Folia histochemica et cytobiologica最新文献

{"title":"Nintedanib alleviates hyperoxia-induced lung injury via targeting NF-κB signalling pathway in rat model of bronchopulmonary dysplasia.","authors":"Rui Hao, Yuping Li, Junhui Li, Zirui Guo, Zhi Yang, Wei Lu","doi":"10.5603/fhc.105218","DOIUrl":"https://doi.org/10.5603/fhc.105218","url":null,"abstract":"<p><strong>Introduction: </strong>Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in premature infants. Hyperoxia is the main pathogenic factor of BPD. Nintedanib is a small-molecule tyrosine kinase inhibitor that has been confirmed to affect several cellular processes in different diseases. The aim of this study was to explore the function of nintedanib in the treatment of BPD.</p><p><strong>Material and methods: </strong>We used newborn Sprague-Dawley rats (postnatal day 1) to establish an in vivo BPD model by hyperoxia induction. Nintedanib was intraperitoneally injected into rats. Haematoxylin and eosin (H&E) staining was applied to detect lung injury in BPD rats. Cell apoptosis was determined by TUNEL (TdT-mediated dUTP nick end labelling) assay. Western blotting was applied to detect level changes of inflammatory factors IL-1β (interleukin-1 beta), CXCL-1 (C-X-C motif chemokine ligand 1), MCP-1 (monocyte chemotactic protein-1), as well as the phosphorylation of IkB (NF kappa B inhibitor) and NF-kB (nuclear factor kappa-B) in lung samples.</p><p><strong>Results: </strong>Hyperoxia resulted in lung injury in neonatal rats, while nintedanib treatment relieved the injury. Furthermore, nintedanib alleviated hyperoxia-induced apoptosis in rat lungs. We further observed that an inflammatory response caused by hyperoxia in lung samples was attenuated by nintedanib administration. Additionally, nintedanib inactivated the NF-κB pathway in BPD rats.</p><p><strong>Conclusions: </strong>Nintedanib alleviates hyperoxia-induced lung injury via targeting the NF-κB signalling pathway.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149442","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":"Mechanisms of alleviating sepsis-induced rat lung and kidney damage by inhibiting expression of miRNA-939.","authors":"Anwaier Apizi, Jian Li, Yan Li, Zhaoxia Yu, Ruifeng Chai","doi":"10.5603/fhc.101988","DOIUrl":"https://doi.org/10.5603/fhc.101988","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis, a life-threatening condition caused by a host response that goes out of control, leads to severe organ dysfunction. MicroRNA 939 (miRNA-939) plays a pivotal role in this process by post-transcriptionally regulating the mRNA expression of key enzymes in the NO/cGMP pathway. This pathway is crucial in the development of refractory hypotension and organ failure in sepsis. The aim of the study was to explore the effects of miRNA-939 on a caecum ligation puncture (CLP) rat model of sepsis in kidneys and lungs in order to elucidate its role in modulating the NO/cGMP pathway and related organ protection mechanisms.</p><p><strong>Material and methods: </strong>To explore the effects of miRNA-939 on sepsis, we established three groups of rats: a sham surgery group, a sepsis model group, and an intervention group treated with LNA-antimiR targeting miRNA-939, which was administered via tail vein injection (the locked nucleic acid (LNA) group). We assessed miRNA-939 levels in serum, kidneys and lungs using a reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase (sGC) were quantified using Western blotting. Serum nitric oxide (NO) levels were determined using the nitrate reductase method.</p><p><strong>Results: </strong>Compared to the sham group, the rats in the sepsis model group exhibited significantly elevated levels of miRNA-939 in serum, with distinct peaks at 12, 24, and 36 h post-sepsis induction. Similarly, the protein levels of iNOS and sGC (sGCα1 and sGCβ1 subunits) in kidneys and lungs were markedly higher in the sepsis group. Serum NO levels were also significantly elevated in the sepsis group compared to the sham group. Importantly, inhibition of miRNA-939 in the LNA group led to a significant reduction in the tissue levels of iNOS, sGCα1, sGCβ1, and serum NO within the NO/cGMP pathway, alongside mitigating inflammatory damage to kidneys and lungs.</p><p><strong>Conclusions: </strong>Inhibiting miRNA-939 significantly reduces the expression of iNOS, sGCα1, sGCβ1, and NO in the NO/cGMP pathway in CLP-exposed rats, thereby alleviating inflammatory organ damage in sepsis. These findings highlight the therapeutic potential of targeting miRNA-939 in the management of sepsis-induced organ dysfunction.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150002","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":"Upregulation of SIRT1 ameliorates apoptosis of rat nucleus pulposus cells under oxidative stress through FoxO1/β-catenin pathway.","authors":"Hongtao Hu, Sheng Wang, Haijun Teng, Sishun Zhao, Weisheng Hong","doi":"10.5603/fhc.104395","DOIUrl":"https://doi.org/10.5603/fhc.104395","url":null,"abstract":"<p><strong>Introduction: </strong>Age-related degenerative changes in intervertebral discs (IVDs) can lead to lower back pain, and even paralysis. This topic is therefore garnering growing attention in an increasingly ageing society. The oxidative stress-induced degenerative process is a major contributor to apoptosis in nucleus pulposus cells. However, the regulatory mechanism of NAD-dependent protein deacetylase Sirtuin-1 (SIRT1) on apoptosis in oxidative stress-induced rat nucleus pulposus cells remains unclear.</p><p><strong>Material and methods: </strong>Rat nucleus pulposus cells (NPCs) were induced to undergo degenerative changes through H₂O₂ exposure, simulating the ageing oxidative stress process. Subsequently, the SIRT1 activator SRT2104 was employed to explore the impact of SIRT1 on the expression of markers of ageing oxidative stress process in NPCs. The FoxO1 inhibitor AS1842856 was used to investigate the role of the downstream signalling pathway FoxO1/β-catenin in ageing NPCs under the influence of SRT2104. TUNEL staining and other assays such as CCK were used to observe the effects of H₂O₂ on cell apoptosis and viability, respectively. The influence of the aforementioned treatments on the ageing phenotype was observed through β-galactosidase staining, immunofluorescence staining, flow cytometry analysis, and protein electrophoresis.</p><p><strong>Results: </strong>Under H₂O₂-induced oxidative stress, both the mRNA and protein levels of SIRT1 decreased in rat NPCs. Conversely, specific activation of SIRT1 inhibited apoptosis and reduced the expression of senescence-associated secretoryphenotype (SASP) and ageing-related proteins. Meanwhile, inhibiting FoxO1 expression with AS1842856 significantly upregulated β-catenin protein levels, suppressing the apoptosis process in ageing NPCs under oxidative stress.</p><p><strong>Conclusions: </strong>These results suggest that activation of the SIRT1/FoxO1/β-Catenin axis can diminish ageing-related phenotypes and cell apoptosis in NPCs, inhibiting the oxidative stress-induced ageing process triggered by H₂O₂. These findings may offer a new perspective for the treatment of intervertebral disc degeneration (IDD) in the future.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149835","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":"MiR-494-3p knockdown promotes osteogenic differentiation of bone marrow mesenchymal stem cells in ovariectomised rats by targeting Sirt1/TLR4/NF-κB pathway.","authors":"Jianping Lei, Song Guo, Jiabing Kuang, Bo Shen, Zixi Li","doi":"10.5603/fhc.104450","DOIUrl":"https://doi.org/10.5603/fhc.104450","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoporosis is a bone disease characterised by low bone mass, deterioration of bone tissue, and disruption of bone microarchitecture. MicroRNAs have been found to play an important role in osteoporosis. MicroRNA (miR)-494 is inhibited during bone angiogenesis, and its overexpression reduces osteogenic differentiation gene expression. Sirtuin 1 (Sirt1) is a histone deacetylase with multiple cellular activities including increasing bone mass and delaying the onset of osteoporosis. MiR-494-3p has been predicted in computer-assisted bioinformatics analysis to target the 3'UTR of Sirt1 mRNA. The aim of the present study was to assess the effect of miR-494-3p on ovariectomy (OVX)-induced osteoporosis in rats and the relevant mechanisms.</p><p><strong>Material and methods: </strong>Osteoporosis in female rats was induced by OVX, and bone microarchitectural changes were evaluated by means of microCT. MiR-494-3p and Sirt1 expression in femurs were evaluated by RT-qPCR or Western blotting. Bone marrow mesenchymal stem cells (BMSCs) were isolated from rat femurs and identified by flow cytometry. Then, BMSCs were transfected with miR-494-3p inhibitor/mimic, si-Sirt1 and negative controls as well as pcDNA3.1-TLR4 and empty pcDNA3.1 vector. Osteogenic cell differentiation was assessed via Alizarin Red, alkaline phosphatase (ALP) and Oil Red O staining.</p><p><strong>Results: </strong>. MiR-494-3p level was upregulated, and Sirt1 mRNA and protein levels were downregulated, in femurs of OVX rats. Functionally, miR-494-3p inhibited osteogenic differentiation of cultured rat BMSCs. Mechanistically, miR-494-3p regulated the Sirt1 3'UTR to activate TLR4/NF-κB signalling, and Sirt1 inhibition and TLR4 overexpression reversed the enhancing effect of miR-494-3p knockdown on osteogenic differentiation.</p><p><strong>Conclusions: </strong>. MiR-494-3p represses osteogenic differentiation of BMSCs in OVX rats through Sirt1/TLR4/NF-κB signalling.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149953","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 STAT1 alleviates oxidative damage in retinal pigment epithelial cells and exhibits neuroprotective effects in autoimmune optic neuritis by upregulating IFI30 lysosomal thiol reductase.","authors":"Siqi Ma, Jiajia Yuan","doi":"10.5603/fhc.104300","DOIUrl":"10.5603/fhc.104300","url":null,"abstract":"<p><strong>Introduction: </strong>Oxidative damage-induced retinal pigment epithelial (RPE) cell apoptosis and optic nerve inflammation and demyelination are closely related to the pathogenesis of optic neuritis (ON). STAT1 has been found to be activated in the retina and optic nerve of ON rats. This study aimed to determine whether STAT1 depletion exerts neuroprotective effects against ON in both cellular and animal models.</p><p><strong>Material and methods: </strong>ARPE-19 cells were stimulated by H₂O₂ to induce oxidative stress, followed by STAT1 and IFI30 silencing. CCK-8 and flow cytometry assays assessed ARPE-19 cell viability and apoptosis. RT-qPCR, Western blotting, DCFH-DA staining, and commercial kits detected the levels of STAT1, IFI30, apoptosis markers, and antioxidant/oxidative markers. CHIP and luciferase reporter assays validated the binding between STAT1 and IFI30 promoter. Female C57BL/6 mice were immunised with myelin oligodendrocyte glycoprotein (MOG) peptide (MOG35-55) to induce experimental autoimmune encephalomyelitis, an animal model of ON. Optic nerve inflammation, demyelination, axonal loss, and retinal ganglion cell (RGC) apoptosis in encephalomyelitis (EAE) mice after STAT1 knockdown were evaluated via haematoxylin and eosin, luxol fast blue, immunofluorescence, and Brn3a-TUNEL double staining.</p><p><strong>Results: </strong>STAT1 silencing reversed the H₂O₂-induced increase of cell apoptosis and oxidative stress and the decrease in cell viability in ARPE-19 cells. STAT1 bound with the IFI30 promoter region and negatively regulated its expression. IFI30 knockdown antagonised the protection of STAT1 silencing against H₂O₂-induced oxidative stress and apoptosis in ARPE-19 cells. STAT1 depletion alleviated optic nerve inflammation, demyelination, axonal loss, and RGC apoptosis in EAE mice.</p><p><strong>Conclusions: </strong>STAT1 silencing exhibits neuroprotective effects against ON by upregulating IFI30.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"11-27"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729647","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":"Expression of O-GlcNAcylation in pulp tissue and dental pulp stem cells of healthy dental organs.","authors":"María Cristina Franco-Arellanes, Perla Xóchitl Toledo-Valdes, Cynthia Díaz-Hernández, Risk Díaz-Castillejos, Eunice Daysi García-Reyes, Saira Karina Ramírez-Thomé, Beatriz Xóchitl Ávila-Curiel, María Cristina Castañeda-Patlán, Edgar Zenteno, Carlos Josué Solórzano-Mata","doi":"10.5603/fhc.103756","DOIUrl":"10.5603/fhc.103756","url":null,"abstract":"<p><strong>Introduction: </strong>O-GlcNAcylation is a post-translational modification in which a single N-Acetyl-D-Glucosamine (GlcNAc) molecule is added to Ser or Thr residues of proteins. The O-N-acetylglucosaminyl transferase (OGT) enzyme is responsible for adding GlcNAc to the target proteins and N-acetyl-β-D-glucosaminidase (OGA) that removes the GlcNAc residue. O-GlcNAcylation has been described in the pathophysiology of several diseases; however, little has been studied in dental tissue. The aim of the present work is to characterise the product of O-GlcNAcylation and its enzymes at the tissue level in the dental pulp, as well as its expression in dental pulp stem cells (DPSCs) both in situ and in vitro. This enables the recognition of the behaviour of O-GlcNAcylation in pulp tissue without pathology.</p><p><strong>Material and methods: </strong>Pulp tissue was obtained from 10 healthy donors, and the expression of O-GlcNAc, OGT, and OGA was analysed using immunofluorescence with specific antibodies in different regions of the dental pulp. DPSCs were isolated, cultured, and identified with anti-STRO1 (antibody specific for human CD34+ cells, useful for DPSC identification). The expression of O-GlcNAc in DPSCs was confirmed in vitro through Western blot.</p><p><strong>Results: </strong>Different regions of the dental pulp and DPSCs express O-GlcNAc and the enzymes OGT and OGA. O-GlcNAc and OGT expression was more prominent in the odontoblastic layer, cell-rich zone, and in the central core. OGA was distributed throughout the pulp tissue with lower immunoreactivity compared to OGT.</p><p><strong>Conclusions: </strong>Our results suggest that O-GlcNAcylation may play a relevant role in human dental pulp homeostasis and in physiology of DPSCs.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729645","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":"Enhanced migration and adhesion protein expression by polyethylene glycol 4-modified SVVYGLR peptide in an in vitro human gingival fibroblast wound healing model.","authors":"Peiying Xiong, Chengcheng Yu, Zhihui Chen, Luyuan Chen, Yonglong Hong, Buling Wu","doi":"10.5603/fhc.104010","DOIUrl":"https://doi.org/10.5603/fhc.104010","url":null,"abstract":"<p><strong>Introduction: </strong>This study was aimed at exploring the effect of four units of polyethylene glycol (PEG4)-modified Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR) peptide (SV peptide) on the proliferative potential and migrative capability of human gingival fibroblasts (HGFs) and the activation of adhesion-related proteins.</p><p><strong>Material and methods: </strong>PEG4-SV peptide was synthesised using peptide solid phase synthesis. The proliferative response of HGFs to varying concentrations of PEG4-SV peptide was quantitatively evaluated using a Cell Counting Kit-8 (CCK-8) assay. The migratory capacity of HGFs in response to PEG4-SV peptide treatment was evaluated using an in vitro wound healing assay. The expression levels of adhesion-related genes, including collagen type I (COL-1), vinculin (VCL), focal adhesion kinase (FAK), and integrin β1(ITGB1), were quantitatively analysed using qRT-PCR. To assess the aforementioned adhesion-related proteins, immunofluorescence and Western blotting were performed.</p><p><strong>Results: </strong>Primary HGFs were isolated through enzymatic digestion using dispase, and subsequently characterised by positive immunoreactivity for both vimentin and CD90 (Thy-1) markers. Compared to the control group, PEG4-SV at concentrations of 10, 20, and 40 μg/mL significantly promoted the proliferation of HGFs. The wound area in the SV group exhibited a significantly smaller size in the monolayer cell culture at 24 and 48 h. The expression of adhesion-related genes and proteins (collagen type I, vinculin, FAK and integrin β1), were significantly upregulated after treatment with 20 μg/mL PEG4-SV.</p><p><strong>Conclusions: </strong>These results demonstrate that PEG4-SV peptide may have the ability to promote soft tissue healing around an implant surface and form tight soft tissue sealing on the transmucosal part of the implant.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"63 1","pages":"41-50"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149789","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":"Electroacupuncture stimulation inhibited astrogliosis and microglia polarisation to alleviate spinal cord injury via Janus kinase 2/signal transducer and activator of transcription 3 signalling pathway.","authors":"Jianuo Li, Yuhuai Guo, Xiangxin Zeng, Hongzhao Tian, Yapeng Han, Shuo Cai, Min Sun","doi":"10.5603/fhc.104273","DOIUrl":"https://doi.org/10.5603/fhc.104273","url":null,"abstract":"<p><strong>Introduction: </strong>The aberrant activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway is involved in spinal cord injury (SCI) progression. Electroacupuncture (EA) stimulation is effective in alleviating SCI, but the mechanism is poorly understood.</p><p><strong>Material and methods: </strong>An SCI model was constructed by cord contusion at T10, and AG490 (a JAK2 inhibitor) served as a positive control in this study. We evaluated the effects of EA on locomotor activity and spinal damage in SCI rats. The effects of EA on astrocytes and microglia and on the JAK2/STAT3 signalling pathway in the cells were investigated.</p><p><strong>Results: </strong>Behavioural tests showed that hind limb motor function of rats was improved after EA stimulation. The therapeutic effects of EA stimulation in restoring motor function, alleviating injured spinal cords, and inhibiting spinal cord neuronal apoptosis in SCI rats, were similar to those of AG490. Increased STAT3 activation was observed in astrocytes and microglia in the spinal cord of SCI rats, and this was reversed by EA stimulation. EA alleviated astrogliosis and inhibited microglia M1 polarisation in SCI rat spinal cords. In addition, RNA expression levels of pro-inflammatory factors IL-6, CXCL1, and TNF-α in rat spinal cords were suppressed by EA stimulation, while the expression level of the anti-inflammatory factor heme oxygenase 1 was increased. Meanwhile, the expression of p-JAK2, p-STAT3, and JAK2/STAT3 downstream targets SOCS3 and COX-2 in the spinal cord of SCI rats was inhibited by EA stimulation. Interestingly, the observed effects were comparable to those treated with EA.</p><p><strong>Conclusions: </strong>Our findings demonstrate that EA stimulation ameliorates SCI in rats and exerts an inhibitory effect on the JAK2/STAT3 signalling pathway.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"63 1","pages":"28-40"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149840","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":"Nootkatone mitigates periodontal inflammation and reduces alveolar bone loss via Nrf2/HO-1 and NF-κB pathways in rat model of periodontitis.","authors":"Ye Yin, Zeyu Ma, Peiliang Shi","doi":"10.5603/fhc.101862","DOIUrl":"10.5603/fhc.101862","url":null,"abstract":"<p><strong>Introduction: </strong>Periodontitis (PD) is a chronic inflammatory disease leading to alveolar bone loss. This study investigated the effect of nootkatone and regulatory mechanism in reducing periodontal inflammation and alveolar bone loss in a rat model.</p><p><strong>Material and methods: </strong>Twenty male Sprague-Dawley rats were divided into control, periodontitis, and nootkatone-treated groups (45 or 90 mg/kg). Ligature induction method was adopted to establish the PD model. After 21 days, rats received daily gavage of either saline or nootkatone for 10 days. Alveolar bone loss was assessed using micro-CT. Histological analyses included hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Masson's trichrome stainings. Immunohistochemistry for heme oxygenase 1 (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2) were performed in periodontal tissues. Content of inflammatory cytokines IL-1β, IL-6, and TNF-α in gingival tissues around ligature were assessed using ELISA kits. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were analyzed and Western blot for NF-κB expression in gingival tissues were performed.</p><p><strong>Results: </strong>Nootkatone significantly reduced the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC), enhanced bone mineral density (BMD), bone volume (BV), and BV/total volume (TV) ratio in ligature-induced rats. Higher dose of nootkatone (90 mg/kg) did not show more significant therapeutic effect than lower dose (45 mg/kg). Histological staining showed decreased osteoclasts' number and improved bone architecture in the nootkatone group. Content of IL-1β, IL-6, and TNF-α and inflammatory cell infiltration level in gingival tissues around the ligature were decreased in the nootkatone-treatment rats. Nootkatone increased Nrf2 and HO-1 protein expression and decreased NF-κB protein level, suppressing MDA levels and enhancing SOD activity.</p><p><strong>Conclusions: </strong>In a rat model, nootkatone effectively mitigates periodontal inflammation and alveolar bone loss through the Nrf2/HO-1 and NF-κB pathways. These findings suggest nootkatone as a promising therapeutic agent for the treatment of periodontitis.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"145-153"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079880","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":"CCL19 promotes TNF-alpha/IFN-gamma-induced production of cytokines by targeting CCR7/NF-κB signalling in HaCaT cells.","authors":"Ying Zeng, Xiaoqi Nie, Yunhua Deng","doi":"10.5603/fhc.104038","DOIUrl":"https://doi.org/10.5603/fhc.104038","url":null,"abstract":"<p><strong>Introduction: </strong>Atopic dermatitis (AD) is the most common allergic skin disease. The dysfunction of keratinocytes is closely associated with AD progression. Nevertheless, the specific functions of CC chemokine ligand 19 (CCL19) and its receptor CC chemokine receptor 7 (CCR7) in human HaCaT keratinocytes are still unclear.</p><p><strong>Material and methods: </strong>AD cell models in vitro were established by treating HaCaT cells with TNF-alpha (TNF-α, 10 ng/mL) and IFN-gamma (IFN-γ, 10 ng/mL). Cell viability was estimated by MTT assay. The protein levels of CCL19 and CCR7 were tested via Western blotting. The expression of CCL19 protein was knocked down by transfecting si-CCL19 into HaCaT cells. The contents of inflammatory factors i.e. thymus and activation-regulated chemokine (TARC), interleukin 6 (IL-6), and prostaglandin E2 were measured by ELISA, and the nitric oxide content was detected by Griess reagent. The protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were tested via Western blotting.</p><p><strong>Results: </strong>TNF-α and IFN-γ induced cytotoxicity and upregulated the expression of CCL19 and CCR7 in HaCaT cells. CCL19 knockdown alleviated cytokines-induced cytotoxicity and the release of TARC, IL-6, PGE2 and nitric oxide in TNF-α + IFN-γ-treated HaCaT cells. Furthermore, the protein levels of iNOS and COX-2 were also repressed by CCL19 knockdown. In addition, knockdown of CCL19 decreased CCR7 protein content and inhibited the phosphorylation of IκBα and p65, implying that knockdown of CCL19 inactivated CCR7/NF-κB signalling in HaCaT cells. Rescue assays validated that CCR7 overexpression reversed the effects of CCL19 silencing on the viability and levels of inflammatory factors in TNF-α + IFN-γ-induced HaCaT cells.</p><p><strong>Conclusions: </strong>This study proves that CCL19 can promote TNF-α + IFN-γ-induced skin inflammatory responses by targeting CCR7/NF-κB pathway in HaCaT cells.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":"62 4","pages":"203-211"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381987","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}