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1.
Hemoglobin ; 48(1): 4-14, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38419555

RESUMO

Long noncoding RNAs (lncRNAs) are important because they are involved in a variety of life activities and have many downstream targets. Moreover, there is also increasing evidence that some lncRNAs play important roles in the expression and regulation of γ-globin genes. In our previous study, we analyzed genetic material from nucleated red blood cells (NRBCs) extracted from premature and full-term umbilical cord blood samples. Through RNA sequencing (RNA-Seq) analysis, lncRNA H19 emerged as a differentially expressed transcript between the two blood types. While this discovery provided insight into H19, previous studies had not investigated its effect on the γ-globin gene. Therefore, the focus of our study was to explore the impact of H19 on the γ-globin gene. In this study, we discovered that overexpressing H19 led to a decrease in HBG mRNA levels during erythroid differentiation in K562 cells. Conversely, in CD34+ hematopoietic stem cells and human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells, HBG expression increased. Additionally, we observed that H19 was primarily located in the nucleus of K562 cells, while in HUDEP-2 cells, H19 was present predominantly in the cytoplasm. These findings suggest a significant upregulation of HBG due to H19 overexpression. Notably, cytoplasmic localization in HUDEP-2 cells hints at its potential role as a competing endogenous RNA (ceRNA), regulating γ-globin expression by targeting microRNA/mRNA interactions.


Assuntos
RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , gama-Globinas/genética , gama-Globinas/metabolismo , Regulação para Cima , RNA Mensageiro/genética , Expressão Gênica
2.
J Cancer ; 15(3): 858-870, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213721

RESUMO

Purpose: The objective of this study was to examine the expression and role of Centromere protein W (CENPW) in bladder cancer (BLCA), as well as its potential mechanistic impact on the progression of BLCA. Methods: In this study, we conducted a comparative analysis of the mRNA expression level of CENPW in BLCA tissues and adjacent normal tissues using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we investigated the association between CENPW expression and patient prognosis. Furthermore, we performed in vitro and in vivo experiments to assess the impact of CENPW knockdown on various tumor biological phenotypes in BLCA. Finally, we conducted an analysis to elucidate the underlying mechanisms responsible for the observed phenotypic alterations in BLCA. Results: The expression of CENPW was found to be upregulated in BLCA, and its higher expression was associated with a poorer disease-specific survival (DSS). CENPW was found to have close associations with the cell cycle, mitosis, and DNA replication. In vitro and in vivo experiments demonstrated that the inhibition of CENPW led to a suppression of BLCA progression. Specifically, the knockdown of CENPW resulted in cell cycle arrest phase and induced apoptosis in BLCA by potentially inactivating the signal transducer and activator of transcription3 (STAT3) signaling pathway. Conclusion: CENPW has the potential to function as a molecular marker indicating an unfavorable prognosis in BLCA. Additionally, CENPW exhibits promise as a novel therapeutic target for BLCA.

3.
BJU Int ; 133(1): 34-43, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37696625

RESUMO

OBJECTIVE: To estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China. MATERIALS AND METHODS: We conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random-effects meta-analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates. RESULTS: A total of 46 studies conducted in 22 provinces across China were included in this meta-analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6-11.1%), 7.8% (95% CI 5.8-10.0%), 3.2% (95% CI 0.6-5.7%), 0.5% (95% CI 0.1-0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46-1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis. CONCLUSIONS: The prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time.


Assuntos
Cálculos Renais , Cálculos da Bexiga Urinária , Urolitíase , Masculino , Feminino , Humanos , Prevalência , China/epidemiologia , Urolitíase/epidemiologia , Cálculos Renais/epidemiologia
4.
Am J Cancer Res ; 13(6): 2213-2233, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424829

RESUMO

Bladder cancer (BLCA) is a common malignant neoplasm of the urinary system. Glycolysis is an essential metabolic pathway regulated by various genes with implications for tumor progression and immune escape. Scoring the glycolysis for each sample in the TCGA-BLCA dataset was done using the ssGSEA algorithm for quantification. The results showed that the score in BLCA tissues was markedly greater than those in adjacent tissues. Additionally, the score was found to be correlated with metastasis and high pathological stage. Functional enrichment analyses of the glycolysis-related genes showed they were related to roles associated with tumor metastasis, glucose metabolism, cuproptosis, and tumor immunotherapy in BLCA. Using 3 different machine learning algorithms, we identified chondroitin polymerizing factor (CHPF) as a central glycolytic gene with high expression in BLCA. In addition, we showed CHPF is a valuable diagnostic marker of BLCA with an area under the ROC (AUC) of 0.81. Sequencing BLCA 5637 cells after siRNA-mediated CHPF silencing and bioinformatics revealed that CHPF positively correlated with the markers of epithelial-to-mesenchymal transformation (EMT), glycometabolism-related enzymes, and immune cell infiltration. In addition, CHPF silencing inhibited the infiltration of multiple immune cells in BLCA. Genes that promote cuproptosis negatively correlated with CHPF expression and were up-regulated after CHPF silencing. High CHPF expression was a risk factor for overall and progression-free survival of patients who received immunotherapy for BLCA. Finally, using immunohistochemistry, we demonstrated that the CHPF protein had high expression in BLCA, increasing in high-grade tumors and those with muscle invasion. The CHPF expression levels were also positively associated with 18F-fluorodeoxyglucose uptake in PET/CT images. We conclude that the glycolysis-related gene CHPF is an effective diagnostic and treatment target for BLCA.

5.
Iran J Basic Med Sci ; 26(5): 603-608, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051106

RESUMO

Objectives: Calgranulins S100A8 and S100A9 are common in renal stones and they are up-regulated in both urinary exosomes and kidneys of stone patients. Renal sources and important regulators for S100A8 and S100A9 in nephrolithiasis were explored in this study. Materials and Methods: We identified S100A8 and S100A9 abundance in various renal cells by searching the Single Cell Type Atlas. Macrophages were polarized from human myeloid leukemia mononuclear cells. Human proximal renal tubular epithelial cells (HK-2) were stimulated with calcium oxalate monohydrate (COM). Coculture experiments involving HK-2 cells and macrophages were conducted. qPCR, Western blotting, ELISA, and immunofluorescence were used for detecting interleukin 6 (IL6), S100A8, and S100A9. Results: The Single Cell Type Atlas showed that S100A8 and S100A9 in human kidneys primarily originated from macrophages. M1 was the predominant macrophage type expressing S100A8 and S100A9. Direct culture with COM did not affect the expression of these two calgranulins in M1 macrophages but coculture with COM-treated HK-2 cells did. COM could promote HK-2 cells to secrete IL6. IL6 could up-regulate S100A8 and S100A9 expression in macrophages of M1 type. In addition, 0.5 µM SC144 (a kind of IL6 inhibitor) significantly prevented COM-treated HK-2 cells from up-regulating S100A8 and S100A9 expression in macrophages of M1 type. Conclusion: M1-polarized macrophages were the predominant cell type expressing S100A8 and S100A9 in the kidneys of nephrolithiasis patients. CaOx crystals can promote renal tubular epithelial cells to secrete IL6 to up-regulate S100A8 and S100A9 expression in macrophages of M1 type.

6.
BMC Microbiol ; 23(1): 105, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37062822

RESUMO

BACKGROUND: Attenuated live bacterial therapy and medical BSA materials have their own advantages in anti-cancer research, and their combination is expected to overcome some of the disadvantages of conventional anti-cancer therapeutics. METHODS AND OBJECTIVE: Utilizing the high affinity between biotin and streptavidin, BSA modification on the surface of Escherichia coli (E. coli) was achieved. Then, the adhesion and targeting abilities of BSA modified E. coli was explored on different bladder cancer cells, and the underlying mechanism was also investigated. RESULTS: BSA modification on the surface of E. coli enhances its ability to adhere and target cancer cells, and we speculate that these characteristics are related to the expression of SPARC in different bladder cancer cell lines. CONCLUSION: BSA and live bacteria have their own advantages in anti-cancer research. In this study, we found that E. coli surface-modified by BSA had stronger adhesion and targeting effects on bladder cancer cells with high expression of SPARC. These findings pave the way for the future studies exploring the combination of BSA combined with live bacteria for cancer therapy.


Assuntos
Soroalbumina Bovina , Neoplasias da Bexiga Urinária , Humanos , Soroalbumina Bovina/metabolismo , Escherichia coli/metabolismo , Bactérias/metabolismo , Biotina
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(11): 1030-1035, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36328433

RESUMO

Objective To screen nanobodies against prostate specific membrane antigen (PSMA). Methods Based on the naive phage display library, three rounds of screening were performed targeting the PSMA antigen, and positive clones were identified by ELISA and sequencing was performed. The positive cloned gene sequence was inserted into the pET28a prokaryotic expression vector and transformed into E.coli BL21. The expression of the recombinant protein was induced by IPTG and purified using Ni column, with the purified product verified by SDS-PAGE. Results Four PSMA nanobodies VHH1, VHH2, VHH3 and VHH4 were obtained by screening. The VHH1 failed to obtain protein expression, while the VHH2, VHH3 and VHH4 proteins were expressed. The purity of anti-PSMA nanobodies showed high and relative molecular mass (Mr) of about 17 000. Conclusion The sequence of anti-PSMA nanobody was successfully obtained by screening the naive phage nanobody library and were subjected to prokaryotic expression and purified.


Assuntos
Bacteriófagos , Anticorpos de Domínio Único , Masculino , Humanos , Anticorpos de Domínio Único/genética , Bacteriófagos/genética , Próstata , Glutamato Carboxipeptidase II/genética , Glutamato Carboxipeptidase II/metabolismo , Escherichia coli/genética
8.
Curr Cancer Drug Targets ; 23(1): 71-86, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35708078

RESUMO

OBJECTIVE: Identification and validation of genes that functionally account for the growth and metastasis of prostate cancer. METHODS: DU145-KO cell line was constructed by transfecting DU145 cells with lentivirus packaged with the genome-wide knock-out library. The DU145-KO cells were transplanted into the armpits of immunocompromised Nu/Nu mice, followed by the tissue collection from the lung at week 3 (early lung tissue) or week 7 (late lung tissue with micro-metastasis), as well as from primary tumor site at week 7 (late primary tumor) after inoculation. Lung metastasis was retrieved at various time points for DNA sequencing analysis to identify enriched sgRNAs, thus candidate genes/miRNAs. Further bioinformatics analysis and limited functional validation studies were carried out. RESULTS: DU145-KO cells promoted the formation of transplanted tumors in mice and promoted the growth and metastasis of primary tumors, compared to the controls (DU145-NC cells). The analysis of sequence data showed that the abundance of sgRNAs significantly changed in the primary tumor and micro-metastasis site. Fifteen target genes (C1QTNF9B, FAM229A, hsa-mir-3929, KRT23, TARS2, CRADD, GRIK4, PLA2G15, LOXL1, SLITRK6, CDC42EP5, SLC2A4, PTGDS, MYL9 and ACOX2 for the enriched sgRNAs) have been selected for experimental validation, which showed that knock-out of any of these genes led to the enhanced potential of invasion and metastasis of DU145 cells. CONCLUSION: Genome-wide CRISPR-Cas9 knock-out screening technology combined with highthroughput sequencing analysis identified genes that potentially relate to prostate tumor invasion and metastasis. Analysis of these genes provided insights into biological pathways relevant to the disease and disclosed innovative markers for diagnosis or prognosis as well as potential targets for therapy.


Assuntos
MicroRNAs , Neoplasias da Próstata , Humanos , Masculino , Camundongos , Animais , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Detecção Precoce de Câncer , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , MicroRNAs/genética , Reguladores de Proteínas de Ligação ao GTP/genética
9.
Mil Med Res ; 9(1): 14, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35361280

RESUMO

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Estreitamento Uretral , Idoso , Humanos , Masculino , Próstata , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Estreitamento Uretral/etiologia , Estreitamento Uretral/cirurgia
10.
Aging Dis ; 13(1): 8-23, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35111358

RESUMO

The circadian rhythm is an internal timing system, which is generated by circadian clock genes. Because the circadian rhythm regulates numerous cellular, behavioral, and physiological processes, organisms have evolved with intrinsic biological rhythms to adapt the daily environmental changes. A variety of pathological events occur at specific times, while disturbed rhythms can lead to metabolic syndrome, vascular dysfunction, inflammatory disorders, and cancer. Therefore, the circadian clock is considered closely related to various diseases. Recently, accumulated data have shown that the penis is regulated by the circadian clock, while erectile function is impaired by an altered sleep-wake cycle. The circadian rhythm appears to be a novel therapeutic target for preventing and managing erectile dysfunction (ED), although research is still progressing. In this review, we briefly summarize the superficial interactions between the circadian clock and erectile function, while focusing on how disturbed rhythms contribute to risk factors of ED. These risk factors include NO/cGMP pathway, atherosclerosis, diabetes mellitus, lipid abnormalities, testosterone deficiency, as well as dysfunction of endothelial and smooth muscle cells. On the basis of recent findings, we discuss the potential role of the circadian clock for future therapeutic strategies on ED, although further relevant research needs to be performed.

11.
Front Oncol ; 11: 647110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084744

RESUMO

The overall aging of the world population has contributed to the continuous upward trend in the incidence of prostate cancer (PC). Trials on PC therapy have been extensively performed, but no study has analyzed the overall trends and characteristics of these trials, especially for those carried out in China. This study aimed to provide insights on the future direction of drug development in PC, thus supplying essential supportive data for stakeholders, including researchers, patients, investors, clinicians, and pharmaceutical industry. The details of the clinical trials of drug therapies for PC during January 1, 2010, to January 1, 2020, were collected from Pharmaprojects. A total of 463 clinical trials on different therapies with 132 different drugs were completed. The long-acting endocrine therapy with few side effects, radiotherapy combined with immune checkpoint inhibitors, gene-targeted chemotherapeutics, and novel immunotherapeutic products changed the concept of PC treatment. In mainland China, 31 trials with 19 drugs have been completed in the 10 assessment years. China has initiated a few trials investigating a limited number of drug targets, centered in a markedly uneven geographical distribution of leading clinical trial units; hence, the development of PC drugs has a long way to go. Given the large patient pool, China deserves widespread attention for PC drug research and development. These findings might have a significant impact on scientific research and industrial investment.

12.
Mol Clin Oncol ; 15(1): 144, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34094542

RESUMO

Malignant peripheral nerve sheath tumor (MPNST) is a rare disease. The present study discusses the case of a 30-year-old male patient who presented with complaints of pain in the left testis and groin over 1 month. Ultrasonography and computed tomography (CT) imaging revealed the presence of a space-occupying lesion localized in the left testis. The mass was completely resected using an open surgical approach and was diagnosed as a primary MPNST of the left testis on postoperative histopathological examination. As this type of tumor is rare, there is currently no standard diagnostic or treatment method for MPNST. Pathological examination, enhanced CT imaging and immunohistochemical investigation are helpful for establishing the diagnosis and surgical resection is considered to be an effective treatment.

14.
J Oncol ; 2021: 9982192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35003260

RESUMO

Increasing evidence has shown that overexpression of P-element-induced wimpy-testis (PIWI)-like protein 1 (PIWIL1) was associated with unfavorable prognosis of patients with various types of cancers. Herein, we conducted this meta-analysis to identify the clinicopathological and prognostic value of the PIWIL1 expression in cancers. Three electronic databases (PubMed, Web of Science, and Embase) were comprehensively retrieved for relevant studies up to August 4th, 2019. RevMan 5.3 and STATA 12.0 statistical software programs were used to explore the relationships between PIWIL1 expression and the prognosis and clinicopathological features in cancer patients. A total of 13 studies recruiting 2179 patients with 9 types of solid tumors were finally included in the meta-analysis. The results indicated that patients with high PIWIL1 expression tended to have a shorter survival, and additionally deeper tumor invasion, higher clinical stage, and more lymph node metastasis. PIWIL1 could serve as a biomarker for prognosis and clinicopathological characteristics in various cancers.

15.
Zhonghua Nan Ke Xue ; 27(11): 963-968, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-37422865

RESUMO

Objective: To investigate the effects of monobromobiphenyl ether (4-BDE) on the expression of γH2AX in the rat testis, and the possible mechanism of 4-BDE affecting the reproductive function of the male rats. METHODS: Twenty-four SD male rats were randomly divided into 4 groups: control and low-, medium- and high-dose 4-BDE, the control rats treated intragastrically with olive oil, and the animals in the latter three groups with 4-BDE at 50, 100 and 200 mg/kg/d, respectively, all for 30 consecutive days. Then all the rats were killed and the testis tissues harvested for HE staining, examination of the apoptosis of the cells by TUNEL and determination of the expressions of H2AX mRNA and γH2AX by q-PCR and Western blot. RESULTS: HE staining manifested occasional reduction or absence of spermatogonial and Sertoli cells in the seminiferous tubules in the medium- and high-dose 4-BDE groups. Compared with the controls, the rats exposed to 4-BDE showed a significant dose-dependent increase in the apoptosis of the testis tissue (P < 0.05), even more significant in the medium- and high-dose 4-BDE groups than in the low-dose group (P < 0.05). There was a dose-effect relationship in the apoptosis index, but with no statistically significant difference between the medium- and high-dose 4-BDE groups (P > 0.05). The results of q-PCR exhibited no statistically significant difference in the expression level of H2AX mRNA either between the control and 4-BDE-exposed rats (P > 0.05) or among the three 4-BDE groups (P > 0.05). The expression of the γH2AX protein was remarkably higher in the 4-BDE groups than in the control (P < 0.05), but not significantly different among the 4-BDE groups (P > 0.05). CONCLUSIONS: Exposure to 4-BDE at 100 or 200 mg/kg/d damages the structure of seminiferous tubules, increases the apoptosis of testicular cells, significantly up-regulates the expression of the γH2AX protein, and consequently increases DNA double-strand breaks (DSB) in the rat testis. The apoptosis of testicular cells may be related to DSB./.

16.
Drug Discov Today ; 26(2): 296-300, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32949528

RESUMO

Gene therapy involves the introduction of new genes into cells, to modify or manipulate the expression of a gene or to alter the biological properties, for the purpose of treating disease. It is designed to treat genetic diseases at their root, by correcting the mutation responsible, its success in treatment of blood cancers and rare diseases is encouraging, and it is also beginning to show promising effects against solid tumors. Here, we comprehensively analyze all the active clinical trials of gene therapy for solid tumors from January 2010 to April 2020. Our analysis highlights the increasing trends in gene therapy trials in China and elsewhere, as well as the potential of oncolytic viruses as gene therapy products for solid tumors in vivo.


Assuntos
Terapia Genética/métodos , Neoplasias/terapia , Vírus Oncolíticos/genética , Vetores Genéticos , Humanos , Mutação , Neoplasias/genética
17.
Asian J Androl ; 23(1): 64-68, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32930102

RESUMO

We conducted the present study to assess the correlation of the prostatic anatomical parameters, especially the ratio of peripheral zone thickness and transitional zone thickness, with clinical and uroflowmetry characteristics suggestive of benign prostate hyperplasia (BPH). A total of 468 consecutive patients with a detailed medical history were identified. All patients were evaluated by scoring subjective symptoms with the International Prostate Symptom Score (IPSS) and quality of life (QoL). The prostatic anatomical parameters were measured using transrectal ultrasonography, and postvoid residual urine and maximum flow rate (Qmax) values were also determined. Pearson's correlation analysis revealed that both total prostate volume (TPV; r = 0.160, P < 0.001) and transitional zone volume (TZV; r = 0.104, P = 0.016) increased with patients' age; however, no correlations were observed of TPV, TZV, transitional zone index (TZI), and transitional zone thickness (TZT) with IPSS or QoL (all P >0.05). Peripheral to transitional zone index (PTI) was found negatively correlated with total IPSS (r = -0.113, P = 0.024), storage IPSS (r = -0.103, P = 0.041), and voiding IPSS (r = -0.123, P = 0.014). As regards the uroflowmetry characteristics, PTI (r = 0.157, P = 0.007) was indicated to be positively correlated with Qmaxand negatively correlated with TZI (r = -0.119, P = 0.042) and TZT (r = -0.118, P = 0.045), but not correlated with TPV, TZV, or peripheral zone thickness (PZT) (all P > 0.05). Postvoid residual urine (PVR) had not correlated with all the prostatic anatomical variables (all P > 0.05). This is the first study that formally proposed the concept of PTI, which is an easy-to-measure prostate anatomical parameter which significantly correlates with total IPSS, storage IPSS, voiding IPSS, and Qmax, suggesting that PTI would be useful in evaluating and managing men with lower urinary tract symptoms (LUTS)/BPH. However, well-designed studies are mandatory to verify the clinical utility of PTI.


Assuntos
Próstata/patologia , Hiperplasia Prostática/patologia , Idoso , Humanos , Masculino , Próstata/anatomia & histologia , Próstata/diagnóstico por imagem , Hiperplasia Prostática/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia , Urodinâmica
18.
Biol Cell ; 113(1): 14-27, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32942336

RESUMO

BACKGROUND INFORMATION: Diabetes-induced testicular dysfunction is characterised by abnormal apoptosis of spermatogenic cells, but the underlying mechanism is poorly understood. This study aimed to investigate the roles of clusterin (CLU) in testicular damage associated with diabetes pathogenesis, as well as the molecular mechanism. A rat diabetes model was established using streptozocin, and the mouse spermatogenic cell line GC-1 spg was treated with high glucose as a cellular model. CLU was overexpressed in GC-1 spg cells, followed by detection of serum testosterone, cell proliferation, cell apoptosis and autophagy. RESULTS: CLU expression was significantly reduced and LC3 expression was elevated in testis tissues in the rat diabetes model and high glucose-treated GC-1 spg cells. High glucose led to suppressed viability, enhanced apoptosis, reduced Bcl-2 expression, elevated Bax expression and cleavage of Caspase-3/-9 in GC-1 spg cells, and these effects were abrogated by CLU overexpression. Additionally, CLU overexpression repressed LC3 and Beclin-1 expression, reduced the LC3II/LC3I ratio and promoted p62 expression in GC-1 spg cells in the presence of high glucose, and these effects were all mitigated by rapamycin treatment. Inhibition of PI3K/AKT/mTOR signalling with LY294002 activated autophagy in CLU-overexpressing GC-1 spg cells under high glucose conditions. CLU overexpression repressed autophagy and alleviated testicular damage in diabetic rats, which was also abrogated by LY294002 treatment. CONCLUSIONS: CLU expression is suppressed during diabetes-induced testicular damage, whereas CLU overexpression alleviates diabetes-induced testicular damage by activating PI3K/AKT/mTOR signalling to inhibit autophagy and further repress spermatogenic cell apoptosis.


Assuntos
Clusterina/fisiologia , Diabetes Mellitus Experimental/patologia , Testículo , Animais , Apoptose , Linhagem Celular , Proliferação de Células , Masculino , Camundongos , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Testículo/metabolismo , Testículo/patologia
19.
Zhonghua Nan Ke Xue ; 26(6): 513-517, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33356039

RESUMO

OBJECTIVE: To evaluate the clinical application value of the bladder outlet obstruction index (BOOI) in the diagnosis of BPH. METHODS: We retrospectively analyzed the urodynamic parameters and BOOI of 199 cases of BPH diagnosed from July 2016 to September 2018, which were divided into a BOO (n = 119), a suspected BOO (n = 39) and a non-BOO group (n = 41) based on the BOOI. We obtained the prostate volume (PV), IPSS, IPSS-voiding symptom score (IPSS-VS), quality of life score (QOL), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) from the patients, compared them among the three groups and analyzed their correlation to BOOI using Pearson's linear correlation analysis. RESULTS: No statistically significant differences were observed in age (P = 0.195), PSA (P = 0.380), IPSS (P = 0.380), IPSS-VS (P = 0.380), QOL (P = 0.380), Qmax (P = 0.380) and PVR (P = 0.912) among the three groups of patients, but PV was remarkably larger in the BOO than in the suspected BOO and non-BOO groups (ï¼»58.8 ± 30.0ï¼½ vs ï¼»49.8 ± 33.9ï¼½ and ï¼»45.5 ± 26.0ï¼½ ml, P = 0.031). Pearson's linear correlation analysis showed that BOOI was not correlated significantly to IPSS (r = -0.020, P = 0.778), IPSS-VS (r= -0.013, P = 0.853), QOL (r = -0.107, P = 0.132), Qmax (r = -0.130, P = 0.066) or PVR (r = -0.056, P = 0.433), nor obviously to PV (|r| = 0.178<0.4) though with P = 0.012. CONCLUSIONS: BOOI is not significantly correlated to PV, IPSS, IPSS-VS, QOL, Qmax or PVR, and therefore BOO cannot be diagnosed exclusively with BOOI.


Assuntos
Hiperplasia Prostática , Obstrução do Colo da Bexiga Urinária , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Qualidade de Vida , Estudos Retrospectivos , Obstrução do Colo da Bexiga Urinária/diagnóstico , Urodinâmica
20.
Zhonghua Nan Ke Xue ; 26(9): 777-782, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33377698

RESUMO

OBJECTIVE: To study the effect of taurine on the reproductive toxicity damage induced by formaldehyde (FM) in adult male rats. METHODS: Forty-eight SD adult male rats were equally randomized into a normal control, an FM poisoning (FMP), a taurine intervention (TI), and an TI+FMP group. The control rats were given normal diet and gavage of saline, the rats of the FMP group treated intraperitoneally with FM at 10 mg/kg qd alt, those of the TI group intragastrically with taurine at 100 mg/kg qd, and those of the TI+FMP group with both FM and taurine at the above doses. After 30 days of treatment, the blood of the abdominal cardinal vein of the rats was extracted for measurement of the levels of serum hormones, the body weight, testis weight and testicular coefficient obtained, the testis tissue subjected to HE staining, and the expressions of Bcl-2 and Bax determined by Western blot. RESULTS: There were no statistically significant differences among the four groups of rats in the body weight, testis weight or testicular coefficient (P > 0.05). The rats in the FMP group showed obviously decreased testicular spermatogenic cells and disordered layers and loose structure of seminiferous tubules, which were basically restored to normal after taurine intervention. Compared with the normal controls, the animals of the TI group exhibited no significant abnormality, but those of the FMP group presented markedly reduced levels of serum T, LH and FSH (P < 0.05), and dramatically increased level of Gonadotropin-releasing hormone (GnRH) (P < 0.01). The levels of serum hormones were all significantly improved (P < 0.05) and that of the apoptotic protein Bax basically returned to normal (P < 0.05) after taurine intervention. CONCLUSIONS: Taurine has a certain protective effect against male reproductive toxicity caused by formaldehyde.


Assuntos
Formaldeído/toxicidade , Taurina/uso terapêutico , Testículo/efeitos dos fármacos , Animais , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Testículo/patologia
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