α, and COX-2 pathways.","authors":"Mamdouh Eldesoqui ,&nbsp;Eman M. Embaby ,&nbsp;Rania A. Fouad ,&nbsp;Yara M. Alrajhi ,&nbsp;Zeinab A. Mohammed ,&nbsp;Emad A. Albadawi ,&nbsp;Rasha Hamed Al‑Serwi ,&nbsp;Ahmed A. El-Mansi ,&nbsp;Mahmoud Hendawy ,&nbsp;Magda E. Ahmed","doi":"10.1016/j.tice.2025.103144","DOIUrl":"10.1016/j.tice.2025.103144","url":null,"abstract":"<div><h3>Background<em>:</em></h3><div>Malathion (Mal), a commonly used organophosphate insecticide, causes significant lung damage through oxidative stress, inflammation, and stimulation of pulmonary fibrosis. Curcumin (Cur), a natural polyphenolic molecule, possesses strong antioxidant, anti-inflammatory, and antifibrotic functions.</div></div><div><h3>Objective</h3><div>This work aimed to evaluate the protective effects of Cur against Mal-induced lung injury in rats by modulating the Nrf2/HO-1, NF-κB/TNF-α, and COX-2 signaling pathways.</div></div><div><h3>Methods</h3><div>Twenty-four adult male Sprague Dawley rats were randomly divided into four equal groups: control, Cur-treated (150 mg/kg/day), Mal-treated (100 mg/kg/day), and Mal+Cur (received Cur followed by Mal after 3 h) groups. Both Mal and Cur were administered orally via gavage for four weeks. Oxidative stress markers, inflammatory mediators, and fibrotic alterations were assessed in lung tissues using biochemical and histological methods. The expression of key signaling molecules, including Nrf2/HO-1 (antioxidant response), NF-κB/TNF-α (inflammatory response), and COX-2 (pro-inflammatory enzyme), was measured via immunohistochemistry and quantitative PCR.</div></div><div><h3>Results</h3><div>Compared to the control group<em>,</em> Mal exposure led to marked oxidative damage, evidenced by elevated Malondialdehyde (MDA) levels (p &lt; 0.0001) and decreased superoxide dismutase (SOD) and acetylcholinesterase (AChE) levels (p &lt; 0.0001). This was accompanied by increased expression of pro-inflammatory (TNF-α, IL-1β, IL-6, and PGE2 (p &lt; 0.0001)) and pro-fibrotic (hydroxyproline) markers, and significant histopathological alterations. Co-administration of curcumin significantly attenuated these effects, restoring AChE activity, enhancing Nrf2/HO-1/ antioxidant signaling, and suppressing NF-κB/TNF-α and COX-2 inflammatory pathways.</div></div><div><h3>Conclusion<em>:</em></h3><div>These data demonstrate that curcumin protects against malathion-induced lung injury by modulating oxidative stress, inflammation, and fibrosis-related pathways, highlighting its therapeutic potential for mitigating organophosphate-induced respiratory damage.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103144"},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145106395","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":"Immunohistochemical investigation of GST-M, GST-P, and TP53 gene expression in obesity patients under laparoscopic sleeve gastrectomy","authors":"Onur Di̇ri̇can ,&nbsp;Pınar Kaygin ,&nbsp;Burcu Kaplan ,&nbsp;Sezen Yilmaz Sarialtin ,&nbsp;Gülçin Güler Şi̇mşek ,&nbsp;Serpil Oğuztüzün ,&nbsp;Hakan Buluş ,&nbsp;Serap Yesi̇lki̇r Baydar ,&nbsp;Abbas Ali Husseini ,&nbsp;Selim Öğüt","doi":"10.1016/j.tice.2025.103143","DOIUrl":"10.1016/j.tice.2025.103143","url":null,"abstract":"<div><div>Obesity is linked to increased oxidative stress, contributing to various comorbidities. Glutathione S-transferases (GSTs) enzymes and tumor suppressor protein 53 (TP53) are key regulators of oxidative stress. This study aimed to examine the expression of GST-M, GST-P, and TP53 in sleeve gastrectomy tissues of obese patients. In this retrospective study, 126 obese patients who underwent sleeve gastrectomy were analyzed. Immunohistochemical staining assessed the expression of GST-M, GST-P, and TP53 in sleeve gastrectomy tissue samples. Correlation between protein expression and association with demographic, clinical, and serological data was examined. GST-P and GST-M exhibited low expression (absent/weak), while TP53 showed significantly higher expression in the sleeve gastrectomy tissue of patients with obesity. A positive and significant correlation was identified between GST-M and TP53 staining levels, while GST-P expression level did not display any correlation with GST-M and TP53. Distinct patterns of protein expression for GST-P, GST-M, and TP53 in the sleeve gastrectomy tissues of obesity patients. TP53 plays a key role in oxidative stress regulation in obesity, whereas GST-M and GST-P appear less effective.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103143"},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087441","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 role of icariin in promoting autophagic repair of intervertebral disc nucleus pulposus cells via the PI3K-Akt-mTOR pathway","authors":"Shiwei Zheng ,&nbsp;Tao Li ,&nbsp;Qianchun Li","doi":"10.1016/j.tice.2025.103140","DOIUrl":"10.1016/j.tice.2025.103140","url":null,"abstract":"<div><h3>Background</h3><div>The pathological mechanism of intervertebral disc degeneration (IVDD) is closely related to impaired autophagic function in nucleus pulposus (NP) cells. Icariin has demonstrated protective effects in osteoarthritis, but its role in autophagy regulation in IVDD remains unclear. It was to investigate impact of icariin on autophagic repair of intervertebral disc NP cells via PI3K/Akt/mTOR signaling pathway (SPW) and its dose-response relationship.</div></div><div><h3>Methods</h3><div>A rat model of IVDD was established using percutaneous annular puncture. Forty SD rats were rolled into sham surgery group (SG), model group (MG), and icariin-treated groups (low-dose (LDG): 10 mg/kg, medium-dose (MDG): 40 mg/kg, high-dose (HDG): 80 mg/kg). CCK-8 assay assessed cell proliferation. TEM showed autophagosome formation. The expression level (EL) of autophagy-related proteins and PI3K/Akt/mTOR SPW proteins was measured by Western blot. A PI3K/Akt/mTOR pathway-specific intervention experiment was conducted. The HDG+IGF-1 group was established as 80 mg/kg icariin administered by gavage plus daily intraperitoneal injection of the PI3K/Akt pathway agonist IGF-1 (100 μg/kg). The HDG+LY294002 group was constituted as 80 mg/kg icariin administered by gavage plus daily intraperitoneal injection of the PI3K inhibitor LY294002 (10 mg/kg).</div></div><div><h3>Results</h3><div>MG exhibited greatly reduced cell proliferation (<em>P</em> &lt; 0.01), a decrease in the number of autophagosomes, accumulation of p62, and decreased EL of ATG5, Beclin-1, and p-ULK1/ULK1 versus SG. LC3-II/I ratio decreased, while PI3K p85, p-Akt/Akt, and p-mTOR/mTOR were markedly elevated (<em>P</em> &lt; 0.01). After icariin intervention, HDG showed the most pronounced effects, notably outperforming the effects of LDG and MDG (<em>P</em> &lt; 0.01). Pathway-specific intervention results demonstrated that compared with the HDG, autophagosome numbers were significantly reduced in the HDG+IGF-1 group (<em>P</em> &lt; 0.01), whereas autophagosome numbers were significantly increased in the HDG+LY294002 group (<em>P</em> &lt; 0.01). Relative to the HDG, the proliferation rate of NP cells at 24 h, 48 h, and 72 h was significantly decreased in the HDG+IGF-1 group (<em>P</em> &lt; 0.01), while the proliferation rate at the same time points was significantly increased in the HDG+LY294002 group (<em>P</em> &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>Icariin can dose-dependently inhibit PI3K/Akt/mTOR SPW, promote autophagy and proliferation in NP cells, with the most marked effects observed at a dose of 80 mg/kg. This provides a new therapeutic strategy for IVDD.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103140"},"PeriodicalIF":2.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158500","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":"Dual molecular axis of resistance and immunoresponsiveness to BCG in pT1 non-muscle invasive bladder cancer: Insights from HER-2, SERBP1, HABP4, and IFN-γ profiling","authors":"João Carlos Cardoso Alonso ,&nbsp;Juliana Mattoso Gonçalves ,&nbsp;Gabriela Cardoso de Arruda Camargo ,&nbsp;Gabriela de Oliveira ,&nbsp;André da Silva Santos ,&nbsp;Adriano Angelo Cintra ,&nbsp;Fabio Guimaraes ,&nbsp;Leandro Luiz Lopes de Freitas ,&nbsp;Martim Corrêa Bottene ,&nbsp;Jean Felipe Prodocimo Lestingi ,&nbsp;Jörg Kobarg ,&nbsp;Wagner José Fávaro","doi":"10.1016/j.tice.2025.103137","DOIUrl":"10.1016/j.tice.2025.103137","url":null,"abstract":"<div><div>Bacillus Calmette–Guérin (BCG) immunotherapy remains the cornerstone of adjuvant treatment for high-risk non–muscle invasive bladder cancer (NMIBC); however, therapeutic failure is particularly frequent in pT1 disease, resulting in early recurrence and progression to muscle-invasive cancer. Identifying biomarkers to anticipate BCG failure is a current clinical priority to improve patient stratification and enable risk-adapted, bladder-sparing interventions. We retrospectively analyzed a cohort of 48 patients with histologically confirmed pT1 NMIBC treated with standard intravesical BCG at two tertiary centers. The median age was 67 years (range: 41–93), 79.2 % were male, 81.2 % had high-grade tumors, 70.8 % had multifocal lesions, and 75.0 % presented tumors &gt; 3 cm. Formalin-fixed, paraffin-embedded tumor samples were obtained prior to BCG and, when available, at recurrence or progression. Immunohistochemical expression of HER-2, SERBP1, HABP4, and IFN-γ was quantified using semi-quantitative scoring and H-scores. Associations with recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated using Kaplan–Meier survival analysis and Cox regression. HER-2 and SERBP1 were significantly overexpressed in BCG-refractory tumors, with high immunorectivities conferring markedly reduced RFS (HER-2: 7.78 vs. 11.71 months, p &lt; 0.001; SERBP1: 7.64 vs. 11.52 months, p &lt; 0.0001) and inferior PFS (p &lt; 0.05). In contrast, high HABP4 and IFN-γ immunorectivities were strongly associated with sustained recurrence- and progression-free survival (both p &lt; 0.0001). Hazard ratios for recurrence and progression exceeded 5.0 for HER-2/SERBP1-high and IFN-γ/HABP4-low profiles. These findings define two molecular phenotypes—immune-evasive versus immune-active—that may inform precision risk stratification, early intervention, and personalized therapeutic decision-making in high-risk NMIBC.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103137"},"PeriodicalIF":2.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087430","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}