Quercetin is one of the natural components from natural plant and it induces cell apoptosis in many human cancer cell lines. However, no available reports show that quercetin induces apoptosis and ...altered associated gene expressions in human gastric cancer cells, thus, we investigated the effect of quercetin on the apoptotic cell death and associated gene expression in human gastric cancer AGS cells. Results indicated that quercetin induced cell morphological changes and reduced total viability via apoptotic cell death in AGS cells. Furthermore, results from flow cytometric assay indicated that quercetin increased reactive oxygen species (ROS) production, decreased the levels of mitochondrial membrane potential (ΔΨm), and increased the apoptotic cell number in AGS cells. Results from western blotting showed that quercetin decreased anti‐apoptotic protein of Mcl‐1, Bcl‐2, and Bcl‐x but increased pro‐apoptotic protein of Bad, Bax, and Bid. Furthermore, quercetin increased the gene expressions of TNFRSF10D (Tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain), TP53INP1 (tumor protein p53 inducible nuclear protein 1), and JUNB (jun B proto‐oncogene) but decreased the gene expression of VEGFB (vascular endothelial growth factor B), CDK10 (cyclin‐dependent kinase 10), and KDELC2 (KDEL Lys‐Asp‐Glu‐Leu containing 2) that are associated with apoptosis pathways. Thus, those findings may offer more information regarding the molecular, gene expression, and signaling pathway for quercetin induced apoptotic cell death in human gastric cancer cells.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Erectile dysfunction (ED) is an agonizing complication of diabetes mellitus (DM) and it is challenging to treat ED in DM patients. Platelet-rich plasma (PRP) is a unique therapeutic strategy ...comprising intrinsic growth factors. An attempt was made to explore the potentiality of the PRP treatment in DM-induced ED rats in various groups (control, DM-non-ED, DM-ED, and DM-ED treated with PRP). Streptozotocin (STZ) was used to induce DM in rats. The blood glucose levels of the DM rats were maintained at >300 mg/dl. In the 18-week experiment, survival rate, body weight, intracavernous pressure (ICP) variations, and arterial blood pressure were analyzed. The tissue restoration results were validated by histological, immunofluorescence, and transmission electron microscopic analysis. PRP treatment of DM-ED rats significantly increased all parameters of erectile function compared to pre-treatment of PRP and DM-ED treated with vehicle. The histological results revealed that PRP treatment substantially enhanced the regeneration of myelinated nerves and decreased the atrophy of corporal smooth muscle. Notably, the PRP treatment immensely enhanced the survival rate in post-surgery DM-ED rats. These results indicated certain benefits of PRP treatment in delaying damage and preventing post-surgery complications in DM patients. Hence, PRP treatment is a novel multifactorial strategy for DM-ED patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Traditional bladder volume measurement from B-mode (two-dimensional) ultrasound has been found to produce inaccurate results, and thus in this work we aim to improve the accuracy of measurement from ...B-mode ultrasound. A total of 75 electronic medical records including ultrasonic images were reviewed retrospectively from 64 patients. We put forward a novel bladder volume measurement method, in which a three-dimensional (3D) reconstruction model was established from conventional two-dimensional (2D) ultrasonic images to estimate the bladder volume. The differences and relationships were analyzed among the actual volume, the traditional estimated volume, and the new reconstruction model estimated volume. We also compared the data in different volume groups from small volume to high volume. The mean actual volume is 531.8 mL and the standard deviation is 268.7 mL; the mean percentage error of traditional estimation is −28%. In our new bladder measurement method, the mean percentage error is −10.18% (N = 2), −4.72% (N = 3), −0.33% (N = 4), and 2.58% (N = 5). There is no significant difference between the actual volume and our new bladder measurement method (N = 4) in all data or the divided four groups. The estimated volumes from the traditional method or our new method are highly correlated with the actual volume. Our data show that the three-dimensional bladder reconstruction model provides an accurate measurement from conventional B-mode ultrasonic images compared with the traditional method. The accuracy is seen across different groups of volume, and thus we can conclude that this is a reliable and economical volume measurement model that can be applied in general software or in apps on mobile devices.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF) and are associated with congenital bilateral absence of the vas deferens (CBAVD), which is ...the major cause of infertility in male patients with CF. However, most Taiwanese patients with CBAVD do not carry major CFTR mutations. Some patients have a single copy deletion of the solute carrier family 9 isoform 3 (SLC9A3) gene. SLC9A3 is a Na+/H+ exchanger, and depleted Slc9a3 in male mice causes infertility due to the abnormal dilated lumen of the rete testis and efferent ductules. Furthermore, SLC9A3 interacts with CFTR in the pancreatic duct and functions as a genetic modifier of CF. However, SLC9A3 function and its relation to CFTR expression in the male reproductive tract in vivo remain elusive. In the present study, we found that CFTR expression was dramatically decreased in the epididymis and vas deferens of Slc9a3 knockout mice. Adult Slc9a3-/- mice showed not only significantly decreased epididymis and vas deferens weight but also increased testis weight. Furthermore, Slc9a3-/- mice developed obstructive azoospermia because of abnormal abundant secretions and calcification in the lumen of the reproductive tract. Ultrastructural analysis of the epithelium in Slc9a3-/-epididymis and vas deferens displayed disorganized and reduced number of stereocilia and numerous secretory apparatuses. Our data revealed that interdependence between SLC9A3 and CFTR is critical for maintaining a precise microenvironment in the epithelial cytoarchitecture of the male reproductive tract. The Slc9a3-deficient mice with impaired male excurrent ducts in this study provide proof for our clinical findings that some Taiwanese of CBAVD carry SLC9A3 deletion but without major CFTR mutations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interstitial cystitis (IC) is a chronic inflammatory disease characterized by bladder pain and increased urinary frequency. Although the C57BL/6J (B6) and FVB/NJ (FVB) mouse strains are commonly used ...as animal models for studies involving the urinary system, few reports have compared their lower urinary tract anatomy, despite the importance of such data. Our study aimed to characterize bladder function changes in FVB and B6 mouse strains with lipopolysaccharide (LPS)-induced IC, to understand mouse model-based bladder research. The bladder function parameters were measured by cystometrogram. Histological assay was examined by hematoxylin and eosin stain, Masson's trichrome stain, and immunofluorescence staining. Results indicated that the two strains in the control group exhibited different bladder structures and functions, with significant anatomical differences, including a larger bladder size in the FVB than in the B6 strain. Furthermore, cystometry tests revealed differences in bladder function pressure. LPS-treated B6 mice presented significant changes in peak pressure, with decreased intercontraction intervals; these results were similar to symptoms of IC in humans. Each strain displayed distinct characteristics, emphasizing the care required in choosing the appropriate strain for bladder-model studies. The results suggested that the B6 mouse strain is more suitable for IC models.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neurogenic erectile dysfunction resulting from cavernous nerve (CN) injury is a major complication caused by radical prostatectomy. The use of platelet‐rich plasma (PRP) on the nerve‐injured site has ...shown promising results for the nerve regeneration. However, the effects of PRP injection in corpus cavernosum after bilateral CN injury have never been investigated.
To assess the neuroprotective effect of PRP injection in corpus cavernosum after bilateral CN injury.
Male Sprague‐Dawley rats were randomly divided into three groups: Group I underwent sham operation, while the remaining two groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of PRP or normal saline only injection in the corpus cavernosum, respectively. Four weeks later, erectile function (EF) was assessed by CN electrosimulation, and CNs as well as penile tissue were collected for histology.
Intracavernous pressure (ICP) monitored during electrical stimulation of CNs; myelinated axons number of CNs and dorsal penile nerve; collagen type change, number of apoptotic cells, and mRNA expression of caspase‐3 and transforming growth factor‐β1 (TGF‐β1) in the corpus cavernosum.
Four weeks after surgery, in the vehicle‐only group, the functional evaluation showed a lower mean maximal ICP than that in the sham group (P < 0.05). PRP treatments resulted in significant recovery of EF, as compared with the vehicle‐only group (P < 0.05). Histologically, the PRP‐treated group had a significant preservation of myelinated axons of CNs compared with the vehicle‐only group (P < 0.05) and reduced the apoptotic index. The mRNA expression of TGF‐β1 in the corpus cavernosum tissue was significantly decreased in the PRP group compared with the vehicle‐only group (P < 0.05).
PRP injection in the corpus cavernosum increased the number of myelinated axons and facilitated recovery of EF in the bilateral CN injury rat model. Wu C‐C, Wu Y‐N, Ho H‐O, Chen K‐C, Sheu M‐T, and Chiang H‐S. The neuroprotective effect of platelet‐rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med 2012;9:2838–2848.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This study explored the specific effects of ketamine on bladder function followed by a sequence of histological changes in a rat bladder at fixed time course intervals. The rats were grouped into ...normal control and experimental animals, and ketamine (100 mg/kg/day) was administrated to the experimental animals for 2, 4, and 8 weeks, respectively; similarly, the control animals received saline. All animals were evaluated for bladder function and histological responses to the treatment. Ultrastructural changes were observed by transmission electron microscopy (TEM). The results showed progressive bladder dysfunctions with hyperactive bladder conditions according to the time course and frequency of exposure to ketamine. Significantly, decreased inter contraction intervals, residual urine volume, peak micturition pressure, and increased micturition frequency were observed. Bladder histology results revealed substantial inflammation and comprehensive submucosa edema in week 2 and 4 rats along with fibrosis and significant bladder detrusor hypertrophy in week 8 rats. TEM analysis revealed bladder wall thickening, deformed blood vessels, detrusor hypertrophy, wobbled gap junction, and barrier dysfunction at different time course levels in experimental animals. These results provided a profound knowledge about the prognosis and step-by-step pathophysiology of the disease, which might help in developing new therapeutic interventions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent ...episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels of carboxymethyl lysine, an advanced glycation end product. Elevated collagenous deposition in DN group was also attenuated through CmNo1 administration. Moreover, the enhanced levels of transforming growth factor-β1, a fibrosis-inducing protein in glomerulus were also markedly dampened. Furthermore, auxiliary risk factors in DN like serum triglycerides and cholesterol were found to be increased but were decreased by CmNo1 treatment. Conclusively, the results suggests that CmNo1 exhibit potent and efficacious renoprotective action against hyperglycemia-induced DN.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The intracavernosal (IC) injection of chitosan activated platelet rich plasma (cPRP) has shown to improve the erectile dysfunction in cavernous nerve injury rat model. However, the action target of ...PRP in improving neurogenic erectile dysfunction remains unclear. We aimed to determine the effect of cPRP action at early stage that further mediates its effect on erectile function (EF) recovery in the bilateral cavernous nerve crushing (BCNC) injury rat model.
Fifty-four rats were randomly divided into two equal groups: intracavernosal ( IC) injection of saline after BCNC (group 1) and IC injection of cPRP after BCNC (group 2). Five animals in each group were euthanized at 3, 7 and 14 day (d) post-injection, and the tissues were harvested to conduct transmission electron microscopy and histological assays. Six animals in each group were used to determine the recovery of EF at 14 and 28 d post-injury.
IC injections of cPRP increased all EF parameters at 28 d and 14 d post-injury (p < 0.05). cPRP injections simultaneously prevented the loss of neuronal nitric oxide synthase-positive neurons (p < 0.05) and nerve fibers (p < 0.05) in the major pelvic ganglion and cavernous nerve (CN), respectively, compared with saline injections. This simultaneous accelerated the regeneration of myelinated axons of the CN, reduced apoptosis, and enhanced the proliferation of the corporal smooth muscle cells at an earlier stage.
These results suggest that the application of cPRP was beneficial to restore EF via neuroprotective and tissue-protective effects at early stage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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