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1.
Medicine (Baltimore) ; 103(31): e38950, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093738

RESUMO

To identify the best combination of potential predictors of septic shock in patients with obstructive acute pyelonephritis associated with ureteral stones (OAPN-US) according to Sepsis-3 criteria. Patients who underwent percutaneous nephrostomy (PCN) with OAPN-US were retrospectively evaluated. Recursive feature elimination (RFE) was applied to patients with and without septic shock to identify factors associated with the prediction of progression to septic shock. We compared combinations of the selected features based on area under the receiver operating curve (AUROC) to determine which combination was most effective. This study included 81 patients who were treated with PCN due to OAPN-US. A comparison was made between 37 patients with septic shock (SS) and 44 patients without septic shock (NSS). SS group had a higher age, poorer Eastern Cooperative Oncology Group status, and significantly higher levels of positivity in urine cultures and blood cultures. There were also differences in laboratory tests between the 2 groups. Procalcitonin (PCT), international normalized ratio (INR), and absolute lymphocyte count (ALC) were selected based on RFE. We compared the predictive power for SS when each marker was used alone, when 2 markers were combined, and when all 3 markers were combined. Among these combinations, using all 3 variables together yielded the highest AUROC of 0.942. Of the 3 variables, PCT had the highest Gini importance score, indicating that it was the most influential factor. Clinical characteristics were different between the SS and the NSS groups. In patients with OAPN-US, the combination of PCT, ALC, and INR was an excellent predictor of septic shock.


Assuntos
Pró-Calcitonina , Pielonefrite , Choque Séptico , Cálculos Ureterais , Humanos , Estudos Retrospectivos , Cálculos Ureterais/complicações , Feminino , Choque Séptico/complicações , Masculino , Pielonefrite/complicações , Pielonefrite/diagnóstico , Pessoa de Meia-Idade , Idoso , Pró-Calcitonina/sangue , Nefrostomia Percutânea , Adulto , Biomarcadores/sangue , Curva ROC , Contagem de Linfócitos
2.
Tissue Eng Regen Med ; 21(7): 995-1005, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38896385

RESUMO

BACKGROUND: Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives. METHODS: We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS). RESULTS: From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself. CONCLUSION: The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources.


Assuntos
Hemostasia , Plasma Rico em Plaquetas , Poliésteres , Poliésteres/química , Animais , Plasma Rico em Plaquetas/química , Hemostasia/efeitos dos fármacos , Porosidade , Ratos , Masculino , Hemostáticos/farmacologia , Hemostáticos/química , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia , Ratos Sprague-Dawley , Humanos
3.
Exp Mol Med ; 56(1): 235-249, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38253797

RESUMO

Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells. Metabolomic analysis revealed that CYB5R3 overexpression increased the production of nicotinamide adenine dinucleotide (NAD+) and oxidized glutathione (GSSG). Ectopic CYB5R3 is mainly localized in the ER, where CYB5R3-dependent ER stress signaling is induced via activation of protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme 1 alpha (IRE1α). Moreover, NAD+ activates poly (ADP-ribose) polymerase16 (PARP16), an ER-resident protein, to promote ADP-ribosylation of PERK and IRE1α and induce ER stress. In addition, CYB5R3 induces the generation of reactive oxygen species and caspase-9-dependent intrinsic cell death. Our findings highlight the importance of CYB5R3 as a tumor suppressor for the development of CYB5R3-based therapeutics for lung cancer.


Assuntos
Neoplasias Pulmonares , Proteínas Serina-Treonina Quinases , Animais , Humanos , Camundongos , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Apoptose/genética , Citocromo-B(5) Redutase/metabolismo , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/genética , Endorribonucleases/metabolismo , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases , NAD/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
4.
World J Clin Cases ; 11(25): 5994-5999, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37727477

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is the third most common malignancy in the genitourinary tract. The lungs, bone, lymph nodes, liver, and brain are common metastatic sites of RCC. However, there is limited literature on single omental metastasis of RCC. CASE SUMMARY: We present the case of a 44-year-old man with single omental metastasis of RCC after laparoscopic radical nephrectomy. Pathological diagnosis of the resected left kidney revealed pT3a clear cell RCC (Fuhrman grade III). At 6 mo postoperatively, abdominal computed tomography revealed a 12-mm enhancing nodule in the left lower peritoneum. At 7 mo after initial operation, laparoscopic removal of the left omental nodule was performed. The pathological results indicated metastatic clear cell RCC. Currently, the patient is being treated with adjuvant pembrolizumab. CONCLUSION: Omental metastasis of RCC owing to laparoscopic radical nephrectomy is rare. Urologists should be aware of the diverse nature of RCC.

5.
Int J Mol Sci ; 24(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37569708

RESUMO

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.


Assuntos
Colite , Hidrolisados de Proteína , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Inflamação , Obesidade/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Camundongos Endogâmicos C57BL
6.
BMC Urol ; 23(1): 109, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37322432

RESUMO

INTRODUCTION: Traditionally, a pigtail catheter (PCN) is placed for preoperative renal access before performing percutaneous nephrolithotomy (PCNL). However, PCN can hamper the passage of the guidewire to the ureter, due to which, access tract can be lost. Therefore, Kumpe Access Catheter (KMP) has been proposed for preoperative renal access before PCNL. In this study, we analyzed the efficacy and safety of KMP for surgical outcomes in modified supine PCNL compared to those in PCN. MATERIALS AND METHODS: From July 2017 to December 2020, 232 patients underwent modified supine PCNL at a single tertiary center, of which 151 patients were enrolled in this study after excluding patients who underwent bilateral surgery, multiple punctures, or combined operations. Enrolled patients were divided into two groups according to the type of pre-PCNL nephrostomy catheter used: PCN versus KMP. A pre-PCNL nephrostomy catheter was selected based on the radiologist's preference. A single surgeon performed all PCNL procedures. Patient characteristics and surgical outcomes, including stone-free rate, operation time, radiation exposure time (RET), and complications, were compared between the two groups. RESULTS: Of the 151 patients, 53 underwent PCN placement, and 98 underwent KMP placement for pre-PCNL nephrostomy. Patient baseline characteristics were comparable between the two groups, except for the renal stone type and multiplicity. The operation time, stone-free rate, and complication rate were not significantly different between the two groups; however, RET was significantly shorter in the KMP group. CONCLUSION: The surgical outcomes of KMP placement were comparable to those of PCN and showed shorter RET during modified supine PCNL. Based on our results, we recommend KMP placement for pre-PCNL nephrostomy, particularly for reducing RET during supine PCNL.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Nefrolitotomia Percutânea/métodos , Rim , Nefrostomia Percutânea/métodos , Cálculos Renais/cirurgia , Cateteres Urinários , Resultado do Tratamento , Estudos Retrospectivos
7.
Tissue Eng Regen Med ; 20(2): 225-237, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600004

RESUMO

BACKGROUND: Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients' quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. METHODS: From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 µg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. RESULTS: The mean pain scores in the SVF 20 µl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. CONCLUSION: This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.


Assuntos
Cistite Intersticial , Ratos , Humanos , Feminino , Animais , Cistite Intersticial/terapia , Fração Vascular Estromal , Qualidade de Vida , Modelos Animais de Doenças , Tecido Adiposo , Dor
8.
Int J Impot Res ; 35(5): 447-453, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35347300

RESUMO

This study compares the efficacy of the early low-intensity shock wave therapy (LI-SWT) plus daily tadalafil with daily tadalafil only therapy as penile rehabilitation for postprostatectomy erectile dysfunction in patients with prostate cancer who underwent bilateral interfascial nerve-sparing radical prostatectomy (robotic or open). From April 2019 to March 2021, 165 patients were enrolled, and 80 of them successfully completed this prospective study. Daily tadalafil were administered to all the patients. LI-SWT consisted of a total of six sessions. Each session was performed on days 4, 5, 6, and 7, and on the second and fourth weeks after surgery. Each LI-SWT session consisted of 300 shocks at an energy density of 0.09 mJ/mm2 and a frequency of 120 shocks per minute that were delivered at each of the five treatment points for 15 min. Thirty-nine patients were treated with tadalafil-only (group A) while 41 were treated with tadalafil and LI-SWT simultaneously (group B). At postoperative 6 months, the proportion of patients with erection hardness scores (EHS) ≥ 3 (4/39 vs. 12/41) was significantly higher in group B (p = 0.034), and LI-SWT was the only independent factor for predicting EHS ≥ 3 (OR, 3.621; 95% CI, 1.054-12.437; p = 0.041). There were no serious side effects related to early LI-SWT. Early LI-SWT plus daily tadalafil therapy as penile rehabilitation for postprostatectomy erectile dysfunction is thought to be more efficacious than tadalafil only. Further large-scaled randomized controlled trials will be needed to validate these findings.


Assuntos
Disfunção Erétil , Masculino , Humanos , Tadalafila/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Ereção Peniana , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Prospectivos , Prostatectomia/efeitos adversos , Resultado do Tratamento
9.
Cancers (Basel) ; 14(22)2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36428651

RESUMO

No definitive criteria regarding the performance of preoperative chest computed tomography (CT) in patients with cT1a renal cell carcinoma (RCC) exists. We aimed to establish an objective standard for the optimal timing of preoperative chest CT in patients with RCC. Data from 890 patients who underwent surgical treatment for RCC between January 2011 and December 2020 were retrospectively collected. The primary endpoint was detection of lung metastasis on chest CT before nephrectomy. A multivariable logistic regression model predicting positive chest CT scans was used. Predictors included preoperative cTN stage, presence of systemic symptoms, Charlson comorbidity index (CCI), platelet count/hemoglobin ratio, albumin/globulin ratio (AGR), and De Ritis ratio. The overall rate of positive chest CT scans before nephrectomy was 3.03% (27/890). Only one patient had lung metastasis before surgery for cT1a. cT stage (≥cT1b), CCI ≥4, and low AGR were associated with a higher risk of positive chest CT scans. The best cutoff value for AGR was 1.39. After 890-sample bootstrap validation, the concordance index was 0.80. The net benefit of the proposed strategy was superior to that of the select-all and select-none strategies according to decision curve analysis. Therefore, when chest CT scans were performed with a risk of a positive result ≥10%, 532 (59.8%) negative chest CT scans could be prevented. Only 24 (2.7%) potentially positive chest CT scans were misdiagnosed. Therefore, we recommend chest CT in patients with ≥cT1b disease, CCI ≥4, and low AGR.

10.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362028

RESUMO

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.


Assuntos
Inibidores de Proteínas Quinases , Neoplasias da Bexiga Urinária , Animais , Humanos , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Nus , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteômica , Piruvato Desidrogenase Quinase de Transferência de Acetil , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Quinases da Família src/efeitos dos fármacos , Quinases da Família src/metabolismo
11.
Biochem Biophys Res Commun ; 629: 128-134, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-36116375

RESUMO

Chronic Kidney Disease (CKD) is increasingly recognized as a global public health issue. Diabetic nephropathy (DN), also known as diabetic kidney disease, is a leading cause of CKD. Regenerative medicine strategy employing nephron progenitor cells (NPCs) is worthy of consideration as an alternative to shortage of donor organs for kidney transplantation. In previous study, we successfully generated induced NPCs (iNPCs) from human urine-derived cells that resembled human embryonic stem cell-derived NPCs. Here, we aimed to investigate the therapeutic potential of iNPCs in DN animal model. The results revealed the therapeutic effect of iNPCs as follows: (1) diminished glomerular hypertrophy, (2) reduced tubulointerstitial fibrosis, (3) low blood urea nitrogen, serum creatinine and albuminuria value, (4) decreased inflammation/fibrosis, (5) enhanced renal regeneration and (6) confirmed safety. This study demonstrates that human iNPCs have a therapeutic potential as a cell source for transplantation in patients with kidney diseases.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Insuficiência Renal Crônica , Animais , Creatinina , Diabetes Mellitus/patologia , Nefropatias Diabéticas/tratamento farmacológico , Fibrose , Humanos , Rim/patologia , Camundongos , Néfrons , Insuficiência Renal Crônica/patologia , Células-Tronco
12.
Onco Targets Ther ; 15: 963-971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091874

RESUMO

Bladder cancer, one of the most frequently diagnosed cancers worldwide, is associated with high morbidity and mortality and a poor prognosis. The bladder cancer types include 1) non-muscle invasive bladder cancer (NMIBC) and 2) muscle invasive bladder cancer (MIBC). Metastases and chemoresistance in MIBC patients are the leading causes of the high death rate. c-Jun N-terminal kinase (JNK) is an important factor for the undifferentiated state of cancer cells. JNK belongs to the mitogen-activated protein kinases (MAPKs) family; it is activated by various extracellular stimuli, such as stress, radiation, and growth factors and mediates diverse cellular functions, such as apoptosis, autophagy, proliferation, invasion, and migration by mediating AKT (Ak strain transforming), ATG (Autophagy related), mTOR (Mammalian target of rapamycin), and caspases 3, 8, and 9. This review describes the JNK-related functions, mechanisms, and signaling in bladder cancer.

13.
Biomed Res Int ; 2022: 4492132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386305

RESUMO

Background: Obesity induced by excessive nutrients can cause fatty liver and metabolic dysfunction, which leads to hepatic dysfunction and local/systemic inflammatory responses. Previously, we analyzed the antioxidant, antilipotoxicity, and anti-inflammatory effects of protein hydrolysates in vitro. The aim of the present study is to investigate the antiobesity and hepatoprotective effects of protein hydrolysates derived from Protaectia brevitas (PHPB) in an obese mouse model. Methods: For this in vivo study, 40 mice were included and divided into four groups: (1) normal diet group, (2) high-fat-diet (ctrl(-)) group, (3) high-fat-diet and silymarin-treated (ctrl(+)) group, and (4) high-fat-diet and PHPB-treated group. After 6 weeks of treatment, body weight and the amount of daily food intake were observed. Moreover, the major organs and blood of animals were collected for the analysis of serum chemistry, histopathological examination, and obesity- and inflammation-related gene expressions. Results: The body weight and the amount of daily food intake significantly decreased in the PHPB-treated group compared with those in the ctrl(-) group. The levels of serum ALT, AST, ALP, creatinine, blood urea nitrogen, glucose, bilirubin, total cholesterol, TG, low-density lipoprotein, IL-6, TNF-α, and IGF-1 significantly reduced in the PHPB-treated group, whereas the serum free fatty acid, albumin, high-density lipoprotein, and adiponectin concentrations increased. In the analysis of weight of the liver, kidney, lungs, spleen, and fat tissues (from epididymal, perirenal, and mesentery tissues), the PHPB-treated group showed decreased values compared with the ctrl(-) group. In the histopathological analysis, the PHPB-treated group showed significantly reduced macrovesicular fatty change and inflammatory cell infiltration in the liver, and the size of the adipocyte in the epididymis also significantly decreased. The obesity- and inflammation-related gene (IL-6, TNF-α, IGF-1, leptin, AP2/FABP4, AMPK-α2, ß3AR, and PPAR-γ) expressions in the liver and epididymal adipose tissue were reduced in the PHPB-treated group. Conclusions: Overall, the results of this study suggest that the protein hydrolysates that derived from Protaectia brevitas produce antiobesity and hepatoprotective effects via anti-inflammatory activities.


Assuntos
Fármacos Antiobesidade , Fígado Gorduroso , Tecido Adiposo/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado Gorduroso/patologia , Inflamação/patologia , Fator de Crescimento Insulin-Like I , Interleucina-6 , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Hidrolisados de Proteína/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
14.
Biomed Res Int ; 2022: 3628543, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402618

RESUMO

There is growing interest in human adipose tissue-derived collagen as a replacement for animal origin or synthetic materials. Large amounts of adipose tissues around the kidney are being discarded after kidney surgery; thus, we planned to use this tissue as a potentially ideal source of human collagen. Optimization of the collagen extraction process can contribute to the quality, quantity, supply, and cost of collagen production. To extract highly purified and concentrated collagen from human perirenal adipose tissue, we developed a novel extraction process that is superior to the conventional methods in terms of extraction yield, in vitro cytocompatibility, and physicochemical aspects. The sequence of the process and optimized conditions are as follows: (1) destaining with 0.5% H2O2 for 1 h at 4°C, (2) noncollagenous proteins elimination with 1.5 M NaOH for 24 h at 4°C, (3) atelocollagen preparation with 1.0% pepsin for 48 h at 25°C, and (4) collagen hydrolysis with 1.0 M NaOH for 10 min at 60°C. The final product showed significantly increased hydroxyproline (355.26 ± 18.71 pg/mL) and glycine (22.752 µg/mL) content than the conventional acetic acid hydrolyzed collagen (164.13 ± 1.11 pg/mL and 0.947 µg/mL, respectively). The lyophilized collagen showed more specific peaks for amides A, B, I, II, and III on FT-IR analysis and showed a further native architecture of collagen fibrils in scanning electron microscope images. Therefore, the optimized process can be an effective protocol for extracting collagen from human perirenal adipose tissue.


Assuntos
Colágeno , Peróxido de Hidrogênio , Tecido Adiposo , Animais , Colágeno/química , Humanos , Hidróxido de Sódio , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Biomed Res Int ; 2022: 2220641, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35127940

RESUMO

BACKGROUND: Human renal proximal tubular epithelial (RPTE) cell is a very useful tool for kidney-related experiments in vitro/ex vivo. However, only a few primary RPTE cells can be obtained through kidney biopsy, the proliferation rate of primary cell is very low, and the cultured cell properties are easily altered in artificial conditions. Thus, RPTE cell usage is very tricky; we applied porcine kidney-derived extracellular matrix (renal ECM) as coating, hydrogel, and scaffold material to increase cell proliferation and maintain cellular properties providing three-dimensional (3D) niche, which can be a valuable cell delivery vehicle. METHODS: Porcine renal ECM was prepared by decellularization using 1% Triton X-100, solubilized with 0.5 M acetic acid. The final protein concentration was adjusted to 10 µg/µL (pH 7.0). The efficacies as coating, hydrogel, and scaffold materials were analyzed through cell morphology, proliferation rate, renal-associated gene expressions, chemical composition, and microstructure evaluation. The efficacies as a coating material were compared with Matrigel, collagen type 1 (col1), gelatin, fibrinogen, and thrombin. After confirmation of coating effects, the effective concentration range was decided. The efficacies as hydrogel and scaffold materials were compared with hyaluronic acid (HA) and col1, respectively. RESULTS: As the coating material, renal ECM showed a higher cell proliferation rate compared to other materials, except for Matrigel. Renal-associated gene expressions were significantly enhanced in the renal ECM than other materials. Coating effect on cell proliferation was dependent on the renal ECM concentration, and the effective concentration ranged from 30 to 100 µg. As the hydrogel material, renal ECM showed a distinct inner cell network morphology and significantly increased renal-associated gene expressions, compared to HA hydrogel. As the scaffold material, renal ECM showed specific amide peaks, enhanced internal porosity, cell proliferation rate, and renal-associated gene expression compared to the col1 scaffold. CONCLUSIONS: We concluded that renal ECM can be a suitable material for RPTE cell culture and usage. More practically, the coated renal ECM stimulates RPTE cell proliferation, and the hydrogel and scaffold of renal ECM provide useful 3D culture niche and cell delivery vehicles maintaining renal cell properties.


Assuntos
Matriz Extracelular , Hidrogéis , Animais , Proliferação de Células , Células Epiteliais , Matriz Extracelular/metabolismo , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Rim , Suínos , Alicerces Teciduais/química
16.
J Biomed Mater Res A ; 110(4): 928-942, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34913580

RESUMO

The objective of this study was to select the optimal delipidation solvent for preparation of human perirenal adipose tissue-derived extracellular matrix (ECM). Human perirenal adipose tissue can be obtained in large amounts during surgery, and it can be an alternative source of human ECM. Delipidation is an essential procedure for the ECM preparation, because lipid strongly inhibits regeneration of target tissue. Isopropanol has been widely used as a delipidation solvent for adipose tissue. However, because adipose tissue is mostly composed of nonpolar lipid, a nonpolar solvent might be more effective for delipidation. We evaluated the delipidation efficiency of acetone, chloroform, methanol, ether, ethanol, isopropanol, water, chloroform/methanol, ethanol/heptane, ether/methanol, hexane/ethanol, and butanol/methanol solvents for ECM extraction from human perirenal adipose tissue. Among them, acetone-treated adipose tissue showed the greatest delipidation efficiency (93.05%), significantly lower residual DNA content, and the greatest residual collagen concentration (42.49 ± 0.05 µg/g). In addition, acetone-treated tissue also had well-preserved ultrastructure with high porosity and significantly low in vitro cytotoxicity. These results suggested that acetone may be an optimal delipidation solvent for extraction of ECM from human perirenal adipose tissue.


Assuntos
Tecido Adiposo , Matriz Extracelular , Matriz Extracelular/química , Humanos , Solventes/química , Água
17.
J Clin Med ; 10(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34768543

RESUMO

Perirenal adipose tissue, one of the fat masses surrounding the kidneys, can be obtained from healthy donors during a kidney transplant. Perirenal adipose tissue has only ever been known as a connective tissue to protect the kidneys and renal blood vessels from external physical stimulation. Yet, recently, as adipose tissue has begun to be considered an endocrine organ, and perirenal adipose tissue is now regarded to have a direct effect on metabolic diseases. The characteristics of perirenal adipose tissue from a healthy donor are that: (1) There are a large number of brown adipose cells (70-80% of the total), (2) Most of the brown adipose cells are inactive in the resting cell cycle, (3) Activating factors are constant low-temperature exposure, hormones, metastasis factors, and environmental factors, (4) Anatomically, a large number of brown adipose cells are distributed close to the adrenal glands, (5) Beige cells, produced by converting white adipocytes to brown-like adipocytes, are highly active, (6) Activated cells secrete BATokines, and (7) Energy consumption efficiency is high. Despite these advantages, all of the perirenal adipose tissue from a healthy donor is incinerated as medical waste. With a view to its use, this review discusses the brown adipocytes and beige cells in perirenal adipose tissue from a healthy donor, and proposes opportunities for their clinical application.

18.
Urol J ; 19(4): 281-288, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655075

RESUMO

PURPOSE: In this study, we evaluated the predictability of a modified Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model and preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: From August 2005 to May 2016, a total of 281 patients received intravesical bacillus Calmette-Guérin therapy after transurethral resection of a bladder tumor. The pathologic stage of all patients was Ta or T1. Of 281 patients, 84 (29.9%) experienced recurrence and 14 (5.0%) developed progression. The mean follow-up period was 46 months. The cut-off value for NLRs was 2.29. RESULTS: One hundred-eight patients (38.4%) displayed a high NLR (> 2.29). In Kaplan-Meier curve analysis, a high NLR was associated with lower recurrence-free survival (RFS) (P < .001) and progression-free survival (PFS) (P = .002). CUETO scores were associated with RFS (P < .001), but not with PFS (P = .423). A combination of NLRs and the CUETO risk model correlated with RFS (P < .001) and PFS (P = .002). In multivariate analysis, female gender, concomitant carcinoma in situ (CIS), tumor number >3, recurrent tumors, and a high NLR were independent factors predicting recurrence (all P < .05). Concomitant CIS, recurrent tumors, and a high NLR were independent factors for predicting progression (all P < .05). CONCLUSION: In patients with NMIBC, an NLR >2.29 was identified as a significant factor for predicting tumor recurrence and progression. Inclusion of preoperative NLR enhanced the accuracy of the CUETO model to predict disease progression.


Assuntos
Neoplasias da Bexiga Urinária , Vacina BCG/uso terapêutico , Progressão da Doença , Feminino , Humanos , Linfócitos/patologia , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia
19.
PLoS One ; 16(4): e0250254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33901217

RESUMO

OBJECTIVE: This prospective study sought to clarify the developmental endothelial locus-1 (Del-1) protein as values of diagnosis and risk stratification of prostate cancer (PCa). DESIGN: From February 2017 to December 2019, a total 458 patients who underwent transrectal ultrasound guided prostate biopsy or surgery of benign prostatic hyperplasia agreed to research of Del-1 protein. We prospectively compared and analyzed the Del-1 protein and prostate specific antigen (PSA) in relation to the patients' demographic and clinicopathological characteristics. RESULTS: Mean age was 68.86±8.55 years. Mean PSA and Del-1 protein was 21.72±89.37, 0.099±0.145, respectively. Two hundred seventy-six (60.3%) patients were diagnosed as PCa. Among them, 181 patients underwent radical prostatectomy (RP). There were significant differences in Del-1 protein between benign and PCa group (0.066±0.131 vs 0.121±0.149, respectively, p<0.001). When we set the cut-off value of del-1 protein as 0.120, in patients with 3≤PSA≤8, positive predictive value and specificity of Del-1 protein (≥0.120) for predicting PCa were 88.9% (56/63) and 93.5% (101/108), respectively. Among 181 patients who underwent RP, there were significant differences in Del-1 protein according to stage (pT2 vs pT3a vs ≥pT3b) (0.113±0.078, 0.171±0.121, 0.227±0.161, respectively, p<0.001) and to Gleason score (6 (3+3) or 7 (3+4) vs 7 (4+3) or 8 (4+4) vs 9 or 10) (0.134±0.103, 0.150±0.109, 0.212±0.178, respectively, P = 0.044). Multivariate analysis showed that PSA, Del-1 protein and high Gleason score (≥9) were the independent prognostic factors for predicting higher pT stage (≥3b). Furthermore, age, PSA and Del-1 protein were independent prognostic factors for predicting significant PCa. CONCLUSION: Patients with PCa showed higher expression of Del-1 protein than benign patients. Del-1 protein increased with the stage and Gleason score of PCa. Collaboration with PSA, Del-1 protein can be a non-invasive useful marker for diagnosis and risk stratification of PCa.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Moléculas de Adesão Celular/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Próstata/patologia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Medição de Risco
20.
Investig Clin Urol ; 62(2): 186-194, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33660446

RESUMO

PURPOSE: Recently, the needs for supine percutaneous nephrolithotomy (PCNL) have become more increased because of an easy approach for endoscopic combined intrarenal surgery. However, making a nephrostomy tract during supine PCNL is more difficult than prone position due to movable kidney. To overcome this limitation, we used a modified nephrostomy tract dilation (MTD) technique using guidewire traction. MATERIALS AND METHODS: From January 2014 to June 2019, a total of 259 patients underwent PCNL in the modified supine position. Among them, the MTD technique was performed in 171 patients. For the MTD technique, two hydrophilic guidewires were passed from the nephrostomy tract and brought out through the urethra, then both proximal and distal ends were contralaterally pulled with tension for the easy placement of a fascia-cutting needle and a balloon catheter. We analyzed the efficacy of this technique in comparison with the conventional method. RESULTS: Intraoperative radiation exposure time (RET) (68.87 vs. 212.11 s) and hospital stay (5.90 vs. 6.74 days) were significantly shorter, while the success rate (77.2% vs. 63.6%) was significantly higher in the MTD group. Multivariate analysis showed that only the maximal stone diameter (odds ratio [OR], 1.928; 95% confidence interval [CI], 1.314-2.828; p=0.001) and MTD technique (OR, 0.017; 95% CI, 0.007-0.040; p<0.001) were independent factors for predicting short RET (<120 s). CONCLUSIONS: This study demonstrated that MTD technique can be effectively and safely performed in modified supine position PCNL, and it can be helpful in reducing RET and enhancing success rates.


Assuntos
Dilatação/instrumentação , Dilatação/métodos , Nefrolitotomia Percutânea/instrumentação , Nefrolitotomia Percutânea/métodos , Posicionamento do Paciente , Adulto , Idoso , Dilatação/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Decúbito Dorsal , Resultado do Tratamento
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