Expression Of Fibroblast Growth Factor Research Articles

Pulsed electromagnetic field prevents tooth relapse after orthodontic tooth movement in rat models.

Relapse after orthodontic treatment remains a crucial problem. Pulsed electromagnetic fields (PEMFs) accelerate osteoblastogenesis and inhibit osteoclastogenesis. However, their effect on tooth movement during the retention phase of orthodontic treatment has not been studied. This study investigated the role of PEMF stimulation in preventing tooth relapse after orthodontic tooth movement (OTM) in rat models. Thirty-six male Wistar rats were divided into control, PEMF 7, and PEMF 14 groups. The maxillary first molar was moved mesially with a 50g force of a Nickel Titanium closed coil spring for 21 days. Therefore, PEMF stimulations, including a frequency of 15Hz and intensity of 2.0mT, were applied to a retention phase for 2h daily for 7 and 14 days. The tooth relapse distance was evaluated on days 1, 3, 7, and 14; the number of osteoblasts, osteoclasts, and fibroblasts was assessed by hematoxylin and eosin staining; and the expression of fibroblast growth factor 2 (FGF-2) and type I collagen (Col-I) was evaluated by immunohistochemistry. The data were analyzed using one-way analysis of variance and post hoc test with p<0.05 considered statistically significant. Tooth relapse distance was significantly decreased in the PEMF 7 and PEMF 14 groups compared to the control group. A significant increase was detected in osteoblasts, fibroblasts, FGF-2, and Col-I in both PEMF groups, while osteoclasts decreased (p<0.05). The reduction of tooth relapse could be attributed to PEMF stimulation for 7 and 14 days by accelerating alveolar bone formation and periodontal ligament remodeling.

CD34hi subset of synovial fibroblasts contributes to fibrotic phenotype of human knee osteoarthritis.

Osteoarthritis (OA) shows various clinical manifestations depending on the status of its joint components. We aimed to identify the synovial cell subsets responsible for OA pathophysiology by comprehensive analyses of human synovium samples in single-cell resolution. Two distinct OA synovial tissue groups were classified by gene expression profiles in RNA-Seq: inflammatory and fibrotic. The inflammatory group exhibited high expression of inflammatory cytokines, histologically inflammatory infiltrate, and a more severe pain score. The fibrotic group showed higher expression of fibroblast growth factor (FGFs) and bone morphogenetic proteins (BMPs), showed histologically perivascular fibrosis, and showed a lower pain score. In single-cell RNA-Seq (scRNA-Seq) of synovial cells, MERTKloCD206lo macrophages and CD34hi fibroblasts were associated with the inflammatory and fibrotic groups, respectively. Among the 3 fibroblast subsets, CD34loTHY1lo and CD34loTHY1hi fibroblasts were influenced by synovial immune cells, whereas CD34hi fibroblasts were influenced by mural and endothelial cells. Particularly, in CD34hi fibroblast subsets, CD34hiCD70hi fibroblasts promoted proliferation of Tregs, potentially suppressing synovitis and protecting articular cartilage. Elucidation of the mechanisms underlying the regulation of these synovial cell subsets may lead to novel strategies for OA therapeutics.

Recombinant Porcine FGF1 Promotes Muscle Stem Cell Proliferation and Mitochondrial Function for Cultured Meat Production.

Cultured meat is an emerging technology with the potential to meet future protein demands while addressing the challenges associated with traditional livestock farming. The production of cultured meat requires efficient, animal component-free in vitro systems for muscle stem cell (MuSC) expansion. Fibroblast growth factor 1 (FGF1) is a critical growth factor that regulates the MuSC function. In this study, we established an efficient method for the soluble expression and purification of recombinant porcine FGF1 (rpFGF1) in Escherichia coli, achieving a yield of 48 mg of purified protein per liter of culture. Treatment with rpFGF1 significantly enhanced the proliferation of porcine MuSC under serum-free conditions. Furthermore, rpFGF1 induced mitochondrial fission and mitophagy by activating the ERK-dependent phosphorylation of DRP1 at Ser616, resulting in improved mitochondrial function and proliferation capacity in porcine MuSC. These findings highlight the potential of rpFGF1 in the development of serum-free media for scalable and sustainable cultured meat production.

High FGF18 expression levels predict poor prognosis in endometrial carcinoma patients and promote tumor growth and metastasis.

To investigate if fibroblast growth factor 18 (FGF18) expression plays an important role in endometrial carcinoma (EC). The clinicopathological associations and prognostic value of FGF18 expression were retrospectively analyzed in 190 patients with EC. FGF18 expression was stably knocked down in EC cell lines. Changes in cell proliferation, migration, and invasion rates were examined via cell behavior experiments. Tumor growth was investigated using a xenograft mouse model. RNA sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) in HEC-1-B cells after FGF18 knockdown, followed by pathway enrichment analysis of the DEGs. High FGF18 expression levels were closely correlated with EC clinicopathological features, such as histological subtype, FIGO stage, depth of myometrial invasion, and tumor size. Moreover, EC patients with high FGF18 expression levels had poorer overall survival. FGF18 knockdown in EC cells revealed its role in promoting tumor cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. RNA-seq of HEC-1-B cells revealed that the DEGs were enriched in signaling pathways related to cell proliferation and migration. Overexpression of FGF18 may serve as a prognostic biomarker for EC patients and is a potential therapeutic target for treating this disease.

Accumulation of altered serum bile acids predicts liver injury after portoenterostomy in biliary atresia.

Little is known on the mechanism of liver injury mediated by bile acids following Kasai portoenterostomy (KPE) in biliary atresia (BA). We sought to quantify individual serum bile acids, 7-alpha-hydroxy-4-cholesten-3-one (C4), and fibroblast growth factor 19 (FGF19) after KPE and to evaluate their prognostic utility and transcriptomic regulation. Serum (n=244) and liver specimens (n=105) prospectively obtained from BA patients (n=54) after KPE were included. Bile acids were analyzed using mass spectrometry, gene expression with quantitative PCR, and histopathology using a neural network model. Following KPE, serum bile acids correlated positively with biochemical liver injury, pediatric end-stage liver disease score, liver stiffness, histological ductular reaction, and liver fibrosis. Bile acids were higher among patients who developed portal hypertension (79.6 vs. 11.9 μmol/l, p<0.0001), esophageal varices (91.6 vs. 16.2 μmol/l, p<0.0001), or required liver transplantation (LT, 115.3 vs. 22.0 μmol/l, p<0.0001) during follow up; bile acids predicted these outcomes in time-dependent regression models. Accumulation of conjugated bile acids, cholic acid, and taurine conjugates predicted LT risk while associating with histological liver injury. Serum C4 (0.04 vs. 0.00 μmol/l, p=0.04) and liver CYP7A1 were higher in native liver survivors than in LT patients (fold-change 16.9 vs. 7.0, p=0.02). Primary bile acids correlated negatively with C4 (R=-0.38, p<0.001) and CYP7A1 (R=-0.49, p=0.01). Unlike in native liver survivors (R=-0.19, p=0.66), serum FGF19 correlated with liver FGF19 (R=0.59, p=0.04) without an inverse association with serum primary bile acids in LT patients (R=0.26, p=0.08). Accumulation and altered composition of serum bile acids predicted progressive liver disease and poorer transplant-free survival following KPE. Poor prognosis was associated with low bile acid synthesis and aberrantly increased liver FGF19. Biliary atresia (BA), a fibro-obliterating biliary disease of infants, remains the most common indication for pediatric liver transplantation caused by rapid progression of liver injury. To identify predictive biomarkers of disease progression and to elucidate the pathophysiology of BA liver injury, we profiled serum bile acids and studied their liver metabolism after Kasai portoenterostomy. Accumulation and altered composition of circulating bile acids predicted progression of liver disease and need for liver transplantation. Patients with poor prognosis showed low bile acid synthesis and abnormal liver expression of fibroblast growth factor 19.

Impact of Maternal BPA Exposure during Pregnancy on Obesity in Male Offspring: A Mechanistic Mouse Study of Adipose-Derived Exosomal miRNA.

The widespread use of bisphenol A (BPA) has led to universal exposure among the population, raising concerns about its health effects. Epidemiological studies have linked environmentally relevant levels of BPA exposure to obesity. We aimed to uncover the complex mechanisms by which oral exposure during pregnancy with BPA affects the offspring. We conducted a two-stage mouse study. In stage 1, we gavaged dams with BPA at 0.05, 0.5, and during pregnancy, and we tracked the offspring's weight and diet to 12 wk of age. In stage 2, exosomes from BPA-exposed dams and offspring were injected into pregnant mice and 3-wk-old males, respectively, and the mice were observed up to 12 wk. We then sequenced exosomal microRNAs (miRNAs) in male offspring whose dams had been exposed to BPA during pregnancy and checked their expression in adipose, liver, and serum samples at weeks 3, 6, 9, and 12. Finally, we explored the functions of exosomes and exosomal miRNAs secreted by adipose-derived mesenchymal stem cells, and we investigated whether the exosomes and miRNAs they secreted could affect glucose uptake, triglyceride synthesis, and the expression of genes related to glucose and lipid metabolism in alpha mouse liver 12 cells. Gavage of of BPA during pregnancy in dams led to obesity in male offspring mice, and injection of exosomes from male offspring with BPA exposure during pregnancy also induced similar outcomes in the next generation of male pups. Exosomal miRNA sequencing identified differentially expressed miRNAs associated with BPA-induced obesity in male offspring, revealing sustained high expression of miRNAs in adipose tissue and a gradual increase in the liver and serum over time. Further mechanistic studies showed that exosomes derived from BPA-treated adipose-derived stem cells reduced the expression of peroxisome proliferator-activated receptor-gamma and fibroblast growth factor 21, leading to impaired insulin signaling and lipid metabolism in hepatocytes. Overexpression of miR-124-3p in hepatocytes mimicked these effects; in contrast, knockdown of miR-124-3p or inhibition of exosome secretion reversed them. The present study corroborates the regulatory function of adipose-derived exosomal miRNAs in obesity in male offspring mice resulting from BPA exposure during pregnancy. Exosomal miRNA may be a key and novel molecular biomarker in the adverse effects of chemical exposure during pregnancy. https://doi.org/10.1289/EHP14888.

The Complexity and Significance of Fibroblast Growth Factor (FGF) Signaling for FGF-Targeted Cancer Therapies.

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 subfamily is particularly interesting because of its unique protein structure and role in endocrine function. The abnormal expression of FGFs in different cancer types (breast, colorectal, hepatobiliary, bronchogenic, and others) is examined and correlated with patient prognosis. The classification of FGF ligands based on their mode of action, whether autocrine, paracrine, endocrine, or intracrine, is illustrated, and an analysis of the binding specificity of FGFs to FGFRs is also provided. Moreover, the latest advances in cancer therapeutic strategies involving small molecules, ligand traps, and monoclonal antibody-based FGF inhibitors are presented. Lastly, we discuss how the dysregulation of FGF and FGFR expression affects FGF signaling and its role in cancer development.

Analysis of Fibroblast Growth Factor 2 Impact and Mechanism on Broncho-Pulmonary Dysplasia

Objective: Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is an important mechanism for the onset and development of broncho-pulmonary dysplasia (BPD). Fibroblast growth factor 2 (FGF2) is involved in the development and repair of injury in many organs, particularly the lung. The role of FGF2 in BPD is currently unclear. The aim of our study was to investigate the expression of FGF2 in lung tissue of BPD mice, to further clarify the effect of FGF2 on EMT in alveolar epithelial cells and to actively search for possible signaling pathways. Methods: The BPD model was induced by exposure to hyperoxia. Lung tissue samples were collected and hematoxylin and eosin staining was used to determine the modeling effect. Quantitative real-time polymerase chain reaction (QRT-PCR), immunohistochemistry was used to detect FGF2 expression in BPD mice. To further investigate the effect of FGF2 supplementation and deficiency on EMT in alveolar epithelial cells, A549 cells were cryopreserved, resuspended, cultured, and passaged. Transforming growth factor-β1 (TGF-β1) was used to induce EMT. FGF2 small interfering RNA fragments were synthesized and screened. Fibroblast growth factor receptor 1 (FGFR1) expression was inhibited by BGJ398. (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium) (MTS) assay was used to detect the effect of FGF2 and infigratinib (BGJ398) on cell proliferation. We used qRT-PCR and Western blot to detect the expression of epithelial cell markers, mesenchymal cell markers and EMT-related signaling pathway proteins. Results: Our results showed that the successful established hyperoxia mice model were characteristic by BPD. Hyperoxia decreased FGF2 on day 4, upregulated FGF2 on day 21, which resulted in EMT. In vitro, we found that FGF2 alone increased the expression of mesenchymal markers, decreased the expression of epithelial markers and activated phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), small mother against decapentaplegic (Smad), mitogen-activated protein kinase (P38), and extracellular signal-regulated kinase (ERK) signaling pathways. FGF2 could not reverse but synergistically promote Transforming growth factor-β1 (TGF-β1)-induced EMT of alveolar epithelial cells. Silencing FGF2 increased the expression of epithelial marker E-cadherin, inhibited the PI3K/AKT, Smad, and P38 signaling pathways activated by TGF-β1, but activated ERK signaling. FGF2 receptor inhibitor BGJ398 reversed TGF-β1-induced EMT, decreased the expression of FGFR1, and inhibited ERK signaling pathway activation. Conclusions: FGF2 was closely associated with EMT in BPD mice. Both high and low levels of FGF2 promoted EMT in A549. The FGF2 receptor inhibitor BGJ398 reversed TGF-β1-induced EMT in A549 by inhibiting the FGFR1/P-ERK signaling pathway.

Improvement of Dentin Growth Parameters (Beta-catenin, bFGF, CD105, and BMP4) with Propolis as Adjuvant in Dental Caries Treatment.

The purpose of the study was to evaluate the efficacy of calcium hydroxide (Ca(OH)2) and propolis in pulp capping for dental caries treatment, focusing on dentin growth parameters. The study also aims to determine the role of propolis as a natural adjuvant therapy in enhancing reparative dentin development while emphasizing the importance of proper technique and material preparation with markers for the expression of beta-catenin, bFGF, CD105, and BMP4. The left bottom molar teeth from 28 Wistar rats were divided into four groups. The first group, the control group, was given only aqua dest, and the second group received drilling treatment and additional therapies with Ca(OH)2 (Ca(OH)2) 0.625 μg. The third group was given drilling treatment and additional therapies with a combination of propolis with Ca(OH)2 0.781 μg until day 7. Finally, the fourth group received a combination of propolis with Ca(OH)2 0.781 μg until day 14. This research analyzed the expression of essential basic fibroblast growth factor (bFGF), CD105, beta-catenin, and bone morphogenetic protein 4 (BMP4). This research reports that the average expression of BMP4 and bFGF showed a significant result in treatment with additional therapies with propolis and Ca(OH)2. The experiment indicates that propolis and Ca(OH)2 could induce reparative dentine on days 7 and 14. Propolis as an adjuvant shows better reparative dental formation with improvement in the expression of bFGF and BMP4 in 14 days of therapy.

Low-energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration, and modulating the inflammation induced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: an experimental animal study.

Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical, and immunofluorescence staining. The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions [run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan score] and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1β, IL6, and macrophages (CD68) while increasing leukocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair, and regeneration in SCI. This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.

Sequencing of messenger RNA in the healing process of diabetes foot ulcer.

Transcriptome analysis of skin wound tissues from diabetic foot ulcer (DFU) patients to assess changes in the microenvironment during wound healing is performed by messenger RNA (mRNA) sequencing. All 5 patients with initial DFU area ≥ 3 cm2 were selected for wound specimen collection at two time points of 0% and 50% wound healing. A total of 10 skin wound samples were obtained for mRNA sequencing. According to the sequencing results, quantitative polymerase chain reaction (qPCR) validation was performed on 12 relevant genes related to angiogenesis, fibroblast proliferation, and wound inflammation. All patients received electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) dressing for DFU treatment. The mRNA sequencing results of DFU skin specimens showed that compared to the 0% and 50% wound healing time points, there were 4347 differentially expressed genes, including 2827 upregulated genes and 1520 downregulated genes. Enrichment analysis of the differentially expressed genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the upregulated genes were mainly associated with biological processes such as cell adhesion, adhesion junctions, epidermal development, and skin barrier formation. The qPCR analysis results indicated that the increased expression of fibroblast growth factor, vascular endothelial growth factor, and CD200 gene was related to DFU healing. The healing process of DFU wounds involves the interaction of multiple factors, especially in inflammation control, angiogenesis, and fibroblast proliferation.

FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice

Fibronectin type III domain-containing (FNDC) proteins play critical roles in cellular homeostasis and cardiac injury, and our recent findings define FNDC5 as a promising cardioprotectant against doxorubicin- and aging-related cardiac injury. FNDC4 displays a high homology with FNDC5; however, its role and mechanism in cardiac ischemia/reperfusion (I/R) injury remain elusive. Here, we show that cardiac and plasma FNDC4 levels are elevated during I/R injury in a hypoxia-inducible factor 1α (HIF1α)-dependent manner. Cardiac-specific FNDC4 overexpression facilitates, while cardiac-specific FNDC4 knockdown inhibits cardiomyocyte survival and angiogenesis in I/R-stressed hearts of male mice through regulating the proteasomal degradation of HIF1α. Interestingly, FNDC4 does not directly stimulate angiogenesis of endothelial cells, but increases the expression and secretion of fibroblast growth factor 1 from cardiomyocytes to enhance angiogenesis in a paracrine manner. Moreover, therapeutic administration of recombinant FNDC4 protein is sufficient to alleviate cardiac I/R injury in male mice, without resulting in significant side effects. In this work, we reveal that FNDC4 alleviates cardiac I/R injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis, and define FNDC4 as a promising predictive and therapeutic target of cardiac I/R injury.

LINC00342 regulates the PI3K-AKT signaling pathway via the miR-149-5p/FGF11 axis and affects the progression of oral cancer

BackgroundA large number of long non-coding RNAs (lncRNAs) have been implicated in the progression of oral cancer (OC). This study aimed to investigate the role of a novel lncRNA, LINC00342, in OC and elucidate its molecular mechanism.MethodsDifferential expression of lncRNA/miRNA/mRNA was analyzed using the Gene Expression Omnibus database and validated with RT-qPCR. Additionally, the expression levels of these molecules in OC cells and their effects on cell viability and cell cycle were assessed using the Cell Counting Kit-8 and flow cytometry. RNA bindings was analyzed by dual luciferase, and Western blot was used to detect the activation of relevant pathways.ResultsThis study showed that, in contrast to miR-149-5p, the expression of LINC00342 and fibroblast growth factor 11 (FGF11) were upregulated in OC cells (LINC00342: 10.00 ± 1.06 (FaDu) and 3.55 ± 0.25 (CAL-27) vs 1.00 ± 0.07 (HOECs), P < 0.05; FGF11: 7.31 ± 0.33 (FaDu) and 3.43 ± 0.08 (CAL-27) vs 1.00 ± 0.10 (HOECs), P < 0.05). Dual-luciferase assays confirmed that LINC00342 bind to miR-149-5p in a direct targeting manner. Furthermore, inhibition of LINC00342 expression resulted in decreased proliferation rate (FaDu: 136.22 ± 22.10% vs 59.36 ± 8.98% (control), P < 0.05; CAL-27: 131.40 ± 11.58% vs 49.83 ± 11.19 (control), P < 0.05) and migration ability of OC cells, cell cycle arrest in G1 phase, and inhibition of PI3K-AKT signaling. Inhibition of miR-149-5p or overexpression of FGF11 reversed the effects of si-LINC00342.ConclusionsLINC00342 promotes PI3K-AKT signaling by activating FGF11 through adsorption of miR-149-5p, thereby regulating the progression of OC.

Treatment of Full-Thickness Cutaneous Wounds Using a Novel Fish Skin Acellular Dermal Powder as Hydrogel with Gene Expression of Some Growth Factors Genes

The purpose of this study is to evaluate how well fish skin acellular dermal powder hydrogel (FADPH) promotes the healing of cutaneous wounds in Iraqi bucks. 48 of full-thickness cutaneous wounds (3X3 cm) created on the dorsal back of twelve bucks, each two wounds on both sides. Then, divided into two groups according to treatment method (6 bucks /group). The wounds in control group (A), were left without treatment and the wounds in treatment group (B) were treated by topical application of (FADPH). The outcomes were assessed clinically, morphometrically scoring at (7, 14, 35, and 42) days post treatment, and gene expression by RT-PCR of two genes including fibroblast growth factor (FGF) and epidermal growth factor (EGF) at three times periods (0,7 and 14) days and histopathological assessment at (7,14, 35 and 42) days post treatment. The scoring results of group B showed that the percentages of scoring results were significantly higher than that of control wounds at the level of (P&lt;0.001) from the first 7 days until the end of the study. Also, results of gene expression of FGF and EGF was considerably higher in the treated group than control group at the level of (p&lt;0.001). The histopathological results in group B showed faster re- epithelialization of the epidermis, proliferation of fibrin and regenerated epithelia, dense collagen fibers, and finally complete regeneration of the epidermal layer at the end of study in compared with group A which was showed slowly development in wound healing proses and highly inflammatory reaction. In conclusion, FADM hydrogel enhanced and accelerated the healing of skin wounds in male goats.

The Immobilization of an FGF2-Derived Peptide on Culture Plates Improves the Production and Therapeutic Potential of Extracellular Vesicles from Wharton's Jelly Mesenchymal Stem Cells.

The skin is an essential organ that protects the body from external aggressions; therefore, damage from various wounds can significantly impair its function, and effective methods for regenerating and restoring its barrier function are crucial. This study aimed to mass-produce wound-healing exosomes using a fragment of the fibroblast growth factor 2 (FGF2)-derived peptide (FP2) to enhance cell proliferation and exosome production. Our experiments demonstrated increased cell proliferation when Wharton's jelly mesenchymal stem cells (WJ MSCs) were coated with FP2. Exosomes from FP2-coated WJ MSCs were analyzed using nanoparticle-tracking analysis, transmission electron microscopy, and Western blotting. Subsequently, fibroblasts were treated with these exosomes, and their viability and migration effects were compared. Anti-inflammatory effects were also evaluated by inducing pro-inflammatory factors in RAW264.7 cells. The treatment of fibroblasts with FP2-coated WJ MSC-derived exosomes (FP2-exo) increased the expression of FGF2, confirming their wound-healing effect in vivo. Overall, the results of this study highlight the significant impact of FP2 on the proliferation of WJ MSCs and the anti-inflammatory and wound-healing effects of exosomes, suggesting potential applications beyond wound healing.

Simiao Wan attenuates high-fat diet-induced hyperlipidemia in mice by modulating the gut microbiota–bile acid axis

Ethnopharmacological relevanceHyperlipidemia is a lipid metabolism disorder and a risk factor for obesity, diabetes, and coronary heart disease. It occurs mostly in the old adults; however, its incidence rate is increasing annually and there is a trend towards younger adults. Current clinical drugs for treating hyperlipidemia have multiple side effects. Therefore, it is necessary to develop safe and effective drugs from natural products to prevent and treat hyperlipidemia. Simiao Wan (SMW) is a classic Chinese medicine prescription first recorded in the Cheng Fang Bian Du of the Qing Dynasty. Studies have shown that SMW has excellent efficacy in metabolic diseases, which can effectively improve hyperlipidemia combined with other metabolic diseases. However, its underlying mechanism in hyperlipidemia treatment is yet to be clarified. Aim of the studyTo investigate the hypolipidemic effect of SMW on hyperlipidemic mice and explore whether the gut microbiota-bile acid (BA) axis is the potential mechanism. Materials and methodsA hyperlipidemic mouse model was established using a high-fat diet (HFD), and the hypolipidemic effect of SMW was detected in vivo. We performed 16S ribosomal RNA sequencing and BA metabolism analysis to explore the hypolipidemic mechanisms of SMW. Western blotting was conducted to detect the expression of proteins involved in the gut microbiota-BA axis to determine the potential lipid-lowering pathway. ResultsExcessive obesity in hyperlipidemic mice was alleviated after 8 weeks of SMW treatment. The total cholesterol and low-density lipoprotein cholesterol levels decreased significantly, whereas high-density lipoprotein cholesterol levels increased. SMW also reduced hepatic lipid and inguinal white adipose tissue accumulation in HFD-induced hyperlipidemic mice. Furthermore, intestinal bile saline hydrolase (BSH) level, associated with BA excretion, decreased. Meanwhile, SMW decreased the abundance of BSH-enriched microbes in hyperlipidemic mice. SMW increased the intestinal conjugated-BAs contents in hyperlipidemic mice, especially tauro-β-muricholic acid and tauro-ursodeoxycholic acid, which are ileac farnesoid X receptor (FXR) antagonists. Inhibited intestinal FXR signaling with SMW was accompanied by a decreased expression of intestinal fibroblast growth factor 15 and the activation of hepatic FXR, which promoted hepatic cholesterol conversion to BA. ConclusionSMW indirectly attenuated HFD-induced hyperlipidemia in mice by regulating the gut microbiota-BA axis. Our results provide a pharmacological basis for SMW treating hyperlipidemia and suggest a new idea for developing lipid-lowering drugs.

Effect of Aloe vera Gel and Sodium Metabisulphite on Expression of Fibroblast Growth Factor in Incision Wound of Rats

An incision wound is a wound caused by being sliced. Two ingredients that play a key role in the wound-healing process are glucomannan and acemannan, which are rich in polysaccharides and growth hormones. Growth hormones stimulate fibroblast activity and proliferation. The present study involved 35 Sprague Dawley male rats, aged 2-3 months old and weighing 200-300 grams. The study comprised seven groups including, negative control group (G1), positive control (aquades, G2), betadine 10% (G3), gel base (0.5 mg, G4), gel base + sodium metabisulfite 0.2 gr (G5), gel base + Aloe vera 5% (G6), and gel base + Aloe vera 5% + sodium metabisulfite 0.2 gr (G7). Each group had five replications. Initially, a 4-cm incision was made on the dorsal skin of each rat. The study lasted 15 days with observations made on days 3, 7, and 15. After the observation period, the rats were anesthetized and then terminated to collect skin tissues for microscopic examination. The tissue samples were then stained immunohistochemically to assess fibroblast growth factor (FGF) expressions. The results showed that the highest FGF expression was observed in the 5% Aloe vera + 2% metabisulfite group (G7), while the lowest FGF expression was in the negative control group (G1). It is concluded that Aloe vera L. extract gel at 5% + 2% metabisulfite (G7) significantly enhances the expression of FGF. Keywords: Aloe vera L, Fibroblast growth factor, Incision wound, Skin, Sodium metabisulfite

A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids

Organoids generating major cortical cell types in distinct compartments are used to study cortical development, evolution and disorders. However, the lack of morphogen gradients imparting cortical positional information and topography in current systems hinders the investigation of complex phenotypes. Here, we engineer human cortical assembloids by fusing an organizer-like structure expressing fibroblast growth factor 8 (FGF8) with an elongated organoid to enable the controlled modulation of FGF8 signaling along the longitudinal organoid axis. These polarized cortical assembloids mount a position-dependent transcriptional program that in part matches the in vivo rostrocaudal gene expression patterns and that is lost upon mutation in the FGFR3 gene associated with temporal lobe malformations and intellectual disability. By producing spatially oriented cell populations with signatures related to frontal and temporal area identity within individual assembloids, this model recapitulates in part the early transcriptional divergence embedded in the protomap and enables the study of cortical area-relevant alterations underlying human disorders.

LTBP2 down-regulated FGF2 to repress vascular smooth muscle cell proliferation and vascular remodeling in a rat model of intracranial aneurysm

This work probed into the role of latent transforming growth factor beta binding protein 2 (LTBP2) in intracranial aneurysm (IA). The rats underwent IA modeling and then stereotactic injection of short hairpin RNA against LTBP2 (shLTBP2). Hematoxylin-eosin (HE) staining was employed to assess IA model and vascular remodeling. Rat vascular smooth muscle cells (VSMCs) were transfected with shLTBP2, LTBP2 overexpression plasmid and fibroblast growth factor 2 (FGF2) overexpression plasmid. The mRNA and protein expressions of LTBP2, FGF2 and mitochondrial apoptosis-related factors (Caspase-3, Cyt-c, Mcl-1) were tested through qRT-PCR and Western blot. Cell viability, proliferation and apoptosis were examined by cell counting kit-8, EdU assay and flow cytometry. The up-regulated LTBP2 and down-regulated FGF2 were detected in IA rats. LTBP2 knockdown promoted vascular remodeling and Mcl-1 level, and restrained cell apoptosis and expressions of Caspase-3 and Cyt-c in IA model rats. Moreover, LTBP2 knockdown potentiated cell viability, proliferation and FGF2 level, and repressed apoptosis in rat VSMCs, while overexpressed LTBP2 exerted opposite effects. FGF2 overexpression promoted proliferation and Mcl-1 level, and inhibited apoptosis and expressions of Caspase-3 and Cyt-c in rat VSMCs, which also reversed the effects of overexpressed LTBP2 on these aspects. Collectively, LTBP2 down-regulates FGF2 to repress VSMCs proliferation and vascular remodeling in an IA rat model.

Fibroblast growth factor 21 alleviates acetaminophen induced acute liver injury by activating Sirt1 mediated autophagy

Background and aimsAcetaminophen (APAP) is the main cause of acute liver injury (ALI) in the Western. Our previous study has shown that fenofibrate activated hepatic expression of fibroblast growth factor 21 (FGF21) can protect the liver form APAP injuries by promoting autophagy. However, the underlying mechanism involved in FGF21-mediated autophagy remains unsolved. MethodsThe ALI mice model was established by intraperitoneal injection of APAP. To investigate the influence of FGF21 on autophagy and Sirt1 expression in APAP-induced ALI, FGF21 knockout (FGF21KO) mice and exogenously supplemented mouse recombinant FGF21 protein were used. In addition, primary isolated hepatocytes and the Sirt1 inhibitor EX527 were used to observe whether FGF21 activated autophagy in APAP injury is regulated by Sirt1 at the cellular level. ResultsFGF21, Sirt1, and autophagy levels increased in mice with acute liver injury (ALI) and in primary cultured hepatocytes. Deletion of the FGF21 gene exacerbated APAP-induced liver necrosis and oxidative stress, and decreased mitochondrial potential. It also reduced the mRNA and protein levels of autophagy-related proteins such as Sirt1, LC3-II, and p62, as well as the number of autophagosomes. Replenishment of FGF21 reversed these processes. In addition, EX527 partially counteracted the protective effect of FGF21 by worsening oxidative damage, mitochondrial damage, and reducing autophagy in primary liver cells treated with APAP. ConclusionFGF21 increases autophagy by upregulating Sirt1 to alleviate APAP-induced injuries.