OBJECTIVE: To compare surgical outcomes of regenerative treatment (RT) including basic fibroblast growth factor (bFGF) (Group-R) with the conventional method (Group-C) for patients with tympanic membrane perforation (TMP), both of whom underwent transcanal endoscopic ear surgery.
METHODS: The study population of Group-R included 61 ears of 59 patients treated with RT-TMP in which TMP edges were disrupted mechanically and a gelatin sponge immersed in bFGF was inserted into the TMP. Fibrin glue was then dripped over the sponge. Group-C consisted of 13 patients who underwent conventional surgery before adopting the RT-TMP. Patients\' characteristics and outcomes including TMP closure rates, and change in hearing level were evaluated three or more weeks after the surgery.
RESULTS: The baseline characteristics including size of TMP were not significantly different between the two groups. Although Group-R had significantly shorter operating time than Group-C, the complete TMP closure rates were 69 % (9/13) and 85 % (52/61), respectively. Air-conduction hearing thresholds showed significant improvements, and analysis of variance showed that Group-R achieved significant interactions other than at 8 kHz, implying better improvement in cases with TMP closure. The air-bone gaps also improved at all frequencies in both groups. Specifically, at 4 kHz, there was a trend showing better improvement in Group-R.
CONCLUSIONS: RT-TMP had a high TMP closure rate and good hearing improvement, with no significant differences compared with those of conventional surgery. This new therapy is simple and safe, and requires less operating time, and it could help improve the quality of life of patients with TMP.

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.

OBJECTIVE: 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.
METHODS: 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.
CONCLUSIONS: 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.

CONCLUSIONS: 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.

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.

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.

UNASSIGNED: To explore the therapeutic effect of basic fibroblast growth factor (bFGF) on spinal cord injury (SCI) in rats and the influence of Notch/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
UNASSIGNED: A total of 40 10-week-old male Sprague Dawley (SD) rats were selected to establish T 10-segment SCI model by a free falling object. Among them, 32 successful models were randomly divided into model group and bFGF group, with 16 in each group. Another 16 SD rats were selected as sham-operation group, with only T 10 processes, dura mater, and spinal cord exposed. After modeling, the rats in bFGF group were intraperitoneally injected with 100 μg/kg bFGF (once a day for 28 days), and the rats in model group and sham-operation group were injected with normal saline in the same way. The survival of rats in each group were observed after modeling. Basso-Beattie-Bresnahan (BBB) scores were performed before modeling and at immediate, 14 days, and 28 days after modeling to evaluate the functional recovery of hind limbs. Then, the spinal cord tissue at the site of injury was taken at 28 days and stained with HE, Nissl, and propidium iodide (PI) to observe the pathological changes, neuronal survival (number of Nissl bodies) and apoptosis (number of PI red stained cells) of the spinal cord tissue; immunohistochemical staining and ELISA were used to detect the levels of astrocyte activation markers [glial fibrillary acidic protein (GFAP)] and inflammatory factors [interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ)] in tissues, respectively. Western blot was used to detect the expressions of Notch/STAT3 signaling pathway related proteins [Notch, STAT3, phosphoryl-STAT3 (p-STAT3), bone morphogenetic protein 2 (BMP-2)] in tissues.
UNASSIGNED: All rats survived until the experiment was completed. At immediate after modeling, the BBB scores in model group and bFGF group significantly decreased when compared to sham-operation group ( P<0.05). At 14 and 28 days after modeling, the BBB scores in model group significantly decreased when compared to sham-operation group ( P<0.05); the bFGF group showed an increase compared to model group ( P<0.05). Compared with before modeling, the BBB scores of model group and bFGF group decreased at immediate after modeling, and gradually increased at 14 and 28 days, the differences between different time points were significant ( P<0.05). The structure of spinal cord tissue in sham-operation group was normal; in model group, there were more necrotic lesions in the spinal cord tissue and fewer Nissl bodies with normal structures; the number of necrotic lesions in the spinal cord tissue of the bFGF group significantly reduced compared to the model group, and some normally structured Nissl bodies were visible. Compared with sham-operation group, the number of Nissl bodies in spinal cord tissue significantly decreased, the number of PI red stained cells, GFAP, IL-1β, TNF-α, IFN-γ, Notch, p-STAT3 /STAT3, BMP-2 protein expression levels significantly increased in model group ( P<0.05). The above indexes in bFGF group significantly improved when compared with model group ( P<0.05).
UNASSIGNED: bFGF can improve motor function and pathological injury repair of spinal cord tissue in SCI rats, improve neuronal survival, and inhibit neuronal apoptosis, excessive activation of astrocytes in spinal cord tissue and inflammatory response, the mechanism of which may be related to the decreased activity of Notch/STAT3 signaling pathway.
UNASSIGNED: 探讨bFGF对脊髓损伤（spinal cord injury，SCI）大鼠的治疗作用及Notch/STAT3信号通路的影响。.
UNASSIGNED: 取10周龄雄性SD大鼠40只，采用自由落体打击法建立T 10 节段SCI模型，其中32只造模成功随机分为模型组、bFGF组，每组16只；另取16只SD大鼠仅暴露T 10棘突、硬脊膜和脊髓，作为假手术组。造模后bFGF组腹腔注射100 μg/kg bFGF（1次/d，共28 d），模型组和假手术组大鼠同法注射生理盐水。造模后观察各组大鼠存活情况，于造模前及造模后即刻、14 d、28 d行BBB评分评估后肢功能。造模后28 d取损伤部位脊髓组织，行HE、Nissl和碘化丙啶（propidium iodide，PI）染色，观察脊髓组织病理变化、神经元存活（尼氏体数量）和凋亡（PI红染细胞数量）情况；免疫组织化学染色和ELISA法分别检测组织中星形胶质细胞活化标志物 ［胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）］ 及炎症因子 ［IL-1β、TNF-α、干扰素γ（interferon γ，IFN-γ）］水平；Western blot检测组织Notch/STAT3信号通路相关蛋白 ［Notch、STAT3、磷酸化-STAT3（phosphoryl-STAT3，p-STAT3）、BMP-2］ 表达。.
UNASSIGNED: 各组大鼠均存活至实验完成。造模后即刻，模型组及bFGF组BBB评分均较假手术组降低（ P<0.05）；14、28 d时模型组BBB评分较假手术组降低（ P<0.05），bFGF组较模型组升高（ P<0.05）。模型组、bFGF组与造模前比较，造模后即刻BBB评分降低，14 、28 d评分逐渐升高，各时间点间差异均有统计学意义（ P<0.05）。假手术组脊髓组织结构正常；模型组脊髓组织出现较多坏死灶，结构正常尼氏体较少；bFGF组脊髓组织坏死灶较模型组明显减少，可见部分结构正常尼氏体。与假手术组比较，模型组脊髓组织尼氏体数量减少，PI红染细胞数量增多，GFAP、IL-1β、TNF-α、IFN-γ以及Notch、p-STAT3/STAT3、BMP-2蛋白表达水平升高（ P<0.05）；而bFGF组上述指标均较模型组改善（ P<0.05）。.
UNASSIGNED: bFGF能改善SCI大鼠运动功能和脊髓组织病理损伤，有利于神经元存活，抑制神经元凋亡、脊髓组织星形胶质细胞过度活化及炎症反应，其作用机制可能与Notch/STAT3信号通路活性降低有关。.

OBJECTIVE: To investigate the feasibility of different thermosensitive composite hydrogels from chitosan derivatives as scaffold materials for periodontal tissue engineering.
METHODS: Three chitosan derivatives with different biological characteristics were prepared, namely, sulfonated chitosan (SCS), phosphorylated chitosan (PCS), and phosphorylated sulfonated chitosan (PSCS). Three thermosensitive composite hydrogels were constructed using basic fibroblast growth factor (bFGF), the chitosan derivatives, and collagen. Twenty male Wistar rats were randomly divided into control group, blank group, bFGF/SCS/collagen composite thermosensitive hydrogel group, bFGF/PCS/collagen compo-site thermosensitive hydrogel group, and bFGF/PSCS/collagen composite thermosensitive hydrogel group. Then, three-wall intrabony defects were established. The defects were treated with the different kinds of thermosensitive composite hydrogels. After 6 weeks of surgery, the animals were killed, and specimens were collected. Then, gross observation, hematoxylin-eosin staining, and Masson staining were performed.
RESULTS: The bFGF/chitosan derivatives/collagen composite thermosensitive hydrogel groups and the control group had statistical differences in the relative alveolar bone height, relative epithelial down growth and grading count score of periodontal tissue regeneration (P<0.05).
CONCLUSIONS: bFGF/chitosan derivatives/collagen composite thermosensitive hydrogels have good application prospects in periodontal tissue engineering.
目的: 探讨不同种壳聚糖衍生物温敏型复合水凝胶作为支架材料应用于牙周组织工程的可行性。方法: 制备磺化壳聚糖（SCS）、磷酸化壳聚糖（PCS）及磷酸化磺化壳聚糖（PSCS）3种具有不同生物学特性的壳聚糖衍生物，构建3种碱性成纤维细胞生长因子（bFGF）/壳聚糖衍生物/胶原温敏型复合水凝胶。选取20只雄性wistar大鼠，大鼠双侧上颌第一磨牙近中建立三壁骨袋，随机分为空白对照组、空白凝胶组、bFGF/SCS/胶原温敏型复合水凝胶组、bFGF/PCS/胶原温敏型复合水凝胶组、bFGF/PSCS/胶原温敏型复合水凝胶组，术后6周处死大鼠，采集标本，进行大体、苏木精-伊红染色、Masson染色观察。结果: 术后6周，3种bFGF/壳聚糖衍生物/胶原温敏型复合水凝胶组与空白对照组在相对牙槽骨高度比值、相对上皮根向下移比及牙周组织再生分级计数等方面的差异均具有统计学意义（P<0.05）。结论: bFGF/壳聚糖衍生物/胶原温敏型复合水凝胶在牙周组织工程邻域具有良好的应用前景。.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 < 0.05), indicating that bFGF promoted perforation closure.
UNASSIGNED: The study demonstrated that bFGF with collagen/gelatin carrier promoted wound healing in a rabbit model of nasal septum perforation.

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.