Journal of Molecular Histology最新文献

{"title":"High expression of HM13 correlates with poor prognosis in hepatocellular carcinoma","authors":"Lili Yan,&nbsp;Zhihui Tan,&nbsp;Ji Lv,&nbsp;Hongyu Jia,&nbsp;Shanshan Li,&nbsp;Tao Wang,&nbsp;Yanan Du,&nbsp;Haiyang Song,&nbsp;Jiewei Sun,&nbsp;Wenjin Jiang,&nbsp;Zhiying Xu,&nbsp;Meimei Xu","doi":"10.1007/s10735-024-10241-1","DOIUrl":"10.1007/s10735-024-10241-1","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) has a high mortality rate, and the identification of early prognostic markers is crucial for improving patient outcomes. This study aimed to investigate the correlation between the expression of Histocompatibility Minor 13 (HM13) and the prognosis of HCC patients. HM13 protein expression was assessed in HCC tissues and cells through immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and western blot. The relationship between <i>HM13</i> expression and clinicopathological data of HCC was evaluated. Bioinformatics analyses, including Gene Expression Omnibus (GEO) database, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter (K-M plotter), were employed to analyze HM13 expression and its association with patient survival. <i>HM13</i> was significantly overexpressed in HCC tissues and cells compared to normal controls. IHC revealed that HM13 protein was primarily localized in the cytoplasm and highly expressed in HCC tissues. Interestingly, patients with high <i>HM13</i> expression had significantly poorer overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS) than those with low expression. <i>HM13</i> expression was associated with Edmondson grade, metastasis, microvascular invasion, and alpha-fetoprotein (AFP) levels. Multivariate analysis identified HM13 as an independent prognostic factor for poor OS in HCC. <i>HM13</i> was markedly overexpressed in HCC and correlated with poor prognosis, suggesting its potential as a promising biomarker for early prognostic detection in HCC patients.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003310","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":"Dendrobine alleviates oleic acid-induced lipid accumulation by inhibiting FOS/METTL14 pathway","authors":"Junpei Zhang,&nbsp;Hongyun Zhang,&nbsp;Ying Chen,&nbsp;Shiyao Chen,&nbsp;Hailing Liu","doi":"10.1007/s10735-024-10246-w","DOIUrl":"10.1007/s10735-024-10246-w","url":null,"abstract":"<div><p>Dendrobine (DDB), an alkaloid isolated from the Chinese herb Dendrobium, has antioxidant and anti-inflammatory effects; however, whether DDB reduces oleic acid (OA)-induced lipid accumulation remains unclear. OA-induced lipid accumulation model of HepG2 cells were treated with DDB. Cellular lipid deposition was assessed by Oil Red O (ORO) staining and triglyceride and total cholesterol detection. RNA-Sequencing (RNA-seq), biological function analysis, and transcription factor (TFs) prediction were combined to identify key TF in the DDB-treated OA model. Finally, the roles of FOS and METTL14 were examined using a DDB-induced lipid accumulation model. DDB inhibited OA-induced lipid accumulation. We identified 895 differentially expressed genes (DEGs) that were mainly enriched in various biological processes of lipid synthesis and transport. Four transcription factors (SOX9, MLXIPL, FOS, and JUN) associated with lipid metabolism and FOS levels in the OA-induced lipid accumulation model after DDB treatment had the greatest changes in expression change. Overexpression of FOS alleviates the inhibitory effect of DDB on OA-induced lipid accumulation. METTL14 is a target gene of FOS, and simultaneous interference with METTL14 in cells with high FOS expression restored the alleviating effect of DDB on lipid accumulation. DDB alleviated OA-induced lipid accumulation by inhibiting the FOS/METTL14 pathway.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970380","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":"Exploration of N6-methyladenosine modification in ascorbic acid 2-glucoside constructed stem cell sheets","authors":"Zhiye Yao,&nbsp;Liang Chen,&nbsp;Yumei Liu,&nbsp;Bowen Feng,&nbsp;Caisheng Liu,&nbsp;Yanling Chen,&nbsp;Shaoru He","doi":"10.1007/s10735-024-10240-2","DOIUrl":"10.1007/s10735-024-10240-2","url":null,"abstract":"<div><p>The aim of this study was to explore the mechanism of bone marrow stem cells (BMSCs) sheets constructed with different doses of Ascorbic acid 2-glucoside (AA-2G) in conjunction with N6-methyladenosine (m6A)-associated epigenetic genes analysing transcriptome sequencing data. Experimental groups of BMSCs induced by different AA-2G concentrations were set up, and the tissue structures were observed by histological staining of cell slices and scanning electron microscopy. Expression patterns of DEGs were analysed using short-time sequence expression mining software, and DEGs associated with m6A were selected for gene ontology analysis and pathway analysis. The protein-protein interaction (PPI) network of DEGs was analysed and gene functions were predicted using the search tool of the Retrieve Interacting Genes database. There were 464 up-regulated DEGs and 303 down-regulated DEGs between the control and high-dose AA-2G treatment groups, and 175 up-regulated DEGs and 37 down-regulated DEGs between the low and high-dose AA-2G treatment groups. The profile 7 exhibited a gradual increase in gene expression levels over AA-2G concentration. In contrast, profile 0 exhibited a gradual decrease in gene expression levels over AA-2G concentration. In the PPI network of m6A-related DEGs in profile 7, the cluster of metallopeptidase inhibitor 1 (Timp1), intercellular adhesion molecule 1 (Icam1), insulin-like growth factor 1 (Igf1), matrix metallopeptidase 2 (Mmp2), serpin family E member 1 (Serpine1), C-X-C motif chemokine ligand 2 (Cxcl2), galectin 3 (Lgals3) and angiopoietin-1 (Angpt1) was the top hub gene cluster. The expression of all hub genes was significantly increased after AA-2G intervention (<i>P</i> &lt; 0.05), and the expression of Igf1 and Timp1 increased with increasing intervention concentration. The m6A epigenetic modifications were involved in the AA-2G-induced formation of BMSCs. Igf1, Serpine1 and Cxcl2 in DEGs were enriched for tissue repair, promotion of endothelial and epithelial proliferation and regulation of apoptosis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915827","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":"A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms","authors":"Morteta H. Al-Medhtiy,&nbsp;Mohammed T Mohammed,&nbsp;Mohammed M. Hussein M. Raouf,&nbsp;Ayman M. Al-Qaaneh,&nbsp;Ahmed A.j. Jabbar,&nbsp;Fuad Othman Abdullah,&nbsp;Ramzi A. Mothana,&nbsp;Abdullah R. Alanzi,&nbsp;Rawaz Rizgar Hassan,&nbsp;Mahmood Ameen Abdulla,&nbsp;Musher Ismail saleh,&nbsp;Sidgi Hasson","doi":"10.1007/s10735-024-10229-x","DOIUrl":"10.1007/s10735-024-10229-x","url":null,"abstract":"<div><p>Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911278","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":"Hypoxic microenvironment promotes diabetic wound healing by polarizing macrophages to the M2 phenotype in vivo","authors":"Feiyu Cai,&nbsp;Peng Wang,&nbsp;Mengling Yuan,&nbsp;Wenjiao Chen,&nbsp;Yi Liu","doi":"10.1007/s10735-024-10244-y","DOIUrl":"10.1007/s10735-024-10244-y","url":null,"abstract":"<div><h3>Background</h3><p>In diabetic wounds, M2 polarization of macrophages regulates the transition from an inflammatory phase to a proliferative phase. Prior investigations have demonstrated the potential of deferoxamine (DFO) in creating a localized hypoxic microenvironment, which could stimulate angiogenesis by promoting vascular endothelial growth factor (VEGF) secretion in diabetic wound healing. Nevertheless, there is still no clear information on whether this chemically induced hypoxic microenvironment modulates macrophage polarization to promote diabetic wound healing.</p><h3>Methods</h3><p>The 18 diabetic mice were randomly divided into three groups: a control group (<i>n</i> = 6), a 100µM DFO group (<i>n</i> = 6), and a 200µM DFO group (<i>n</i> = 6). Subsequently, a full-thickness wound with a diameter of 1.00 cm was created on the dorsal region of the diabetic mice. Observe wound closure regularly during treatment. At the end of the observation, tissue specimens were collected for a series of experiments and analyses, including hematoxylin and eosin (H&amp;E), Masson, immunofluorescent, and immunohistochemical staining. The role and mechanism of DFO in regulating macrophage polarization were studied using RAW264.7 cells.</p><h3>Results</h3><p>In comparison to the control group, the administration of DFO notably facilitates wound healing in diabetic mice. In diabetic wounds, DFO increases blood supply by upregulating VEGF, which promotes angiogenesis. Additionally, The expression of HSP70 and CD206 were also upregulated by DFO in both vivo and in vitro, while iNOS expression was downregulated. Additionally, knk437 inhibited the expression of HSP70 in RAW264.7 cells, resulting in a reduction of M2 polarization and an increase in M1 polarization.</p><h3>Conclusion</h3><p>The induction of a hypoxic microenvironment by DFO has been found to exert a substantial influence on the process of diabetic wound healing. DFO treatment enhances the capacity of diabetic wounds to stimulate angiogenesis and modulate macrophage polarization that may be associated with HSP70 expression, thereby expediting the transition of these wounds from an inflammatory to a proliferative state.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911279","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":"Trophoblast fusion in fetal growth restriction is inhibited by CTGF in a cell-cycle-dependent manner","authors":"Ketong Liu,&nbsp;Suwen Wu,&nbsp;Yutong Cui,&nbsp;Xiang Tao,&nbsp;Yanhong Li,&nbsp;Xirong Xiao","doi":"10.1007/s10735-024-10239-9","DOIUrl":"10.1007/s10735-024-10239-9","url":null,"abstract":"<div><p>Fetal growth restriction (FGR) is a relatively common complication of pregnancy, and insufficient syncytialization in the placenta may play an important role in the pathogenesis of FGR. However, the mechanism of impaired formation of the syncytiotrophoblast layer in FGR patients requires further exploration. In the present study, we demonstrated that the level of syncytialization was decreased in FGR patient placentas, while the expression of connective tissue growth factor (CTGF) was significantly upregulated. CTGF was found to inhibit trophoblast fusion via regulating cell cycle progress of BeWo cells. Furthermore, we found that CTGF negatively regulates cell cycle arrest in a p21-dependent manner as overexpression of p21 could rescue the impaired syncytialization induced by CTGF-overexpression. Besides, we also identified that CTGF inhibits the expression of p21 through ITGB4/PI3K/AKT signaling pathway. Our study provided a new insight for elucidating the pathogenic mechanism of FGR and a novel idea for the clinical therapy of FGR.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911280","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":"Revealing the molecular mechanisms in wound healing and the effects of different physiological factors including diabetes, age, and stress","authors":"Muhammad Summer,&nbsp;Shaukat Ali,&nbsp;Umaima Fiaz,&nbsp;Tauqeer Hussain,&nbsp;Rana Rashad Mahmood Khan,&nbsp;Hashim Fiaz","doi":"10.1007/s10735-024-10223-3","DOIUrl":"10.1007/s10735-024-10223-3","url":null,"abstract":"<div><p>Wounds are the common fates in various microbial infections and physical damages including accidents, surgery, and burns. In response, a healthy body with a potent immune system heals that particular site within optimal time by following the coagulation, inflammation, proliferation, and remodeling phenomenon. However, certain malfunctions in the body due to various diseases particularly diabetes and other physiological factors like age, stress, etc., prolong the process of wound healing through various mechanisms including the Akt, Polyol, and Hexosamine pathways. The current review thoroughly explains the wound types, normal wound healing mechanisms, and the immune system’s role. Moreover, the mechanistic role of diabetes is also elaborated comprehensively.</p><h3>Graphical abstract</h3><p>Comparative analysis of the molecular events during different wound healing phases in healthy and diabetic/stressed/aged individuals.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905429","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 protective effect of benfotiamine on gastric ulcers in male rats: an experimental study","authors":"Mohammad Shokati Sayyad,&nbsp;Mohammad Hossein Khanjani,&nbsp;Milad Amirbeik,&nbsp;Mohammad Seyedabadi,&nbsp;Fereshteh Talebpour Amiri,&nbsp;Vida Motamednia,&nbsp;Nastaran Rezaei,&nbsp;Fatemeh Shaki","doi":"10.1007/s10735-024-10237-x","DOIUrl":"10.1007/s10735-024-10237-x","url":null,"abstract":"<div><p>Gastric ulcers are a common gastrointestinal disorder associated with significant morbidity and mortality. It can also increase the risk of gastric cancer. This study aimed to investigate the effect of benfotiamine on experimentally-induced gastric ulcers in male rats. In this study, 30 Wistar male rats were divided randomly into six groups: control (normal), indomethacin, omeprazole, and treatment groups, including 50, 100, and 200 mg/kg of benfotiamine. Gastric ulcer was induced by indomethacin gavage. Omeprazole and different therapeutic doses of benfotiamine were administered for three days. Twenty-four hours after the last treatment, the rats were euthanized, and samples were collected.</p><p>The results demonstrated that 100 and 200 mg/kg of benfotiamine treatment significantly improved indomethacin-induced gastric tissue damage. Moreover, benfotiamine at 100 and 200 mg/kg effectively attenuated the levels of pro-inflammatory cytokines IL-6 and TNF-α and oxidative stress markers MDA and ROS while increasing the antioxidant GSH. These findings suggest that benfotiamine’s gastroprotective effects are mediated through its antioxidant and anti-inflammatory properties, which help mitigate the tissue damage and inflammatory response associated with indomethacin-induced gastric ulcers.</p><p>However, further research is needed to elucidate the precise molecular mechanisms underlying these beneficial effects and to evaluate the potential therapeutic application of benfotiamine in clinical settings.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900547","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":"Impact of acute stress disorder on surfactant protein D levels in acute lung injury","authors":"Ke Wang,&nbsp;Zhenpeng Huang,&nbsp;Jiawei He,&nbsp;Lingwang Kong,&nbsp;Mingwei Chen","doi":"10.1007/s10735-024-10231-3","DOIUrl":"10.1007/s10735-024-10231-3","url":null,"abstract":"<div><p>Many people sustain acute lung injuries in road traffic collisions, but few studies have dealt with such injuries in live models. This study aimed to explore the basic pathophysiological and inflammatory changes in adult rabbits following acute thoracic trauma. We randomly assigned 50 rabbits to control and injury groups. Rabbits in the injury group were subjected to right chest pressure (2600 g) using a Hopkinson bar. Measurements were taken in the control group and 0, 24, 48, and 72 h after injury in the injury group. Injury severity was evaluated in gross view; with haematoxylin and eosin (H&amp;E) staining; and through the serum changes of tumor necrosis factor alpha (TNF-α), surfactant protein D (SP-D), and neutrophils. Secretion changes in SP-D in right lung injured tissues were estimated by western blotting and qPCR. Serum TNF-α levels increased rapidly immediately after injury, gradually recovering after 24, 48, and 72 h (p &lt; 0.01). The percentage of neutrophils in the accompanying blood showed a consistent trend. Gross necropsy and H&amp;E staining indicated different levels of bleeding, alveoli exudation, and inflammatory transformation after impact. ELISA depicted the same trend in circulation (F = 22.902, p &lt; 0.01). Western blotting showed that SP-D protein levels in tissues decreased at 0 h and increased at 24, 48, and 72 h. We demonstrate the feasibility of a model of impact lung injury. Primary impact caused injury without external signs. Inflammation began immediately, and the lungs began recovering at 24, 48, and 72 h, as shown by increased SP-D levels in circulation and tissues.With complaints of ALI and inflammation, SP-D may be a potential biomarker after chest trauma.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896392","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":"Mandible development under gestational protein restriction: cellular and molecular mechanisms","authors":"Bruno Calsa,&nbsp;Luan dos Santos Menezes,&nbsp;José Guilherme Neves,&nbsp;José Antônio Rocha Gontijo,&nbsp;Milton Santamaria-Jr,&nbsp;Patrícia Aline Boer","doi":"10.1007/s10735-024-10242-0","DOIUrl":"10.1007/s10735-024-10242-0","url":null,"abstract":"<div><p>Insufficient evidence regarding how maternal undernutrition affects craniofacial bone development persists. With its unique focus on the impact of gestational protein restriction on calvaria and mandible osteogenesis, this study aims to fill, at least in part, this gap. Female mice were mated and randomized into NP (normal protein) or LP (low protein) groups. On the 18th gestational day (GD), male embryos were collected and submitted to microtomography (µCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), PCR, and autophagy dynamic analyses. The study shows that the LP offspring exhibited lower body mass than the NP group, with µCT analysis revealing no volumetric differences in fetus’s head. EDS analysis showed lower calcium and higher phosphorus percentages in mandibles and calvaria. SEM assessment evidenced higher hydroxyapatite crystal-like (HC) deposition on the calvaria surface in LP fetus. Conversely, lower HC deposition was observed on the mandible surface, suggesting delayed matrix mineralization in LP fetuses with a higher percentage of collagen fibers in the mandible bone. The autophagy process was reduced in the mesenchyme of LP fetuses. PCR array analysis of 84 genes revealed 27 genes with differential expression in the LP progeny—moreover, increased mRNA levels <i>of Akt1</i>,<i> Mtor</i>,<i> Nfkb</i>, and <i>Smad1</i> in the LP offspring. In conclusion, the results suggest that gestational protein restriction anticipated bone differentiation in utero, before 18GD, where this process is reduced compared to the control, leading to the reduction in bone area at 15 postnatal day previously observed. These findings provide insights into the molecular and cellular mechanisms of mandible development and suggest potential implications for the Developmental Origins of Health and Disease (DOHaD).</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892535","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}