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Thoracic Cancer May 2024Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer....
BACKGROUND
Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in breast cancer remain poorly understood.
METHODS
Breast cancer cells were cultured and treated with different doses (0, 20, 40, and 60 μM) of BBR for 48 h. Cell viability, proliferation, apoptosis, invasion, and migration were assessed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase-like 3 (METTL3), and insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) mRNA levels and protein levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Interaction between METTL3 and FGF7 m6A was assessed using methylated RNA immunoprecipitation (MeRIP)-qPCR and RNA immunoprecipitation (RIP) assay. Binding ability between IGF2BP3 and FGF7 mRNA was analyzed using RIP assay.
RESULTS
BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis. FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR-treated tumor cells. FGF7 upregulation relieved the repression of BBR on breast cancer cell malignant behaviors. In mechanism, METTL3 stabilized FGF7 mRNA through the m6A-IGF2BP3-dependent mechanism and naturally improved FGF7 expression. BBR treatment inhibited breast cancer growth in vivo.
CONCLUSION
BBR treatment blocked breast cancer cell growth and metastasis partly by regulating METTL3-mediated m6A modification of FGF7 mRNA, providing a promising therapeutic target for breast cancer treatment.
PubMed: 38709912
DOI: 10.1111/1759-7714.15321 -
European Journal of Medical Research May 2024This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge...
BACKGROUND
This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model.
METHODS
CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter.
RESULTS
Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth.
CONCLUSION
GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.
Topics: Animals; Mesenchymal Stem Cells; Humans; Culture Media, Conditioned; Mice; Umbilical Cord; Hair; Insulin-Like Growth Factor I; Vascular Endothelial Growth Factor A; Hepatocyte Growth Factor; Gelatin; Tissue Scaffolds; Mice, Inbred C57BL; Cells, Cultured; Fibroblast Growth Factor 7
PubMed: 38704575
DOI: 10.1186/s40001-024-01830-7 -
Annals of Burns and Fire Disasters Sep 2023Our previous study on how the combination of stromal vascular fraction cells (SVFs) and platelet-rich plasma (PRP) affect deep dermal burn healing showed promising...
The Combination of Stromal Vascular Fraction Cells and Platelet-Rich Plasma Increases Fibroblast Growth Factor 7 and Promotes Angiogenesis in Full Thickness Burn Injury: Rat Experimental Study.
Our previous study on how the combination of stromal vascular fraction cells (SVFs) and platelet-rich plasma (PRP) affect deep dermal burn healing showed promising results. In this study, we assessed the effect on full-thickness burns by evaluating FGF7 serum level and capillary count. Forty-eight Wistar rats were divided into four major groups: (1) locally injected with combined SVFs and PRP; (2) topically applied Vaseline; (3) locally injected with placebo; (4) and rats without burns. These groups were divided further into smaller groups based on the day of euthanasia (8th hour, 4th day, 7th day, 14th day, and 21st day). FGF7 serum level was measured using ELISA, and capillaries were counted using a microscope. A one-way ANOVA test, post hoc, and regression tests were used. On day 4, both FGF7 and capillary counts showed significant differences between groups (p=0.000 and 0.048, respectively). On day 7, only FGF7 result showed a significant difference (p=0.000). On day 14, FGF7 and capillary counts showed significant differences (p=0.000, 0.018 respectively). The SVFs and PRP-treated groups showed superior results compared to other groups. The injection of combined SVFs and PRP increased FGF7 and capillary counts.
PubMed: 38680441
DOI: No ID Found -
Cancers Apr 2024Children undergoing antineoplastic treatment often present severe side effects due to the dosage and duration of treatments, with oral mucositis emerging as one of the... (Review)
Review
Children undergoing antineoplastic treatment often present severe side effects due to the dosage and duration of treatments, with oral mucositis emerging as one of the most prevalent and painful inflammatory conditions. There is a growing body of evidence on therapeutic interventions such as cryotherapy, low-level laser therapy, and natural compounds for this condition. The aim of this systematic review was to identify and compare therapies for the management of cancer treatment-induced oral mucositis in pediatric patients. From 2655 articles obtained in initial searches, 39 articles were considered in this systematic review, after applying inclusion/exclusion criteria. Low-level laser therapy, palifermin, honey, and zinc demonstrated reductions in oral mucositis incidence, duration, severity, and pain reported by the patient. Although there are several therapies in place for the prevention and treatment of oral mucositis in children, evidence of their efficacy is still inconclusive to establish accurate clinical protocols.
PubMed: 38672630
DOI: 10.3390/cancers16081548 -
Signal Transduction and Targeted Therapy Apr 2024The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2...
The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
Topics: Animals; Humans; Male; Mice; Angiotensin-Converting Enzyme 2; COVID-19; Fibroblast Growth Factor 7; Human Embryonic Stem Cells; Insulin Secretion; Islets of Langerhans; Organoids; SARS-CoV-2
PubMed: 38654010
DOI: 10.1038/s41392-024-01790-8 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Mar 2024Craniomaxillofacial development involves a series of highly ordered temporal-spatial cellular differentiation processes in which a variety of cell signaling factors,... (Review)
Review
Craniomaxillofacial development involves a series of highly ordered temporal-spatial cellular differentiation processes in which a variety of cell signaling factors, such as fibroblast growth factors, play important regulatory roles. As a classic fibroblast growth factor, fibroblast growth factor 7 (FGF7) serves a wide range of regulatory functions. Previous studies have demonstrated that FGF7 regulates the proliferation and migration of epithelial cells, protects them, and promotes their repair. Furthermore, recent findings indicate that epithelial cells are not the only ones subjected to the broad and powerful regulatory capacity of FGF7. It has potential effects on skeletal system development as well. In addition, FGF7 plays an important role in the development of craniomaxillofacial organs, such as the palate, the eyes, and the teeth. Nonetheless, the role of FGF7 in oral craniomaxillofacial development needs to be further elucidated. In this paper, we summarized the published research on the role of FGF7 in oral craniomaxillofacial development to demonstrate the overall understanding of FGF7 and its potential functions in oral craniomaxillofacial development.
Topics: Humans; Fibroblast Growth Factor 7; Animals; Skull; Maxillofacial Development; Tooth
PubMed: 38645865
DOI: 10.12182/20240360505 -
American Journal of Physiology. Renal... Jun 2024Urothelium forms a distensible yet impermeable barrier, senses and transduces stimuli, and defends the urinary tract from mechanical, chemical, and bacterial injuries....
Urothelium forms a distensible yet impermeable barrier, senses and transduces stimuli, and defends the urinary tract from mechanical, chemical, and bacterial injuries. Biochemical and genetic labeling studies support the existence of one or more progenitor populations with the capacity to rapidly regenerate the urothelium following injury, but slow turnover, a low mitotic index, and inconsistent methodologies obscure progenitor identity. The progenitor properties of basal keratin 5 urothelial cells (K5-UCs) have been previously investigated, but those studies focused on embryonic or adult bladder urothelium. Urothelium undergoes desquamation and apoptosis after birth, which requires postnatal proliferation and restoration. Therefore, we mapped the fate of bladder K5-UCs across postnatal development/maturation and following administration of cyclophosphamide to measure homeostatic and reparative progenitor capacities, respectively. In vivo studies demonstrate that basal K5-UCs are age-restricted progenitors in neonates and juveniles, but not in adult mice. Neonatal K5-UCs retain a superior progenitor capacity in vitro, forming larger and more differentiated urothelial organoids than adult K5-UCs. Accordingly, K5-UC transcriptomes are temporally distinct, with enrichment of transcripts associated with cell proliferation and differentiation in neonates. Induction of urothelial proliferation is sufficient to restore adult K5-UC progenitor capacity. Our findings advance the understanding of urothelial progenitors and support a linear model of urothelial formation and regeneration, which may have significant impact on therapeutic development or tissue engineering strategies. Fate mapping reveals an important linear relationship, whereby bladder basal urothelial cells give rise to intermediate and superficial cells in an age-restricted manner and contribute to tissue repair. Neonatal basal cells reprise their role as superior progenitors in vitro and display distinct transcriptional signatures, which suggest progenitor function is at least partially cell intrinsic. However, the urothelium progenitor niche cannot be overlooked, since FGF7 rescues adult basal cell progenitor function.
Topics: Animals; Urothelium; Urinary Bladder; Regeneration; Stem Cells; Keratin-5; Cell Proliferation; Cell Differentiation; Animals, Newborn; Gene Expression Regulation, Developmental; Fibroblast Growth Factor 7; Mice; Mice, Inbred C57BL; Cyclophosphamide; Cells, Cultured; Age Factors; Transcriptome
PubMed: 38634130
DOI: 10.1152/ajprenal.00378.2023 -
Journal of Translational Medicine Mar 2024Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant...
BACKGROUND
Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression.
METHODS
Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression.
RESULTS
Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth.
CONCLUSION
Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.
Topics: Humans; Female; Cancer-Associated Fibroblasts; Fibroblast Growth Factor 7; Cell Line, Tumor; Signal Transduction; Ovarian Neoplasms; Hypoxia-Inducible Factor 1, alpha Subunit; Epithelial-Mesenchymal Transition; Cell Movement
PubMed: 38491511
DOI: 10.1186/s12967-024-05085-y -
Frontiers in Veterinary Science 2023Follicular cysts are a common reproductive disorder in mammals that is usually caused by stress. However, the pathogenesis of follicular cysts in sows remains unclear....
Follicular cysts are a common reproductive disorder in mammals that is usually caused by stress. However, the pathogenesis of follicular cysts in sows remains unclear. To provide new insights into the mechanisms of follicular cyst formation in pigs, we conducted a combined transcriptomic and metabolomic analysis on theca interna and mural granulosa cells of follicular cysts and mature follicles. We identified 2,533 up-regulated and 1,355 down-regulated genes in follicular cysts, compared with mature follicles. These differentially expressed genes were mainly found in signaling pathways related to tumor formation and cortisol synthesis and secretion as shown by Ingenuity Pathway Analysis, which predicted 4,362 upstream regulatory factors. The combined gene expression and pathway analysis identified the following genes as potential biomarkers for porcine follicular cysts: . Metabolomics analysis found significant differences in 87 metabolites, which were enriched in unsaturated fatty acid biosynthesis, and sphingolipid signaling pathways. These results provide valuable information on the molecular mechanisms of follicular cyst formation, which may facilitate the development of new therapeutics to prevent and treat follicular cysts.
PubMed: 38274662
DOI: 10.3389/fvets.2023.1298132 -
Food Science of Animal Resources Jan 2024This study was designed to examine the effect of LB-P9 on hair regeneration. The treatment of LB-P9 conditioned medium increased the proliferation of both hair follicle...
This study was designed to examine the effect of LB-P9 on hair regeneration. The treatment of LB-P9 conditioned medium increased the proliferation of both hair follicle dermal papilla cells and hair germinal matrix cells (hGMCs). Moreover, the expression levels of hair growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 7 were significantly elevated in hGMCs co-cultured with LB-P9. After time-synchronized depilation, mice were orally administered with either 4×10 colony forming unit (CFU) of LB-P9 (low dose) or 4×10 CFU of LB-P9 (high dose), once daily for 4 weeks. Compared with the vehicle (phosphate-buffered saline)-administrated group, the LB-P9-treated groups exhibited accelerated hair regrowth rate and enhanced hair thickness in a dose-dependent manner. Supporting this observation, both hair follicle numbers and the dermal thickness in skin tissues of the LB-P9-treated groups were increased, compared to those of the vehicle-treated group. These results might be explained by the increased level of β-catenin and number of hair follicle stem cells (CD34CD49f cells) in the skin tissues of mice administered with LB-P9, compared to the vehicle-treated mice. Also, increased serum levels of hair growth factors such as VEGF and insulin-like growth factor-1, and superoxide dismutase were found in the LB-P9-treated groups, compared to those of the vehicle-treated group. Taken together, these results might demonstrate that the oral administration of LB-P9 promotes hair regeneration by the enhancement of dermal papilla proliferation through the stimulation of hair growth factor production.
PubMed: 38229856
DOI: 10.5851/kosfa.2023.e74