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Neurogenic bladder (NB) after spinal cord injury (SCI) is a common complication that inhibits normal daily activities and reduces the quality of life. Regrettably, the current therapeutic methods for NB are inadequate. Therefore, numerous studies have been conducted to develop new treatments for NB associated with SCI. Moreover, a myriad of preclinical and clinical trials on the effects and safety of stem cell therapy in patients with SCI have been performed, and several studies have demonstrated improvements in urodynamic parameters, as well as in sensory and motor function, after stem cell therapy. These results are promising; however, further high-quality clinical studies are necessary to compensate for a lack of randomized trials, the modest number of participants, variation in the types of stem cells used, and inconsistency in routes of administration.
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Objective@#We aimed to determine whether bone marrow-derived mesenchymal stem cells (BDMSCs) effectively attenuate the degeneration of human nucleus pulposus cells (NPCs). @*Methods@#Four NPC lines were obtained from 3 subjects who underwent spinal surgery for cervical disc herniation (n=1) or lumbar disc herniation (n=2). For co-culture wells without contact, BDMSCs and adipose-derived mesenchymal stem cells (ADMSCs) were seeded on tissue culture plates and maintained for 3 days. Senescence-associated β-gal (SA-β-gal) staining was represented as a percentage of the total number of stained cells (%). The cells with intracellular lipid droplets (LDs) were represented as the percentage of the number of cells with LDs. Glycosaminoglycan (GAG) secretion was measured at 450 nm, using a commercial kit, to analyze optical density. @*Results@#The ratio of cells stained with SA-β-gal to the total number of cells reduced significantly when co-cultured with BDMSCs and ADMSCs (p<0.001 vs. p<0.001). The proportion of NPCs containing LDs was lower when co-cultured with BDMSCs than with ADMSCs (p<0.001). The optical density related to GAG secretion was lower in BDMSCs and ADMSCs co-cultured with NPCs than in the controls (p<0.001 vs. p<0.001). @*Conclusion@#SA-β-gal staining showed significant attenuation of degenerative changes in NPCs co-cultured with BDMSCs. Moreover, the unexpected increase in LDs was significantly higher in NPCs co-cultured with ADMSCs than in those co-cultured with BDMSCs. However, GAG secretion was significantly decreased in NPCs co-cultured with MSCs.
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Purpose@#Neurogenic bladder (NB) associated with spinal cord injury (SCI) is a serious health problem. However, no effective treatment has been developed for SCI patients with NB. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors have been proposed as a promising option for inducing neural regeneration. Therefore, we investigated the effects of a tissue gene nerve (TGN), PTEN inhibitor, on voiding function, motor function, and the expression of growth factors after SCI. @*Methods@#In this experiment, female rats were randomly divided into 3 groups (n=10 in each group): the sham-operation group, the SCI-induced group, and the SCI-induced and TGN-treated group. Cystometry; the Basso, Beattie, and Bresnahan (BBB) scale test; the ladder walking test; hematoxylin and eosin staining; and Western blotting for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) were performed to evaluate functional and molecular changes. @*Results@#After SCI, the rats exhibited decreased walking ability according to the BBB scale test and impaired coordinative function according to the ladder walking test. The PTEN inhibitor promoted enhanced walking ability and coordinative function. Cystometry showed voiding impairment after SCI and improved voiding function was observed after PTEN treatment. Overexpression of VEGF, BDNF, and NGF were observed after SCI. Administration of PTEN inhibitors significantly attenuated the overexpression of growth factors due to SCI. @*Conclusion@#PTEN inhibitor treatment diminished the overexpression of growth factors and promoted the repair of damaged tissue. PTEN inhibitor-treated rats also showed improved motor function and improved voiding function. Therefore, we suggest TGN as a new therapeutic agent that can be applied after SCI.
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Shift workers often experience problems associated with circadian disruption associated with artificial light at night and nocturia is commonly noted in night-shift workers. Nocturia associated with circadian disruption is due to increased urine production of the kidney and decreased storage function of the bladder. A recent discovery of peripheral clock genes in the bladder and their role in contractile property of the bladder support that micturition is closely related to the circadian rhythm. Moreover, there are clinical studies showed that shift workers more often experienced nocturia due to circadian disruption. However, comparing with other health problems, concerns on nocturia and voiding dysfunction associated with circadian disruption are insufficient. Therefore, further studies about voiding dysfunction associated with the circadian disruption in shift workers are necessary.
Subject(s)
Circadian Clocks , Circadian Rhythm , Kidney , Nocturia , Urinary Bladder , UrinationABSTRACT
BACKGROUND: Bioprinting has recently appeared as a powerful tool for building complex tissue and organ structures. However, the application of bioprinting to regenerative medicine has limitations, due to the restricted choices of bio-ink for cytocompatible cell encapsulation and the integrity of the fabricated structures. METHODS: In this study, we developed hybrid bio-inks based on acrylated hyaluronic acid (HA) for immobilizing bioactive peptides and tyramine-conjugated hyaluronic acids for fast gelation. RESULTS: Conventional acrylated HA-based hydrogels have a gelation time of more than 30 min, whereas hybrid bioink has been rapidly gelated within 200 s. Fibroblast cells cultured in this hybrid bio-ink up to 7 days showed < 90% viability. As a guidance cue for stem cell differentiation, we immobilized four different bio-active peptides: BMP-7-derived peptides (BMP-7D) and osteopontin for osteogenesis, and substance-P (SP) and Ac-SDKP (SDKP) for angiogenesis. Mesenchymal stem cells cultured in these hybrid bio-inks showed the highest angiogenic and osteogenic activity cultured in bio-ink immobilized with a SP or BMP-7D peptide. This bio-ink was loaded in a three-dimensional (3D) bioprinting device showing reproducible printing features. CONCLUSION: We have developed bio-inks that combine biochemical and mechanical cues. Biochemical cues were able to regulate differentiation of cells, and mechanical cues enabled printing structuring. This multi-functional bio-ink can be used for complex tissue engineering and regenerative medicine.
Subject(s)
Bioprinting , Cues , Fibroblasts , Hyaluronic Acid , Hydrogels , Hydrogels , Mesenchymal Stem Cells , Osteogenesis , Osteopontin , Peptides , Regeneration , Regenerative Medicine , Stem Cells , Tissue EngineeringABSTRACT
PURPOSE: Rotenone is the most widely used neurotoxin for the making Parkinson disease (PD) animal model. The neurodegenerative disorder PD shows symptoms, such as slowness of movements, tremor at resting, rigidity, disturbance of gait, and instability of posture. We investigated whether treadmill running improves motor ability using rotenone-caused PD rats. The effect of treadmill running on PD was also assessed in relation with apoptosis of cerebellar Purkinje cells. METHODS: Treadmill running was applied to the rats in the exercise groups for 30 minutes once a day for 4 weeks, starting 4 weeks after birth. We used rota-rod test for the determination of motor coordination and balance. In this experiment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for calbindin, glial fibrillary acidic protein (GFAP), Iba-1, and western blot analysis for Bax and Bcl-2 were performed. RESULTS: Treadmill running enhanced motor balance and coordination by preventing the loss of Purkinje cells in the cerebellar vermis. Treadmill running suppressed PD-induced expression of GFAP-positive reactive astrocytes and Iba-1-positive microglia, showing that treadmill running suppressed reactive astrogliosis and microglia activation. Treadmill running suppressed TUNEL-positive cell number and Bax expression and enhanced Bcl-2 expression, demonstrating that treadmill running inhibited the progress of apoptosis in the cerebellum of rotenone-induced PD rats. CONCLUSIONS: Treadmill running improved motor ability of the rotenone-induced PD rats by inhibiting apoptosis in the cerebellum. Apoptosis suppressing effect of treadmill running on rotenone-induced PD was achieved via suppression of reactive astrocyte and inhibition of microglial activation.
Subject(s)
Animals , Rats , Apoptosis , Astrocytes , Blotting, Western , Calbindins , Cell Count , Cerebellar Vermis , Cerebellum , Gait , Glial Fibrillary Acidic Protein , Immunohistochemistry , Microglia , Models, Animal , Neurodegenerative Diseases , Parkinson Disease , Parturition , Posture , Purkinje Cells , Rotenone , Running , TremorABSTRACT
BACKGROUND: The fabrication of microchannels in hydrogel can facilitate the perfusion of nutrients and oxygen, which leads to guidance cues for vasculogenesis. Microchannel patterning in biomimetic hydrogels is a challenging issue for tissue regeneration because of the inherent low formability of hydrogels in a complex configuration. We fabricated microchannels using wire network molding and immobilized the angiogenic factors in the hydrogel and evaluated the vasculogenesis in vitro and in vivo. METHODS: Microchannels were fabricated in a hyaluronic acid-based biomimetic hydrogel by using “wire network molding” technology. Substance P was immobilized in acrylated hyaluronic acid for angiogenic cues using Michael type addition reaction. In vitro and in vivo angiogenic activities of hydrogel with microchannels were evaluated. RESULTS: In vitro cell culture experiment shows that cell viability in two experimental biomimetic hydrogels (with microchannels and microchannels + SP) was higher than that of a biomimetic hydrogel without microchannels (bulk group). Evaluation on differentiation of human mesenchymal stem cells (hMSCs) in biomimetic hydrogels with fabricated microchannels shows that the differentiation of hMSC into endothelial cells was significantly increased compared with that of the bulk group. In vivo angiogenesis analysis shows that thin blood vessels of approximately 25–30 µm in diameter were observed in the microchannel group and microchannel + SP group, whereas not seen in the bulk group. CONCLUSION: The strategy of fabricating microchannels in a biomimetic hydrogel and simultaneously providing a chemical cue for angiogenesis is a promising formula for large-scale tissue regeneration.
Subject(s)
Humans , Angiogenesis Inducing Agents , Biomimetics , Blood Vessels , Cell Culture Techniques , Cell Survival , Cues , Endothelial Cells , Fungi , Hyaluronic Acid , Hydrogels , Hydrogels , In Vitro Techniques , Mesenchymal Stem Cells , Oxygen , Perfusion , Regeneration , Substance PABSTRACT
PURPOSE: To evaluate whether mild chemical irritation of the bladder in neonatal rats is associated with persistent vanilloid receptor transient receptor potential vanilloid subfamily 1 (TRPV1) activity in adult rats. METHODS: Female Sprague-Dawley rats were used. Ten-day-old rat pups underwent bladder sensitization via intravesical infusion of 0.2% acetic acid in saline with or without prior bladder desensitization with capsaicin. After 8 weeks, 3 groups of rats (control [group 1], bladder sensitization [group 2], and bladder desensitization [group 3]) underwent cystometry. Inflammation of bladder tissue and the expression of TRPV1 in bladder tissue and dorsal root ganglia (DRG) were also evaluated. RESULTS: The bladder sensitization group showed more frequent voiding contractions. TRPV1 expression in adult bladder tissue was elevated in group 2. TRPV1 mRNA levels in the bladder and DRG were significantly higher in group 2 than in group 1. Moreover, group 2 had significantly more DRG neurons (identified by uptake of the retrograde label Fast Blue) that exhibited TRPV1 immunoreactivity. CONCLUSIONS: We found a significant association between neonatal bladder sensitization and persistent TRPV1 activity in adult rats. This is the first study to focus on the underlying pathogenesis of bladder overactivity from childhood to adulthood. Our findings could lead to the development of new strategies for the treatment and prevention of adult urinary symptoms arising from childhood urinary tract dysfunction.
Subject(s)
Adult , Animals , Female , Humans , Rats , Acetic Acid , Capsaicin , Cystitis, Interstitial , Diagnosis-Related Groups , Ganglia, Spinal , Inflammation , Neurons , Rats, Sprague-Dawley , RNA, Messenger , TRPV Cation Channels , Urinary Bladder , Urinary Tract , Urinary Tract InfectionsABSTRACT
PURPOSE: We compared the efficacy of tamsulosin between 0.2 mg and 0.4 mg in Asian prostatic hyperplasia (BPH) patients using network meta-analysis due to lack of studies with direct comparison. METHODS: The literature search was conducted using the MEDLINE, Embase, and Cochrane Library. Keywords used were “BPH,”“tamsulosin,”“placebo.” Experimental groups were defined as tamsulosin 0.2 mg (Tam 0.2) and 0.4 mg (Tam 0.4) and common control group was defined as placebo for indirect treatment comparison. Mixed treatment comparison was performed including one direct comparison study. RESULTS: Seven studies met the eligible criteria. Indirect treatment comparison revealed that total International Prostate Symptoms Score (IPSS) and quality of life score of IPSS were not significantly different in Tam 0.2 and Tam 0.4 (P>0.05). There was no significant difference of maximal flow rate and postvoid residual urine volume in Tam 0.2 and Tam 0.4 (P>0.05). Mixed treatment comparison including one direct comparison study showed inconsistency (P<0.001). Therefore, analysis using direct treatment comparison effect sizes of Tam 0.2 vs. placebo and Tam 0.4 vs. placebo was done and there was no significant difference. CONCLUSIONS: Network meta-analysis showed no difference of efficacy between tamsulosin 0.2 mg and 0.4 mg and the evidence of tamsulosin 0.4 mg as initial dose for Asian BPH patient seems to be insufficient. Therefore, initial dose of tamsulosin for Asian BPH patient should be 0.2 mg.
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Humans , Male , Asian People , Prostate , Prostatic Hyperplasia , Quality of LifeABSTRACT
No abstract available.
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No abstract available.
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Aged , Humans , Male , Bone Marrow/pathology , Genome, Human , Isochromosomes/genetics , Karyotyping , Leukemia, Myeloid, Acute/complications , Loss of Heterozygosity , Oligonucleotide Array Sequence Analysis , Thrombocytosis/etiologyABSTRACT
PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is a possible consequence of several neurological disorders. NLUTD may produce debilitating symptoms and serious complications, such as chronic renal failure, and recurrent urinary tract infections. Many animal studies of NLUTD symptoms have focused on animal models of cerebral ischemia. In the present study, we investigated the effects of treadmill exercise on memory function and its relation to cell proliferation and apoptosis in the hippocampus, following transient global ischemia in gerbils. METHODS: To induce transient global ischemia in gerbil, both common carotid arteries were occluded for 5 minutes. Gerbils in the exercise groups were forced to run on a treadmill exercise for 30 minutes once a day for 2 weeks. Step-down avoidance task and Y maze task were performed. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-staining, immunohistochemistry for 5-bromo-2'-deoxyridine, doublecortin, caspase-3, and Western blot for brain-derived neurotrophic factor (BDNF), Bax, Bcl-2, cytochrome c, caspase-3 were conducted. RESULTS: Ischemia caused memory impairment with an increase of cell proliferation, BDNF expression, and apoptosis in the hippocampus. Treadmill exercise improved memory function with further increase of cell proliferation and BDNF expression and a decrease of apoptosis. CONCLUSIONS: The animal model that we have developed and our assessment of the relation between exercise and brain function can be useful tools for future investigations of NLUTD symptoms associated with stroke, particularly ischemic stroke. The present study suggests that treadmill exercise promoted the recovery of brain function after cerebral ischemia.
Subject(s)
Animals , Apoptosis , Blotting, Western , Brain , Brain Ischemia , Brain-Derived Neurotrophic Factor , Carotid Artery, Common , Caspase 3 , Cell Proliferation , Cytochromes c , Exercise Test , Exercise , Gerbillinae , Hippocampus , Immunohistochemistry , Ischemia , Kidney Failure, Chronic , Memory , Models, Animal , Nervous System Diseases , Neurons , Stroke , Urinary Tract , Urinary Tract InfectionsABSTRACT
PURPOSE: Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils. METHODS: Gerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c. RESULTS: Our results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils. CONCLUSIONS: Berberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.
Subject(s)
Apoptosis , Berberine , Blotting, Western , Brain Ischemia , Caspase 3 , Cytochromes c , DNA Fragmentation , Gerbillinae , Hippocampus , Immunohistochemistry , Memory, Short-Term , Microglia , Neurons , Neuroprotective Agents , Phosphatidylinositol 3-Kinases , PhosphotransferasesABSTRACT
PURPOSE: Methylphenidate is the most widely used central nervous system stimulant in patients with attention deficit hyperactivity disorder. However, few studies have assessed its effects on voiding. Various doses of methylphenidate were investigated for their effects on cystometric parameters in conscious mice. METHODS: Ten male C57BL/6 mice, weighing between 20 and 23 g, were used in this study. To compare the acute drug responses before and after the oral medication was administered in the awake condition, we injected the solution through a catheter inserted into the stomach. Methylphenidate (1.25, 2.5, and 5 mg/kg) in an injection volume of 0.05 mL was administered. RESULTS: Four mice that received high doses of methylphenidate (2.5 and 5 mg/kg) showed no voiding contraction, with urine leakage. Six mice that received a low dose of methylphenidate (1.25 mg/kg) showed typical micturition cycles before and after administration. The micturition pressure decreased and bladder capacity increased without an increased residual volume after administration. CONCLUSIONS: Methylphenidate has differential, dose-dependent effects on the function of the lower urinary tract, due to the dependent relationship between the brain and lower urinary tract. Especially at higher doses, this drug may interfere with normal micturition. Therefore, more detailed clinical or experimental studies are warranted in the future.