BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2025
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IF 4.2
Shibo Zhu,Sunwei Tang,Zijie Ye,Wei Jia
One of the most prevalent male urogenital anomalies is hypospadias. The general etiology of hypospadias is still not completely clear, despite the fact that the number of patients with the hypospadias is rising. HNF-1α was predicted as the most activated upstream regulator of severe hypospadias in our previous research. Our study aims to investigate the mechanism by which HNF-1α regulates hypospadias. We found that HNF-1α was highly expressed in hypospadias tissues, and was positively associated with fibrinogen related genes FGA and FGB, respectively. In animal experiments, silencing of HNF-1α resulted in a more narrow urethral groove, and a decreased periurethral pathologic fibrosis. Meanwhile, the inflammation cytokines and oxidative stress related factors were significantly reduced after inhibition of HNF-1α expression. In addition, the protein levels of STAT3, FGA and FGB were also depressed after HNF-1α knockdown. Mechanistically, we showed that the HNF-1α transcriptionally activated STAT3, and subsequently increased the expressions of FGA and FGB. Additionally, suppression of HNF-1α improved the murine hypospadias via inactivating the STAT3. Therefore, our findings confirmed that HNF-1α promoted hypospadias and periurethral fibrosis by activating STAT3. Targeting HNF-1α might the future direction for hypospadias treatment.
研究领域:
医学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 18
·14217-14226
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IF 4.6
Zhihuan Zheng,Ziqiang Wu,Chao Li,Lei Zhou,Weibin Hou,Wei Xiong,Shuo Tan
As a prevalent complication following urinary system trauma, urethral stricture is characterized by progressive fibrosis and luminal narrowing often leading to recurrent dysuria and impaired renal function. Current treatments including surgical interventions face challenges such as high recurrence rates and secondary stenosis. Hydrogel-based drug delivery systems offer therapeutic potential but are limited by material swelling under urinary flow and insufficient modulation of inflammatory microenvironments. This study introduces an innovative anti-swelling carrageenan biogel scaffold (Car/Ga) functionalized with glycyrrhizic acid (Ga), a dual anti-inflammatory and immunoregulatory phytochemical. The Car matrix ensures structural stability in biological fluids by resisting swelling-induced obstruction while Ga targets trauma-induced inflammatory cascades through M1 macrophage polarization mitigation to reduce fibrotic progression. In vitro and in vivo evaluations demonstrate that the Car/Ga system synergistically combines urine stability with immunomodulatory bioactivity, significantly reducing pro-inflammatory cytokine levels (iNOS) and promoting M2 macrophage polarization (Arg1). Histological analyses reveal attenuated collagen deposition and enhanced epithelial regeneration in urethral stricture models, highlighting its capacity to disrupt the inflammation–fibrosis cycle. By addressing both urine stability and immunological dysregulation, this dual-functional biogel represents a transformative strategy for precise urethral repair, demonstrating potential for clinical translation in urethral repair applications.
研究领域:
泌尿外科
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生物材料学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
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2014
·Vol. 16
·期 12
·1-11
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IF 2.278
Huang Xiao,Wang Zhen,Dai Hong,Wang Chunmei,Xia Bing,Chen Lan,Pan Jun
Although urethral carcinoma has a low incidence, it suffers from a poor curative rate for the low retention of medicine around urethra. In the present study, we developed a kind of magnetic targeting perfusion chemotherapy to detain the chemotherapeutic drugs. Docetaxel (TXT) grafted magnetic nanoparticles, of which size was around 40 nm, were obtained by the conjugation of TXT to amino-functionalized iron oxide (NH 2 @Fe 3 O 4 ). They have shown great potential to be targeted to and stayed in desired position of urethra under the externally applied magnetism through in vitro mimic urethral study. Furthermore, they have validly inhibited the growth of direct-contacted human urethral squamous carcinoma cells in vitro (up to 56.34 %) by the combination effects of TXT and NH 2 @Fe 3 O 4 , however, less than 3 % of TXT released from the nanoparticles, which was very few to impair the adjacent normal cells and tissues. Therefore, this kind of novel agentia was expected to hold great potential in clinic urethral carcinoma therapy.
研究领域:
药学
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纳米技术
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Guochang Liu,Ming Fu,Feng Li,Wen Fu,Zhang Zhao,Huimin Xia,Yuqing Niu
The repair and regeneration of tissues using tissue-engineered scaffolds represent the ultimate goal of regenerative medicine. Despite rapid developments in the field, urethral tissue engineering methods are still insufficient to replicate natural urethral tissue because the bioactivity of existing scaffolds is inefficient, especially for large tissue defects, which require large tissue-engineered scaffolds. Here, we describe the efficiency of gelatine-functionalized, tubular nanofibrous scaffolds of poly( l -lactic acid) (PLLA) in regulating the phenotypic expression of epithelial cells (ECs) and smooth muscle cells (SMCs) for urethral reconstruction. Flexible PLLA/gelatine tubular nanofibrous scaffolds with hierarchical architecture were fabricated by electrospinning. The PLLA/gelatine nanofibrous scaffold exhibited enhanced hydrophilicity and significantly promoted the adhesion, oriented elongation, and proliferation of New Zealand rabbit autologous ECs and SMCs simultaneously. Compared with pure PLLA nanofibrous scaffold, PLLA/gelatine nanofibrous scaffolds upregulated the expression of keratin (AE1/AE3) in ECs and actin (α-SMA) in SMCs as well as the synthesis of elastin. Three months of in vivo scaffold replacement of New Zealand rabbit urethras indicated that a tubular cellularized PLLA/gelatine nanofibrous scaffold maintained urethral patency and facilitated oriented SMC remodeling, lumen epithelialization, and angiogenesis. Our observations showed the synergistic effects of nano-morphology and biochemical clues in the design of biomimetic scaffolds, which can effectively promote urethral regeneration.
研究领域:
再生医学
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组织工程学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Biology
·
2024
·
IF 3.2
Weidong Zhong,Jinshui Chen,Qifeng Xie,Wenyue Cheng,Meibiao Zhao,Yang Sun,Jing Dai,Jian Zhang
Biological scaffolds are widely utilized in hernia treatment due to their exceptional pro-regenerative properties, which mitigate scar formation. However, serious complications occurred, caused by inflammatory response, premature degradation, and mechanical failure. Consequently, improvements of the biological scaffold are necessary to mitigate these risks. In this study, a novel biological scaffold integrating basement membrane-containing urinary bladder matrix (UBM) and small intestinal submucosa (SIS) is developed, and its safety and effectiveness are assessed in comparison to a commercial SIS (c-SIS) scaffold. The introduction of UBM as top surface layers significantly promotes cell adhesion, facilitating rapid formation of isolated regeneration zone. Proteomic analysis has demonstrated a more efficient decellularization of the UBM/SIS scaffold, which subsequently mitigates inflammation in murine models, and promotes the polarization of macrophages toward the pro-healing M2 phenotype in a rat model of abdominal wall muscle defect. Furthermore, a two-year repair trial is conducted on a full-thickness abdominal wall muscle defect in canine model and confirmed that the UBM/SIS scaffold exhibits reduced seroma occurrences and enhanced tissue repair performances. Overall, the efficacy of this novel biological scaffold suggests its potential to minimize hernia recurrence in clinical practice and mitigate patient suffering from severe inflammatory responses.
研究领域:
生物医学工程
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再生医学
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材料科学
✓ 已验证
DOI
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Zhenpeng Zhu,Jianming Zhao,Xing Ji,Weimin Hu,Wenyuan Leng,Chunru Xu,Xiaoyu Li,Kunlin Yang,Xuesong Li,Yudong Zheng,Jian Lin
The treatment of urethral stricture disease and the prevention of restenosis present considerable challenges in the field of urology. Tissue-engineered materials, particularly bacterial cellulose scaffolds, have emerged as promising solutions due to their abundant sources, excellent mechanical properties, and biocompatibility. However, for attaining superior treatment for patients with USD, further modification of bacterial cellulose is necessary. We have fabricated a dual-network scaffold with enhanced antibacterial properties and cytokines absorption ability through in-situ polymerization of cationic polyurethane micelles and cyclodextrin on oxidized bacterial cellulose. This scaffold also enables long-term sustained release of loaded drug components. Animal model studies have confirmed that this scaffold can achieve urethral repair outcomes comparable to those of normal urethral tissue. This innovative material provides a robust foundation for advancing new concepts and methodologies in the treatment of urethral stricture disease, potentially transforming clinical approaches to this challenging condition.
研究领域:
生物医学工程
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泌尿外科
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Jixiang Zhu,Fanwen Yang,Fupo He,Xiumei Tian,Shuo Tang,Xiaoming Chen
A tubular gelatin scaffold for the time-dependent controlled release of epidermal growth factor (EGF) and mitomycin C (MMC) was fabricated. EGF was incorporated using silk fibroin carriers, and MMC was planted using polylactide (PLA) microspheres. The relationship between scaffold properties and crosslinking degrees was evaluated. As the crosslinking degree was increased from 23.7% to 65.3%, the mechanical properties of the scaffold obviously improved, and the compressive modulus increased to approximately 65 kPa. The mass degradation of the scaffold was also controlled from 9 days to approximately 1 month. In vitro release tests indicated that the scaffold mainly released EGF in the early period and MMC in the later period. Urethral epithelial cells (UECs) and urethral scar derived fibroblast cells (UFCs) were coseeded in the scaffold at a ratio of 1:1. After 9 days of coculture, immunostaining results displayed that the proportion of UECs continuously increased to approximately 71%. These changes in cell proportion were confirmed by the results of Western blot analysis. Therefore, the scaffold promoted the growth but inhibited the regeneration of UFCs. This scaffold for time-dependent controlled release of multiple biofactors may be potentially useful in urethral reconstruction and other tissue engineering studies.
研究领域:
生物医学工程
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组织工程
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药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INVESTIGATIVE SURGERY
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2018
·
IF 1.122
Yue Zhou,Jinpu Peng,Xining Cao,Chao Yan,Fangyuan Huang,Lianju Shen,Chunlan Long,Xing Liu,Guanghui Wei
Objective: The aim of this study was to identify a theoretical support for the prevention of urethral fistula following hypospadias repair, by comparing the preputial wound healing process in Sprague-Dawley (SD) rats with and without hypospadias induced by flutamide. Methods: Fifteen pregnant SD rats were randomly divided into three groups. These rats in one group received the androgen receptor antagonist flutamide (25 mg/kg/day) from gestation days 11–17, to establish a rat model of hypospadias for further study of the molecular mechanisms of the hypospadias etiology. The pregnant rats in the control groups were not administered flutamide. The pups from the control and experiment groups underwent an incision on the dorsal prepuce on postnatal day 25 and were sacrificed on postoperative days 3, 7, and 14 to collect penis samples. The penis morphology was examined in all groups. Subsequently, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMactin), and signal transducers and activators of the transcription 3 (STAT3) expression levels in the different groups were measured at the indicated time points postoperatively using qRT-PCR and Western blot. Results: There was less regeneration of the subcutaneous tissue in hypospadias rats than in the sham-operated group (P < 0.05) on postoperative day 3. No differences were found in the regeneration of the subcutaneous tissue between these groups on postoperative days 7 or 14. Additionally, there were no differences in the epithelial cell regeneration between the control and the hypospadias groups at any postoperative timepoint. Moreover, the expression levels of TGF-β1, α-SMactin, and STAT3 were all significantly lower in hypospadias group than that in the sham-operated group (P < 0.05). Conclusion: The results from the present work suggest that preputial wound healing is retarded in rats with hypospadias induced by flutamide and that this retardation might result from multi-gene regulation.
研究领域:
泌尿外科
·
分子生物学
·
动物模型
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Wenzhuo Fang,Ying Wang,Kaile Zhang,Ming Yang,Meng Liu,Yangwang Jin,Xianjie Xiu,Yuhui Wang,Zhenwei Yu,Ranxing Yang,Qiang Fu
The harsh microenvironment of the urethral injury often carries high risks of early undesirable healing as well as late scar tissue formation. Indeed, the infection and inflammatory response in the early stages as well as blood vessel formation and tissue regeneration in the later stages fundamentally impact the outcomes of urethral wound healing. Innovatively, an integrated whole-process repair hydrogel (APF/C/L@dECM) is designed. After rigorous testing, it is found that hydrogels formed by hydrophobic association and double cross-linking of amide bonds can procedurally regulate wound healing in all phases to match the repair process. In rabbit models of urethral wound, APF/C/L@dECM hydrogel can achieve scarless reconstruction with significantly better results than other hydrogels. Noteworthily, multi-stage mechanistic explorations reveal the expression profiles of inflammation, vascularization, and extracellular matrix secretion-related genes in wound tissue at different times. In summary, this study develops an overall treatment for urethral injury through a whole-process repair system that promotes healthy healing of urethral wounds and prevents the formation of scar tissue.
研究领域:
组织工程
·
伤口愈合
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生物材料
·
再生医学
·
泌尿外科
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Communications
·
2024
·
IF 3.7
Jing Bai,Xianli Wang,Xin Ye,Xiaoyu Li,Xi Tan,Cheng Wang,Yunfei Guo,Jiaqi Dong,Yi Shao,Chenglin Chu,Feng Xue,Li Tao,Liqu Huang
Due to bacteria in urine and inadequate blood supply, urethral defect repair faces great clinical difficulties. Inspired by the natural structure of the urethra, in this study, we designed a multifunctional hydrogel urethral patch with a Janus structure. The inner layer was a double-network hydrogel of polyvinyl alcohol/carboxymethyl chitosan (PVA/CMCS) enhanced by natural phytic acid (PA) and Mg 2+ (Mg 2+ -PA/PVA/CMCS). The outer layer was composed of poly (L-lactic acid) (PLLA) nanofibers to form a hydrophobic barrier, coupling via a micelle layer to ensure interfacial bonding. The patch exhibited mechanical properties matching soft tissues, with maximum tensile strength and toughness of 1.69±0.13 MPa and 24.7±0.9 MJ/m 3 , respectively, under the strengthening effect of Mg 2+ -PA chelation. Therein, the 4 % Mg 2+ -PA/PVA/CMCS composite patch could maintain unilateral hydrophobicity for at least 14 days and demonstrated an antibacterial rate of 99.0 %±0.1 % against E. coli . In PBS, the patch could deliver Mg 2+ for at least 7 days and stabilize the surrounding pH environment for up to 28 days. In vitro cell experiments indicated that the 4 % Mg 2+ -PA/PVA/CMCS composite patch could promote the human umbilical vein endothelial cell (HUVEC) proliferation and migration, with the angiogenic protein expression enhanced more than 1.2 times compared with the Control group. In conclusion, the patch constructed in this study may provide a new approach to clinical urethral injury repair.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
材料科学
·
再生医学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yangwang Jin,Ying Wang,Ranxing Yang,Wenzhuo Fang,Kaile Zhang,Meng Liu,Yuhui Wang,Ming Yang,Qiang Fu
The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.
研究领域:
组织工程
·
再生医学
·
生物材料
·
泌尿外科
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）