1.Human amniotic mesenchymal stem cells overexpressing neuregulin-1 promote skin wound healing in mice
Taotao HU ; Bing LIU ; Cheng CHEN ; Zongyin YIN ; Daohong KAN ; Jie NI ; Lingxiao YE ; Xiangbing ZHENG ; Min YAN ; Yong ZOU
Chinese Journal of Tissue Engineering Research 2025;29(7):1343-1349
BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.
2.Ablation of IGFBP5 expression alleviates neurogenic erectile dysfunction by inducing neurovascular regeneration
Jiyeon OCK ; Guo Nan YIN ; Fang-Yuan LIU ; Yan HUANG ; Fitri Rahma FRIDAYANA ; Minh Nhat VO ; Ji-Kan RYU
Investigative and Clinical Urology 2025;66(1):74-86
Purpose:
To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED).
Materials and Methods:
Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure.These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays.
Results:
Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression.
Conclusions
Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice.
3.Role of pericytes in regulating penile angiogenesis and nerve regeneration.
Asian Journal of Andrology 2025;27(1):13-19
Pericytes are multifunctional mural cells that surround the abluminal wall of endothelial cells and are associated with vascular development, vascular permeability, and angiogenesis. Additionally, pericytes demonstrate stem cell-like properties and contribute to neuroinflammatory processes. Pericytes have been extensively studied in the central nervous system. However, specific mechanisms underlying its involvement in various physiological and pathological conditions, especially in erectile dysfunction (ED), remain poorly understood. Advancements in in vitro and in vitro techniques, such as single-cell RNA sequencing, are expanding our understanding of pericytes. Recent studies have shown that pericyte dysfunction is considered an important factor in the pathogenesis of vascular and neurological ED. Therefore, this study aims to analyze the specific role of pericytes in ED, focusing on diabetic and neurogenic ED. This article provides a comprehensive review of research findings on PubMed from 2000 to 2023, concerning pericyte dysfunction in the process of ED, offering valuable insights, and suggesting directions for further research.
Pericytes/physiology*
;
Humans
;
Male
;
Penis/innervation*
;
Erectile Dysfunction/physiopathology*
;
Nerve Regeneration/physiology*
;
Neovascularization, Physiologic/physiology*
;
Animals
;
Angiogenesis
4.Exogenous administration of heparin-binding epidermal growth factor-like growth factor improves erectile function in mice with bilateral cavernous nerve injury.
Minh Nhat VO ; Mi-Hye KWON ; Fang-Yuan LIU ; Fitri Rahma FRIDAYANA ; Yan HUANG ; Soon-Sun HONG ; Ju-Hee KANG ; Guo Nan YIN ; Ji-Kan RYU
Asian Journal of Andrology 2025;27(6):697-706
Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals
;
Male
;
Heparin-binding EGF-like Growth Factor/therapeutic use*
;
Erectile Dysfunction/etiology*
;
Mice
;
Penis/drug effects*
;
Nerve Regeneration/drug effects*
;
Penile Erection/drug effects*
;
Peripheral Nerve Injuries/drug therapy*
;
Cell Proliferation/drug effects*
;
Apoptosis/drug effects*
;
Cell Movement/drug effects*
;
Prostatectomy/adverse effects*
;
Mice, Inbred C57BL
;
Reactive Oxygen Species/metabolism*
5.Photobiomodulation as a Potential Therapy for Erectile Function: A Preclinical Study in a Cavernous Nerve Injury Model
Limanjaya ANITA ; Min-Ji CHOI ; Guo Nan YIN ; JiYeon OCK ; Mi-Hye KWON ; Beom Yong RHO ; Doo Yong CHUNG ; Jun-Kyu SUH ; Ji-Kan RYU
The World Journal of Men's Health 2024;42(4):842-854
Purpose:
To identify the optimal photobiomodulation (PBM) parameters using molecular, histological, and erectile function analysis in cavernous nerve injury.
Materials and Methods:
A cavernous nerve injury was induced in 8-week-old C57BL/6J male mice that were subsequently divided randomly into age-matched control groups. Erectile function tests, penile histology, and Western blotting were performed 2 weeks after surgery and PBM treatment.
Results:
The PBM treatment was administered for five consecutive days with a light-emitted diode (LED) device that delivers 660 nm±3% RED light, and near infra-red 830 nm±2% promptly administered following nerve-crushing surgery and achieved a notable restoration of erectile function approximately 90% of the control values. Subsequent in-vitro and ex-vivo analyses revealed the regeneration of neurovascular connections in both the dorsal root ganglion and major pelvic ganglion, characterized by the sprouting of neurites. Furthermore, the expression levels of neurotrophic, survival, and angiogenic factors exhibited a substantial increase across all groups subjected to PBM treatment.
Conclusions
The utilization of PBM employing LED with 660 nm, 830 nm, and combination of both these wavelengths, exhibited significant efficacy to restore erectile function in a murine model of cavernous nerve injury. Thus, the PBM emerges as a potent therapeutic modality with notable advantages such as efficacy, noninvasiveness, and non-pharmacological interventions for erectile dysfunction caused by nerve injury.
6.Three-dimensional finite element analysis of effects of different bone densities on various intraarticular structures after unicompartmental knee arthroplasty
Mengfei LIU ; Pengcheng MA ; Can YIN ; Kan JIANG ; Xiaochen JU
Chinese Journal of Tissue Engineering Research 2024;28(24):3801-3806
BACKGROUND:Osteoporosis is a common comorbidity in patients with knee osteoarthritis.The impact of osteoporosis on the prognosis of unicompartmental knee arthroplasty is a trending topic of current research. OBJECTIVE:To investigate the effect of different bone densities on the stress value and stress distribution of each structure in the joint after unicompartmental knee arthroplasty using finite element analysis,and to evaluate the correlation between osteoporosis and complications. METHODS:CT and MRI were adopted to obtain the lower limb image data of a volunteer.Geomagic Studio,Ansys workbench,and Mimics were used to establish a finite element model of the knee joint with normal sclerotin condition(T-value≥-1.0).The finite element model of the knee joint with osteopenia(-2.5
7.The Quantitative Evaluation of Automatic Segmentation in Lumbar Magnetic Resonance Images
Yao-Wen LIANG ; Yu-Ting FANG ; Ting-Chun LIN ; Cheng-Ru YANG ; Chih-Chang CHANG ; Hsuan-Kan CHANG ; Chin-Chu KO ; Tsung-Hsi TU ; Li-Yu FAY ; Jau-Ching WU ; Wen-Cheng HUANG ; Hsiang-Wei HU ; You-Yin CHEN ; Chao-Hung KUO
Neurospine 2024;21(2):665-675
Objective:
This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans.
Methods:
Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net’s segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness.
Results:
The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements.
Conclusion
Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.
8.The Quantitative Evaluation of Automatic Segmentation in Lumbar Magnetic Resonance Images
Yao-Wen LIANG ; Yu-Ting FANG ; Ting-Chun LIN ; Cheng-Ru YANG ; Chih-Chang CHANG ; Hsuan-Kan CHANG ; Chin-Chu KO ; Tsung-Hsi TU ; Li-Yu FAY ; Jau-Ching WU ; Wen-Cheng HUANG ; Hsiang-Wei HU ; You-Yin CHEN ; Chao-Hung KUO
Neurospine 2024;21(2):665-675
Objective:
This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans.
Methods:
Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net’s segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness.
Results:
The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements.
Conclusion
Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.
9.Photobiomodulation as a Potential Therapy for Erectile Function: A Preclinical Study in a Cavernous Nerve Injury Model
Limanjaya ANITA ; Min-Ji CHOI ; Guo Nan YIN ; JiYeon OCK ; Mi-Hye KWON ; Beom Yong RHO ; Doo Yong CHUNG ; Jun-Kyu SUH ; Ji-Kan RYU
The World Journal of Men's Health 2024;42(4):842-854
Purpose:
To identify the optimal photobiomodulation (PBM) parameters using molecular, histological, and erectile function analysis in cavernous nerve injury.
Materials and Methods:
A cavernous nerve injury was induced in 8-week-old C57BL/6J male mice that were subsequently divided randomly into age-matched control groups. Erectile function tests, penile histology, and Western blotting were performed 2 weeks after surgery and PBM treatment.
Results:
The PBM treatment was administered for five consecutive days with a light-emitted diode (LED) device that delivers 660 nm±3% RED light, and near infra-red 830 nm±2% promptly administered following nerve-crushing surgery and achieved a notable restoration of erectile function approximately 90% of the control values. Subsequent in-vitro and ex-vivo analyses revealed the regeneration of neurovascular connections in both the dorsal root ganglion and major pelvic ganglion, characterized by the sprouting of neurites. Furthermore, the expression levels of neurotrophic, survival, and angiogenic factors exhibited a substantial increase across all groups subjected to PBM treatment.
Conclusions
The utilization of PBM employing LED with 660 nm, 830 nm, and combination of both these wavelengths, exhibited significant efficacy to restore erectile function in a murine model of cavernous nerve injury. Thus, the PBM emerges as a potent therapeutic modality with notable advantages such as efficacy, noninvasiveness, and non-pharmacological interventions for erectile dysfunction caused by nerve injury.
10.Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury
Yan HUANG ; Guo Nan YIN ; Fang-Yuan LIU ; Fitri Rahma FRIDAYANA ; Lashkari NILOOFAR ; Minh Nhat VO ; Ji-Kan RYU
Investigative and Clinical Urology 2024;65(4):400-410
Purpose:
To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erectile function in mice after cavernous nerve injury (CNI).
Materials and Methods:
Lentiviruses containing Ago2 open reading frame (ORF) mouse clone (Ago2 O/E) were used to overexpress Ago2, and lentiviruses ORF negative control particles (NC) were used as a negative control. Three days before preparing the CNI model, we injected lentiviruses into the penises of 8-week-old male C57BL/6 mice. Animals were then divided into four groups: the sham operation control group and the CNI+phosphate-buffered saline, CNI+NC, and CNI+Ago2 O/E groups. One week later, erectile function was assessed by electrically stimulating cavernous nerves bilaterally and obtaining intracavernous pressure parameters. Penile tissue was also collected for molecular mechanism studies.
Results:
Ago2 overexpression improved erectile function in mice after CNI-induced erectile dysfunction (ED). Immunofluorescence staining and Western blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erectile function in CNI-induced ED mice.
Conclusions
Our findings demonstrate that Ago2 overexpression can reduce penile cell apoptosis, restore penile mitochondrial function, and improve erectile function in CNI-induced ED mice.

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