Journal of Molecular Histology最新文献

{"title":"Myrtenol ameliorates ulcerative colitis by modulating ANXA1/PINK1/Parkin-mediated mitophagy","authors":"Yimin Li,&nbsp;Xiaobing Gong,&nbsp;Yinghua Peng,&nbsp;Yadang Kuang,&nbsp;Jiaxuan Huang,&nbsp;Mengli Zheng,&nbsp;Leilei Zhan,&nbsp;Jiewen Liang,&nbsp;Weiyi Guo","doi":"10.1007/s10735-025-10486-4","DOIUrl":"10.1007/s10735-025-10486-4","url":null,"abstract":"<div><p>Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by recurrent and intermittent episodes of inflammation. (-)-Myrtenol (MYR) has been shown to exhibit anti-inflammatory, antioxidant, and gastroprotective properties; however, its therapeutic potential in UC remains unexplored. In this study, we established in vitro UC models using lipopolysaccharide (LPS)-induced Caco-2 cells and in vivo models using dextran sulfate sodium (DSS)-induced mice to investigate the effects of MYR on UC. Our findings demonstrated that MYR protected Caco-2 cells from LPS-induced apoptosis and restored mitochondrial function by activating mitophagy. Mechanistically, MYR exerted its protective effects by upregulating ANXA1 expression in LPS-challenged Caco-2 cells, which subsequently activated the PINK1/Parkin pathway. Consistent with these in vitro results, experiments in the DSS-induced mouse model revealed that MYR alleviated UC symptoms and mitigated mitochondrial damage through the regulation of the ANXA1/PINK1/Parkin pathway-mediated mitophagy. In conclusion, MYR reduced apoptosis in LPS-induced Caco-2 cells and ameliorated UC symptoms in DSS-induced mice by enhancing mitophagy and alleviating mitochondrial dysfunction via the ANXA1/PINK1/Parkin pathway.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752016","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 effect of USP17 knockdown on autophagic ferroptosis in gastric cancer by regulating the BNIP3–NCOA4–FTH1 axis","authors":"Jintao Tang,&nbsp;Lebin Yang,&nbsp;Xiongying Chen,&nbsp;Kai Yin,&nbsp;Chunyun Wang","doi":"10.1007/s10735-025-10526-z","DOIUrl":"10.1007/s10735-025-10526-z","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric cancer (GC) is one of the most crucial malignancies worldwide because of the high lethality. This study aims to explore the mechanism by which ubiquitin-specific protease 17 (USP17) mediates autophagic ferroptosis in GC. In the present study, we cultured human GC cell line AGS in vitro and knocked BNIP3 or NCOA4 down using specific small interfering-RNA. Erastin was chosen as a ferroptosis inducer while Ferrostatin-1 was utilized as an inhibitor of ferroptosis. Then, the levels of mitophagy-related proteins, USP17, BNIP3, mitochondrial marker proteins, NCOA4, and FTH1 were quantified through RT-qPCR and Western blot tests. Also, the JC-1 method was adopted to detect mitochondrial membrane potential. Additionally, CCK-8 cell viability test was performed. Ultimately, glutathione, reactive oxygen species, malondialdehyde, and active Fe²⁺ were determined as indicators related to ferroptosis using corresponding kits. The interaction between USP17 and BNIP3 was assessed through co-immunoprecipitation. Genetic inhibition of BNIP3 reduced mitophagy and increased ferroptosis in GC cells. Subsequently, upon BNIP3 silencing, we found up-regulated NCOA4 and down-regulated FTH1, with autophagy inhibition resulting in the similar changes in the NCOA4–FTH1 pathway and cellular Fe²⁺ levels. NCOA4 inhibition partly counteracted BNIP3 deficiency-induced ferroptosis, indicating that BNIP3-dependent autophagic ferroptosis was associated with the NCOA4–FTH1 pathway. Furthermore, it was found that USP17 stabilized BNIP3 by reducing its ubiquitination level, which was linked to the regulatory role of USP17 in ferroptosis. USP17 knockdown modulates autophagic ferroptosis in GC by affecting the stability of BNIP3 and mediating the NCOA4–FTH1 pathway.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752034","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":"METTL14 alleviates sepsis-induced acute kidney injury by targeting Hmox1-mediated ferroptosis through m6A modification","authors":"Chengyi Yang,&nbsp;Le Zhao,&nbsp;Jia Di,&nbsp;Xin Zhou","doi":"10.1007/s10735-025-10521-4","DOIUrl":"10.1007/s10735-025-10521-4","url":null,"abstract":"<div>\u0000 \u0000 <p>The m6A methyltransferase METTL14 plays a role in cellular stress responses, but its function in sepsis-associated acute kidney injury (S-AKI) remains unclear. This study investigates METTL14’s involvement in regulating ferroptosis and inflammation through HMOX1 in S-AKI. We analyzed renal tissues from S-AKI patients and a CLP-induced murine model for histological and molecular changes. In vitro, LPS-treated HK-2 cells were used to mimic S-AKI, with METTL14 expression manipulated via lentiviral transfection. Ferroptosis and inflammatory responses were evaluated using ELISA, qPCR, immunohistochemistry, and western blotting. ROS and lipid peroxidation were assessed with C11-BODIPY, while MeRIP and actinomycin D assays explored m6A modification and mRNA stability of HMOX1. Survival outcomes were assessed over 7 days post-CLP surgery. HMOX1 modulation was further examined using Hemin (inducer) and ZnPP (inhibitor) in vivo. METTL14 was significantly downregulated in both human S-AKI patient tissues and murine CLP models. Its overexpression improved renal function, reduced histological injury and mortality, and suppressed pro-inflammatory cytokines (IL-6, IL-1β, TNF-α). Mechanistically, we identified METTL14 as a novel regulator of HMOX1, promoting its m6A-dependent degradation and thereby limiting iron accumulation and lipid peroxidation associated with ferroptosis. This regulatory axis was confirmed by pharmacological modulation, where Hemin reversed METTL14’s protective effects, while ZnPP rescued METTL14-deficient mice. Additionally, METTL14 reduced ROS generation and stabilized redox homeostasis. METTL14 protects against S-AKI by suppressing ferroptosis via m6A-dependent regulation of HMOX1. These findings reveal a novel epitranscriptomic pathway and suggest METTL14 as a promising therapeutic target for S-AKI.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717234","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":"Evaluation of the effects of monosodium glutamate on the development of the cerebellum in chicken embryos","authors":"Ferhan Bölükbaş,&nbsp;Yasemin Öznurlu","doi":"10.1007/s10735-025-10522-3","DOIUrl":"10.1007/s10735-025-10522-3","url":null,"abstract":"<div><p>Monosodium glutamate (MSG) is a globally used food additive in the modern diet. This study aimed to search the impact of varying doses of MSG administered on embryonic development of the cerebellum. A total of 410 fertilized chicken eggs were randomly assigned to five groups: an untreated control group, a vehicle control group, and groups receiving low-dose (0.12 mg/g egg), medium-dose (0.6 mg/g egg), and high-dose (1.2 mg/g egg) MSG, respectively. The test solutions were injected into the yolk of eggs through a sterile insulin injector. On the 15th, 18th, and 21st days of incubation, the eggs from each group were randomly opened, and six live embryos were obtained. Cerebellum samples of embryos from each group were taken. The number of Purkinje cells in the cerebellum demonstrated a reduction in MSG-treated groups by the 15th, 18th, and 21st days of incubation (<i>p </i>&lt; 0.05). It was noted that the organization of Purkinje cells was irregular, and degeneration and necrosis were also observed in the MSG-treated groups. A notable decrease in the thickness of both the outer and inner granular layers was observed in the MSG-treated groups on the 15th, 18th, and 21st day of incubation. While molecular layer thickness increased on day 15 and 21, decreased on day 18 (<i>p</i> &lt; 0.05). Total cortex thickness decreased significantly in MSG-treated groups. PCNA-positive cells in the cerebellum were found in Purkinje cells, molecular layer cells, and outer and inner granular layer cells. However, there was a decrease in PCNA ( +) cell density in MSG-treated groups (<i>p</i> &lt; 0.05).</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688535","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":"Lagerstroemia Speciosa (L.) Pers mitigates acetaminophen-induced acute liver toxicity in rats through modulations of oxidative stress, inflammation, apoptosis and the NF-κB/TNF-α/iNOS, Nrf2/HO-1, signaling pathways","authors":"Nagham E. Elsheshtawy,&nbsp;Fatma M. Abdelhamid,&nbsp;Engy F. Risha,&nbsp;Hebatallah A. Mahgoub,&nbsp;Ahmed I. Ateya,&nbsp;Mohamed E. El-Boshy","doi":"10.1007/s10735-025-10493-5","DOIUrl":"10.1007/s10735-025-10493-5","url":null,"abstract":"<div><p>Acetaminophen (APAP) is a widely used analgesic and antipyretic, but its toxicity can lead to liver injury or failure. This study evaluated the hepatoprotective mechanisms of <i>L. speciosa</i> ethanolic leaf extract (LSE) against APAP-induced hepatic damage. Rats were randomly divided into five groups: Control (Cont), APAP (2 g/kg b.w. single oral dose on day 22), LSE (500 mg/kg b.w./day), APAP + LSE, and APAP + NAC (initial NAC dose of 100 mg/kg b.w. two hours post-APAP, followed by maintenance doses every 12 h). APAP-intoxicated rats showed leukocytosis, decreased erythrocyte count, Hb, and PCV, increased serum bilirubin, and elevated ALT, AST, and ALP activities. APAP intoxication also decreased plasma protein levels, albumin, and globulin while increasing liver MDA and depleting GSH. The expressions of hepatic SOD and CAT were reduced, while NF-κB, TNF-α, iNOS, Nrf2, and HO-1 were significantly upregulated. Also, APAP increased Bax and decreased Bcl-2. LSE improved most parameters, suppressing oxidative stress, inflammation, and apoptosis and regulating NF-κB, TNF-α, iNOS, Nrf2, HO-1, Bax, and Bcl-2 expression. Nevertheless, the deeper upstream molecular targets of LSE require further exploration. Its effects were comparable to NAC, with NAC showing slightly superior outcomes in some markers. Our findings suggest that LSE contains hepatoprotective phytochemicals capable of mitigating oxidative damage, inflammation, and apoptosis induced by APAP, supporting its potential as a natural alternative for managing drug-induced liver injury.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688537","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":"METTL14 induces ferroptosis to inhibit colorectal cancer progression by inhibiting TRIB3 via an m6A-YTHDF2-dependent manner","authors":"Daquan Zhang,&nbsp;Xiaoyu Liu,&nbsp;Binyu Luo,&nbsp;Xiao Zhang,&nbsp;Qing Teng,&nbsp;Xingmei Xia,&nbsp;Bin liao","doi":"10.1007/s10735-025-10496-2","DOIUrl":"10.1007/s10735-025-10496-2","url":null,"abstract":"<div><p>Ferroptosis, a form of regulated cell death caused by iron-dependent accumulation of lipid peroxides, is recently demonstrated as a vital player in cancer development. Tribbles homolog 3 (TRIB3) is a contributing factor to the malignant progression of several human cancers, including colorectal cancer (CRC). However, its regulatory effect and mechanism in CRC are obscure. qRT-PCR and western blot assays determined the mRNA and protein expression of TRIB3, methyltransferase-like 14 (METTL14), and YT521-B homology domain family 2 (YTHDF2). Cell ferroptosis was evaluated by measuring the levels of intracellular reactive oxygen species (ROS), lipid ROS, malondialdehyde (MDA), and glutathione (GSH). Cell malignant progression were assessed by CCK-8, EdU, transwell, and xenograft assays. The m6A sites of TRIB3 were confirmed using m6A RNA immunoprecipitation (Me-RIP) assay. The binding between TRIB3 and METTL14 or YTHDF2 was validated using RIP or luciferase reporter experiments. We observed higher expression of TRIB3 and lower expression of METTL14 in CRC tissues and cells. Knockdown of TRIB3 increased ferroptosis by promoting the generation of intracellular ROS, lipid ROS, and MDA and inhibiting the production of GSH. Suppressing TRIB3 also decreased tumor growth by increasing ferroptosis in mice. Mechanistically, knockdown of METTL14 reduced the m6A modification of TRIB3 and elevated TRIB3 mRNA expression. Moreover, METTL14-methylated TRIB3 was was recognized by YTHDF2, which resulted in the degradation of TRIB3 mRNA. TRIB3 overexpression reversed METTL14-mediated ferroptosis in CRC cells. Silencing YTHDF2 also abrogated the promotive effect of METTL14 on ferroptosis in CRC cells. Additionally, knockdown of TRIB3 induced ferroptosis by inactivating the SLC7A11/GPX4 signaling. METTL14 suppressed the SLC7A11/GPX4 signaling by targeting TRIB3. METTL14 suppressed CRC cell proliferation, migration, and invasion by downregulating TRIB3. Our findings suggest that METTL14 suppressed TRIB3 expression via an m6A-YTHDF2-dependent manner, thus inducing ferroptosis to inhibit the malignant progression of CRC. TRIB3 is potentially exploited as a molecular target for CRC treatment based on ferroptosis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681834","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":"Therapeutic effects of Euphorbia altissima on excisional wound model: role of apoptosis, oxidative stress, and inflammatory molecules","authors":"Hanan Ibrahim Althagbi,&nbsp;Khalid M. Alqaisi,&nbsp;Noralhuda Ayad Ibrahim,&nbsp;Parween Abdul-Samad Ismail,&nbsp;Ahmed A. J. Jabbar,&nbsp;Rawaz Rizgar Hassan,&nbsp;Muzhda Haydar Saber,&nbsp;Ahmed Hameed Al-Dabhawi,&nbsp;Goran Noori Saleh,&nbsp;Talal Salem Al-Qaisi","doi":"10.1007/s10735-025-10519-y","DOIUrl":"10.1007/s10735-025-10519-y","url":null,"abstract":"<div><p><i>Euphorbia</i> <i>Altissima</i> (<i>E.</i> <i>altissima)</i> is a traditional medicinal herb used for many inflammatory-related health disorders, including skin problems. The study estimates the phytochemicals, acute toxicity, and wound-healing action of methanolic extracts of <i>Euphorbia</i> <i>Altissima</i> (MEEA) in excisional rat models. Twenty-four Sprague Dawley rats were excised at their dorsal neck and were addressed with either positive control, intrasite gel, or MEEA (250 and 500 mg/kg) for a two-week trial. Phytochemical, histopathological, and immunohistochemical assays were employed to depict wound healing potentials. Phytochemical profiling showed the increased total phenolic (283.10 mg GAE/g) and flavonoid contents (211.5 mg rutin/g) in methanolic extracts of <i>E.</i> <i>altissima</i>. MEEA supplementation did not cause any observable toxic damage, with the absence of any morbidity or mortality in rats ingested with up to 5 g/kg. MEEA addressing resulted in the acceleration indicated by closer and smaller wounds in a dose-dependent manner compared to positive control rats. Histological analysis demonstrated fewer inflammatory cells, more fibroblasts, and higher collagen deposition in skin tissues treated with MEEA than in positive controls. MEEA addressing caused significant modulation of tissue immunohistochemical (decreased Bax and increased HSP 70) proteins and serum inflammatory (reduced TNF-α, IL-6, and magnified IL-10) chemicals, aiding in faster wound recovery. Moreover, hydroxyproline and endogenous antioxidants were higher, and MDA contents were lower in skin tissues addressed with MEEA. This study elucidates MEEA as an efficient wound healer, supporting its folkloric use and providing scientific evidence for future exploration, including molecular identification and isolation as viable sources of therapeutic formulation.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666806","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":"Epstein-Barr virus modulates iron metabolism and ferritin expression to promote tumorigenesis in gastric cancer","authors":"Xia Zhao,&nbsp;Duo Shi,&nbsp;Lingling Sun,&nbsp;Zhiyuan Gong,&nbsp;Wen Liu,&nbsp;Yan Zhang,&nbsp;Bing Luo","doi":"10.1007/s10735-025-10515-2","DOIUrl":"10.1007/s10735-025-10515-2","url":null,"abstract":"<div><p>Iron is crucial for cell survival and maintaining normal physiological functions. Viral infections can disrupt cellular iron metabolism, leading to inflammation and cancer. Ferritin, a key iron-binding protein, consists of ferritin heavy chain 1 (FTH1) and ferritin light chain (FTL) and helps regulate systemic iron balance, both implicated in various tumor developments. Epstein-Barr virus (EBV), the first oncogenic virus discovered in humans, can induce the development of EBV-associated gastric cancer (EBVaGC). However, the regulatory mechanisms and functions of FTH1 and FTL in EBVaGC are poorly understood. This study aimed to investigate how EBV regulates FTH1 and FTL and their roles in the development of EBVaGC. We show that EBV is able to remodel intracellular iron metabolism, affecting the expression of FTH1 and FTL. EBV-encoded LMP2A promotes the expression of FTH1 and FTL by up-regulating p62 and blocking the autophagy degradation pathway, thus participating in the occurrence and development of EBVaGC. Knocking down FTL inhibits cell migration and proliferation, and promotes apoptosis, whereas FTH1 knockdown has negligible effects on these cellular functions. Additionally, we found that ferritin enhanced the inflammatory state of gastric cancer cells. Overall, our findings highlight the significant impact of EBV on ferritin, underscoring a previously unrecognized role of ferritin in the progression of EBVaGC. This novel pathway could offer new therapeutic targets for the treatment of EBVaGC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658041","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":"Pannexin1 via P2rx7/amphiregulin contributes to cardiac fibrosis post myocardial infarction","authors":"Na Deng,&nbsp;Liwei You,&nbsp;Haijun Guo,&nbsp;Yingying Wei,&nbsp;Fujia Xu,&nbsp;Dandan Chen,&nbsp;Sihan Luo,&nbsp;Surong Huang,&nbsp;Siying Zuo,&nbsp;Wei Li,&nbsp;Xiaoyun Si","doi":"10.1007/s10735-025-10517-0","DOIUrl":"10.1007/s10735-025-10517-0","url":null,"abstract":"<div><p>The primary pathological mechanism underlying ventricular remodeling and cardiac dysfunction following myocardial infarction (MI) is predominantly mediated by cardiomyocyte apoptosis. Pannexin1 (PANX1) channels, which open during apoptosis, facilitate the release of ATP from dying cells. However, the functional significance of PANX1 in mediating cardiomyocyte apoptosis and its contribution to myocardial infarction progression remain to be fully elucidated. To investigate the regulatory role of PANX1 in cardiomyocyte apoptosis following MI and elucidate its underlying molecular mechanisms. We conducted both in vivo and vitro studies. In vivo, we observed a significant elevation of PANX1 expression levels in post-MI mice, which facilitated macrophage recruitment and subsequently triggered upregulation of amphiregulin(AREG). In vitro, HL-1 cells exposure to hypoxia/reoxygenation (H/R) induced apoptosis, accompanying with the upregulation of PANX1, enhanced extracellular ATP release. And these alterations promoted the recruitment of RAW264.7 cells, subsequently elevating AREG levels. These effects were mitigated by the knockdown of PANX1. To confirm PANX1’s role in MI hearts, AAV-9-PANX1-RNAi and negative control vectors were administered into the hearts of mice. Over 28 days post-MI, PANX1 knockdown significantly enhanced cardiac function and attenuated myocardial fibrosis. Our findings reveal that PANX1 plays a crucial role in facilitating a link between apoptotic cardiomyocyte and macrophage, contributing to modulate myocardial fibrosis and cardiac dysfunctional recovery post-MI via the AREG. Furthermore, the PANX1/P2rx7/AREG pathway is essential for facilitating a link between apoptotic cardiomyocytes and macrophages in mice following MI.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641366","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":"Does Moringa oleifera leaf extract protect the brain against 3-acetylpyridine-induced cerebellar ataxia in rat?","authors":"Doaa Mohamad Hassan,&nbsp;Nourhan Tharwat Sabra,&nbsp;Maha Eid Farghaly,&nbsp;Ahmed Yahia Sedeak","doi":"10.1007/s10735-025-10511-6","DOIUrl":"10.1007/s10735-025-10511-6","url":null,"abstract":"<div><p>There is no treatment for some neurological conditions, like cerebellar ataxia (CA). <i>Moringa Oleifera</i> (MO) has been revealed to have neuroprotective properties, but little is known about how it could protect against CA. In this study, we studied the neuroprotective effects of MO in an animal model of CA induced by 3-acetylpyridine (3-AP), which showed deficits in balance and motor coordination. Although cerebellar neuroinflammatory responses are evident in CA, it is yet unclear how neuroinflammation might influence CA. Here, we investigate whether MO, which has anti-inflammatory, antioxidant, and neuroprotective qualities, can help with cerebellar neurodegeneration and locomotor activity deficits. We divided 24 adult male rats into four equal groups. The control group received saline orally, the MO group received MO extract orally, the 3-AP group was injected with 3-AP, and the 3-AP + MO combined group received both 3-AP and MO for four weeks. The animals underwent a motor coordination test on the experiment’s first and last days. At the end of the experiment, the animals were euthanized, the cerebellums were dissected, and they were then subjected to standard biochemical, histological, and immunohistochemical studies. The combined group showed remarkable improvement in the CA. The cerebellar neurodegeneration and declination of locomotor activity had improved. Our findings imply that MO may protect against the CA degenerative condition and improve cerebellar function.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635861","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}