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Basic fibroblast growth factor (FGF2 or bFGF) is critical for optimal wound healing. Experimental studies show that local application of FGF2 is a promising therapeutic approach to stimulate tissue regeneration, including for the treatment of chronic wounds that have a low healing potential or are characterised by a pathologically altered healing process. However, the problem of low efficiency of growth factors application due to their rapid loss of biological activity in the aggressive proteolytic environment of the wound remains. Therefore, ways to preserve the efficacy of FGF2 for wound treatment are being actively developed. This review considers the following strategies to improve the effectiveness of FGF2-based therapy: (1) use of vehicles/carriers for delivery and gradual release of FGF2; (2) chemical modification of FGF2 to increase the stability of the molecule; (3) use of genetic constructs encoding FGF2 for de novo synthesis of protein in the wound. In addition, this review discusses FGF2-based therapeutic strategies that are undergoing clinical trials and demonstrating the efficacy of FGF2 for skin wound healing. [ABSTRACT FROM AUTHOR]

The direct antitumor effect of bevacizumab (BEV) has long been debated. Evidence of the direct antitumor activities of drugs are mainly obtained from in vitro experiments, which are greatly affected by experimental conditions. In this study, we evaluated the effect of BEV-containing medium renewal on the results of in vitro cytotoxicity experiments in A549 and U251 cancer cells. We observed starkly different results between the experiments with and without BEV-containing medium renewal. Specifically, BEV inhibited the tumor cell growth in the timely replacement with a BEV-containing medium but promoted tumor cell growth without medium renewal. Meanwhile, compared with the control, a significant basic fibroblast growth factor (bFGF) accumulation in the supernatant was observed in the group without medium renewal but none in that with replaced medium. Furthermore, bFGF neutralization partially reversed the pro-proliferative effect of BEV in the medium non-renewed group, while exogenous bFGF attenuated the tumor cell growth inhibition of BEV in the medium-renewed group. Our data explain the controversy over the direct antitumor effect of BEV in different studies from the perspective of the compensatory autocrine cytokines in tumor cells. [ABSTRACT FROM AUTHOR]

There is great interest in developing effective therapies for the treatment of skin wounds accompanied by deep tissue losses and severe infections. We have attempted to prepare biohybrids formed of agglomerates of mesenchymal stem cells (MSCs) with gelatin hydrogel beads (GEL beads) delivering bacteriophages (phages) as antibacterial agents and/or basic fibroblast growth factor (bFGF) for faster and better healing, providing combined therapies for these types of skin wounds. The gelatin beads were produced through a two-step process using basic and/or acidic gelatins with different isoelectric points. Escherichia coli (E. coli) and its specific T4 phages were propagated. Phages and/or bFGF were loaded within the GELs and their release rates and modes were obtained. The phage release from the basic GEL beads was quite fast; in contrast, the bFGF release from the acidic GEL beads was sustained, as anticipated. MSCs were isolated from mouse adipose tissues and 2D-cultured. Agglomerates of these MSCs with GEL beads were formed and maturated in 3D cultures, and their time-dependent changes were followed. In these 3D culture experiments, it was observed that the agglomerates with GEL beads were very healthy and the MSCs formed tissue-like structures in 7 days, while the MSC agglomerates were not healthy and shrunk considerably as a result of cell death. [ABSTRACT FROM AUTHOR]

Main conclusion: We generated transplastomic tobacco lines that stably express a human Basic Fibroblast Growth Factor (hFGFb) in their chloroplasts stroma and purified a biologically active recombinant hFGFb. Main: The use of plants as biofactories presents as an attractive technology with the potential to efficiently produce high-value human recombinant proteins in a cost-effective manner. Plastid genome transformation stands out for its possibility to accumulate recombinant proteins at elevated levels. Of particular interest are recombinant growth factors, given their applications in animal cell culture and regenerative medicine. In this study, we produced recombinant human Fibroblast Growth Factor (rhFGFb), a crucial protein required for animal cell culture, in tobacco chloroplasts. We successfully generated two independent transplastomic lines that are homoplasmic and accumulate rhFGFb in their leaves. Furthermore, the produced rhFGFb demonstrated its biological activity by inducing proliferation in HEK293T cell lines. These results collectively underscore plastid genome transformation as a promising plant-based bioreactor for rhFGFb production. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mesenchymal stem cells are susceptible to senescence during in vitro expansion, which greatly hinders their application in vivo and in vitro. How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE: To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS: Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method. Passage 2 cells were selected as normal control group. Passage 7 and later algebraic cells were selected as aging model group. Vascular endothelial growth factor (50 μg/L), basic fibroblast growth factor (10 μg/L), and their combination were administered. Cell proliferation was detected by CCK-8 assay. Cell senescence was observed by β-galactosidase activity staining. Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining, respectively, and the levels of senescence-related genes P16, P21, and P53 were detected by qRT-PCR. Gene expression levels of P16, P21, and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION: (1) Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells, which began to enter the plateau stage on day 9, and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9 (P < 0.05). (2) The phenotypic markers of the cells in the combined intervention group did not change, and the cell morphology changed from broad to slender. (3) Compared with the model group, the positive rate of β-galactosidase was significantly decreased (P < 0.01); the number of nuclei increased (P < 0.001); the total area of cytoskeleton increased (P < 0.01); colony formation ability was enhanced (P < 0.05); expression level of P16 was decreased (P < 0.01) in the combined intervention group. These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype. [ABSTRACT FROM AUTHOR]

Aims and objectives: The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study. Method: Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events. Results: In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte–keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP. Conclusion: Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a chronic, progressive cerebrovascular occlusive disease. Ring finger protein 213 (RNF213) is a susceptibility gene of MMD. Previous studies have shown that the expression levels of angiogenic factors increase in MMD patients, but the relationship between the susceptibility gene RNF213 and these angiogenic mediators is still unclear. The aim of the present study was to investigate the pathogenesis of MMD by examining the effect of RNF213 gene knockdown on the expression of matrix metalloproteinase-9 (MMP-9) and basic fibroblast growth factor (bFGF) in rat bone marrow-derived mesenchymal stem cells (rBMSCs). Firstly, 40 patients with MMD and 40 age-matched normal individuals (as the control group) were enrolled in the present study to detect the levels of MMP-9 and bFGF in serum by ELISA. Secondly, Sprague-Dawley male rat BMSCs were isolated and cultured using the whole bone marrow adhesion method, and subsequent phenotypic analysis was performed by flow cytometry. Alizarin red and oil red O staining methods were used to identify osteogenic and adipogenic differentiation, respectively. Finally, third generation rBMSCs were transfected with lentivirus recombinant plasmid to knockout expression of the RNF213 gene. After successful transfection was confirmed by reverse transcription-quantitative PCR and fluorescence imaging, the expression levels of bFGF and MMP-9 mRNA in rBMSCs and the levels of bFGF and MMP-9 protein in the supernatant of the culture medium were detected on the 7th and 14th days after transfection. There was no significant difference in the relative expression level of bFGF among the three groups on the 7th day. For the relative expression level of MMP-9, there were significant differences on the 7th day and 14th day. In addition, there was no statistically significant difference in the expression of bFGF in the supernatant of the RNF213 shRNA group culture medium, while there was a significant difference in the expression level of MMP-9. The knockdown of the RNF213 gene affects the expression of bFGF and MMP-9. However, further studies are needed to determine how they participate in the pathogenesis of MMD. The findings of the present study provide a theoretical basis for clarifying the pathogenesis and clinical treatment of MMD. [ABSTRACT FROM AUTHOR]

Objective To study changes and correlation of peripheral bold endothelial progenitor cells (EPCs) and serum bFGF, VEGF and MMP-9 in rats with peripheral nerve injury (PNI). Methods Forty-two SD rats were divided into the control group, the PNI 1 d group, the PNI 3 d group, the PNI 5 d group, the PNI 7 d group and the PNI 14 d group according to random number table method, with 7 rats in each group. The sciatic nerve injury model was established in all groups except the control group. In each group, blood samples were collected by living heart puncture at a predetermined time point. Mononuclear cells were extracted by Ficoll density gradient centrifugation. CD34 and CD133 double positive cells were labeled with EPCs, and the number of EPCs in each group was detected by flow cytometry. The contents of bFGF, VEGF and MMP-9 in peripheral blood of each group were detected by enzyme-linked immunosorbent assay, and the correlation between the number of EPCs and bFGF, VEGF and MMP-9 was analyzed. Results Compared with the control group, EPCs in peripheral blood were increased in the PNI 3 d group, the PNI 5 d group and PNI 7 d group. bFGF contents in peripheral blood were increased in the PNI 3 d group, the PNI 5 d group, the PNI 7 d group and the PNI 14 d group, and VEGF contents in peripheral blood were increased in the other groups. The content of MMP-9 in peripheral blood was increased in the PNI 5 d group, the PNI 7 d group and the PNI 14 d group (P＜0.05). The number of EPCs in peripheral blood in the PNI 5 d group and the PNI 7 d group was positively correlated with serum bFGF level (r=0.784 and 0.788, P＜ 0.05) and serum VEGF level (r=0.889 and 0.852, P＜0.05). The number of EPCs in peripheral blood of the PNI 5 d group, the PNI 7 d group and the PNI 14 d group was positively correlated with serum MMP-9 level (r=0.788, 0.852 and 0.873, P＜ 0.05), and it was positively correlated with serum VEGF level (r=0.889 and 0.852, P＜0.05). The number of EPCs in peripheral blood was positively correlated with serum MMP-9 level in the PNI 5 d group, the PNI 7 d group and the PNI 14 d group (r=0.788, 0.852 and 0.873, P＜0.05). Conclusion EPCs, bFGF, VEGF and MMP-9 are involved in the pathophysiological process of blood supply repair after PNI. [ABSTRACT FROM AUTHOR]

Background. Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc). Objectives. This study aimed to examine the association between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-a), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc. Materials and methods. This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-a, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer. Results. The bFGF and IFN-a concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level =95.7 pg/mL and IFN-a level =3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-a concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9). Conclusions. The SSc group was characterized by higher serum concentrations of bFGF and IFN-a compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-a and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of nasal septum perforation solely by surgical intervention presents significant challenges. This study evaluated the effect of basic fibroblast growth factor (bFGF) in combination with collagen/gelatin on wound healing of nasal septum perforation in a rabbit animal model. Methods: A nasal septum perforation rabbit model was created. bFGF was added to a collagen/gelatin fixture and placed adjacent to the perforation, which is a complete defect. The rabbits were divided into three groups: the sham group that underwent the surgical procedure only, bFGF (−) group that received collagen/gelatin fixture without bFGF, and bFGF(+) group that received collagen/gelatin fixture with bFGF. The dimensions of the perforations were measured after 4 weeks, and the septum was subjected to histological examination. Results: All perforations remained open in the sham group (closure rate: 20.4%–83.1%). The closure rates of the bFGF(−) and bFGF(+) groups were 49.4%–68.8% and 72.7%–100%, respectively. No significant difference was noted in the closure rates between the sham and bFGF(−) groups; however, significant differences were observed between the sham and bFGF(+) groups, and the bFGF(−) and bFGF(+) groups (p

Abstract Background Patients with rheumatological diseases are at high risk of developing irreversible fibrotic changes, both articular and extra-articular, as a result of tissue damage caused by the chronic phase of persistent inflammation. Thus, our purpose was to study early markers of fibrosis formation in children with juvenile idiopathic arthritis (JIA). Methods Seventy patients with juvenile idiopathic arthritis, namely, polyarthritis (64.29%) and oligoarthritis (35.71%) variant JIA (mean age 13.3 years, 64.29% girls, 35.71% boys), were included in this 4-year prospective study. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were determined by ELISA kits. Results We evaluated bFGF (mean: 7478.21 pg/ml; min: 4171.56 pg/ml; max: 18,011.25 pg/ml) and VEGF (mean: 342.47 pg/ml; min: 23.68 pg/ml; max: 2158.91 pg/ml) levels in children with JIA. Children with JIA had a higher VEGF level when JIA onset occurred after 15 years of age and they had a high disease activity; additionally, a higher bFGF level was observed in children older than 14 years and in those with a JIA onset after 15 years of age, the oligoarticular variant, a moderate disease activity and regardless of MTX administration but more often when MTX was administered at a dosage from 10 to 12.5 mg/m2/week. Conclusions Laboratory screening of fibrosis formation predictors could help identify patients who may be at greater risk of adverse outcomes. Children with JIA had higher bFGF and VEGF levels when JIA onset occurred after 15 years of age, depending on disease activity.

AIM: To investigate the clinical value of serum vitamin A(Vit A)and basic fibroblast growth factor(bFGF)levels predicting retinopathy of prematurity(ROP).METHODS: Prospective cohort studies. A total of 411 premature or low birth weight infants with gestational age less than 37 wk or birth weight less than 2 500 g who were delivered in Hainan Branch, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2020 to December 2022 were selected as subjects. The Vit A and bFGF levels in peripheral blood were detected at 7 d and 35 d after birth, respectively.RESULTS: A total of 392 premature infants or low birth weight infants completed clinical study, including 51 cases in stage 1-2 ROP group, 23 cases in stage 3-5 ROP group and 318 cases in the group without ROP. At 7 d postnatal, the serum Vit A(0.44±0.17 μmol/L)and bFGF(0.53±0.16 ng/L)levels in stage 1-2 ROP group were lower than those in the group without ROP(0.50±0.12 μmol/L and 0.63±0.15 ng/L; all P

High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes.

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Chronic tympanic membrane perforations (TMP) pose a significant clinical challenge, but basic fibroblast growth factor (FGF-2) shows promise for their treatment, despite its instability in aqueous solutions which hampers the sustained delivery crucial for the healing process. Addressing this, our research focused on the development of stabilized FGF-2 formulations, F5 and F6, incorporating dual, generally regarded as safe (GRAS) excipients to enhance stability and therapeutic efficacy. F5 combined FGF-2 (1600 ng/mL) with 0.05% w/v methylcellulose (MC) and 20 mM alanine, while F6 used FGF-2 with 0.05% w/v MC and 1 mg/mL human serum albumin (HSA). Our findings demonstrate that these novel formulations not only significantly improve the cytoproliferation of human dermal fibroblasts but also exhibit the most potent chemoattractant effects, leading to the highest fibroblast monolayer closure rates (92.5% for F5 and 94.1% for F6 within 24 h) compared to other FGF-2 solutions tested. The comparable performance of F5 and F6 underscores their potential as innovative, less invasive, and cost-effective options for developing otic medicinal products aimed at the effective treatment of chronic TMP. [ABSTRACT FROM AUTHOR]

Background: Patients with rheumatological diseases are at high risk of developing irreversible fibrotic changes, both articular and extra-articular, as a result of tissue damage caused by the chronic phase of persistent inflammation. Thus, our purpose was to study early markers of fibrosis formation in children with juvenile idiopathic arthritis (JIA). Methods: Seventy patients with juvenile idiopathic arthritis, namely, polyarthritis (64.29%) and oligoarthritis (35.71%) variant JIA (mean age 13.3 years, 64.29% girls, 35.71% boys), were included in this 4-year prospective study. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were determined by ELISA kits. Results: We evaluated bFGF (mean: 7478.21 pg/ml; min: 4171.56 pg/ml; max: 18,011.25 pg/ml) and VEGF (mean: 342.47 pg/ml; min: 23.68 pg/ml; max: 2158.91 pg/ml) levels in children with JIA. Children with JIA had a higher VEGF level when JIA onset occurred after 15 years of age and they had a high disease activity; additionally, a higher bFGF level was observed in children older than 14 years and in those with a JIA onset after 15 years of age, the oligoarticular variant, a moderate disease activity and regardless of MTX administration but more often when MTX was administered at a dosage from 10 to 12.5 mg/m2/week. Conclusions: Laboratory screening of fibrosis formation predictors could help identify patients who may be at greater risk of adverse outcomes. Children with JIA had higher bFGF and VEGF levels when JIA onset occurred after 15 years of age, depending on disease activity. [ABSTRACT FROM AUTHOR]

Intramuscular lipoma is uncommon in the oral region, and its etiology is unknown. REGROTH® is a periodontal tissue regenerative medicine containing recombinant fibroblast growth factor 2 (FGF-2). In this report, we present a case of intramuscular lipoma-like lesion developed in the right cheek. A 49-year-old Japanese male was referred to our hospital in September 2020 with a chief complaint of painless swelling of the right cheek. About 1 year before the visit, he underwent flap surgery for a periodontal disease of the right lower second molar at the nearby dental clinic. The alveolar bone defect in the second molar was filled with a total amount of the REGROTH Dental Liquid Kit 600 μg® and covered with the gingival periosteal flap. Two months later, however, diffuse swelling with redness was observed from the operated right lower molar area to the cheek. The diffuse swelling improved with anti-inflammatory treatment, and then recurred repeatedly, eventually a large mass of the cheek remained. The imaging and surgical findings at our hospital showed that unencapsulated tumor was surrounded by the masseter and buccinator muscles, was in close contact with the buccal side of right lower molars. Tumor was histologically an intramuscular lipoma infiltrating the surrounding muscle tissues. The occurrence of this lesion adjacent to the flap operation site in the short postoperative period suggests that the surgical operation using the REGROTH® is involved in the tumor development. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem (iPS) cells are generated from somatic cells and can differentiate into various cell types. Therefore, these cells are expected to be a powerful tool for modeling diseases and transplantation therapy. Generation of domestic cat iPS cells depending on leukemia inhibitory factor has been reported; however, this strategy may not be optimized. Considering that domestic cats are excellent models for studying spontaneous diseases, iPS cell generation is crucial. In this study, we aimed to derive iPS cells from cat embryonic fibroblasts retrovirally transfected with mouse Oct3/4, Klf4, Sox2, and c-Myc. After transfection, embryonic fibroblasts were reseeded onto inactivated SNL 76/7 and cultured in a medium supplemented with basic fibroblast growth factor. Flat, compact, primary colonies resembling human iPS colonies were observed. Additionally, primary colonies were more frequently observed in the KnockOut Serum Replacement medium than in the fetal bovine serum (FBS) medium. However, enhanced maintenance and proliferation of iPS-like cells occurred in the FBS medium. These iPS-like cells expressed embryonic stem cell markers, had normal karyotypes, proliferated beyond 45 passages, and differentiated into all three germ layers in vitro. Notably, expression of exogenous Oct3/4, Klf4, and Sox2 was silenced in these cells. However, the iPS-like cells failed to form teratomas. In conclusion, this is the first study to establish and characterize cat iPS-like cells, which can differentiate into different cell types depending on the basic fibroblast growth factor.

Abstract Background The background is that intravenous adrenaline administration is recommended for advanced cardiovascular life support in adults and endotracheal administration is given low priority. The reason is that the optimal dose of adrenaline in endotracheal administration is unknown, and it is ethically difficult to design studies of endotracheal adrenaline administration with non-cardiopulmonary arrest. We otolaryngologists think so because we administered adrenaline to the vocal folds for hemostasis after intracordal injection under local anesthesia, but have had few cases of vital changes. We hypothesized that examining vital signs before and after adrenaline administration for hemostasis would help determine the optimal dose of endotracheal adrenaline. Methods We retrospectively examined the medical records of 79 patients who visited our hospital from January 2018 to December 2020 and received adrenaline in the vocal folds and trachea for hemostasis by intracordal injection under local anesthesia to investigate changes in heart rate and systolic blood pressure before and after the injection. Results The mean heart rates before and after injection were 83.96 ± 18.51 (standard deviation) beats per minute (bpm) and 81.50 ± 15.38 (standard deviation) bpm, respectively. The mean systolic blood pressure before and after the injection were 138.13 ± 25.33 (standard deviation) mmHg and 135.72 ± 22.19 (standard deviation) mmHg, respectively. Heart rate and systolic blood pressure had P-values of 0.136, and 0.450, respectively, indicating no significant differences. Conclusions Although this study was an observational, changes in vital signs were investigated assuming endotracheal adrenaline administration. The current recommended dose of adrenaline in endotracheal administration with cardiopulmonary arrest may not be effective. In some cases of cardiopulmonary arrest, intravenous and intraosseous routes of adrenaline administration may be difficult and the opportunity for resuscitation may be missed. Therefore, it is desirable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of endotracheal adrenaline administration can be clarified, early adrenaline administration will be possible, which will improve return of spontaneous circulation (ROSC) and survival discharge rates.

There is great interest in developing effective therapies for the treatment of skin wounds accompanied by deep tissue losses and severe infections. We have attempted to prepare biohybrids formed of agglomerates of mesenchymal stem cells (MSCs) with gelatin hydrogel beads (GEL beads) delivering bacteriophages (phages) as antibacterial agents and/or basic fibroblast growth factor (bFGF) for faster and better healing, providing combined therapies for these types of skin wounds. The gelatin beads were produced through a two-step process using basic and/or acidic gelatins with different isoelectric points. Escherichia coli (E. coli) and its specific T4 phages were propagated. Phages and/or bFGF were loaded within the GELs and their release rates and modes were obtained. The phage release from the basic GEL beads was quite fast; in contrast, the bFGF release from the acidic GEL beads was sustained, as anticipated. MSCs were isolated from mouse adipose tissues and 2D-cultured. Agglomerates of these MSCs with GEL beads were formed and maturated in 3D cultures, and their time-dependent changes were followed. In these 3D culture experiments, it was observed that the agglomerates with GEL beads were very healthy and the MSCs formed tissue-like structures in 7 days, while the MSC agglomerates were not healthy and shrunk considerably as a result of cell death.

Resveratrol is a natural polyphenol found in grapes and beneficial for human health. Resveratrol regulates basic fibroblast growth factor (bFGF)-induced osteoprotegerin synthesis through Akt pathway in osteoblast-like MC3T3-E1 cells. In this study, we investigated resveratrol effects on bFGF-induced macrophage colony-stimulating factor (M-CSF) synthesis in MC3T3-E1 cells. bFGF significantly stimulated release and mRNA expression of M-CSF, which was reduced by resveratrol and SRT1720, sirtuin 1 (SIRT1) activator. Inauhzin, SIRT1 inhibitor, reversed inhibitory effects of resveratrol on bFGF-induced mRNA expression of M-CSF. Deguelin, Akt inhibitor, and LY294002, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced bFGF-induced M-CSF synthesis. Inauhzin reversed inhibitory effects of resveratrol on bFGF-induced Akt phosphorylation. Suppressive effect of resveratrol on bFGF-induced osteoprotegerin mRNA expression was confirmed in the identical samples using in experiment of M-CSF mRNA expression. Therefore, resveratrol reduces bFGF-induced M-CSF synthesis in addition to osteoprotegerin synthesis by inhibiting PI3-kinase/Akt pathway and suppressive effects are mediated through SIRT1 activation in osteoblasts. [ABSTRACT FROM AUTHOR]

To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (−) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation. [Display omitted] [ABSTRACT FROM AUTHOR]

Ideal regeneration of hard tissue and dental pulp has been reported with the use of a combination of bioactive glass and basic fibroblast growth factor (bFGF). However, no previous study has investigated the molecular mechanisms underlying the processes induced by this combination in dental pulp cells. This study aimed to examine the cellular phenotype and transcriptional changes induced by the combination of bioactive glass solution (BG) and bFGF in dental pulp cells using phase-contrast microscopy, a cell counting kit-8 assay, alkaline phosphatase staining, and RNA sequence analysis. bFGF induced elongation of the cell process and increased the number of cells. Whereas BG did not increase ALP activity, it induced extracellular matrix-related genes in the dental pulp. In addition, the combination of BG and bFGF induces gliogenesis-related genes in the nervous system. This is to say, bFGF increased the viability of dental pulp cells, bioactive glass induced odontogenesis, and a dual stimulation with bioactive glass and bFGF induced the wound healing of the nerve system in the dental pulp. Taken together, bioactive glass and bFGF may be useful for the regeneration of the dentin-pulp complex. [ABSTRACT FROM AUTHOR]

Wharton's jelly-derived mesenchymal stem cell (WJ-MSC)-derived exosomes contain a diverse cargo and exhibit remarkable biological activity, rendering them suitable for regenerative and immune-modulating functions. However, the quantity of secretion is insufficient. A large body of prior work has investigated the use of various growth factors to enhance MSC-derived exosome production. In this study, we evaluated the utilization of thermostable basic fibroblast growth factor (TS-bFGF) with MSC culture and exosome production. MSCs cultured with TS-bFGF displayed superior proliferation, as evidenced by cell cycle analysis, compared with wild-type bFGF (WT-bFGF). Stemness was assessed through mRNA expression level and colony-forming unit (CFU) assays. Furthermore, nanoparticle tracking analysis (NTA) measurements revealed that MSCs cultured with TS-bFGF produced a greater quantity of exosomes, particularly under three-dimensional culture conditions. These produced exosomes demonstrated substantial anti-inflammatory and wound-healing effects, as confirmed by nitric oxide (NO) assays and scratch assays. Taken together, we demonstrate that utilization of TS-bFGF for WJ-MSC-derived exosome production not only increases exosome yield but also enhances the potential for various applications in inflammation regulation and wound healing. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. Methods: We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. Results: Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. Conclusions: Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs. [ABSTRACT FROM AUTHOR]

To discuss the effect of hydrogel-based delivery of basic fibroblast growth factor (bFGF) on the function of the NIH3T3 fibroblast cells after oxygen-glucose deprivation (OGD), and to clarify the improvement effect of bFGF-loaded hydrogel on the oxidative stress responses in the fibroblasts under the OGD condition. Methods The bFGF-containing agarose hydrogel was prepared, and the NIH3T3 cells at logarithmic growth phase were divided into blank group, 20% agarose group, and 20% agarose + glutaraldehyde group. The viabilities of the NIH3T3 cells after co-cultured with the hydrogel-eluted fluid for 6, 12, and 24 h were detected by CCK-8 assay. The NIH3T3 cells were divided into control group, OGD group, and OGD + different masses of bFGF-loaded groups (OGD + 1 ng bFGF group, OGD+10 ng bFGF group, and OGD+100 ng bFGF group). The expression levels of α-smooth muscle actin (α-SMA), type Ⅰ collagen, and type Ⅲ collagen proteins in the NIH3T3 cells in various groups were detected by Western blotting method； the content of malondialdehyde (MDA) and activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the NIH3T3 cells were detected by assay kits； the in vitro release rate of bFGF in the NIH3T3 cells in various groups was detected by enzyme-linked immunosorbent assay (ELISA) method. Results The CCK-8 assay results showed that compared with blank group, the viability of the NIH3T3 cells between blank group, 20% agarose group, and 20% agarose+ glutaraldehyde group at different elution times had no significant difference(P>0.05). The Western blotting results showed that the expression levels of α-SMA and type Ⅰ collagen proteins in the NIH3T3 cells in OGD group were significantly higher than that in control group (P<0.05 or P<0.01).Compared with OGD group, the expression levels of α-SMA and type Ⅰ collagen proteins in the NIH3T3 cells in OGD+1 ng bFGF, OGD+10 ng bFGF, and OGD+100 ng bFGF groups were significantly decreased (P<0.05 or P<0.01) in a dose-dependent manner.Compared with control group, the level of MDA and activity of LDH in the NIH3T3 cells in OGD group were increased(P<0.05), while the activity of SOD was decreased (P<0.05). Compared with OGD group, the level of MDA and the activity of LDH in the NIH3T3 cells in OGD + 1 ng bFGF group were decreased (P<0.05), while the activity of SOD was increased (P<0.05).The ELISA results showed that about 10% bFGF was released from the hydrogel within 4 h, about 15% bFGF was relleased from the bydrogel with in 12 h, and about 21% bFGF was released from the hydrogel within 24 h. Conclusion The bFGF-loaded hydrogel can modulate the transformation of the fibroblasts under the OGD condition, inhibit the expression of typeⅠ collagen protein, and improve the oxidative stress responses in the fibroblasts. Moreover, this system exhibits a sustained drug-release ability. [ABSTRACT FROM AUTHOR]

Background: The background is that intravenous adrenaline administration is recommended for advanced cardiovascular life support in adults and endotracheal administration is given low priority. The reason is that the optimal dose of adrenaline in endotracheal administration is unknown, and it is ethically difficult to design studies of endotracheal adrenaline administration with non-cardiopulmonary arrest. We otolaryngologists think so because we administered adrenaline to the vocal folds for hemostasis after intracordal injection under local anesthesia, but have had few cases of vital changes. We hypothesized that examining vital signs before and after adrenaline administration for hemostasis would help determine the optimal dose of endotracheal adrenaline. Methods: We retrospectively examined the medical records of 79 patients who visited our hospital from January 2018 to December 2020 and received adrenaline in the vocal folds and trachea for hemostasis by intracordal injection under local anesthesia to investigate changes in heart rate and systolic blood pressure before and after the injection. Results: The mean heart rates before and after injection were 83.96 ± 18.51 (standard deviation) beats per minute (bpm) and 81.50 ± 15.38 (standard deviation) bpm, respectively. The mean systolic blood pressure before and after the injection were 138.13 ± 25.33 (standard deviation) mmHg and 135.72 ± 22.19 (standard deviation) mmHg, respectively. Heart rate and systolic blood pressure had P-values of 0.136, and 0.450, respectively, indicating no significant differences. Conclusions: Although this study was an observational, changes in vital signs were investigated assuming endotracheal adrenaline administration. The current recommended dose of adrenaline in endotracheal administration with cardiopulmonary arrest may not be effective. In some cases of cardiopulmonary arrest, intravenous and intraosseous routes of adrenaline administration may be difficult and the opportunity for resuscitation may be missed. Therefore, it is desirable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of endotracheal adrenaline administration can be clarified, early adrenaline administration will be possible, which will improve return of spontaneous circulation (ROSC) and survival discharge rates. [ABSTRACT FROM AUTHOR]

Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.

Background: Angiogenesis is a physiological process leading to capillary density enhancement and better blood distribution in skeletal muscles, which triggers in response to physical training. The present study aimed to investigate the changes in physiological factors involved in angiogenesis in response to circuit or traditional resistance training. Methods: Thirty-six healthy sedentary students who were studying at Shahid Rajaee Teacher Training University of Tehran (age: 22.1±2.3 years; height: 172.7±5.1 cm) volunteered to participate in the study (from October 2021 to February 2022). Following a pre-test to evaluate one repetition maximum (1RM) of selected movements (Leg Press, Leg Curl, Leg Extension, Bench Pull, Seated Row, Biceps Curl), subjects randomly divided into Circuit Resistance training (CRT) (training protocol included 4 circles/3 times a week/8 weeks circuit performance/50-55% 1 Repetition Maximum (1RM), n=12), Traditional resistance training (RT) (training protocol included 8 repetition/3 set/3 time per week/8 weeks of same movements with 75% 1RM followed by 2 minutes break to rest between the sets; n=12) and the control group without any regular training (n=12). We assessed the level of Vascular Endothelial Growth Factor (VEGF), plasma level of growth hormone (GH), and Basic Fibroblast Growth Factor (BFGF) to the mentioned training methods. Data were evaluated by utilizing SPSS version 14. Results: Present findings showed that CRT and RT protocols resulted in significant increases in post-test compared to pre-test in VEGF (P=0.00), GH (P=0.04), and BFGF (P=0.00). In addition, the magnitude of changes in VEGF and GH were significantly greater than the magnitude of changes in control group in post-test (P=0.03, and 0.001, respectively). Furthermore, there was a strong correlation between absolute values of GH and VEGF (r=0.74 and r=0.71) following CRT (P=0.01) and RT (P=0.02). Conclusion: This study demonstrated that CRT and RT might enhance angiogenesis through an increase in VEGF, bFGF and GH, leading to better blood distribution in muscles.

AIM: To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) simultaneously for retinal vascular disease in vivo. METHODS: After a laser induced rabbit retinal vein occlusion (RVO) model was made, 0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control. Intracameral samples were taken on the day before laser treatment and days 1, 3, 7, 14, 21, and 28 after treatment. Enzyme-linked immunosorbent assay (ELISA) was used to test the bFGF and VEGF-A concentrations in the aqueous humor. RESULTS: Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes. In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day. After nintadanib injection in the study eye, both bFGF and VEGF-A showed a significant reduction on the 4th day (7th day after laser treatment) when compared to the control eye, and kept on low level in the following several weeks. CONCLUSION: Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent, which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.

Abstract Background Research on regenerative medicine using basic fibroblast growth factor (bFGF) has recently advanced in the field of laryngology. We previously reported that local administration of bFGF 1 month after recurrent laryngeal nerve (RLN) paralysis compensated for atrophy of the thyroarytenoid muscle. The objective of this study was to elucidate the effects of early bFGF administration on the thyroarytenoid muscle after RLN transection and to investigate the underlying mechanisms. Methods A rat model of RLN paralysis was established in this study. One day after RLN transection, low- (200 ng) or high-dose (2000 ng) bFGF or saline (control) was administered to the thyroarytenoid muscle. The larynges were excised for histological and immunohistochemical examinations at 1, 7, 14, 28, and 56 days after administration. Results The cross-sectional thyroarytenoid muscle area was significantly larger in the high-dose group than in the saline and low-dose groups on days 28 and 56. Immunohistochemistry indicated that bFGF significantly increased the number of satellite cells in the thyroarytenoid muscle up to day 14 and that of neuromuscular junctions on days 28 and 56. Conclusions A single, early local administration of high-dose bFGF prevented atrophic changes in the thyroarytenoid muscles by activating satellite cell proliferation and reforming neuromuscular junctions. As increased neuromuscular junctions are expected to maintain myofiber volume, bFGF administration may prevent thyroarytenoid muscle atrophy in the mid to long term. Graphical abstract

Abstract Objective Although many studies have reported improvements in voice outcomes with intracordal trafermin injection, there is a lack of data documenting its changes in serum basic fibroblast growth factor (bFGF) blood concentration. This study examined whether serum bFGF concentrations change after intracordal trafermin injection. Methods This retrospective study was conducted at Tokyo Voice Center. We investigated serum bFGF concentrations before and after injection in 40 patients who underwent intracordal trafermin injection. There were 26 males and 14 females, with an age ranging from 13 to 88 years (average 53.25 years). They were diagnosed with paralysis (15 patients), atrophy (15 patients), sulcus (8 patients), and others (2 patients: scar and functional), presenting with severe hoarseness that interfered with daily life. Results The mean pre‐ and post‐injective serum bFGF concentration of the 40 patients was 6.689 and 4.658 pg/mL, respectively. The difference in mean serum bFGF concentration between pre‐ and post‐injective was −2.031 pg/mL. The Pearson correlation coefficient was calculated to evaluate the correlation between dosage of trafermin and post‐injective serum bFGF concentration, and a moderate correlation was found at r = 0.52. Generalized linear model regression analysis was performed for the purpose of adjusting for confounding among variables. The only variable that showed a statistically predominant association with post‐injective serum bFGF concentrations was the dosage of trafermin, with an estimated regression coefficient of 0.048. Conclusion In this study, the dosage of trafermin we injected and post‐injective serum bFGF concentrations were dose‐dependent but the amount of changes in the serum bFGF concentration was negligible within the physiological range. Therefore, as with subcutaneous and wound administration, intracordal trafermin injections may be safe. Level of Evidence Level IV.

Objective To investigate the therapeutic effect of liraglutide on acute cerebral infarction (ACI) in patients with type 2 diabetes mellitus (T2DM), and its effect on neurological function and serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Methods A total of 160 patients with ACI accompanied by T2DM admitted to Haikou People's Hospital from March 2020 to March 2022 were randomly divided into observation group and control group (n=80, each). Both groups of patients were given routine treatment for ACI. On this basis, the control group was treated with insulin aspart and insulin glargine, while the observation group was treated with liraglutide and insulin glargine. Both groups received continuous treatment for 3 months. In addition to clinical efficacy, fasting blood glucose (FBG) before and after treatment, 2-hour postprandial blood glucose (2hPG), hemoglobin A1c (HbA1c), insulin resistance index (HOMA-IR), National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) scores of two groups of patients was compared. Enzyme linked immunosorbent assay was used to detect the levels of serum VEGF and bFGF before treatment and after 1 and 3 months of treatment in both groups. Results After treatment, the levels of FBG, bFGF, HbA1c, HOMA-IR, and the scores of NIHSS and mRS in the observation group decreased compared to those before treatment, and the above indicators levels in the observation group were significantly lower than those in the control group (P＜0.05). The total clinical effective rate of the observation group was significantly higher than that of the control group ［95.00%(76/80) vs 83.75%(67/80), χ2=5.331, P=0.021］. After treatment, the levels of serum VEGF and bFGF showed a gradual downward trend in both groups (P＜0.05). After 1 month and 3 months of treatment, the serum VEGF and bFGF levels in the observation group were significantly higher than those in the control group (P＜0.05). Conclusion Liraglutide combined with insulin glargine can effectively control blood sugar, reduce insulin resistance, alleviate neurological damage, upregulate serum VEGF and bFGF levels, and improve clinical efficacy in T2DM patients with ACI.

Background: Angiogenesis is a physiological process leading to capillary density enhancement and better blood distribution in skeletal muscles, which triggers in response to physical training. The present study aimed to investigate the changes in physiological factors involved in angiogenesis in response to circuit or traditional resistance training. Methods: Thirty-six healthy sedentary students who were studying at Shahid Rajaee Teacher Training University of Tehran (age: 22.1±2.3 years; height: 172.7±5.1 cm) volunteered to participate in the study (from October 2021 to February 2022). Following a pre-test to evaluate one repetition maximum (1RM) of selected movements (Leg Press, Leg Curl, Leg Extension, Bench Pull, Seated Row, Biceps Curl), subjects randomly divided into Circuit Resistance training (CRT) (training protocol included 4 circles/3 times a week/8 weeks circuit performance/50-55% 1 Repetition Maximum (1RM), n=12), Traditional resistance training (RT) (training protocol included 8 repetition/3 set/3 time per week/8 weeks of same movements with 75% 1RM followed by 2 minutes break to rest between the sets; n=12) and the control group without any regular training (n=12). We assessed the level of Vascular Endothelial Growth Factor (VEGF), plasma level of growth hormone (GH), and Basic Fibroblast Growth Factor (BFGF) to the mentioned training methods. Data were evaluated by utilizing SPSS version 14. Results: Present findings showed that CRT and RT protocols resulted in significant increases in post-test compared to pre-test in VEGF (P=0.00), GH (P=0.04), and BFGF (P=0.00). In addition, the magnitude of changes in VEGF and GH were significantly greater than the magnitude of changes in control group in post-test (P=0.03, and 0.001, respectively). Furthermore, there was a strong correlation between absolute values of GH and VEGF (r=0.74 and r=0.71) following CRT (P=0.01) and RT (P=0.02). Conclusion: This study demonstrated that CRT and RT might enhance angiogenesis through an increase in VEGF, bFGF and GH, leading to better blood distribution in muscles. [ABSTRACT FROM AUTHOR]

Objective: To analyze the therapeutic effects of Kuntai capsule combined with mifepristone on perimenopausal dysfunctional uterine bleeding (DUB) and its influence on the levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Methods: 88 patients with perimenopausal DUB who were treated in the gynaecological clinic of Hefei First People's Hospital from October 2021 to October 2022 were selected as the study subjects. They were divided into a study group and a control group by random data table method. 44 patients were included into each group. The patients in the two groups were treated with routine symptomatic treatment after entering the group. The patients in the control group were given oral mifepristone capsules, with the dosage of 10 mg each time, once a day. On the basis of the treatment in the control group, the patients in the study group were treated with Kuntai capsule orally, with the dosage of 2 g, three times a day. The patients in the two groups were treated with continuously for 3 months. The therapeutic indexes as well as the endometrial thickness, the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2), bFGF and VEGF before and after treatment for 3 months between the patients in the two groups were compared. The adverse events during treatment between the patients in the two groups were compared. Results: The distribution of efficacy grade in the study group was better than that in the control group, and the effective rate was higher than that in the control group (P<0.05). There was no statistically significant difference in the endometrial thickness and serum levels of sex hormone, bFGF and VEGF between the two groups before treatment (P>0.05). At the end of 3 months of treatment, the endometrial thickness and the serum levels of FSH, LH, PRL and E2 in the two groups were lower than those before treatment, and the serum levels of bFGF and VEGF were higher than those before treatment (P<0.05). The endometrial thickness and the serum levels of FSH, LH, PRL and E2 at the end of 3 months of treatment of the patients in the study group were lower than those in the control group, and the levels of bFGF and VEGF in serum were higher than those in the control group (P<0.05). The adverse reactions in both groups were mild and could be tolerated by patients without treatment. There was no patient who interrupted treatment due to adverse reactions. There was no significant difference between the two groups in the incidence of various adverse events and the total incidence of adverse events (P>0.05). Conclusion: In the treatment of perimenopausal DUB, the traditional Chinese and western medicine treatment scheme of Kuntai capsule combined with mifepristone is superior to that of mifepristone alone in clinical efficacy, which can improve the serum hormone levels, inhibit endometrial hyperplasia and increase the expression levels of angiogenic factors such as bFGF, VEGF more significantly. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of sesame oil on proliferation and function of periodontal ligament fibroblasts isolated from either healthy teeth or teeth with chronic periodontitis. Design: The current study included a total of 16 teeth. Eight periodontally healthy teeth indicated for extraction for orthodontic treatment and 8 teeth with chronic periodontitis. Fibroblasts were isolated from periodontal ligaments and were characterized via flowcytometry. Cultured cells from both healthy and diseased teeth, were then divided into two groups, sesame oil group treated by sesame oil in a dose 2.5 μl of oil/ml of media at 24 hours and untreated group which served as control. MTT assay was used to assess fibroblasts’ proliferation while quantitative PCR was used for quantification of basic fibroblast growth factor to assess fibroblasts’ function. Results: Within the present study, the highest mean cell proliferation value was recorded in group 2 (healthy treated with oil) while the lowest value was recorded in group 3 (periodontitis) with statistically significant difference between groups. The highest mean basic fibroblast growth factor expression was recorded in group 4 (periodontitis treated with oil) and the lowest value was recorded in group 3 (periodontitis) with statistically significant difference between groups demonstrating that sesame oil possesses a positive effect on fibroblasts proliferation and function. Conclusion: Sesame oil is a promising biocompatible antioxidant and anti-inflammatory natural extract that can stimulate periodontal ligament fibroblasts proliferation and function through increasing basic fibroblast growth factor expression in vitro and therefore it may hold the potential to enhance periodontal regeneration in vivo. [ABSTRACT FROM AUTHOR]

Background: Research on regenerative medicine using basic fibroblast growth factor (bFGF) has recently advanced in the field of laryngology. We previously reported that local administration of bFGF 1 month after recurrent laryngeal nerve (RLN) paralysis compensated for atrophy of the thyroarytenoid muscle. The objective of this study was to elucidate the effects of early bFGF administration on the thyroarytenoid muscle after RLN transection and to investigate the underlying mechanisms. Methods: A rat model of RLN paralysis was established in this study. One day after RLN transection, low- (200 ng) or high-dose (2000 ng) bFGF or saline (control) was administered to the thyroarytenoid muscle. The larynges were excised for histological and immunohistochemical examinations at 1, 7, 14, 28, and 56 days after administration. Results: The cross-sectional thyroarytenoid muscle area was significantly larger in the high-dose group than in the saline and low-dose groups on days 28 and 56. Immunohistochemistry indicated that bFGF significantly increased the number of satellite cells in the thyroarytenoid muscle up to day 14 and that of neuromuscular junctions on days 28 and 56. Conclusions: A single, early local administration of high-dose bFGF prevented atrophic changes in the thyroarytenoid muscles by activating satellite cell proliferation and reforming neuromuscular junctions. As increased neuromuscular junctions are expected to maintain myofiber volume, bFGF administration may prevent thyroarytenoid muscle atrophy in the mid to long term. [ABSTRACT FROM AUTHOR]

Background: Platelet‐rich plasma plus basic fibroblast growth factor (PRPF) has been confirmed to be a safe and valuable therapy for androgenetic alopecia (AGA). However, the efficacy of PRPF combined with minoxidil treatment remains unknown. Objective: To assess the efficacy of combined PRPF and minoxidil treatment for AGA. Methods: In this prospective, randomized controlled trial, 75 patients with AGA were randomly divided into three groups and were administered the following treatments: Group 1, direct intradermal PRPF injection; Group 2, topical minoxidil 5% twice daily; and Group 3, PRPF injection combined with minoxidil. The PRPF injection was performed three times, 1 month apart. Hair growth parameters were evaluated using a trichoscope until the sixth month of the study. Patient satisfaction and side effects were recorded during the follow‐up. Results: All patients showed improvements (p < 0.05) in hair count, terminal hair, and decrease in telogen hair ratio after treatment. The efficacy of PRPF complex therapy revealed significant improvements (p < 0.05) in hair count, terminal hair and growth rate, compared with monotherapy. Limitations: Small sample size, short follow‐up time and lack of quantification of GFs in PRPF. Conclusion: The effect of complex therapy exceed both the effects of PRPF monotherapy and minoxidil treatment, which can be a beneficial AGA treatment strategy. [ABSTRACT FROM AUTHOR]

Chronic tympanic membrane perforations (TMP) pose a significant clinical challenge, but basic fibroblast growth factor (FGF-2) shows promise for their treatment, despite its instability in aqueous solutions which hampers the sustained delivery crucial for the healing process. Addressing this, our research focused on the development of stabilized FGF-2 formulations, F5 and F6, incorporating dual, generally regarded as safe (GRAS) excipients to enhance stability and therapeutic efficacy. F5 combined FGF-2 (1600 ng/mL) with 0.05% w/v methylcellulose (MC) and 20 mM alanine, while F6 used FGF-2 with 0.05% w/v MC and 1 mg/mL human serum albumin (HSA). Our findings demonstrate that these novel formulations not only significantly improve the cytoproliferation of human dermal fibroblasts but also exhibit the most potent chemoattractant effects, leading to the highest fibroblast monolayer closure rates (92.5% for F5 and 94.1% for F6 within 24 h) compared to other FGF-2 solutions tested. The comparable performance of F5 and F6 underscores their potential as innovative, less invasive, and cost-effective options for developing otic medicinal products aimed at the effective treatment of chronic TMP.

Wound healing is a multicellular collaborative process in which the adhesion and proliferation of fibroblasts in the wound is the basis for ensuring rapid wound healing, and in this process, it can promote the regeneration and remodeling of tissue and extracellular matrix. Studies have shown that Arg‐Gly‐Asp adhesive peptide (RGD) and basic fibroblast growth factor (bFGF) can stimulate the adhesion and proliferation of fibroblasts by activating the Wnt/β‐catenin signaling pathway, respectively. This study adopts the principle of layer‐by‐layer self‐assembly, and the binding force formed by electrostatic attraction and Schiff base was used to combine bFGF and RGD with collagen membrane to form a biomimetic membrane that is non‐cytotoxic with strong biocompatibility that could promote soft tissue healing. The surface characteristics of MLCM and the sustained release concentration of bFGF in vitro were measured, and the effects of MLCM on cell viability, proliferation, migration, and wound healing by means of Wnt/catenin pathways were studied through cell experiments and animal experiments under the comparison of negative control groups and positive control groups. The results showed that MLCM could stimulate wound healing more actively and had a positive effect on cell activity, proliferation, and migration. During wound healing, MLCM activates the Wnt/β‐catenin signaling pathway and inhibition of Wnt/β‐catenin signaling pathway significantly reduces the positive effects of MLCM on wound healing. [ABSTRACT FROM AUTHOR]

A single injection of basic fibroblast growth factor (bFGF) into the vocal folds of patients with glottal insufficiency has been shown to be effective for a few years. However, the long-term therapeutic effect of a single injection of bFGF into the vocal folds has yet to be demonstrated. In this study, the therapeutic effect of a single injection of bFGF into the vocal folds was investigated over several years by monitoring patients for 36 months following this treatment. Nineteen patients with glottal insufficiency received injections of bFGF diluted to 20 μg/mL in the superficial layer of the lamina propria of the bilateral vocal folds. The following parameters were evaluated at preinjection baseline and 6, 12, 18, 24, and 36 months later, and statistical comparisons were performed. The parameters evaluated were: the Grade, Rough, Breathy, Asthenic, and Strained (GRBAS) scale score; maximum phonation time; acoustic analysis; and glottal wave analysis (GWA) and kymograph edge analysis (KEA) using high-speed digital imaging (HSDI). The amplitude perturbation quotient (APQ) and period perturbation quotient (PPQ) were measured by acoustic analysis. The mean minimum glottal area during vocalization and mean minimum distance between the vocal folds were measured by GWA. The amplitudes of the bilateral vocal folds were measured by KEA. Postinjection, the GRBAS scale score decreased from 6 months after injection, and maximum phonation time was prolonged. The mean minimum glottal area during vocalization and the mean minimum distance between the vocal folds calculated by GWA of HSDI decreased significantly after 6 months. These effects persisted until 36 months postinjection. APQ and PPQ derived from acoustic analysis tended to decrease, but not significantly. There was no clear change in the amplitudes of the bilateral vocal folds calculated by KEA of HSDI before and after injection. These results suggest that the effects of a single injection of bFGF into the vocal folds persist for 36 months. [ABSTRACT FROM AUTHOR]

BACKGROUND: Due to the particularity of the ear structure, the skin at the auricle injury usually has poor motion range and tissue regeneration ability, and it is difficult to heal. Therefore, how to accelerate the wound healing and obtain an ideal repair effect has always been a problem and research hotspot in the field of surgery. OBJECTIVE: To explore the effects of Sanhuang gel on the wound healing, basic fibroblast growth factor and interleukin 17 levels of auricle skin defect in rabbits. METHODS: Sixty male New Zealand rabbits were randomly divided into six groups (n=10 per group). In group A, no treatment was given. In groups B-F, a circular skin defect area with the diameter of 1 cm was made in the auricle. In group B, the wound was injected with physiological saline. In group C, the wound was coated with asiaticoside cream ointment. In group D, the wound was coated with Sanhuang gel. In group E, the wound was injected with PI3K/AKT agonist 740 Y-P. In group F, the wound was coated with Sanhuang gel and injected with 740 Y-P. The treatment was performed twice a day, for 30 consecutive days. The wound healing of rabbit ear was observed and recorded, and the pathological morphology of ear tissue was detected by hematoxylin-eosin staining. The mRNA relative expression levels of basic fibroblast growth factor and interleukin 17 in rabbit ear tissue were detected by real-time PCR. The protein expression of PI3K/AKT pathway in rabbit ear tissue was detected by western blot assay. RESULTS AND CONCLUSION: (1) After treatment, the skin wound healing speed was accelerated. After 30 days of treatment, the wound healing rate of Sanhuang gel and PI3K/AKT agonist alone was higher than that of asiaticoside cream ointment, and the combined application of the two had the highest wound healing rate. (2) Hematoxylin-eosin staining results showed that the epidermis of group B was significantly thickened and blood vessels were dilated; and a large number of infiltrated inflammatory cells and fibrous tissue hyperplasia were seen. Compared with group B, the morphology of groups C, D, E, and F was significantly improved, and new capillaries and numerous proliferated fibroblasts and endothelial cells were seen. Among them, group F had the most obvious improvement. (3) RT-PCR detection showed that the relative expression of basic fibroblast growth factor mRNA decreased and the relative expression of interleukin 17 mRNA increased after auricular skin injury. After different treatments, the relative mRNA expression of the two factors was improved to varying degrees. The improvement effect of Sanhuang gel and PI3K/AKT agonist alone was stronger than that of asiaticoside cream ointment, and the improvement effect of their combination was strongest. (4) Western blot assay showed that the expression of PI3K, AKT, p-PI3K, and p-AKT proteins decreased after auricular skin injury. The expression levels of the four proteins increased to varying degrees after different treatments. The elevating effect of Sanhuang gel and PI3K/ AKT agonist alone was stronger than that of asiaticoside cream ointment, and the elevating effect of their combination was strongest. (5) The results show that Sanhuang gel can promote the wound healing of auricular skin defects, and its mechanism may be associated with the activation of PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are somatic stem cells used in cell transplantation therapy for tissue injuries and inflammatory diseases because of their ability to support tissue regeneration and to suppress inflammation. While their applications are expanding, needs for automation of culture procedures with reduction of animal-derived materials to meet stable quality and suppliability are also increasing. On the other hand, the development of molecules that safely support cell adherence and expansion on a variety of interfaces under the serum-reduced culture condition remains a challenge. We report here that fibrinogen enables MSC culture on various materials with low cell adhesion property even under serum-reduced culture conditions. Fibrinogen promoted MSC adhesion and proliferation by stabilizing basic fibroblast growth factor (bFGF), which was secreted in the culture medium by autocrine, and also activated autophagy to suppress cellar senescence. Fibrinogen coating allowed MSCs expansion even on the polyether sulfone membrane that represents very low cell adhesion, and the MSCs showed therapeutic effects in a pulmonary fibrosis model. This study demonstrates that fibrinogen is currently the safest and most widely available extracellular matrix and can be used as a versatile scaffold for cell culture in regenerative medicine. • Fibrinogen supports self-renewal of MSCs through stabilization of bFGF and activation of autophagy. • MSCs expanded under fibrinogen-coated surface and serum-reduced condition possess stem cell characteristics. • Fibrinogen is useful ECM for surface coating of various materials using bioreactor and cell culture instrument. [ABSTRACT FROM AUTHOR]

Objective: Although many studies have reported improvements in voice outcomes with intracordal trafermin injection, there is a lack of data documenting its changes in serum basic fibroblast growth factor (bFGF) blood concentration. This study examined whether serum bFGF concentrations change after intracordal trafermin injection. Methods: This retrospective study was conducted at Tokyo Voice Center. We investigated serum bFGF concentrations before and after injection in 40 patients who underwent intracordal trafermin injection. There were 26 males and 14 females, with an age ranging from 13 to 88 years (average 53.25 years). They were diagnosed with paralysis (15 patients), atrophy (15 patients), sulcus (8 patients), and others (2 patients: scar and functional), presenting with severe hoarseness that interfered with daily life. Results: The mean pre‐ and post‐injective serum bFGF concentration of the 40 patients was 6.689 and 4.658 pg/mL, respectively. The difference in mean serum bFGF concentration between pre‐ and post‐injective was −2.031 pg/mL. The Pearson correlation coefficient was calculated to evaluate the correlation between dosage of trafermin and post‐injective serum bFGF concentration, and a moderate correlation was found at r = 0.52. Generalized linear model regression analysis was performed for the purpose of adjusting for confounding among variables. The only variable that showed a statistically predominant association with post‐injective serum bFGF concentrations was the dosage of trafermin, with an estimated regression coefficient of 0.048. Conclusion: In this study, the dosage of trafermin we injected and post‐injective serum bFGF concentrations were dose‐dependent but the amount of changes in the serum bFGF concentration was negligible within the physiological range. Therefore, as with subcutaneous and wound administration, intracordal trafermin injections may be safe. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Abstract Background This study is designed to compare the menstrual blood stem cells (MenSCs) and bone marrow stem cells (BMSCs)-secreted factors with or without pre-treatment regimen using basic fibroblast growth factor (bFGF) and 5-aza-2ʹ-deoxycytidine (5-aza) and also regenerative capacity of pre-treated MenSCs and/or BMSCs in a rat model of myocardial infarction (MI). Methods BMSCs and MenSCs were pre-treated with bFGF and 5-aza for 48 h and we compared the paracrine activity by western blotting. Furthermore, MI model was created and the animals were divided into sham, MI, pre-treated BMSCs, and pre-treated MenSCs groups. The stem cells were administrated via tail vain. 35 days post-MI, serum and tissue were harvested for further investigations. Results Following pre-treatment, vascular endothelium growth factor, hypoxia-inducible factor-1, stromal cell-derived factor-1, and hepatocyte growth factor were significantly increased in secretome of MenSCs in compared to BMSCs. Moreover, systemic administration of pre-treated MenSCs, leaded to improvement of cardiac function, preservation of myocardium from further subsequent injuries, promotion the angiogenesis, and reduction the level of NF-κB expression in compared to the pre-treated BMSCs. Also, pre-treated MenSCs administration significantly decreased the serum level of Interleukin 1 beta (IL-1β) in compared to the pre-treated BMSCs and MI groups. Conclusions bFGF and 5-aza pre-treated MenSCs offer superior cardioprotection compare to bFGF and 5-aza pre-treated BMSCs following MI.

Introduction: Currently, flap operation (FOP) using REGROTH® (0.3% basic fibroblast growth factor [FGF-2]) is the standard treatment for periodontal regenerative therapy in Japan. However, the periodontal tissue regenerative effect with REGROTH® monotherapy is inadequate for severe alveolar bone defects. Therefore, in this study, we evaluated the safety and effectiveness of periodontal regenerative therapy for patients with severe periodontitis using REGROTH® (test medicine) combined with Cytrans® Granules (test device: carbonated apatite granules), which is a new artificial bone. Methods: The study participants included 10 patients with severe periodontitis (mean age: 47.4 years). All participants provided written informed consents. In each patient, the intrabony defect site (mean bone defect depth: 5.7 mm) was defined as the test site. FOP was performed for the test site after the baseline investigation; moreover, the test medicine and test device were administered simultaneously. Furthermore, the observation of subjects’ general condition and test sites was conducted and the blood, urine, and periodontal tissue tests were performed up to 36 weeks after FOP. The rate of bone increase (%), clinical attachment level (CAL), probing pocket depth (PPD), bleeding on probing (BOP), tooth mobility (Mo), width of keratinized gingiva (KG), gingival recession (REC), gingival index (GI), and plaque index (PlI) were evaluated during the periodontal tissue investigation. Results: As the primary endpoint, no adverse events related to the test medicine and test device occurred during the entire observation period of this study. Regarding the secondary endpoints, there was a significant increase in new alveolar bone (p = 0.003) and CAL acquisition (p = 0.001) as well as decrease in PPD (p = 0.002) and BOP (p = 0.016) at 36 weeks after administration of the test medicine and test device compared with the preoperative values. Furthermore, at 36 weeks after surgery, the Mo, GI, and PlI decreased to preoperative levels at 40%, 60%, and 30% of sites, respectively. However, at 36 weeks after surgery, there was no difference in KG and REC compared with their preoperative values. Conclusions: The safety of periodontal regenerative therapy using the test medicine in combination with the abovementioned test device was confirmed. In addition, it was suggested that this periodontal regenerative therapy is effective for tissue regeneration in severe alveolar bone defects.This clinical trial was conducted after registering and publicizing as a specified clinical trial in the Japan registry of clinical trials (jRCTs051190045).

Introduction: This study included patients who underwent full-thickness skin reconstruction using a two-stage procedure comprising basic fibroblast growth factor-impregnated collagen gelatin sponge (bFGF-CGS) implantation and autologous skin grafting, and the take rate of skin grafts was compared between groups of patients who underwent autologous skin grafting after a waiting period of

For traditional artificial dermises, a waiting period of approximately three weeks is required after the first implantation before they are adequately vascularized. The objective of this retrospective case series was to investigate whether full-thickness skin defects, requiring surgical reconstruction, could be successfully treated by implantation of a basic fibroblast growth factor (bFGF)-impregnated artificial dermis and secondary skin grafting with a shorter waiting period. Between January 2019 and January 2021, 19 skin defects in 14 patients (7 male and 7 female) were treated with two-stage skin grafting using bFGF-impregnated collagen-gelatin sponge (CGS). All of them were included in this case series, and the waiting period for skin grafting, success rate of skin grafting, infection during the waiting period, and scar quality 6–12 months postoperatively were retrospectively investigated. As a result, all skin grafting surgeries were successfully performed with a waiting period of 13.3 ± 4.3 days. Infection during the waiting period was observed in three lesions (15.8%); however, all infections were controllable. Postoperative scar quality was acceptable (Vancouver Scar Scale score range, 1–8). In conclusion, compared to traditional artificial dermises, bFGF-impregnated CGSs have the potential to shorten the waiting period without decreasing the success rate of skin grafting. Further studies are required to confirm this finding.