Tissue & cell最新文献

{"title":"Resolvin D5: A lipid mediator with a therapeutic effect on hepatic steatosis through SIRT6/autophagy","authors":"Do Su Lim ,&nbsp;Sung Ho Ahn ,&nbsp;Hyeon Ji Gwon ,&nbsp;Wonjun Cho ,&nbsp;A.M. Abd El-Aty ,&nbsp;Haci Ahmet Aydemir ,&nbsp;Naveen Sharma ,&nbsp;Soon Auck Hong ,&nbsp;Tae Woo Jung ,&nbsp;Ji Hoon Jeong","doi":"10.1016/j.tice.2025.102980","DOIUrl":"10.1016/j.tice.2025.102980","url":null,"abstract":"<div><div>Resolvin D5 (RD5), a lipid mediator derived from DHA <em>via</em> 5-lipoxygenase signaling, has been shown to resolve inflammation in various disease models. This study aimed to investigate the role of RD5 in the development of hepatic steatosis in individuals with obesity and explore the detailed mechanisms involved. Protein expression was evaluated <em>via</em> Western blot analysis, whereas hepatic lipid deposition was examined <em>via</em> Oil Red O staining and triglyceride quantification. Autophagosomes were detected <em>via</em> MDC staining. Our findings indicated that RD5 treatment normalized lipogenic lipid accumulation, fatty acid uptake, oxidation, apoptosis, and endoplasmic reticulum (ER) stress in palmitate-treated primary hepatocytes. As a cytoprotective signaling pathway, RD5 treatment increased the expression of SIRT6 and autophagy markers, such as those involved in LC3 conversion and p62 degradation. The beneficial effects of RD5 on hepatic lipid metabolism, apoptosis, and ER stress were negated by SIRT6 small interfering RNA or 3-methyladenine, an inhibitor of autophagy. Furthermore, RD5 administration decreased hepatic steatosis, apoptosis, and ER stress in the livers of high-fat diet (HFD)-fed mice. In line with the <em>in vitro</em> results, RD5 treatment elevated SIRT6 and autophagy levels in the livers of HFD-fed mice. These novel findings suggest that RD5 improves hepatic lipid metabolism, apoptosis and ER stress through SIRT6/autophagy signaling, thereby attenuating hepatic steatosis. RD5 may have therapeutic potential for treating nonalcoholic fatty liver disease with minimal side effects.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102980"},"PeriodicalIF":2.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099102","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":"Autophagic impairment in endometrial polyps: A potential biomarker and therapeutic target","authors":"Burak Sezgi̇n ,&nbsp;Tuba Edgünlü ,&nbsp;Özgür ilhan Çeli̇k ,&nbsp;Nazlı Can ,&nbsp;Ayşegül Demirtaş Bi̇lgi̇ç","doi":"10.1016/j.tice.2025.102978","DOIUrl":"10.1016/j.tice.2025.102978","url":null,"abstract":"<div><div>Endometrial polyps are a common gynecological condition associated with abnormal uterine bleeding, infertility, and potential malignancies. This study investigated the expression of key autophagy proteins LC3A/B, p62, and Beclin-1 in endometrial polyps. Twenty patients with endometrial polyps and ten healthy controls were enrolled in a prospective randomized controlled trial. Tissue samples were collected via operative hysteroscopy. ELISA and immunohistochemistry were employed to assess the expression of LC3A/B, p62, and Beclin-1. While ELISA results did not reveal significant differences between the two groups, immunohistochemical analysis demonstrated significantly lower levels of LC3A/B, p62, and Beclin-1 in endometrial polyps compared to healthy endometrial tissue (p = 0.041, p = 0.012, and p = 0.003, respectively). These findings suggest that impaired autophagy, as evidenced by reduced levels of these key autophagy proteins, may contribute to the pathogenesis of endometrial polyps. Further research is needed to elucidate the precise mechanisms underlying this association and to explore potential therapeutic implications.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102978"},"PeriodicalIF":2.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123494","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":"Hormonal control of the asymmetric uterus of the bat Molossus molossus during pregnancy and lactation: Emphasis on progesterone and estradiol","authors":"Juliana F. Ferraz ,&nbsp;Rodrigo S. de Oliveira ,&nbsp;Cornélio S. Santiago ,&nbsp;Emília M. Soares ,&nbsp;Rejane M. Góes ,&nbsp;Eliana Morielle-Versute ,&nbsp;Sebastião R. Taboga ,&nbsp;Mateus R. Beguelini","doi":"10.1016/j.tice.2025.102974","DOIUrl":"10.1016/j.tice.2025.102974","url":null,"abstract":"<div><div><em>Molossus molossus</em> is an important species of Neotropical insectivorous bat of the family Molossidae. Despite its wide distribution, representativeness, and ecological importance, there are no detailed studies regarding the hormonal control of the female reproductive organs of this species, which presents accentuated morphofunctional asymmetry, with dextro-dominance. Thus, the present study aimed to evaluate the variations in hormone serum levels and in uterine hormonal control of <em>M. molossus</em> during its different reproductive phases, with an emphasis on estradiol and progesterone. Twenty sexually adult females were divided into four sample groups according to the reproductive status — non-reproductive, early pregnancy, late pregnancy and lactating — and subjected to histological, hormonal, and immunohistochemical analysis. The results showed that the uterine dextro-dominance asymmetry of <em>M. molossus</em> is strongly regulated and maintained by the interaction/cross-talk between estradiol and progesterone serum levels with their respective uterine receptors. The right uterine horn presents significantly higher estrogen receptor α and progesterone receptor expression and also greater proliferative activity in the endometrium than the left horn, which favors embryo implantation and development. Significant increases in the estradiol and progesterone serum levels are needed to regulate early pregnancy. The rapid formation of the diffuse portion of the placenta is essential to sustain the high demand for progesterone at the beginning of pregnancy, while the principal portion is not yet formed. Estrogen receptor α and progesterone receptor expression appear to be synchronized to coordinate most of the processes that occur within the uterus of <em>M. molossus</em> throughout the reproductive cycle.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102974"},"PeriodicalIF":2.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071032","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":"Hedera helix folium extract attenuates methotrexate-induced hepatotoxicity by modulating oxidative stress and inflammatory mediators","authors":"Esra Deniz ,&nbsp;Atilla Topcu ,&nbsp;Aykut Ozturk ,&nbsp;Seda Duman Ozturk ,&nbsp;Kerimali Akyildiz","doi":"10.1016/j.tice.2025.102967","DOIUrl":"10.1016/j.tice.2025.102967","url":null,"abstract":"<div><div>Methotrexate (MTX)-induced hepatotoxicity is linked to oxidative damage and inflammatory processes. <em>Hedera helix folium</em> (HHF) extract protects cells against oxidative damage. We investigated the role of HHF extract in tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10)-associated inflammation and oxidative stress in the pathology of MTX-associated liver injury in rats. Forty male rats were divided into one of five equal groups: Control, HHF, MTX, H₁₀₀+MTX and H₂₀₀+MTX. HHF extract was administered via the oral route at 100 mg/kg or 200 mg/kg once daily for seven days, while MTX was administered as a single dose of 20 mg/kg intraperitoneally. Intracardiac blood samples and liver tissue samples were collected at the conclusion of the experiment. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased due to MTX. Increased ALT levels were significantly reduced by low-dose HHF and increased AST levels were significantly reduced by high-dose HHF administration. The application of MTX significantly increased malondialdehyde (MDA) and TNF-α levels, while significantly reducing those of glutathione (GSH) and IL-10. High-dose HHF also significantly lowered MDA and TNF-α levels, while significantly increasing those of GSH and IL-10<em>.</em> Histopathological damage findings observed due to MTX were significantly attenuated with high-dose HHF. In addition, the increased caspase-3, p53, and Bcl2 levels caused by MTX decreased with high-dose HHF administration. HHF extract can alleviate liver damage induced by MTX. This extract, which has the ability to reduce damage due to oxidative stress and inflammation, may represent an alternative approach to preventing MTX-induced liver damage.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102967"},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099103","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":"Dorso-ventral skin of flowered racer snake (coluber flourulentus, perreti schatti, 1988): Histological, Keratin immunohistochemical, and ultrastructural characterization","authors":"Ramadan Kandyel ,&nbsp;Saeed Alasmari ,&nbsp;Salem Alharethi ,&nbsp;Bader Albogami ,&nbsp;Abdulrhman Almadiy ,&nbsp;Doaa Gewily ,&nbsp;Fatma A. Madkour ,&nbsp;Mohamed Abumandour","doi":"10.1016/j.tice.2025.102966","DOIUrl":"10.1016/j.tice.2025.102966","url":null,"abstract":"<div><div>Our study, using SEM and histology, aims to characterize the dorsal and ventral skin of <em>Coluber flourulentus</em>, providing new insights into their Keratin immunohistochemical features. The SEM findings revealed overlapping smooth scales on both surfaces, with minor scale morphology variations; the dorsal scales were finger-shaped with a pointed apex, while the ventral scales were flattened with tooth-like edges. Scales on both surfaces reveal two large, spherical-shaped lenticular sensory organs at their apex, dome-shaped receptors/sensilla on the outer surface, and dome-shaped sensilla with dendrites, a transverse cleft, and various pits and pores. Histologically, the micro-ornamentations on the inner-scale surfaces of both surfaces had similar structures with smooth, spiny scales and two layers. The epidermis layer had several layers, including the basal stratum germinativum, α-keratin, the Mesos layer, the β-layer, and the covered Oberhautchen layer. Skin pigmentation varied between both surfaces: the dorsal dermal layer contains melanophores and iridophores, and the ventral dermal layer contains only dark black melanophores under the epidermal layer. Histochemical collagen fiber observations revealed blue-colored fibers in the dermis of dorsal and ventral surfaces, sparse underneath the basement membrane, and visible around pigment cells and muscle bundles. A dark brown reaction was observed in the epidermal cells of both dorsal and ventral surfaces, with high cytokeratin immunolabeling on the ventral surface and moderate cytokeratin immunoreaction on the dorsal surface. In conclusion, scales were crucial for controlling movements and responding to vibrational stimuli from object movements, including those of potential prey or predators.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102966"},"PeriodicalIF":2.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107089","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":"IL-37 improves palmitic acid-induced lipid deposition in liver cells by inhibiting ferroptosis to regulate macrophage polarization","authors":"Longqi Zhang,&nbsp;Xinyu Liu","doi":"10.1016/j.tice.2025.102977","DOIUrl":"10.1016/j.tice.2025.102977","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD), which acts as a predominant contributor to chronic liver disease, remains a pervasive global epidemic. Interleukin-37（IL-37） is documented to have protective effects against various liver diseases. This work focuses on investigating the role and relevant action mechanism of IL-37 in NAFLD. Immunofluorescence assay and Western blot（WB）were used to estimate M1 macrophage markers. For immunofluorescence analysis, images from five randomly selected fields per sample were captured using a confocal microscope (Leica). Fluorescence intensity was quantified by ImageJ software (version 1.53) with background subtraction, and data were normalized to DAPI-positive cells.The lipid Reactive Oxygen Species（ROS）and cell lipid droplet deposition were assessed via BODIPY 581/591 C11 staining and Oil Red O staining. Fe^2 +, triglycerides and cholesterol levels were assessed utilizing appropriate assay kits. WB was adopted for the estimation of proteins associated with ferroptosis and apoptosis. Protein band intensities were quantified using Image Lab software (Bio-Rad) and normalized to β-actin expression. Three technical replicates were analyzed for each biological replicate (n = 3). Our data revealed that IL-37 alleviated PA-stimulated（Palmitic acid-stimulaed）M1 macrophage polarization. It was also identified that IL-37 suppressed lipid accumulation and apoptosis in RAW264.7 cells through inhibiting the polarization of M1 macrophages. Collectively, IL-37 could improve PA-stimulated lipid accumulation and apoptosis in liver cells through suppressing M1 macrophage polarization, which might be mediated by ferroptosis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102977"},"PeriodicalIF":2.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071030","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":"PADI1 aggravates endoplasmic reticulum stress in trophoblast cells by inhibiting the FAK-ERK signaling pathway","authors":"Jianhua Ning ,&nbsp;Songbin Yang ,&nbsp;Fengchun Gao ,&nbsp;Longbin Wang ,&nbsp;Zeyu Lin ,&nbsp;Di Cheng ,&nbsp;Kefeng Fan","doi":"10.1016/j.tice.2025.102976","DOIUrl":"10.1016/j.tice.2025.102976","url":null,"abstract":"<div><div>Preeclampsia (PE) is a multisystemic syndrome of pregnancy that seriously affects maternal and infant healthcare. Here, we identified PADI1 as an abnormally highly expressed gene in PE and investigated its effect on trophoblast cells. According to the analysis results from GEO datasets GSE186257 and GSE143953, PADI1 is highly expressed in the placental samples of PE patients. PADI1 knockdown promoted the growth and migration of trophoblast cells. HTR-8 and Swan-71 cells were treated with 200 nmol/L TG to simulate ERS in vitro. PADI1 knockdown inhibited TG-induced ERS and apoptosis. Mechanistically, PADI1 knockdown downregulated ERS-related factors including IRE1α, XBP1, CHOP, ATF6 and GRP78. The FAK/ERK1/2 signaling pathway has been identified as a downstream target of PADI1 in trophoblast cells. Inhibition of FAK/ERK1/2 effectively hindered the enhancement of cell activity by PADI1 knockdown in TG-treated trophoblast cells. In conclusion, PADI1 was highly expressed in the placental tissues of PE patients. PADI1 knockdown inhibited the ERS-induced apoptosis in trophoblast cells through FAK/ERK1/2 signaling pathway, suggesting the potential role of PADI1 in PE prevention and treatment.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102976"},"PeriodicalIF":2.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135100","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":"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}