Fgf8 Expression Research Articles

Screening and identification of immune-related genes for immunotherapy and prognostic assessment in colorectal cancer patients

BackgroundIncreasing evidence indicates that the immune microenvironment plays a key role in the genesis and progression of colorectal cancer (CRC). This study aimed to establish an immune-related gene (IRG) signature and determine its clinical prognostic value in patients with CRC.MethodsThe RNA sequencing and associated clinical data of CRC were downloaded from The Cancer Genome Atlas (TCGA) database. We then screened for differentially expressed IRGs by intersecting with IRGs obtained from the Immunology Database and Analysis Portal. Functional enrichment analyses were carried out to determine the potential biological functions and pathways of the IRGs. We also explored the specific molecular mechanisms of the IRGs by constructing regulatory networks. Prognostic IRGs were obtained by LASSO regression analysis, and subsequently, gene models were constructed in the TCGA dataset to confirm the predictive capacity of these IRGs. Finally, we used the TIMER tool to assess the immune properties of prognostic IRGs and correlate them with immune cells.ResultsWe identified 409 differentially expressed IRGs in patients with CRC. Kyoto Encyclopaedia of Genes and Genomes and Gene Ontology enrichment analyses suggested that these differentially expressed IRGs were significantly related to 102 cancer signalling pathways and various biological functions. Based on the prediction and interaction results, we obtained 59 TF–IRG, 48 miRNA–IRG, and 214 drug–IRG interaction networks for CRC. Four prognostic genes (POMC, TNFRSF19, FGF2, and SCG2) were developed by integrating 47 survival-related IRGs and 42 characteristic CRC genes. The results of gene model showed that patients in the low risk group had better survival outcomes compared to those in the high risk group. The expression of POMC, TNFRSF19, FGF2, and SCG2 was significantly correlated with immune cells.ConclusionThis study identified some valid IRGs, and these findings can provide strong evidence for precision immunotherapy in patients with CRC.

Influence of dietary soybean meal replacement with yellow mealworm (Tenebrio molitor) on growth performance, antioxidant capacity, skin color, and flesh quality of mirror carp (Cyprinus carpio var. specularis)

Yellow mealworms (TM) are currently receiving increasing attention as dietary protein source in aquaculture. A 60-day feeding trial was conducted to study the effects of dietary soybean meal (SM) replacement by TM on growth performance, antioxidant capacity, and flesh quality of mirror carp. A total of 630 mirror carp were fed seven diets containing graded concentrations of TM: YM0 (control), YM15, YM30, YM45, YM60, YM75, and YM100, corresponding to 0%, 15%, 30%, 45%, 60%, 75%, and 100% dietary soybean meal replacement. The results indicated dietary TM significantly improved the final body weight (FBW), specific growth rate (SGR), and protein efficiency (PE) (P < 0.05), except for YM100 (P > 0.05). The antioxidant capacity was promoted by increasing muscle total antioxidant capacity (T-AOC) in YM30 and superoxide dismutase (SOD) activity in TM supplemented groups (P < 0.05). The nutritional value was significantly boosted by increasing the muscle protein of YM45 and YM60 groups, the whole-body protein and muscle glycine and proline of YM60 group, and the muscle arginine of YM100 group (P < 0.05). The economic value of mirror carp also increased with the improvement of skin color by increasing yellowness (b*) (P < 0.05). Furthermore, all muscle textural parameters, fiber density, sarcomere length, and the mRNA expression of genes involved in muscle cell growth had similar change trends, increasing initially and then declining with the increase of dietary TM level. The muscle chewiness, cohesiveness, and mfr4 expression in YM15, and the adhesiveness, fiber density, sarcomere length, and mRNA expression of fgf in YM45 were higher than in the control and YM100 (P < 0.05), while no difference was found between control and YM100 (P > 0.05). The mRNA expression levels of myhc and TOR in the muscle of YM60 were significantly higher than those of the control group (P < 0.05), while there was no significant difference in YM100 (P > 0.05). According to the results of principal components analysis (PCA), the muscle textural properties in YM45 were optimal among all groups. As a consequence, TM would be able to completely replace dietary soybean meal without negative influences on growth performance, antioxidant capacity, or flesh quality of mirror carp. Finally, based on FBW, muscle crude protein, muscle fiber diameter, and protein retention efficiency (PRE), the optimal levels of dietary soybean meal replaced by TM were 50.14%, 52.43%, 53.60%, and 55.35%, respectively.

The Lnc-RNA APPAT Suppresses Human Aortic Smooth Muscle Cell Proliferation and Migration by Interacting With MiR-647 and FGF5 in Atherosclerosis

Purpose: LncRNA-Atherosclerotic plaque pathogenesis-associated transcript (APPAT) could be detected in circulating blood and has been demonstrated to correlate with the development of atherosclerosis in our previous work. It could be a potential noninvasive biomarker for earlier diagnoses of clinical cardiovascular disease. Moreover, the expression of miR-647 increased in ox-LDL-treated vascular smooth muscle cells and peripheral blood of patients with coronary heart disease. A negative correlation between APPAT and miR-647 was confirmed, and FGF5 was screened as molecular target of miR-647. However, it is largely unclear how APPAT, miR-647, and FGF5 interact and function in disease development. Here, we aim to explore the underlying molecular mechanism in this progression. Materials and Methods: APPAT, miR-647, and FGF5 expression levels were detected by quantitative reverse transcription polymerase chain reaction; cell proliferation was detected by EdU incorporation assay; cell migration was detected by wound-healing assay; the molecular interaction of APPAT/FGF5 with miR-647 was verified by dual-luciferase reporter assay; the western blot was performed to determine the gene expression at protein levels; subcellular localizations of APPAT and miR-647 were observed by fluorescence in situ hybridization; cytosolic and nucleus fractionation assay was performed to further detect the distribution of miR-647. Results: APPAT and miR-647 have inverse effects on human aortic smooth muscle cells’ (HASMCs) proliferation and migration. APPAT negatively regulated the cell activity, whereas miR-647 did it in a positive way (p<0.05). Three pairs of molecular interplay were found: mutual negative regulation between APPAT and miR-647, APPAT downregulated FGF5, miR-647 regulation on FGF5 (p<0.05). Subcellular location assay confirmed the molecular interaction of APPAT and miR-647. Conclusions: APPAT could suppress the migration and proliferation of ox-LDL-treated HASMCs via interacting with miR-647 and FGF5. We revealed a nontypical competing endogenous RNA mechanism of long noncoding RNA in the progression of atherosclerosis.

Investigation on the growth factor regulatory network of dermal fibroblasts in mouse full-thickness skin defect wounds based on single-cell RNA sequencing

Investigation on the growth factor regulatory network of dermal fibroblasts in mouse full-thickness skin defect wounds based on single-cell RNA sequencing

Diverse actions of sirtuin-1 on ovulatory genes and cell death pathways in human granulosa cells

BackgroundHuman granulosa-lutein cells (hGLCs) amply express sirtuin-1 (SIRT1), a NAD + -dependent deacetylase that is associated with various cellular functions. SIRT1 was shown to elevate cAMP on its own and additively with human chorionic gonadotropin (hCG), it is therefore interesting to examine if SIRT1 affects other essential hGLC functions.MethodsPrimary hGLCs, obtained from the follicular aspirates of women undergoing IVF and SV40-transfected, immortalized hGLCs (SVOG cells), were used. Primary cells were treated with SIRT1 specific activator SRT2104, as well as hCG or their combination. Additionally, siRNA-targeting SIRT1 construct was used to silence endogenous SIRT1 in SVOG cells. PTGS2, EREG, VEGFA and FGF2 expression was determined using quantitative polymerase chain reaction (qPCR). Apoptotic and necroptotic proteins were determined by specific antibodies in western blotting. Cell viability/apoptosis was determined by the XTT and flow cytometry analyses. Data were analyzed using student t-test or Mann–Whitney U test or one-way ANOVA followed by Tukey HSD post hoc test.ResultsIn primary and immortalized hGLCs, SRT2104 significantly upregulated key ovulatory and angiogenic genes: PTGS2, EREG, FGF2 and VEGFA, these effects tended to be further augmented in the presence of hCG. Additionally, SRT2104 dose and time-dependently decreased viable cell numbers. Flow cytometry of Annexin V stained cells confirmed that SIRT1 reduced live cell numbers and increased late apoptotic and necrotic cells. Moreover, we found that SIRT1 markedly reduced anti-apoptotic BCL-XL and MCL1 protein levels and increased cleaved forms of pro-apoptotic proteins caspase-3 and PARP. SIRT1 also significantly induced necroptotic proteins RIPK1 and MLKL. RIPK1 inhibitor, necrostatin-1 mitigated SIRT1 actions on RIPK1 and MLKL but also on cleaved caspase-3 and PARP and in accordance on live and apoptotic cells, implying a role for RIPK1 in SIRT1-induced cell death. SIRT1 silencing produced inverse effects on sorted cell populations, anti-apoptotic, pro-apoptotic and necroptotic proteins, corroborating SIRT1 activation.ConclusionsThese findings reveal that in hGLCs, SIRT1 enhances the expression of ovulatory and angiogenic genes while eventually advancing cell death pathways. Interestingly, these seemingly contradictory events may have occurred in a cAMP-dependent manner.

LncRNA MALAT1 from human adipose-derived stem cell exosomesaccelerates wound healing via miR-378a/FGF2 axis.

Aim: The effects of MALAT1from human adipose-derived stem cell(ADSC) exosomes in skin wound healingwere investigated. Material & methods: The viability, apoptosisand migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometryand scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosisand inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.

Polygonatum sibiricum improves menopause symptoms by regulating hormone receptor balance in an ovariectomized mouse model

Female menopause is a hormone deficiency phenomenon that causes hot flashes, vaginal dryness, depression, nervous tension, insomnia, obesity, and bone loss. There are various hormone replacement therapy (HRT)-based menopausal treatments, but they are accompanied by side effects such as endometrial cancer and hyperplasia. To confirm the menopausal improvement effect of Polygonatum sibiricum (PS), we prepared an ovariectomized animal model, administered 17β-estradiol (E2) and PS, and analyzed various menopausal symptoms. PS restored vaginal epithelium thickness, by increasing the expression of estrogen receptors ERα (ESR1) and ERβ (ESR2), and increased serotonin concentration by reducing serotonin receptor 1 A (5-HT1A) and glucocorticoid receptor (Gr) expression. In addition, PS suppressed obesity by increasing HDL-C and decreasing LDL-C levels and improved the osteoporosis induced by ovariectomy. In particular, by controlling Hand2, Fgf2, and Faf9 expression through PR, the antiproliferative signal was suppressed in uterine epithelium, thereby reducing the risk of side effects of the administration of E2 alone. These results demonstrate that PS alleviates menopausal symptoms without causing endometrial hyperplasia.

Effects of Hyperbaric Oxygen Therapy on the Expression of FGF, MMP-9 and Occludin in the Repair of Gastric Mucosal Erosions

Effects of Hyperbaric Oxygen Therapy on the Expression of FGF, MMP-9 and Occludin in the Repair of Gastric Mucosal Erosions

Gene Expression Profile of Stromal Factors in Cancer-Associated Fibroblasts from Prostate Cancer

Recent investigations point at the stromal microenvironment to assess additional diagnostic information and provide new therapeutic targets in cancer. The aim of the study was to contribute to the characterization of the phenotype of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa) compared with normal prostate-associated fibroblasts (NAFs) and fibroblasts from benign prostatic hyperplasia (BPH). Three patient populations were prospectively recruited: 23 patients with new localized PCa, 14 patients with advanced PCa treated with androgenic deprivation therapy (ADT), and 7 patients with BPH. Gene expression of 20 stroma-derived factors, including the androgen receptor (AR), chaperones (HSPA1A and HSF1), growth factors (FGF2, FGF7, FGF10, HGF, PDGFB, and TGFβ), proteins implicated in invasion (MMP2, MMP9, and MMP11), inflammation (IL6, IL17RB, NFκB, and STAT3), and in-stroma/epithelium interaction (CDH11, CXCL12, CXCL14, and FAP), was evaluated. Localized PCa CAFs showed a significant higher expression of FGF7, IL6, MMP2, and MMP11 compared with NAFs or IL17RB compared with BPH fibroblasts, but significantly lower expression of FGF10 and IL17RB compared with NAFs or CXCL14 compared with BPH fibroblasts. In addition, CAFs from ADT-resistant PCa showed significantly higher MMP11 and NFκB but significant lower TGFβ expression compared with CAFs from ADT-sensitive tumors. Our results contribute to defining the CAFs phenotypes associated to PCa progression, which may contribute to the diagnosis and design of alternative therapies in PCa.

CircCCT3 Enhances Invasion and Epithelial-Mesenchymal Transition (EMT) of Non-Small-Cell Lung Cancer (NSCLC) via the miR-107/Wnt/FGF7 Axis

Background CircRNAs play a role in a variety of biological processes, including tumorigenesis. circCCT3 has been shown to regulate cancer initiation and progression. Unfortunately, whether circCCT3 is involved in non-small-cell lung cancer (NSCLC) metastasis remains unclear. Methods Our study utilized RT-qPCR to examine gene expression levels. A transwell assay was used to measure invasion ability of cells. Starbase software and TargetScan software were used to predict target genes. Results circCCT3 knockdown attenuated invasion and epithelial-mesenchymal transition (EMT) of A549 and Calu-1 cells. miR-107 mimics could rescue circCCT3-induced invasion and EMT. Next, miR-107 mimics and circCCT3 knockdown suppressed Wnt3a and FGF7 expression. An miR-107 inhibitor promoted Wnt3a and FGF7 expressions. Finally, FGF7 greatly restored miR-107-inhibited invasion and EMT of A549 cells. Conclusion Here, we reveal a molecular mechanism circCCT3/miR-107/Wnt/FGF7 responsible for NSCLC metastasis.

Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway.

Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth. Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of HDAC3 in the developing epicardium. We deleted Hdac3 in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly downregulated in Hdac3 KO mouse epicardial cells. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO mouse epicardial cells and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO mouse epicardial cells. Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.

Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer

BackgroundObesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion.MethodsWe hypothesized that preventing weight gain after ovariectomy (OVX) may be sufficient to prevent the formation of new tumors and decrease growth of existing mammary tumors. We tested this hypothesis in a rat model of obesity and carcinogen-induced postmenopausal mammary cancer and validated our findings in a murine xenograft model with implanted human tumors.ResultsIn both models, preventing weight gain after OVX significantly decreased obesity-associated tumor development and growth. Importantly, we did not induce weight loss in these animals, but simply prevented weight gain. In both lean and obese rats, preventing weight gain reduced visceral fat accumulation and associated insulin resistance. Similarly, the intervention decreased circulating tumor-promoting growth factors and inflammatory cytokines (i.e., BDNF, TNFα, FGF-2), with greater effects in obese compared to lean rats. In obese rats, preventing weight gain decreased adipocyte size, adipose tissue macrophage infiltration, reduced expression of the tumor-promoting growth factor FGF-1 in mammary adipose, and reduced phosphorylated FGFR indicating reduced FGF signaling in tumors.ConclusionsTogether, these findings suggest that the underlying mechanisms associated with the anti-tumor effects of weight maintenance are multi-factorial, and that weight maintenance during the peri-/postmenopausal period may be a viable strategy for reducing obesity-associated breast cancer risk and progression in women.

MiR-195-5p facilitates the proliferation, migration, and invasion of human trophoblast cells by targeting FGF2.

Preeclampsia (PE), the most significant adverse exposure to cardiovascular risk during pregnancy, is one of the three major factors contributing to maternal and fetal mortality and the leading cause of preterm birth. Recently, various miRNAs have been reported to participate in PE occurrence and development. Nevertheless, the regulatory impact of miR-195-5p in PE is still indistinct. Quantitative realtime-PCR (qRT-PCR), western blot, and fluorescence in situ hybridization (FISH) assay were performed to examine miR-195-5p and FGF2 expressions in PE serum samples or HTR-8/SVneo and TEV-1 cells. CCK8, flow cytometry, wound scratch, and transwell assays were conducted to determine cell viability, cycle, apoptosis, migration, and invasion. Dual-luciferase reporter assay unveiled the relationship between miR-195-5p and FGF2. Migration-related and invasion-related protein expressions were measured by western blot assay. miR-195-5p was prominently downregulated while FGF2 was increased in serum samples from PE patients and hypoxia-treated human trophoblast cells. FGF2 was predicted as a downstream target of miR-195-5p and targeted association was verified by dual-luciferase reporter assay. Functional experiments elaborated that miR-195-5p could facilitate trophoblast cell proliferation and metastasis but hinder cell cycle and apoptosis. Inversely, overexpressing of FGF2 could reverse the effects of miR-195-5p on trophoblast cell growth. miR-195-5p was decreased in PE serum samples and cell lines, serving as a potential biomarker in protecting PE exacerbation by targeting FGF2.

Integrated Analysis of Immune-Related circRNA-miRNA-mRNA Regulatory Network in Ischemic Stroke.

BackgroundStroke is the leading cause of death and disability worldwide, with ischemic stroke (IS) being the most prevalent type. Circular RNAs (circRNAs) are involved in the pathological process of IS and are promising biomarkers for the diagnosis of IS. However, studies focusing on circRNAs acting as microRNAs (miRNAs) sponges in regulating mRNA expression are currently scarce.MethodsIn this study, expression profiles of circRNAs (GSE195442), miRNAs (GSE117064), and mRNAs (GSE58294) from the Gene Expression Omnibus (GEO) database were analyzed. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by R software. The target miRNAs and target genes were predicted by several bioinformatics methods. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEmRNAs. Subsequently, the protein-protein interaction (PPI) network and the competing endogenous RNA (ceRNA) regulatory network were visualized by Cytoscape software. Finally, we further constructed an immune-related circRNA-miRNA-mRNA regulatory sub-network in IS.ResultsA total of 35 DEcircRNAs, 141 DEmiRNAs, and 356 DEmRNAs were identified. By comprehensive analysis of bioinformatics methods, we constructed a circRNA-miRNA-mRNA regulatory network, including 15 DEcircRNAs, eight DEmiRNAs, and 39 DEmRNAs. FGF9 was identified as an immune-related hub gene. Immune cell analysis indicated a significantly higher level of neutrophils in IS, and the expression of FGF9 was significantly negatively correlated with the level of neutrophils. Eventually, miR-767-5p was predicted as the upstream molecules of FGF9, and circ_0127785 and circ_0075008 were predicted as the upstream circRNAs of miR-767-5p.ConclusionOur study provides novel insights into the molecular mechanisms governing the progression of IS from the perspective of immune-related ceRNA networks.

Single-cell transcriptomics reveals the natural product Shi-Bi-Man promotes hair regeneration by activating the FGF pathway in dermal papilla cells

BackgroundFinasteride and minoxidil are two commonly used drugs for the treatment of hair loss. However, these two drugs have certain side effects. Thus, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. Shi-Bi-Man (SBM) is a hair health supplement that darkens hair and contains ginseng radix, tea polyphenols, polygonum multiflorum, radix angelicae sinensis, aloe, linseed, and green tea extract. PurposeThis study aimed to find potential effective monomer components to promote hair regeneration from SBM and to explore the mechanism of SBM to promote hair regeneration. MethodsSupplementation with the intragastric administration or smear administration of SBM in artificially shaved C57BL/6 mice, observe its hair growth. UPLC/MS and UPLC/LTQ-Orbitrap-MS detect the main components in SBM and the main monomers contained in the skin after smearing, respectively. A network pharmacology study on the main components of SBM and single-cell RNA sequencing was performed to explore the role of SBM for hair regeneration. ResultsSBM significantly induced hair growth compared with a control treatment. TSG and EGCG were the main monomers in the skin after SBM smearing. The results of single-cell sequencing revealed that after SBM treatment, the number of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) increased significantly. Cell interactions and volcano dots show that the interaction of the FGF signaling pathway was significantly enhanced, in which Fgf7 expression was especially upregulated in DPCs. In addition, the Wnt signaling pathway also had a partially enhanced effect on the interactions between various cells in the skin. The network pharmacology study showed that the promotion of the FGF and Wnt pathways by SBM was also enriched in alopecia diseases. ConclusionWe report that SBM has a potential effect on the promotion of hair growth by mainly activating the FGF signaling pathway. The use of SBM may be a novel therapeutic option for hair loss.

Urinary Tract Infections Impair Adult Hippocampal Neurogenesis.

Simple SummaryUrinary tract infections are associated with features of cognitive decline and memory deficits, where the underlying correlation or mechanism is still not clear. In this study, we investigate the effect of urinary tract infections on cognitive functions in rodents and whether it is associated with adult hippocampal neurogenesis, a process that is detrimental for memory formation. We have shown that urinary tract infection affects the time spent exploring a novel arm in the Y-maze test. This was accompanied with a decrease in the proliferation of neural stem cells at an early time point post infection and a persistent decrease in neurogenesis at a later time point (34 days). We also detected decreased levels of neurotrophic factors important for neurogenesis and an elevated expression of interleukin 1β in the hippocampus. Treatment with either anti-inflammatory drugs or anti-biotics does not recover proliferation of neural stem cells. Here, we present hippocampal neurogenesis as a possible contributor to cognitive changes associated with urinary tract infections. Given the significant increase in urinary tract infection occurrence, it is important to address some of the detrimental effects that such an infection can have at the level of the brain.Previous studies have suggested a link between urinary tract infections (UTIs) and cognitive impairment. One possible contributing factor for UTI-induced cognitive changes that has not yet been investigated is a potential alteration in hippocampal neurogenesis. In this study, we aim to investigate the effect of UTI on brain plasticity by specifically examining alterations in neurogenesis. Adult male Sprague Dawley rats received an intra-urethral injection of an Escherichia coli (E. coli) clinical isolate (108 CFU/mL). We found that rats with a UTI (CFU/mL ≥ 105) had reduced proliferation of neural stem cells (NSCs) at an early time point post infection (day 4) and neurogenesis at a later time point (day 34). This was associated with the decreased expression in mRNA of BDNF, NGF, and FGF2, and elevated expression of IL-1β in the hippocampus at 6 h post infection, but with no changes in optical intensity of the microglia and astrocytes. In addition, infected rats spent less time exploring a novel arm in the Y-maze test. Treatment with an anti-inflammatory drug did not revert the effect on NSCs, while treatment with antibiotics further decreased the basal level of their proliferation. This study presents novel findings on the impact of urinary tract infections on hippocampal neurogenesis that could be correlated with cognitive impairment.

The genomic and transcriptome characteristics of lung adenocarcinoma patients with previous breast cancer

BackgroundBreast cancer and lung cancer are the top two malignancies in the female population and the number of patients with breast cancer and subsequent primary lung cancer has increased significantly in recent years. However, the unique molecular characteristics of this group of patients remains unclear.PurposeTo identify the genomic and transcriptome characteristics of primary lung adenocarcinoma patients with previous breast cancer by comparison with single primary lung adenocarcinoma (SPLA) patients.MethodsThe tumor and normal pulmonary tissue specimens of ten primary pulmonary adenocarcinoma patients with previous breast cancer (multiple primary cancer, MPC) and ten SPLA patients were prospectively collected. The whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to analyze the gene mutation and expression differences between MPC and SPC patients.ResultsThe results of WES indicated that the mutations of TRIM73, DLX6 and CNGB1 only existed in MPC patients. The results of RNA-seq manifested the occurrence of second primary lung adenocarcinoma in breast cancer patients was closely associated with cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Besides, the expression levels of FGF10 and VEGFA genes were significantly increased in MPC patients.ConclusionThe occurrence of second primary lung adenocarcinoma may be related to the cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Furthermore, the mutations of TRIM73, DLX6 and CNGB1 and high expression of FGF10 and VEGFA might play an important role in the development of lung adenocarcinoma in breast cancer patients. However, more in-depth investigations are needed to verify above findings.

The Regulation of Spermatogonial Stem Cells in an Adult Testis by Glial Cell Line-Derived Neurotrophic Factor.

This review focuses on the in vivo regulation of spermatogonial stem cells (SSCs) in adult testes by glial cell line-derived neurotrophic factor (GDNF). To study adult mouse testes, we reversibly inhibited GDNF stimulation of SSCs via a chemical-genetic approach. This inhibition diminishes replication and increases differentiation of SSCs, and inhibition for 9 days reduces transplantable SSC numbers by 90%. With more sustained inhibition, all SSCs are lost, and testes eventually resemble human testes with Sertoli cell-only (SCO) syndrome. This resemblance prompted us to ask if GDNF expression is abnormally low in these infertile human testes. It is. Expression of FGF2 and FGF8 is also reduced, but some SCO testes contain SSCs. To evaluate the possible rebuilding of an SSC pool depleted due to inadequate GDNF signaling, we inhibited and then restored signaling to mouse SSCs. Partial rebuilding occurred, suggesting GDNF as therapy for men with SCO syndrome.

Bioinformatics Analysis Screened and Identified Key Genes as Potential Biomarkers for Progression of Lung Cancer.

To screen and identify key genes as potential biomarkers of lung cancer using bioinformatics analysis. Observational study. Department of Critical Care Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China, from August 2018 to April 2021. Independent microarray datasets (GSE85841 and GSE118370) were downloaded from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were screened using GEO2R. Cytohubba was employed to identify the hub genes. Cellular component analysis, hierarchical clustering, and survival analyses of hub genes were performed via BiNGO, UCSC, and cBioPorta. A series of analyses of FGF2 and PIK3R1 were conducted using Oncomine. A total of 463 DEGs were identified and 11 hub genes were determined. BDNF, FGF2, JAK2, NCAM1, CAV1, TJP1, and PIK3R1 may affect the survival probability and life expectancy of lung cancer patients, but the p-values were not statistically significant. FGF2 and PIK3R1 had the highest node degrees, 40 and 32 respectively. The expression of FGF2 and PIK3R1 were significantly lower in the 4 lung cancer data sets compared with non-lung cancer tissues. And the low expression of FGF2 and PIK3R1 is related to tumor grades, family history of cancer, multiple tumors present, and prior therapy of lung cancer. Evaluation of FGF2 and PIK3R1 as potential biomarkers can contribute to the subsequent theoretical analysis of potential molecular mechanisms and development of lung cancer, so that the diagnosis of lung cancer may be more accurate, and it is possible to provide therapeutic and prognostic medicine targets. Lung neoplasms, Differentially expressed genes, Bioinformatical analysis, Microarray analysis, biomarkers.

MicroRNA-149-Mediated MAPK1/ERK2 Suppression Attenuates Hair Follicle Stem Cell Differentiation.

Hair follicle stem cells (HFSCs) are responsible for hair growth and hair follicle regeneration. MicroRNAs have been demonstrated to be involved in the differentiation of HFSCs. Thus, this study aimed to explore the potential role of miR-149 in the differentiation of HFSCs. The isolated HFSCs were identified by flow cytometric sorting. miR-149 expression was determined during differentiation of HFSCs. Gain- and loss-of-function approaches were conducted to explore the roles of miR-149, MAPK1/ERK2, and FGF2/c-MYC in colony formation and proliferation of HFSCs. Furthermore, in vivo assays were undertaken in miR-149 knockout mice to confirm their roles in HFSC differentiation. miR-149 was found to be downregulated during HFSC differentiation, and overexpressed miR-149 restricted the proliferation and differentiation of HFSCs. miR-149 was confirmed to target and inhibit MAPK1/ERK2, which was highly expressed in and positively associated with HFSC differentiation. The MAPK1/ERK2 promotion in HFSC differentiation was achieved by augmenting expression of FGF2 and c-MYC. The in vitro effects of miR-149 were validated in in vivo experiments. Taken together, upregulated miR-149 restricted HFSC differentiation and hair growth by targeting MAPK1/ERK2 to reduce expression of FGF2 and c-MYC, which sheds light on the underlying molecular mechanism of hair growth.