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1.
Front Endocrinol (Lausanne) ; 15: 1393550, 2024.
Article in English | MEDLINE | ID: mdl-38854686

ABSTRACT

Osteoarthritis (OA) is an intricate pathological condition that primarily affects the entire synovial joint, especially the hip, hand, and knee joints. This results in inflammation in the synovium and osteochondral injuries, ultimately causing functional limitations and joint dysfunction. The key mechanism responsible for maintaining articular cartilage function is chondrocyte metabolism, which involves energy generation through glycolysis, oxidative phosphorylation, and other metabolic pathways. Some studies have shown that chondrocytes in OA exhibit increased glycolytic activity, leading to elevated lactate production and decreased cartilage matrix synthesis. In OA cartilage, chondrocytes display alterations in mitochondrial activity, such as decreased ATP generation and increased oxidative stress, which can contribute to cartilage deterioration. Chondrocyte metabolism also involves anabolic processes for extracellular matrix substrate production and energy generation. During OA, chondrocytes undergo considerable metabolic changes in different aspects, leading to articular cartilage homeostasis deterioration. Numerous studies have been carried out to provide tangible therapies for OA by using various models in vivo and in vitro targeting chondrocyte metabolism, although there are still certain limitations. With growing evidence indicating the essential role of chondrocyte metabolism in disease etiology, this literature review explores the metabolic characteristics and changes of chondrocytes in the presence of OA, both in vivo and in vitro. To provide insight into the complex metabolic reprogramming crucial in chondrocytes during OA progression, we investigate the dynamic interaction between metabolic pathways, such as glycolysis, lipid metabolism, and mitochondrial function. In addition, this review highlights prospective future research directions for novel approaches to diagnosis and treatment. Adopting a multifaceted strategy, our review aims to offer a comprehensive understanding of the metabolic intricacies within chondrocytes in OA, with the ultimate goal of identifying therapeutic targets capable of modulating chondrocyte metabolism for the treatment of OA.


Subject(s)
Cartilage, Articular , Chondrocytes , Osteoarthritis , Chondrocytes/metabolism , Chondrocytes/pathology , Humans , Osteoarthritis/metabolism , Osteoarthritis/pathology , Animals , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Glycolysis
2.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1793-1801, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812191

ABSTRACT

Soil nutrients and inorganic elements affect not only the growth and development of medicinal plants but also the formation and accumulation of active ingredients in traditional Chinese medicines. The content of tanshinones and 28 inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma samples from 18 producing areas in 6 provinces was determined, and 35 physical and chemical properties of the corresponding soil samples were determined. The enrichment characteristics of inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma were analyzed. The correlation analysis and stepwise regression analysis were performed to screen out the main soil factors affecting the content of tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. The results showed that the content of tanshinones in the samples from different areas varied significantly, being the highest in the samples from Shandong, the second in the samples from Henan, and low in the samples from Shanxi and Sichuan. K, Mg, Ca, and Na were rich in Salviae Miltiorrhizae Radix et Rhizoma samples, among which Na and K had the highest enrichment coefficients. The results of correlation and regression analyses showed that soil K, Na, Ti, and total nitrogen were the main soil factors affecting the tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. Specifically, the content of tanshinones was positively correlated with Ti and negatively correlated with Na, K, and total nitrogen in the soil. Therefore, during the planting of Salvia miltiorrhiza, the land should be selected with full consideration to the salinity and saline land should be avoided. Secondly, the application of nitrogen and potassium fertilizers can be appropriately reduced, and water-soluble elemental fertilizers for S. miltiorrhiza should be developed.


Subject(s)
Abietanes , Rhizome , Salvia miltiorrhiza , Soil , Salvia miltiorrhiza/chemistry , Abietanes/analysis , Soil/chemistry , Rhizome/chemistry , China , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Nitrogen/analysis
3.
J Nanobiotechnology ; 21(1): 359, 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37789395

ABSTRACT

BACKGROUND: Tendon injuries have a high incidence and limited treatment options. Stem cell transplantation is essential for several medical conditions like tendon injuries. However, high local concentrations of reactive oxygen species (ROS) inhibit the activity of transplanted stem cells and hinder tendon repair. Cerium oxide nanoparticles (CeONPs) have emerged as antioxidant agents with reproducible reducibility. RESULTS: In this study, we synthesized polyethylene glycol-packed CeONPs (PEG-CeONPs), which were loaded into the human umbilical cord mesenchymal stem cells (hUCMSCs) to counteract oxidative damage. H2O2 treatment was performed to evaluate the ROS scavenging ability of PEG-CeONPs in hUCMSCs. A rat model of patellar tendon defect was established to assess the effect of PEG-CeONPs-carrying hUCMSCs in vivo. The results showed that PEG-CeONPs exhibited excellent antioxidant activity both inside and outside the hUCMSCs. PEG-CeONPs protect hUCMSCs from senescence and apoptosis under excessive oxidative stress. Transplantation of hUCMSCs loaded with PEG-CeONPs reduced ROS levels in the tendon injury area and facilitated tendon healing. Mechanistically, NFκB activator tumor necrosis factor α and MAPK activator dehydrocrenatine, reversed the therapeutic effect of PEG-CeONPs in hUCMSCs, indicating that PEG-CeONPs act by inhibiting the NFκB and MAPK signaling pathways. CONCLUSIONS: The carriage of the metal antioxidant oxidase PEG-CeONPs maintained the ability of hUCMSCs in the injured area, reduced the ROS levels in the microenvironment, and facilitated tendon regeneration. The data presented herein provide a novel therapeutic strategy for tendon healing and new insights into the use of stem cells for disease treatment.


Subject(s)
Mesenchymal Stem Cells , Nanoparticles , Tendon Injuries , Humans , Rats , Animals , Antioxidants/pharmacology , Reactive Oxygen Species , Hydrogen Peroxide , Oxidative Stress , Regeneration , Nanoparticles/therapeutic use , Tendons , Tendon Injuries/therapy , Umbilical Cord
4.
Front Cell Dev Biol ; 11: 1246504, 2023.
Article in English | MEDLINE | ID: mdl-37635870

ABSTRACT

Osteoarthritis (OA) is a common and disabling disease. For advanced OA, surgical treatment is still the main treatment. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are self-regenerative pluripotent cells, that coordinate cartilage regeneration by secreting various trophic factors, which adjust the injured tissue environment. hUC-MSCs secret extracellular vesicles and participates in OA treatment by transmitting bioactive molecules related to migration, proliferation, apoptosis, inflammatory reaction, extracellular matrix synthesis and cartilage repair. In addition, the combination of multiple substances represented by cartilage matrix and hUC-MSCs also have a significant synergistic effect on OA treatment. Because hUC-MSCs have shown considerable promise in cartilage repair, some scholars have proposed transplanting mesenchymal stem cells into damaged cartilage to delay OA progression. This article reviews the application of hUC-MSCs as a treatment for OA. With the continuous development of routine clinical applications, more reliable intervention modalities for hUC-MSCs in OA treatment will be discovered for the time to come.

5.
Biomed Pharmacother ; 166: 115343, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37634474

ABSTRACT

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage loss that causes disability worldwide. The accumulation of senescent chondrocytes in aging human cartilage contributes to the high incidence of OA. Heterochromatin instability, the hallmark and driving factor of senescence, regulates the expression of the senescence-associated secretory phenotype that induces inflammation and cartilage destruction. However, the role of heterochromatin instability in OA progression remains unclear. In this work, we identified AURKB as a key senescence-associated chromatin regulator using bioinformatics methods. We found that AURKB was upregulated in OA cartilage and chondrocytes exposed to abnormal mechanical strain. Overexpression of AURKB could cause senescence and heterochromatin instability. Furthermore, the AURKB inhibitor Barasertib reversed senescence and heterochromatin instability in chondrocytes and alleviated OA in a rat model. Mechanistically, abnormal mechanical strain increased AURKB levels through the Piezo1/Ca2+ signaling axis. Blocking Piezo1/Ca2+ signaling by short interfering RNA against Piezo1 and Ca2+ chelator BAPTA could reduce the expression of AURKB and alleviate senescence in chondrocytes exposed to abnormal mechanical strain. In conclusion, our data confirmed that abnormal mechanical strain increases the expression of AURKB by activating the Piezo1/Ca2+ signaling axis, leading to destabilized heterochromatin and senescence in chondrocytes, whereas Barasertib consolidates heterochromatin, counteracts senescence and alleviates OA.


Subject(s)
Chondrocytes , Osteoarthritis , Humans , Animals , Rats , Heterochromatin , Osteoarthritis/genetics , Quinazolines , Aurora Kinase B
6.
Am J Transl Res ; 15(7): 4873-4886, 2023.
Article in English | MEDLINE | ID: mdl-37560235

ABSTRACT

OBJECTIVE: Osteoarthritis (OA) is the most common degenerative joint disease leading to disability worldwide. Cellular senescence is considered to be a fundamental pathogenic mechanism in the development of OA and has attracted increasing attention. However, regulatory mechanisms underlying chondrocyte senescence in OA remain unclear. METHODS: Bioinformatic methods were used to screen key genes. Immunohistochemistry and the quantitative reverse transcription polymerase chain reaction were used to evaluate gene expression. RNA intervention experiments were performed to explore the functions of key genes. RESULTS: We used 494 aging-associated genes provided by the Aging Atlas to identify the co-expression modules associated with age and OA. Thirty age-associated differentially expressed genes (ASDEGs) were identified. Using cytoHubba in Cytoscape, we identified Jun as the hub-ASDEG for OA chondrocytes. We confirmed the downregulation of Jun in OA rats and senescent chondrocytes by immunohistochemistry and quantitative reverse transcription polymerase chain reaction, respectively. Inhibition of proliferation and accelerated senescence were observed in chondrocytes treated with siRNA against Jun. Mechanistically, we observed micronuclei formation and reduced expression of H3K9me3 and heterochromatin protein 1gamma in siRNA-Jun-treated chondrocytes, indicating that destabilization of chromatin occurred during this treatment. CONCLUSION: Jun plays a crucial role in OA development and causes senescence by destabilizing chromatin in chondrocytes. These findings provide new insights into OA progression and suggest promising therapeutic targets.

7.
Food Chem Toxicol ; 175: 113726, 2023 May.
Article in English | MEDLINE | ID: mdl-36925039

ABSTRACT

BACKGROUND: Mechanical strain plays a crucial role in chondrocyte apoptosis and osteoarthritis (OA) disease progression through Piezo1. Trimethylamine-N-oxide (TMAO) is a diet-derived metabolite that correlates positively with multiple chronic diseases. Herein, we explored the potential role of TMAO in sensitizing chondrocytes to Piezo1-mediated mechanotransduction. METHODS: The cytotoxicity of TMAO on chondrocytes was assayed. Piezo1 expression was measured after TMAO intervention. Pathological mechanical loading or Yoda1 (a specific Piezo1 channel activator) was administered in chondrocytes. The calcium levels and cytoskeleton in chondrocytes were observed by fluorescence microscopy. Flow cytometry, western blotting, and mitochondrial membrane potential assays were utilized to evaluate apoptosis. A rat OA model was constructed by anterior cruciate ligament transection. Hematoxylin-eosin staining, Safranin-O/Fast Green staining, immunochemistry, and TUNEL were applied to estimate OA severity. RESULTS: TMAO intervention alone did not affect chondrocyte viability up to 600 µM. TMAO significantly increased Piezo1 expression and up-regulated intracellular calcium levels, further leading to cytoskeletal damage. Mechanical strain or Yoda1 treatment significantly induced chondrocyte apoptosis. Notably, TMAO intervention further aggravated chondrocyte apoptosis and cartilage destruction under pathological mechanical loading. CONCLUSION: TMAO significantly up-regulated Piezo1 expression and sensitized chondrocytes to mechanical loading, which may be closely related to the pathogenesis of OA.


Subject(s)
Chondrocytes , Osteoarthritis , Rats , Animals , Chondrocytes/metabolism , Chondrocytes/pathology , Up-Regulation , Mechanotransduction, Cellular/physiology , Calcium/metabolism , Apoptosis , Oxides
8.
Int J Mol Sci ; 24(5)2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36902483

ABSTRACT

Accumulation of senescent cells is the prominent risk factor for osteoarthritis (OA), accelerating the progression of OA through a senescence-associated secretory phenotype (SASP). Recent studies emphasized the existence of senescent synoviocytes in OA and the therapeutic effect of removing senescent synoviocytes. Ceria nanoparticles (CeNP) have exhibited therapeutic effects in multiple age-related diseases due to their unique capability of ROS scavenging. However, the role of CeNP in OA remains unknown. Our results revealed that CeNP could inhibit the expression of senescence and SASP biomarkers in multiple passaged and hydrogen-peroxide-treated synoviocytes by removing ROS. In vivo, the concentration of ROS in the synovial tissue was remarkably suppressed after the intra-articular injection of CeNP. Likewise, CeNP reduced the expression of senescence and SASP biomarkers as determined by immunohistochemistry analysis. The mechanistic study showed that CeNP inactivated the NFκB pathway in senescent synoviocytes. Finally, safranin O-fast green staining showed milder destruction of articular cartilage in the CeNP-treated group compared with the OA group. Overall, our study suggested that CeNP attenuated senescence and protected cartilage from degeneration via scavenging ROS and inactivating the NFκB signaling pathway. This study has potentially significant implications in the field of OA as it provides a novel strategy for OA treatment.


Subject(s)
Cartilage, Articular , Osteoarthritis , Synoviocytes , Humans , Synoviocytes/metabolism , Senescence-Associated Secretory Phenotype , Reactive Oxygen Species/metabolism , Osteoarthritis/metabolism , Signal Transduction , NF-kappa B/metabolism , Cartilage, Articular/metabolism , Cellular Senescence , Chondrocytes/metabolism
9.
Int J Mol Sci ; 24(4)2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36835440

ABSTRACT

Excessive mechanical strain is the prominent risk factor for osteoarthritis (OA), causing cartilage destruction and degeneration. However, the underlying molecular mechanism contributing to mechanical signaling transduction remains unclear in OA. Piezo type mechanosensitive ion channel component 1 (Piezo1) is a calcium-permeable mechanosensitive ion channel and provides mechanosensitivity to cells, but its role in OA development has not been determined. Herein, we found up-regulated expression of Piezo1 in OA cartilage, and that its activation contributes to chondrocyte apoptosis. The knockdown of Piezo1 could protect chondrocytes from apoptosis and maintain the catabolic and anabolic balance under mechanical strain. In vivo, Gsmtx4, a Piezo1 inhibitor, markedly ameliorated the progression of OA, inhibited the chondrocyte apoptosis, and accelerated the production of the cartilage matrix. Mechanistically, we observed the elevated activity of calcineurin (CaN) and the nuclear transfection of nuclear factor of activated T cells 1 (NFAT1) under mechanical strain in chondrocytes. Inhibitors of CaN or NFAT1 rescued the pathologic changes induced by mechanical strain in chondrocytes. Overall, our findings revealed that Piezo1 was the essential molecule response to mechanical signals and regulated apoptosis and cartilage matrix metabolism via the CaN/NFAT1 signaling axis in chondrocytes, and that Gsmtx4 could be an attractive therapeutic drug for OA treatment.


Subject(s)
Calcineurin , Cartilage, Articular , Ion Channels , NFATC Transcription Factors , Osteoarthritis , Spider Venoms , Humans , Apoptosis , Calcineurin/metabolism , Cartilage, Articular/metabolism , Chondrocytes/metabolism , Ion Channels/metabolism , Mechanotransduction, Cellular , Osteoarthritis/therapy , NFATC Transcription Factors/metabolism , Spider Venoms/therapeutic use
10.
BMC Urol ; 22(1): 140, 2022 Sep 03.
Article in English | MEDLINE | ID: mdl-36057571

ABSTRACT

BACKGROUND: Drainage is indicated in many patients with a perinephric abscess (PA). Surgical drainage is associated with trauma and slow recovery, while percutaneous drainage can be ineffective in some patients. We report on 11 patients with PA treated by percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction under local anesthesia. METHODS: This case series included 11 PA patients operated on from January 2013 to June 2020. All patients received percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction. Data, including operation time, volume of intraoperative blood loss, volume of intraoperative pus suction, time of postoperative drainage tube indwelling, time to restore normal body temperature, length of postoperative hospital stay, and intraoperative and postoperative complications, were collected. RESULTS: The age of the patients was 59 (53-69) years. Eight, six, two, and two patients had hypertension, type 2 diabetes, rheumatoid arthritis, and renal calculi, respectively. The operations were successful forall11 patients. Eight, two, and one patients required one, two, and three channels, respectively, to clear their abscess. The average operation time was 44 (30-65) min, and intraoperative blood loss was 16 (10-20) ml. The volume of intraoperative pus suction was 280 (200-400) ml, time of postoperative drainage tube indwelling was 8.2 (6-12) days, and time to restoring normal body temperature was 0.8 (0.5-2) days. The average postoperative hospital stay was 9.8 (7-14) days. No severe intraoperative or postoperative complications occurred. The postoperative follow-up time was typically 4.8 (3-8) months, and there were no recurrences. CONCLUSION: Percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction might be a feasible method for treating PA.


Subject(s)
Abdominal Abscess , Diabetes Mellitus, Type 2 , Kidney Calculi , Urinary Tract Infections , Abdominal Abscess/etiology , Abscess/etiology , Aged , Blood Loss, Surgical , Drainage/methods , Humans , Kidney Calculi/etiology , Middle Aged , Postoperative Complications/etiology , Suction , Ultrasonography, Interventional , Urinary Tract Infections/etiology
11.
Heliyon ; 8(9): e10530, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36132177

ABSTRACT

During the operation of the magnetically gain-switched chemical oxygen-iodine laser (MGS-COIL), the transition intensity of hyperfine transition line 2-2 can exceed that of line 3-4, which is the dominant line at zero magnetic field. For this reason, a simulation model including both 3-4 and 2-2 transition lines is necessary to describe the mode buildup process in MGS-COIL. In this paper, we assume that 3-4 and 2-2 transition lines simultaneously oscillate in laser cavity. The propagation of optical field is calculated based on FFT. The required frequency, rise time and residual field of the magnetic gain-switch for a high-performance MGS-COIL are analyzed based on simulation results.

12.
Biomed Res Int ; 2022: 7810062, 2022.
Article in English | MEDLINE | ID: mdl-35937406

ABSTRACT

Objective: To research the application of CTU-assisted Doppler ultrasound puncture in uncatheterized PCNL, its influence on patients' complications, and its clinical value in a case-control study. Methods: One hundred and forty-four patients who went through percutaneous nephrolithotomy (PCNL) from March 2019 to June 2021 in our hospital were arbitrarily assigned into the CTU group (n = 72) and CT plain scan group (n = 72). CTA+CTU was adopted to determine the puncture passage in the CTU group, and CT scan was employed in the CT group. The intraoperative blood loss, postoperative blood loss, operation time, hospital stay, primary stone removal rate, and the incidence of intraoperative and postoperative complications were compared. The visual analogue score (VAS) was employed to assess the degree of postoperative wound pain. Results: The first-stage stone removal rate in the CTU group was 95.83% (69/72), which was remarkably higher compared to the CT plain scan group, which was 81.94% (59/72), and the difference was statistically significant (P < 0.05). The overall rates of intraoperative complications were 6.94% (5/72) in the CTU group and 18.06% (13/72) in the CT plain scan group, respectively, which exhibited great differences (P < 0.05). In addition, the overall rates of intraoperative complications were 2.78% (2/72) in the CTU and 13.89% (10/72) in the CT plain scan group, respectively, and the difference was statistically significant (P < 0.05). The operation time and postoperative hospital stays in the CTU group were remarkably shorter compared to the CT group, and the difference was statistically significant (P < 0.05). The intraoperative and postoperative blood loss of CTU group displayed obvious less than that of the CT group, and the difference was statistically significant (P < 0.05). The VAS were compared 24 hours after surgery. After operation, the VAS of 24 hours after operation in the CTU group (0.92 ± 0.12) were remarkably lower compared to the CT group (1.22 ± 0.15), and the difference was statistically significant (P < 0.05). Discussion. PCNL is constantly being optimized by CTU-assisted Doppler ultrasound puncture to improve stone clearance rates, reduce postoperative bleeding, be less painful, provide rapid recovery, and provide safe and feasible results. It is therefore worthwhile to standardize and then widely promote it in clinical practice.


Subject(s)
Kidney Calculi , Nephrolithotomy, Percutaneous , Nephrostomy, Percutaneous , Blood Loss, Surgical , Case-Control Studies , Humans , Kidney Calculi/diagnostic imaging , Kidney Calculi/surgery , Nephrolithotomy, Percutaneous/adverse effects , Nephrostomy, Percutaneous/adverse effects , Nephrostomy, Percutaneous/methods , Postoperative Hemorrhage , Punctures , Retrospective Studies , Treatment Outcome , Ultrasonography, Doppler
13.
Neurosci Lett ; : 135224, 2020 Jun 30.
Article in English | MEDLINE | ID: mdl-32619653

ABSTRACT

This article has been withdrawn at the request of the Editor-in-Chief. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

14.
BMC Urol ; 19(1): 122, 2019 Nov 27.
Article in English | MEDLINE | ID: mdl-31775711

ABSTRACT

BACKGROUND: Accurate puncture and dilation of the target kidney calices for percutaneous nephrolithotomy (PCNL) can be difficult. This study aimed to investigate the advantages of PCNL using optical puncture (i.e. the puncture is visualized on a screen as seen through the needle) combined with balloon dilation vs. conventional puncture methods. METHODS: This was a retrospective study of 58 consecutive patients with kidney stones without hydronephrosis and treated at the Minimally Invasive Urology Center of Zhejiang Provincial People's Hospital between 10/2016 and 12/2017. Twenty-one patients underwent optical puncture combined with balloon dilation PCNL. Thirty-seven patients underwent conventional puncture instrument dilation PCNL (controls). Success rate, tubeless rate, blood loss, pain, and complications were compared between the two groups. RESULTS: The one-time puncture success rate (95.2% [20/21] vs. 67.6% [25/37], P = 0.02) and the postoperative tubeless rate (81.0% [17/21] vs. 54.1% [20/37], P = 0.04) were higher in the optical puncture group compared with controls. The average postoperative hemoglobin reduction was smaller (1.13 ± 0.63 vs. 1.56 ± 0.59 g/dL, P = 0.01), the postoperative VAS score was lower (1.6 ± 0.9 vs. 2.5 ± 1.2, P = 0.004), the rate of postoperative analgesic use was lower (14.3% [3/21] vs. 40.5% [15/37], P = 0.04), and the postoperative mean hospitalization days was shorter (3.7 ± 0.9 vs. 4.4 ± 0.8, P = 0.005) in the optical puncture group vs. controls. There was no case of urinary sepsis, blood transfusion, perirenal hematoma, pleural injury, and visceral organ damage. CONCLUSIONS: Optical puncture combined with balloon dilation PCNL could be associated with good therapeutic effect and low frequency of complications for the treatment of kidney stones without hydronephrosis.


Subject(s)
Kidney Calculi/surgery , Nephrolithotomy, Percutaneous/methods , Adult , Aged , Aged, 80 and over , Dilatation , Female , Humans , Hydronephrosis , Male , Middle Aged , Nephrolithotomy, Percutaneous/instrumentation , Punctures/methods , Retrospective Studies , Young Adult
15.
Gene ; 705: 44-50, 2019 Jul 15.
Article in English | MEDLINE | ID: mdl-30981837

ABSTRACT

Long non-coding RNAs (lncRNAs) are crucial regulators in the progression of various diseases. Although the role of lncRNAs in prostate cancer (PCa) has been studied in recent years, there are still numerous lncRNAs need to be elucidated. This study aims to detect the role of lncRNA small nucleolar RNA host gene 15 (SNHG15) in human prostate cancer. Using qRT-PCR analysis, we identified the upregulation of SNHG15 in PCa cell lines. Loss-of function assays were conducted to determine the regulatory effect of SNHG15 on PCa cell proliferation, migration and epithelial-mesenchymal transition (EMT). According to the results of functional assays, we found that knockdown of SNHG15 impaired cell viability, suppressed cell proliferation, inhibited cell migration and invasion, reversed EMT progress. All these findings revealed the oncogenic function of SNHG15 in PCa. Mechanism investigation revealed that SNHG15 was located in the cytoplasm of PCa cells and acted as a molecular sponge of microRNA-338-3p (miR-338-3p). Moreover, FKBP prolyl isomerase 1A (FKBP1A) was a target of miR-338-3p. This investigation demonstrated that SNHG15 may serve as a competing endogenous RNA (ceRNA) to regulate miR-338-3p and FKBP1A. Finally, the involvement of miR-338-3p and FKBP1A in SNHG15-mediated biological function was demonstrated by performing rescue assays. In summary, our study revealed the function of a novel pathway in PCa.


Subject(s)
MicroRNAs/genetics , Prostatic Neoplasms/genetics , RNA, Long Noncoding/genetics , Tacrolimus Binding Proteins/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cytoplasm/genetics , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Male , Prostatic Neoplasms/metabolism , Tacrolimus Binding Proteins/metabolism , Up-Regulation
16.
Biomed Pharmacother ; 108: 1039-1047, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30372804

ABSTRACT

MicroRNAs (miRNAs) have been widely studied in various human cancers, including bladder cancer. Previous report revealed that miR-125a-5p is downregulated in urothelial carcinomas. However, the biological function and molecular mechanism of miR-125a-5p in bladder cancer has not been elucidated. Therefore, this study focused on the role of miR-125a-5p in bladder cancer. The expression levels of miR-125a-5p were firstly tested in one normal cell line and four bladder cancer cell lines with qRT-PCR. The relative lower expression of miR-125a-5p was detected in bladder cancer cells. To confirm the effects of ectopic expression of miR-125a-5p on the biological behaviors of bladder cancer cells, gain-of-function assays were carried out. According to experimental results, miR-125a-5p overexpression suppressed cell proliferation and cell cycle progression, induced cell apoptosis. Moreover, overexpression of miR-125a-5p suppressed cell migration and invasion and reversed epithelial-mesenchymal transition (EMT). Mechanism investigation indicated that FUT4 is a target mRNA of miR-125a-5p in bladder cancer. The effects of FUT4 on cell proliferation, apoptosis, migration and invasion were identified by conducting gain-of-function assays. Finally, rescue assays indicated that FUT4 can reverse the effects of miR-125a-5p on bladder cancer progression. In summary, miR-125a-5p suppresses bladder cancer progression through targeting FUT4.


Subject(s)
Fucosyltransferases/genetics , Lewis X Antigen/genetics , MicroRNAs/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Apoptosis/genetics , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Down-Regulation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , RNA, Messenger/genetics
17.
Biochem Biophys Res Commun ; 503(4): 2459-2465, 2018 09 18.
Article in English | MEDLINE | ID: mdl-29969630

ABSTRACT

Prostate cancer has become one of commonest urologic tumors in male. In recent years, miRNAs are continually attracting attentions of researchers for their special regulatory function in human cancers. Previous study has revealed that miR-410 acts as a biomarker for the diagnosis of prostate cancer. Whereas, the specific biological function of miR-410-3p in prostate cancer remains unknown. The aim of this study is to explore the function and molecular mechanism of miR-410-3p in prostate cancer. The high expression of miR-410-3p was examined in prostate cancer tissues and cell lines by qRT-PCR. Next, the prognostic value was identified by Kaplan Meier method. High expression of miR-410-3p indicated poor prognosis of prostate cancer patients. To investigate the biological function of miR-410-3p in prostate cancer, loss-of function assays were designed and performed in two prostate cancer cell lines (PC3 and DU145). As a result, downregulated miR-410-3p suppressed cell proliferation, migration and EMT progress. Moreover, flow cytometry analysis was performed to determine that the acceleration effects of miR-410-3p on cell apoptosis. Mechanistically, further analysis demonstrated that the effects of miR-410-3p exert oncogenic functions through downregulating PTEN. All findings in this study revealed that miR-410-3p inhibits prostate cancer progression via downregulating PTEN/AKT/mTOR signaling pathway.


Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , PTEN Phosphohydrolase/metabolism , Prostatic Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Aged , Cell Line, Tumor , Cell Proliferation , Humans , Male , MicroRNAs/metabolism , PTEN Phosphohydrolase/genetics , Prognosis , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Up-Regulation
18.
World J Surg Oncol ; 13: 231, 2015 Jul 31.
Article in English | MEDLINE | ID: mdl-26228387

ABSTRACT

BACKGROUND: Epidemiologic studies have reported various results relating phytoestrogens to prostate cancer (PCa). The aim of this study was to provide a comprehensive meta-analysis on the extent of the possible association between phytoestrogens (including consumption and serum concentration) and the risk of PCa. METHODS: Eligible studies were retrieved via both computer searches and review of references. The summary relative risk ratio (RR) or odds ratio (OR) and 95% confidence interval (CI) were calculated with random effects models. RESULTS: A total of 11 studies (2 cohort and 9 case-control studies) on phytoestrogen intake and 8 studies on serum concentration were included in the meta-analysis. The pooled odds ratio (OR) showed a significant influence of the highest phytoestrogens consumption (OR 0.80, 95% CI 0.70-0.91) and serum concentration (OR 0.83, 95% CI 0.70-0.99) on the risk of PCa. In stratified analysis, high genistein and daidzein intake and increased serum concentration of enterolactone were associated with a significant reduced risk of PCa. However, no significant associations were observed for isoflavone intake, lignans intake, or serum concentrations of genistein, daidzein, or equol. CONCLUSIONS: The overall current literature suggests that phytoestrogen intake is associated with a decreased risk of PCa, especially genistein and daidzein intake. Increased serum concentration of enterolactone was also associated with a significant reduced risk of PCa. Further efforts should be made to clarify the underlying biological mechanisms.


Subject(s)
Phytoestrogens/therapeutic use , Prostatic Neoplasms/prevention & control , Case-Control Studies , Humans , Male , Observational Studies as Topic , Prostatic Neoplasms/etiology , Risk Factors
19.
J Surg Res ; 196(1): 118-23, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-25796111

ABSTRACT

BACKGROUND: Parapelvic renal cysts are more likely to be symptomatic compared with that of simple peripheral renal cysts, and their treatment remains challenging. This study aimed to assess the feasibility and safety of flexible ureteroscopy in managing symptomatic endogenous renal cystic diseases. MATERIALS AND METHODS: Thirty-five patients with symptomatic endogenous renal cystic diseases were treated by ureteroscopic unroofing and drainage into the collecting system. Surgical procedure, patient's outcome, and postoperative complications were retrospectively evaluated. RESULTS: Ureteroscopic unroofing and drainage were successful in 35 patients without conversion to open surgery. For patients with successful surgery, the mean operation and hospitalization times were 25.38 ± 3.71 min and 3.01 ± 0.57 d, respectively, with a curative standard rate of 74.3% (26/35). Three patients experienced Clavien grade I and II complications but no serious perioperative complications occurred. During the follow-up period averaging 36 mo, no cysts were detected in 74.3% of patients (26/35); noticeable relief was observed in four patients showing a simple renal cyst (diameter <2 cm). In five patients who presented with polycystic kidneys, the renal volume was decreased by 93.76 ± 7.38 mL per side, on average, compared with pretreatment values. Pain was relieved in all 30 patients with renal cysts. Hydronephrosis disappeared in all 15 patients diagnosed with this condition at presentation. No secondary cyst lesions (such as infection, hematoma formation, and solid cystic changes) occurred. CONCLUSIONS: The transurethral flexible ureteroscopic incision and drainage for symptomatic endogenous renal cystic diseases has multiple advantages such as minimal trauma, rapid recovery, and a definite curative effect.


Subject(s)
Kidney Diseases, Cystic/surgery , Ureteroscopy/methods , Adult , Aged , Drainage , Female , Humans , Male , Middle Aged , Retrospective Studies , Ureteroscopy/adverse effects
20.
Urol J ; 11(4): 1757-62, 2014 Sep 02.
Article in English | MEDLINE | ID: mdl-25194071

ABSTRACT

PURPOSE: To report our experience of transperitoneal laparoscopic plasty for reconstruction in patients with horseshoe kidney. MATERIALS AND METHODS: We retrospectively analyzed 12 patients with the symptomatic horseshoe kidney who presented to our institution from March 2005 to July 2008 and underwent laparoscopic reconstruction for horseshoe kidney. Computed tomography angiography was performed prior to surgery for evaluation of the anatomic variations, since preoperative knowledge is necessary for achieving reliable vascular control. Five patients had renal stones which were extracted during surgery. All laparoscopic operations were performed by the same urologist. RESULTS: All procedures were completed successfully and no one needed for conversion to open surgery. Mean operative time was 150 min and no major complications were observed. The average follow-up time was 28.7 months. All patients had good renal function and improved drainage with successful reconstruction. CONCLUSION: Laparoscopic reconstruction has since been demonstrated to be an attractive alternative in the management of the horseshoe kidney. It provides a feasible and effective alternative to conventional manage­ment.


Subject(s)
Kidney Pelvis/abnormalities , Kidney Pelvis/surgery , Laparoscopy/methods , Adolescent , Adult , Angiography , Child, Preschool , Female , Humans , Kidney Calculi/surgery , Kidney Pelvis/diagnostic imaging , Male , Middle Aged , Operative Time , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
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