Fibroblast Growth Factor Gene Research Articles

Tropism-shifted AAV-PHP.eB-mediated bFGF gene therapy promotes varied neurorestoration after ischemic stroke in mice.

AAV-PHP.eB is an artificial adeno-associated virus (AAV) that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically. While AAV-PHP.eB has been used in various disease models, its cellular tropism in cerebrovascular diseases remains unclear. In the present study, we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor (bFGF) gene therapy. Mice were injected intravenously with AAV-PHP.eB either 14 days prior to (pre-stroke) or 1 day following (post-stroke) transient middle cerebral artery occlusion. Notably, we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen (mNG). This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A (Ly6A). Furthermore, AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke. Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.

Panoramic RNA expression of fibroblast growth factors in human glioblastoma tissues and the impact on the survival of patients.

Fibroblast growth factors (FGFs) have a key role in various critical steps of tumor growth and progression through effects on angiogenesis, inflammation and the growth and invasion of malignant cells. Nevertheless, the role of the FGF family in human glioblastoma (GBM) has been rarely studied. The objective of the present study was to assess the RNA expression of all FGF family members in tissues obtained from patients with GBM and to analyze the association between FGF expression and the survival of these patients. For this, the RNA expression of FGF family members in the malignant and proximal tissues of 12 patients with GBM was determined by analyzing high-throughput RNA transcriptome sequencing data uploaded to the National Center for Biotechnology Information database. The relationship between FGF genes and the survival of patients with GBM and glioma was also respectively studied by analyzing data from The Cancer Genome Atlas database using the Gene Expression Profiling Interactive Analysis tool. The results showed that the expression of FGF1, FGF17, FGF20 and FGF22 in GBM tissues was lower than that in adjacent tissues, with a difference of >2 times. Analysis of the overall survival of patients with GBM indicated there were no significant relationships between the expression of FGF1, FGF17, FGF20, FGF22 and overall survival. Analysis of the overall survival of patients with glioma showed that glioma patients with low FGF1 expression achieved a longer survival time than patients with high FGF1 expression; however, high expression of FGF17 and FGF22 indicated a longer survival time. In summary, the results of the present study demonstrated the panoramic expression of FGF family members in patients with GBM, and indicated that FGF1, FGF17 and FGF22 did not affect the survival of patients with GBM, but had a notable influence on the survival of patients with glioma.

Effect of duration of estradiol exposure on embryo survival and endometrial gene expression in anestrous embryo recipient mares

Previous studies indicate a positive correlation between the duration of estrus prior to ovulation and likelihood of pregnancy in embryo recipient mares. However, the mechanisms by which the duration of estrus before may affect fertility remains unclear. This study aimed to determine the effect of different durations of estradiol exposure, prior to progesterone administration, on embryo viability in anestrous recipient mares, and endometrial expression of genes thought to influence embryo survival. Three groups of anestrous recipient mares treated with different duration of estradiol were used: long (LE), short (SE) and no treatment (NE). Day 8 embryos were transferred into recipient mares four days after long-acting progesterone administration and recovered 48h later to examine embryo growth and viability. The endometrial gene expression profile of selected genes was also investigated. The likelihood of recovering an embryo 48h after transfer was 46.1% (6/13), 62.5% (5/8) and 85.7% (6/7) for recipient mares from the NE, SE and LE groups, respectively (P = .09). Embryos recovered from the different groups of recipients did not, however, differ in size, morphology or the proportion of nuclei undergoing mitosis (P > .05). Abundance of mRNA for uterocalin (P19) and insulin-like growth factor 1 (IGF1) were increased in the LE compared to the NE group, while fibroblast growth factor 2 (FGF2), progesterone receptor (PGR) and insulin-like growth factor 1 receptor (IGF1R) transcript abundances were increased (P < 0.05) in the NE group compared to both SE and LE groups. In conclusion, a longer exposure of the endometrium to estradiol before progesterone tended to improve embryo survival within 48h of transfer. However, the grade, growth rate, and proportion of mitotic cells in surviving embryos did not differ among groups. If embryos are destined to fail in a suboptimal endometrial environment, they die and disappear quickly. Moreover, a more adequately estradiol-primed uterus, before the progesterone rise, seems to create a uterine environment, in terms of P19, IGF1, FGF2 and PGR gene expression, more conducive to embryo survival and further development.

Association of &lt;i&gt;FGF2&lt;/i&gt; gene polymorphism with economically significant traits of Holstein cows of the Republic of Tatarstan

Improving the reproductive functions of dairy cows may be possible through the use of marker-associated breeding. The FGF2 gene is a candidate gene for bovine fertility, in early pregnancy and affects fetal embryonic development and embryonic mortality. The study of the interaction of the gene of the basic fibroblast growth factor 2 (FGF2 – SNP11646 [A → G]) and economic indicators was carried out on 270 full-aged cows of Holstein population of indigenous selection of Breeding Farm Integrated Agricultural Production Center of the Republic of Tatarstan. In the observed population, the G allele (0.591) and the AG genotype (42.6%) are the most common, and the genetic balance, according to the Hardy-Weinberg law, is preserved. Pearson's consensus criterion is 2χ=3.84, respectively, the expected distribution of FGF2 gene alleles in the study group coincides with the observed one. The maximum live weight at the first fruitful insemination was in full–aged cows carrying the homozygous allele A at the FGF2 gene locus – 435.5 kg, which is higher than in livestock with the GG genotype – by 17.7 kg (4.2 %; p &lt; 0.01). The Doha fertility index for the studied population is average. It was revealed during the study that the level of fertility, with a high degree of reliability, is higher in individuals with the AG genotype – 6.2%, for the same group the earliest age of the first fruitful insemination was noted. A high level of maleness leads to milk losses in cows heterozygous for the FGF2 gene locus, exceeding milk losses observed for the AA genotype by 32.7 % (p &lt; 0.001). There is an inverse correlation between high milk productivity and reproduction traits of cattle, which affects the economic efficiency of dairy production.

FGF2 gene's antisense protein, NUDT6, plays a depressogenic role by promoting inflammation and suppressing neurogenesis without altering FGF2 signalling.

Fibroblast growth factor-2 (FGF2) is involved in the regulation of affective behaviour and shows antidepressant effects through the Akt and extracellular signal regulated kinase (ERK) 1/2 pathways. Nudix hydrolase 6 (NUDT6) protein is encoded from FGF2 gene's antisense strand and its role in the regulation of affective behaviour is unknown. Here, we overexpressed NUDT6 in the hippocampus and investigated its behavioural effects and the underlying molecular mechanisms affecting the behaviour. We showed that increasing hippocampal NUDT6 results in depression-like behaviour in rats without changing FGF2 levels or activating its downstream effectors, Akt and ERK1/2. Instead, NUDT6 acted by inducing inflammatory signalling, specifically by increasing S100 calcium binding protein A9 (S100A9) levels, activating nuclear factor-kappa B-p65 (NF-κB-p65), and elevating microglia numbers along with a reduction in neurogenesis. Our results suggest that NUDT6 could play a role in major depression by inducing a proinflammatory state. This is the first report of an antisense protein acting through a different mechanism of action than regulationof its sense protein. The opposite effects of NUDT6 and FGF2 on depression-like behaviour may serve as a mechanism to fine-tune affective behaviour. Our findings open up new venues for studying the differential regulation and functional interactions of sense and antisense proteins in neural function and behaviour, as well as in neuropsychiatric disorders. KEY POINTS: Hippocampal overexpression of nudix hydrolase 6 (NUDT6), the antisense protein of fibroblast growth factor-2 (FGF2), increases depression-like behaviour in rats. Hippocampal NUDT6 overexpression triggers a neuroinflammatory cascade by increasing S100 calcium binding proteinA9 (S100A9) expression and nuclear NF-κB-p65 translocation in neurons, in addition to microglial recruitment and activation. Hippocampal NUDT6 overexpression suppresses neurogenesis. NUDT6 exerts its actions without altering the levels or downstream signalling pathways of FGF2.

Dissection of a CTCF topological boundary uncovers principles of enhancer-oncogene regulation

Enhancer-gene communication is dependent on topologically associating domains (TADs) and boundaries enforced by the CCCTC-binding factor (CTCF) insulator, but the underlying structures and mechanisms remain controversial. Here, we investigate a boundary that typically insulates fibroblast growth factor (FGF) oncogenes but is disrupted by DNA hypermethylation in gastrointestinal stromal tumors (GISTs). The boundary contains an array of CTCF sites that enforce adjacent TADs, one containing FGF genes and the other containing ANO1 and its putative enhancers, which are specifically active in GIST and its likely cell of origin. We show that coordinate disruption of four CTCF motifs in the boundary fuses the adjacent TADs, allows the ANO1 enhancer to contact FGF3, and causes its robust induction. High-resolution micro-C maps reveal specific contact between transcription initiation sites in the ANO1 enhancer and FGF3 promoter that quantitatively scales with FGF3 induction such that modest changes in contact frequency result in strong changes in expression, consistent with a causal relationship.

Transplantation of Human Embryonic Stem Cell-Derived Pericyte-Like Cells Transduced with Basic Fibroblast Growth Factor Promotes Angiogenic Recovery in Mice with Severe Chronic Hindlimb Ischemia.

Critical limb ischemia (CLI) is a state of severe peripheral artery disease, with no effective treatment. Cell therapy has been investigated as a therapeutic tool for CLI, and pericytes are promising therapeutic candidates based on their angiogenic properties. We firstly generated highly proliferative and immunosuppressive pericyte-like cells from embryonic stem (ES) cells. In order to enhance the angiogenic potential, we transduced the basic fibroblast growth factor (bFGF) gene into the pericyte-like cells and found a significant enhancement of angiogenesis in a Matrigel plug assay. Furthermore, we evaluated the bFGF-expressing pericyte-like cells in the previously established chronic hindlimb ischemia model in which bone marrow-derived MSCs were not effective. As a result, bFGF-expressing pericyte-like cells significantly improved blood flow in both laser Doppler perfusion imaging (LDPI) and dynamic contrast-enhanced MRI (DCE-MRI). These findings suggest that bFGF-expressing pericyte-like cells differentiated from ES cells may be a therapeutic candidate for CLI.

Macrophage plasticity enhanced by camel milk peptide attributes in wound healing in diabetic rats

Diabetes Mellitus during wound healing alters macrophage recruitment, leading to delayed healing. The present study focuses on impact of camel milk peptide (CMP) on macrophage plasticity during their recruitment during wound healing stages. The Swiss albino rats were distributed into three groups: a normal wounded group (control), a wounded diabetic group, and a wounded diabetic group treated with CMP daily. The diabetic rats showed a significantly compromised level of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein (MIP-1α) relative gene expression, anti-CD31, anti-Mac-3, and anti-CD68 staining than the control group. Macrophages were considerably depleted in diabetic group animals upon initiating the inflammatory phase, while the protein significantly reversed the same. Also, there was marked increase in pathogenic bacterial growth at the wound sites of diabetic rats. On the contrary, in CMP-diabetic rats, levels of pathogenic bacteria were comparable to normal control animals. Diabetic rats demonstrated a reduction in matrix metalloproteinase (MMP-9 and MMP-13) expression while increased TNF-α levels compared to control rats. In addition, they also showed significantly reduced expression of VEGF and fibroblast growth factors (FGF) genes and IL-10 during the proliferation phase. However, all these parameters exhibited a considerably reversed trend in the CMP treated diabetic rats. Hence, CMP-treated diabetic rats demonstrated a transition to the M2 phenotype, highlighting macrophage recruitment's critical role in healing of wounds in hyperglycemic rats.

The expression level of fibroblast growth factor gene in serum samples of lung cancer patients.

Lung cancer, one of the most deadly and dangerous types of cancer in the world, kills many men and women every year. Activation of fibroblast growth factor signals plays a role in the pathogenesis of several cancers, including lung cancer. Also, this factor may indicate prognosis and is related to the survival rate in patients with NSCLC. Therefore, this research investigated the level of fibroblast growth factor gene expression in the serum of people with lung cancer. In this research, 60 serum samples of healthy people and 60 serum samples of people with NSCLC were prepared, and personal and clinicopathological information of the studied people were collected by questionnaires. Then, plasma isolation, RNA extraction, cDNA synthesis, primers design, implementation, and changes in fibroblast growth factor gene expression in the serum of healthy and lung cancer patients were evaluated by the Real-time PCR method. REST software was used to analyze the results. The findings showed no significant difference in the expression of the fibroblast growth factor gene in the serum of people with the first to third stages of metastasis. However, in the serum of patients with the fourth stage of metastasis, the expression level of this gene was significantly decreased by 3.92 times compared to normal samples (P<0.05). According to the results of this study, it is possible to use the expression level of the fibroblast growth factor gene in people's serum to predict the metastasis stage of lung cancer.

Angiogenesis related genes in Takayasu Arteritis (TAK):robust association with Tag SNPs of IL-18 and FGF-2 in a South Asian Cohort.

We performed genetic association study for genes encoding angiogenic and angiostatic proteins in patients with Takayasu arteritis (TAK). A total of 96 SNPs involving 60 genes were studied. Genotyping was performed in Fluidigm 96.96 Dynamic Array chip. All statistical analysis for SNP evaluation was performed using PLINK software. Initial analyses revealed five SNPs from three genes [IL-18 (encodes Interleukin-18), FGF2 (encodes Fibroblast Growth Factor-2), and ANGPT1 (encodes Angiopoietin-1)] as significantly different between controls and cases (uncorrected p < 0.05). After permutation-based analysis, two tag SNPs on the promoter region of IL-18 (rs187238 and rs1946518) and one 3'UTR tag SNP (rs1476217) of FGF2 were significantly associated with susceptibility to TAK, with p and OR (95% CI) of 0.0006 and 1.64 (1.25-2.17), 0.03 and 1.28 (1.02-1.64) & 0.016 and 1.33 (1.05-1.67), respectively; while, the two tag SNPs of ANGPT1 gene (rs6469101 and rs16875900) showed a trend (p = 0.055 & p = 0.051, respectively after permutation based correction). There is robust linkage disequilibrium between the two tag SNPs of IL-18 gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs of IL-18 and FGF2 genes on adjacent genes further suggest that these tag SNPs act as genetic risks for development of TAK in South Asians, with possible functional implications towards future biomarker development. Genotype phenotype study by genetic model-based analysis also revealed associations between genotype subsets and clinical features like fever, visual loss, left subclavian and coronary artery involvement in our TAK patients.

The effect of the gene of the main fibroblast growth factor (FGF2) on the dairy productivity of Holstein cattle

The effect of polymorphism of the gene of the basic fibroblast growth factor (SNP11646 A/G) on the milk production of Holstein cows in the conditions of the Republic of Tatarstan was studied. The DNA of 270 full–aged cows was genotyped by PCR - PDRF. As a result, two FGFA – 0,591 and FGFG – 0,409 alleles were identified; and three FGFAA genotypes – 19,6% (53 goals) and FGFAG – 42,6% (115 goals), FGFGG – 37,8% (102 goals). The highest milk yield for full lactation and for 305 days of lactation, a high coefficient of lactation was noted in individuals with the genotype FGF2AG. The best milk quality indicators (high protein content, fewer somatic cells) were found in animals homozygous for the A allele. All cows have a high stable and smoothly decreasing lactation curve, the coefficient of lactation stability is higher for the GG genotype.

Genome-wide identification and evolutionary analysis of the FGF gene family in buffalo

Fibroblast growth factors (FGFs) are important polypeptide growth factors that play a critical role in many developmental processes, including differentiation, cell proliferation, and migration in mammals. This study employs in silico analyses to characterize the FGF gene family in buffalo, investigating their genome-wide identification, physicochemical properties, and evolutionary patterns. For this purpose, genomic and proteomic sequences of buffalo, cattle, goat, and sheep were retrieved from NCBI database. We identified a total of 22 FGF genes in buffalo. Physicochemical properties observed through ProtParam tool showed notable features of these proteins including in-vitro instability, thermostability, hydrophilicity, and basic nature. Phylogenetic analysis grouped 22 identified genes into nine sub-families based on evolutionary relationships. Additionally, analysis of gene structure, motif patterns, and conserved domains using TBtools revealed the remarkable conservation of this gene family across selected species throughout the course of evolution. Comparative amino acid analysis performed through ClustalW demonstrated significant conservation between buffalo and cattle FGF proteins. Mutational analysis showed three non-synonymous mutations at positions R103 > G, P7 > L, and E98 > Q in FGF4, FGF6, and FGF19, respectively in buffalo. Duplication events revealed only one segmental duplication (FGF10/FGF22) in buffalo and two in cattle (FGF10/FGF22 and FGF13/FGF13-like) with Ka/Ks values <1 indicating purifying selection pressure for these duplications. Comparison of protein structures of buffalo, goat, and sheep exhibited more similarities in respective structures. In conclusion, our study highlights the conservation of the FGF gene family in buffalo during evolution. Furthermore, the identified non-synonymous mutations may have implications for the selection of animals with better performance. Communicated by Ramaswamy H. Sarma

The Effect of Altered Mucin1, FGF2, and HBEGF Gene Expression at The Ectopic Implantation Site and Endometrial Tissues in The Tubal Pregnancy Pathogenesis: A Case-Control Study.

Ectopic pregnancy (EP) is defined as implantation and development of an embryo outside of the uterine tissue. Women undergoing assisted reproductive technologies (ART), particularly frozen embryo transfer (FET), are in high-risk populations for EP. Mucin1 (MUC1), fibroblast growth factor-2 (FGF2), and Heparin-binding epidermal growth factor (HBEGF) genes are involved in the endometrial receptivity pathway, leading to normal eutopic implantation; Although, their relevance in the tubal pregnancy after FET is unknown. We aimed evaluation of Mucin1, FGF2, and HBEGF expression fold as endometrial receptive markers in the EP patients following the FET cycle. A case-control study was conducted on ten patients (five EP patients and five women in the pseudo-pregnancy group, as the control samples). Pseudo-pregnancy group was established in women who were candidates for hysterectomy for benign diseases. Fallopian tube biopsies and corresponding endometrial tissues from these patients were taken during the hysterectomy. However, the fallopian tube and endometrial tissues of EP patients were obtained during salpingectomy. The mRNA expressions of Mucin1, FGF2, and HBEGF genes in the fallopian tube and endometrial tissues were measured by real-time polymerase chain reaction (PCR) assay. MUC1 mRNA expression level in the endometrium of the case group was higher than in the control group (P=0.04); however, its mRNA expression in the fallopian samples of the case group in comparison with the control group was significantly decreased (P=0.001). The HBEGF mRNA expression level was not significantly different between the case and control endometrium, whereas its expression was significantly increased in the case fallopian samples compared with the control ones (P=0.001). The same pattern was observed for FGF2 mRNA expression level in the fallopian samples of the case group but was significantly reduced in the endometrial samples in comparison with the control samples (P=0.03). Mucin1, FGF2, and HBEGF gene mRNA expression changes may explain the embryo rejection from the uterus and the establishment of a receptive phenotype in fallopian cells.

Fenugreek Seed Extract Regulates Human Umbilical Vein Endothelial Cell Angiogenesis and Proliferation via the PI3K/Akt/Cyclin D1 Pathway.

The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cells were treated with various concentrations of HAEF and the half-maximal inhibitory concentration (IC50) value was estimated by using the MTT assay. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase enzyme (MMP-2 and MMP-9) gene expression profiles were evaluated by using quantitative RT-PCR (qRT-PCR). Moreover, MMP activities and PI3K, Akt and cyclin D1 protein expression levels were evaluated by gel zymography and Western blotting, respectively. HAEF reduced HUVEC viability, with an IC50 value of 200μg/ml. The qRT-PCR results demonstrated that treatment with HAEF markedly reduced MMP-2/MMP-9, VEGF and bFGF gene expression, as compared to the control group. We also found that MMP-2/MMP-9 enzyme activity and PI3K/Akt/cyclin D1 protein expression were notably decreased in cells treated with HAEF. Our results suggest that HAEF can potentially inhibit angiogenesis, and also affect cellular proliferation by targeting the PI3K/Akt/cyclin D1 pathway. Thus, fenugreek seed extract merits further investigation as a source of compounds with anti-cancer properties.

Comparison of the effects of itraconazole and prednisolone on fibroblast growth factor-2 gene expression and clinical manifestations in patients with persistent severe asthma.

Considering the possible role of fungal sensitization in the treatment of resistant asthma, which may lead to the remodeling of bronchial structure, we theorized that itraconazole could result in better control of asthma. In this regard, this study aimed to compare the effects of itraconazole and prednisolone (routinely prescribed) on clinical, structural, and biomarker findings of the remodeling of asthma. This double-blind controlled randomized clinical trial was performed on 70 adult patients suffering from severe persistent asthma. The intervention group received 200 mg of itraconazole per day, and the control group received 10 mg of prednisolone per day, for 32 weeks, in addition to the classic treatment of asthma. The subjects were randomly divided into two groups, and assigned by sealed envelope. Blinding was performed by repacking the drug in a similar container. Primary outcomes were asthma control test score, fibroblast growth factor 2, and wall area percentage on RB1 bronchus measured by computed tomography. The outcomes were compared in subjects classified as allergic, eosinophilic, T2 low asthma, and four types of inflammatory cell classification in sputum. Seventy subjects finished the 32-week trial (35 subjects in each group). Baseline data did not show significant differences between groups. A comparison of asthma variants showed significantly more severe cough and dyspnea in the allergic variant and higher spirometry results in T2-low asthma. Sputum cytology revealed a mixed pattern as the most frequent type (47%). After the trial, two groups improved in many parameters; however, FGF-2 improved more significantly by itraconazole (4.66±16.92 decreased to 1.14±2.98), and FEV1/FVC was significantly higher in the itraconazole group, compared to the control group. These results did not change in terms of asthma variants and sputum classification. Itraconazole was superior to prednisolone in the treatment of many clinical and spirometry aspects in severe persistent asthma.

Association of TGFB3 and FGFs gene polymorphisms with cleft lip with or without cleft palate a systematic review

Objectives: The objective of this study was to conduct a systematic review of the possible association between transforming growth factor B3 (TGFB3) and fibroblast growth factors (FGFs) gene polymorphisms and nonsyndromic cleft lip with or without cleft palate (NSCL/P). Material and Methods: Two reviewers independently screened studies by examining all titles and abstracts. Studies were included if they met the following criteria: The outcome of interest was NSCL/P; the polymorphisms studied were TGFB3 and FGF; they presented sufficient data, that is, allele/genotype frequency between cases and controls; or their odds ratio with 95% confidence interval. Study quality was independently assessed by a risk of bias assessment for genetic association studies. Results: Based on the inclusion criteria, we have selected a total of six articles (four for TGFB and two for FGF). Particularly for the TGFB gene, we have found significant results in exon 4 in the variant g.15812T&gt;G, and in the single-nucleotide polymorphisms rs2300607 A/T, in the distribution between cases and controls. On the other hand, for the FGF gene, we observed a statistically significant in the genotype rs34010 CA. Conclusion: None of the genetic variations that show the association is verified in different populations; therefore, there is not enough scientific validation regarding the association between TGFB and FGF polymorphism and NSCL/P. The findings of the different studies suggest the need for further investigations with samples composed of a larger number of individuals in different populations, which should be performed with all the standards for genetic studies, thus allowing an understanding of the molecular basis of the disease.

Genome-Wide Identification and Characterization of Bovine Fibroblast Growth Factor (FGF) Gene and Its Expression during Adipocyte Differentiation.

Fibroblast growth factor (FGF) family genes are a class of polypeptide factors with similar structures that play an important role in regulating cell proliferation and differentiation, nutritional metabolism, and neural activity. In previous studies, the FGF gene has been widely studied and analyzed in many species. However, the systematic study of the FGF gene in cattle has not been reported. In this study, 22 FGF genes distributed on 15 chromosomes were identified in the Bos taurus genome and clustered into seven subfamilies according to phylogenetic analysis and conservative domains. Collinear analysis showed that the bovine FGF gene family was homologous to Bos grunniens, Bos indicus, Hybrid-Bos taurus, Bubalus bubalis, and Hybrid-Bos indicus, and tandem replication and fragment replication were the key driving forces for the expansion of the gene family. Tissue expression profiling showed that bovine FGF genes were commonly expressed in different tissues, with FGF1, FGF5, FGF10, FGF12, FGF16, FGF17, and FGF20 being highly expressed in adipose tissue. In addition, real-time fluorescence quantitative PCR (qRT-PCR) detection showed that some FGF genes were differentially expressed before and after adipocyte differentiation, indicating their diverse role in the formation of lipid droplets. This study made a comprehensive exploration of the bovine FGF family and laid a foundation for further study on the potential function in the regulation of bovine adipogenic differentiation.

Identification, Characterization and Functional Analysis of Fibroblast Growth Factors in Black Rockfish (Sebastes schlegelii)

Fibroblast growth factors (FGFs) are short polypeptides that play essential roles in various cellular biological processes, including cell migration, proliferation, and differentiation, as well as tissue regeneration, immune response, and organogenesis. However, studies focusing on the characterization and function of FGF genes in teleost fishes are still limited. In this study, we identified and characterized expression patterns of 24 FGF genes in various tissues of embryonic and adult specimens of the black rockfish (Sebates schlegelii). Nine FGF genes were found to play essential roles in myoblast differentiation, as well as muscle development and recovery in juvelines of S. schlegelii. Moreover, sex-biased expression pattern of multiple FGF genes was recorded in the species' gonads during its development. Among them, expression of the FGF1 gene was recorded in interstitial and sertoli cells of testes, promoting germ-cell proliferation and differentiation. In sum, the obtained results enabled systematic and functional characterization of FGF genes in S. schlegelii, laying a foundation for further studies on FGF genes in other large teleost fishes.

Real-ambient particulate matter exposure-induced FGFR1 methylation contributes to cardiac dysfunction via lipid metabolism disruption

Particulate matter (PM)-induced cardiometabolic disorder contributes to the progression of cardiac diseases, but its epigenetic mechanisms are largely unknown. This study used bioinformatic analysis, in vivo and in vitro multiple models to investigate the role of PM-induced cardiac fibroblast growth factor 1 (FGFR1) methylation and its impact on cardiomyocyte lipid metabolic disruption. Bioinformatic analysis revealed that FGFR1 was associated with cardiac pathologies, mitochondrial function and metabolism, supporting the possibility that FGFR1 may play regulatory roles in PM-induced cardiac functional impairment and lipid metabolism disorders. Individually ventilated cage (IVC)-based real-ambient PM exposure system mouse models were used to expose C57/BL6 mice for six and fifteen weeks. The results showed that PM induced cardiac lipid metabolism disorder, DNA nucleotide methyltransferases (DNMTs) alterations and FGFR1 expression declines in mouse heart. Lipidomics analysis revealed that carnitines, phosphoglycerides and lysophosphoglycerides were most significantly affected by PM exposure. At the cellular level, AC16 cells treated with FGFR1 inhibitor (PD173074) led to impaired mitochondrial and metabolic functions in cardiomyocytes. Inhibition of DNA methylation in cells by 5-AZA partially restored the FGFR1 expression, ameliorated cardiomyocyte injury and mitochondrial functions. These changes involved alterations in AMP-activated protein kinase (AMPK)-peroxisome proliferator activated receptors gamma, coactivator 1 alpha (PGC1α) pathways. Bisulfite sequencing PCR (BSP) and DNA methylation specific PCR (MSP) confirmed that PM exposure induced FGFR1 gene promoter region methylation. These results suggested that, by inducing FGFR1 methylation, PM exposure would affect cardiac injury and deranged lipid metabolism. Overexpression of FGFR1 in mouse heart using adeno-associated virus 9 (AAV9) effectively alleviated PM-induced cardiac impairment and metabolic disorder. Our findings identified that FGFR1 methylation might be one of the potential indicators for PM-induced cardiac mitochondrial and metabolic dysfunction, providing novel insights into underlying PM-related cardiotoxic mechanisms.

A case of Crouzon syndrome with papilloedema and exotropia

Early fusion of skull bones is the root cause of craniosynostosis. Nonsyndromic craniosynostosis affect only one suture of the skull while syndromic craniosynostosis affects multiple sutures and are associated with craniofacial dysmorphisms also abnormalities of extremities and other bony anomalies. 90% of cases are attributed to fibroblast growth factor gene 2 on chromosome 10p 25-q26, is responsible for more than. Crouzon syndrome is an autosomal dominant cause that constitutes 4.5% of craniosynostosis patients incidence of which is 0.16/10,000 population worldwide, most commonly involving coronal and frontosphenoidal suture. There is increased antero-posterior diameter of skull, hypoplasia of maxilla, and shallow orbits. Other features being brachycephaly, mid-face hypoplasia, and wider skull base anteriorly causing hypertelorism. Compensatory growth of uninvolved structure causes frontal bossing. Hydrocephalus, parrot beak-nose, hypoplasia of the maxilla, and high-arched palate is also noted. Relative proptosis is seen in most of the cases due to orbital hypoplasia. Ocular findings include vision impairment, strabismus, glaucoma, nystagmus, occasionally, corneal size abnormalities, keratoconus, corectopia, or aniridia. This case report is unique as it describes a 12 year old female of crouzon syndrome which presented with papilloedema and divergent squint which is rearely associated with this syndrome.