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1.
J Urol ; 211(6): 735-742, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38721932

RESUMO

PURPOSE: Fluoroscopy is usually required during retrograde intrarenal surgery (RIRS). Although fluoroscopy is considered necessary for effective and safe RIRS, there is growing awareness regarding radiation exposure risk to patients and surgeons. We conducted a multicenter-based, randomized, controlled trial to compare the safety and effectiveness of radiation-free (RF) RIRS with radiation-usage (RU) RIRS for kidney stone management. MATERIALS AND METHODS: From August 2020 to April 2022, patients with a unilateral kidney stone (≤20 mm) eligible for RIRS were prospectively enrolled in 5 tertiary medical centers after randomization and divided into the RF and RU groups. RIRS was performed using a flexible ureteroscope with a holmium:YAG laser. The primary end point of this study was the success rate, defined as complete stone-free or residual fragments with asymptomatic kidney stones ≤ 3 mm. The secondary end point of this study was ascertaining the safety of RF RIRS. The success rates were analyzed using a noninferiority test. RESULTS: Of the 140 consecutive randomized participants, 128 patients completed this study (RF: 63; RU: 65). The success rates (78% vs 80%, P = .8) were not significantly different between the groups. The rate of high-grade (grade 2-4) ureter injury was not significantly higher in the RF group compared to the RU group (RF = 3 [4.8%] vs RU = 2 [3.1%], P = .6). In RF RIRS, the success rate was noninferior compared to RU RIRS (the difference was 2.2% [95% CI, 0.16-0.12]). CONCLUSIONS: This study demonstrated that the surgical outcomes of RF RIRS were noninferior to RU RIRS.


Assuntos
Cálculos Renais , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cálculos Renais/cirurgia , Resultado do Tratamento , Fluoroscopia , Idoso , Adulto , Ureteroscopia/métodos , Ureteroscopia/efeitos adversos , Lasers de Estado Sólido/uso terapêutico , Exposição à Radiação/prevenção & controle , Rim/cirurgia
2.
Investig Clin Urol ; 65(2): 132-138, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454822

RESUMO

PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.


Assuntos
Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Resultado do Tratamento , Intervalo Livre de Progressão
3.
Int J Surg Case Rep ; 115: 109290, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38245944

RESUMO

INTRODUCTION AND IMPORTANCE: Immune checkpoint inhibitors (ICIs) have noticeably enhanced oncologic outcomes associated with patient survival in different subtypes of metastatic cancer by enhancing cytotoxic T-cell activity. ICI-associated toxicities are often referred to as immune-related adverse events (irAEs) and occur in nearly every organ system. However, the effect of ICIs on the skeleton is poorly examined, and only a few case series have been published. CASE PRESENTATION: A 37-year-old man who presented with pathologic fractures of the right proximal humerus during adjuvant pembrolizumab therapy following laparoscopic radical nephrectomy for right renal cell carcinoma. CLINICAL DISCUSSION: ICIs are associated with various irAEs virtually affecting all host tissues, most of which have been described well by pharmacovigilance analyses. However, to date, very few studies have examined the effects of ICI on the skeleton. CONCLUSION: Urologic oncologists and urologists should be aware of the rare but potentially fatal bone side effects of ICIs.

4.
Cancer Genomics Proteomics ; 20(6): 592-601, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37889066

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most commonly diagnosed cancers in the world. Approximately 25-30% of patients identified with initial kidney cancer will have metastasized tumors, thus 5-year survival rates for these patients are poor. Therefore, biomarker research is required to identify and predict molecular signatures in RCC. MATERIALS AND METHODS: To address this, we used a mass spectrometry (MS)-based proteomics approach to identify proteins related to clear cell RCC (ccRCC) tissues from patients with T1G2, T1G3, T3G2, T3G3, and metastatic RCC (mRCC) stages. RESULTS: We identified and quantified 2,608 and 2,463 proteins, respectively, in ccRCC tissue and identified 1,449 differentially expressed proteins (DEPs). Bioinformatics analysis revealed that serpin family A member 3 (SERPINA3) qualified as biomarker for ccRCC progression. Using indirect enzyme-linked immunosorbent assay (ELISA), immunoblotting, and immunohistochemistry assays it was found that SERPINA3 expression levels in ccRCC tissues were much higher in stages before metastasis. CONCLUSION: Comparative proteomics analysis of ccRCC tissues provided new evidence of SERPINA3 association with ccRCC progression.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Proteômica/métodos , Prognóstico , Biomarcadores Tumorais/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/metabolismo
5.
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.

6.
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
7.
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
8.
Investig Clin Urol ; 64(2): 161-167, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36882175

RESUMO

PURPOSE: This study aimed to compare the characteristics of asymptomatic and symptomatic nephrolithiasis in patients who underwent surgical treatment for kidney stones. MATERIALS AND METHODS: Between 2015 and 2019, 245 patients who underwent percutaneous nephrolithotomy or retrograde intrarenal surgery for kidney stones were included. The patients were divided into asymptomatic (n=124) and symptomatic (n=121) groups. All patients underwent blood and urine tests, preoperative non-contrast computed tomography, and postoperative stone composition analysis. We retrospectively analyzed and compared the characteristics of the patients and stones, operation time, stone-free rate, and postoperative complications between the two groups. RESULTS: In the asymptomatic group, mean body mass index (BMI) was significantly higher (25.7±3.8 kg/m² vs. 24.3±2.8 kg/m², p=0.002) and urine pH was significantly lower (5.6±0.9 vs. 5.9±0.9, p=0.013). The ratio of calcium oxalate dihydrate stones was significantly higher in the symptomatic group (5.3% vs. 15.5%, p=0.023). No significant differences were observed in stone characteristics, postoperative outcomes, or complications. In the multivariate logistic regression analysis for predicting variables for asymptomatic renal stones, BMI (odds ratio [OR], 1.144; 95% confidence interval [CI], 1.038-1.260; p=0.007), and urine pH (OR, 0.608; 95% CI, 0.407-0.910; p=0.016) were independent predictive variables for asymptomatic renal stones. CONCLUSIONS: This study demonstrated that thorough medical check-ups are needed for the early detection of renal stones in individuals with a high BMI or low urine pH.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Estudos Retrospectivos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/efeitos adversos , Índice de Massa Corporal , Duração da Cirurgia
9.
Prostate Int ; 11(1): 34-39, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36910903

RESUMO

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

10.
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
11.
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
12.
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
13.
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.

14.
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.

15.
Korean J Transplant ; 36(2): 154-158, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35919201

RESUMO

Coronary artery spasm after heart transplantation is a very rare complication. In one observational study and many anecdotal reports, most cases of coronary artery spasm occurred more than 1 year after surgery and had good outcomes. However, cases of intractable coronary artery spasm during the early postoperative period resulting in fatality are limited. This report presents a case of two cardiac arrests caused by coronary artery spasms within a short period of time after heart transplantation.

16.
Sci Rep ; 12(1): 9104, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650234

RESUMO

Hair follicle stem cells are key for driving growth and homeostasis of the hair follicle niche, have remarkable regenerative capacity throughout hair cycling, and display fate plasticity during cutaneous wound healing. Due to the need for a transgenic reporter, essentially all observations related to LGR5-expressing hair follicle stem cells have been generated using transgenic mice, which have significant differences in anatomy and physiology from the human. Using a transgenic pig model, a widely accepted model for human skin and human skin repair, we demonstrate that LGR5 is a marker of hair follicle stem cells across species in homeostasis and development. We also report the strong similarities and important differences in expression patterns, gene expression profiles, and developmental processes between species. This information is important for understanding the fundamental differences and similarities across species, and ultimately improving human hair follicle regeneration, cutaneous wound healing, and skin cancer treatment.


Assuntos
Folículo Piloso , Células-Tronco , Animais , Animais Geneticamente Modificados , Biomarcadores/metabolismo , Folículo Piloso/metabolismo , Humanos , Morfogênese , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Pele , Células-Tronco/metabolismo , Suínos
17.
JAMA Netw Open ; 5(6): e2217132, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704317

RESUMO

Importance: Incident atrial fibrillation (AF) is associated with an increased risk of dementia. However, data on the association between smoking cessation after AF diagnosis and dementia risk are limited. Objective: To evaluate the association between changes in smoking status after AF diagnosis and dementia risk. Design, Setting, and Participants: This nationwide cohort study with 126 252 patients used data from the Korean National Health Insurance Service database, including patients who had a national health checkup examination within 2 years before and after AF diagnosis between January 1, 2010, and December 31, 2016. Based on their smoking status, participants were classified as never smokers, ex-smokers, quit smokers, and current smokers. Ex-smokers were defined as those who had quit smoking before the first examination and remained quit until the second examination. Patients who were current smokers at the first health examination but had quit smoking before the second examination were classed as quit smokers. The index date was the second health examination. Patients were followed up until dementia, death, or the study period ended (December 31, 2017), whichever occurred first. Data were analyzed from January 13, 2020, to March 29, 2022. Exposures: Smoking cessation after newly diagnosed AF. Main Outcomes and Measures: Dementia, including Alzheimer disease and vascular dementia, was the primary outcome. Cox proportional hazards regression model was used to estimate hazard ratios. Results: A total of 126 252 patients (mean [SD] age, 62.6 [12.0] years; 61.9% men) were included in the analysis. The mean (SD) CHA2DS2-VASc score, which measures the risk of ischemic stroke, was 2.7 (1.7). Smoking status of the total study population was as follows: 65 579 never smokers (51.9%), 34 670 ex-smokers (27.5%), 8919 quit smokers (7.1%), and 17 084 current smokers (13.5%). During a median of 3 years of follow-up, dementia occurred in 5925 patients (1.11 per 1000 person-years). After multivariable adjustment, the risk of quit smokers was significantly lower than that of current smokers (hazard ratio, 0.83 [95% CI, 0.72-0.95]). Conclusions and Relevance: The findings of this cohort study suggest that all types of smoking were associated with a significantly higher risk of dementia in patients with new-onset AF. Smoking cessation after AF diagnosis was associated with a lower risk of dementia than among current smokers. These findings may support promoting smoking cessation to reduce dementia risk in patients with new-onset AF.


Assuntos
Fibrilação Atrial , Demência , Abandono do Hábito de Fumar , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Demência/complicações , Demência/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumantes
18.
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
19.
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
20.
J Am Heart Assoc ; 11(7): e023739, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35322686

RESUMO

Background Limited data are available on the clinical impact of healthy lifestyle behaviors on the risk of dementia in patients with new-onset atrial fibrillation (AF). Here, we aimed to evaluate the association between a combination of healthy lifestyle behaviors and the risk of incident dementia in patients with AF. Methods and Results Using the Korean National Health Insurance database between 2009 and 2016, we identified 199 952 adult patients who were newly diagnosed as AF without dementia. Patients were categorized into 4 groups by healthy lifestyle behavior score (HLS) with 1 point each being assigned for no current smoking, alcohol abstinence, and regular exercise. The HLS 0, 1, 2, and 3 groups included 4.4%, 17.4%, 53.4%, and 24.8% of the patients, respectively. We performed an inverse probability of treatment weighting to balance covariates between HLS groups. The HLS 1, 2, and 3 groups were associated with a lower risk of dementia compared with the HLS 0 group (hazard ratio [HR], 0.769; 95% CI, 0.704-0.842 for HLS 1; HR, 0.770; 95% CI, 0.709-0.836 for HLS 2; and HR, 0.622; 95% CI, 0.569-0.679 for HLS 3). The risk of dementia showed a tendency to decrease with an increase in HLS (P-for-trend <0.001). Conclusions A clustering of healthy lifestyle behaviors was associated with a significantly lower risk of dementia in patients with new-onset AF. These findings support the promotion of a healthy lifestyle within an integrated care approach to AF patient management.


Assuntos
Fibrilação Atrial , Demência , Adulto , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Análise por Conglomerados , Estudos de Coortes , Demência/diagnóstico , Demência/epidemiologia , Estilo de Vida Saudável , Humanos , Fatores de Risco
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