ATP-sensitive potassium channel opener, Nicorandil, inhibits NF-κB/AIM2/GSDMD pathway activation to protect against neuroinflammation in ischemic stroke.

The Absent in Melanoma 2 (AIM2) inflammasome contributes to ischemic brain injury by inducing cell pyroptosis and inflammatory responses. Our research group has previously demonstrated that ATP-sensitive potassium channels (KATP channels) openers can modulate neuronal synaptic plasticity post-ischemic stroke for neuroprotection. However, the specific mechanisms of KATP channels in the inflammatory response following ischemic stroke remain unclear. Here, we assessed cellular damage by observing changes in BV-2 morphology and viability. TTC staining, mNSS scoring, Nissl staining, and TUNEL staining were used to evaluate behavioral deficits, brain injury severity, and neuronal damage in mice subjected to Middle Cerebral Artery Occlusion (MCAO). Real-time fluorescence quantitative PCR (RT-qPCR) assessed AIM2 expression after oxygen-glucose deprivation/reperfusion (OGD/R), while Western blotting, immunofluorescence, and Enzyme-Linked Immunosorbent Assay (ELISA) measured pyroptosis-related protein expression, Nuclear Factor-kappa B/Inhibitor of κB alpha (NF-κB/IκBα) signaling activation, and inflammatory cytokine secretion during the acute ischemic phase. We observed an increase in NF-κB nuclear translocation and activation of the NF-κB/IκBα inflammatory pathway after OGD/R. Furthermore, AIM2 protein expression was upregulated and localized within the cytoplasm of BV-2 cells. Notably, low-dose Nicorandil treatment reduced pyroptosis-related protein expression, including AIM2, cleaved cysteinyl aspartate-specific protease-1 (cleaved caspase-1), Gasdermin D Full-length (GSDMD-FL), and Gasdermin D N-terminal (GSDMD-NT), reducing the pore-forming rupture rate of BV-2 cells. Further investigations revealed that the KATP channel inhibitor 5-HD upregulated p-NF-κB p65, NF-κB p65, and p-IκBα expression, promoting microglial cell activation, pyroptosis, and inflammatory factor secretion, attenuating Nicorandil's neuroprotective effect in vivo. Overall, our results suggest that opening KATP channels can improve post-ischemic neurological function by inhibiting AIM2 inflammasome-induced microglial pyroptosis and NF-κB/IκBα signaling activation.

Associations between oxidative balance score and chronic kidney disease events in US adults: a population-based study.

Oxidative Balance Scores (OBS) are utilized to assess an individual's antioxidant status, encompassing both dietary and lifestyle factors that contribute to oxidative balance. This study investigates the relationship between OBS and chronic kidney disease (CKD) prevalence among U.S. adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The study involved a cross-sectional analysis of 13,373 individuals from NHANES, focusing on adults aged 20 years or older. OBS was calculated using 20 components, including dietary and lifestyle factors. CKD was identified based on albumin-to-creatinine ratio and estimated glomerular filtration rate, with patients stratified into mild, moderate, and high-risk groups. Statistical analysis included logistic regression models and restricted cubic splines to explore the OBS-CKD relationship. Our findings indicate a statistically significant negative correlation between OBS and CKD prevalence, particularly in mild and moderate-risk groups. Higher OBS quartiles were associated with a decreased likelihood of CKD (OR 0.70; 95% CI 0.53-0.92; P = 0.013). Restricted cubic splines indicated a non-linear, inverse association between OBS and CKD odds for the overall population (P for nonlinearity = 0.017). For mild and moderate CKD risk groups, the relationships were less pronounced (P for nonlinearity = 0.053 and 0.184, respectively), suggesting variability in the OBS-CKD link across different risk levels. The study highlights the potential of elevated OBS as a primary prevention measure for CKD, particularly in individuals with mild to moderate risk. These findings underscore the importance of antioxidant status in CKD risk management and encourage further research into the role of dietary and lifestyle factors in CKD prevention.

FgGmtB Plays an Important Role in Growth, Reproduction, Virulence and Deoxynivalenol Biosynthesis of Fusarium graminearum.

GDP-mannose transporters (GMTs) have been implicated in the virulence of some important pathogenic fungi, and guanosine diphosphate (GDP) mannose transporters transport GDP-mannose from the cytosol to the Golgi lumen prior to mannosylation, where mannose attaches to the modified protein. GMTs could be potential targets for new antifungal drugs, as disruption of any step in GDP-mannose biosynthesis can affect fungal viability, growth, or virulence. To date, the GDP-mannose transporter has been extensively studied in yeast, but its biological function in fungi, particularly F. graminearum, is still unclear. In this experimental study, the role of the GDP-mannose transporter in F. graminearum was investigated by analysing the VRG4 gene. FgGmtA and FgGmtB were blastp-derived from their Scvrg4 protein sequences and proved to be their functional homologues. The mutant and complementary strains of FgGmtA, FgGmtB and FgGmtA&B genes were generated and used to evaluate the effect of the two GMTs genes on mycelial growth, asexual reproduction, sexual reproduction, cell wall sensitivity, glyphosate synthesis and drug susceptibility. Only in the FgGmtB and FgGmtA&B mutants was the rate of mycelial growth slowed, conidium production increased, sexual reproduction impaired, cell wall sensitivity increased, glycemic content decreased, and drug sensitivity reduced. The results of the pathogenicity assessment of GMTs showed that only FgGmtB affects the patogenicity of F. graminearum. At the same time, the effect of GMTs on the ability of rhinoceros to synthesise DON toxins was investigated and the results showed that the ability of ΔFgGmtB and ΔFgGmtA&B mutants to produce the DON toxin was significantly reduced, and the expression of toxin-related genes was also reduced.

CDK13 promotes lipid deposition and prostate cancer progression by stimulating NSUN5-mediated m5C modification of ACC1 mRNA.

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

SF3B4 promotes Twist1 expression and clear cell renal cell carcinoma progression by facilitating the export of KLF 16 mRNA from the nucleus to the cytoplasm.

Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.

Ultrahigh Sensitivity Mach-Zehnder Interferometer Sensor Based on a Weak One-Dimensional Field Confinement Silica Waveguide.

We report a novel Mach-Zehnder interferometer (MZI) sensor that utilizes a weak one-dimensional field confinement silica waveguide (WCSW). The WCSW has a large horizontal and vertical aspect ratio and low refractive index difference, which features easy preparation and a large evanescent field for achieving high waveguide sensitivity. We experimentally achieved WCSW ultrahigh waveguide sensitivity of 0.94, MZI sensitivity of 44,364 π/RIU and a low limit of detection (LOD) of 6.1 × 10-7 RIU.

RBM24 exacerbates bladder cancer progression by forming a Runx1t1/TCF4/miR-625-5p feedback loop.

RNA-binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.

Single mode operation and ultrawide tuning of on-chip optofluidic dye lasers.

Single transverse mode lasers that can be continuously tuned over ultrawide wavelength ranges with a narrow linewidth are very important components for lab-on-a-chip systems. Such lasers that can be tuned over the whole visible spectrum or even beyond have not been demonstrated hitherto regardless of many years of research in this area. This article presents an on-chip optofluidic distributed Bragg reflector (DBR) dye laser constituted by a combination of a T-shaped optofluidic waveguide (T waveguide) and two ridge-waveguide-based fluidic DBR gratings, in which the T waveguide provides gain for lasing and the DBR gratings select the lasing wavelength. This configuration guarantees that the fundamental mode has a much lower loss (consequently much lower lasing threshold) than all the higher order modes. By fabricating PDMS devices of such structure and changing the fluid in DBR gratings as well as the gain fluid in the T waveguide, we demonstrate a single mode optofluidic dye laser that can be continuously tuned over a wavelength range of more than 450 nm with a linewidth less than 0.1 nm. Mode patterns obtained when using different laser dyes in the T waveguide verify fundamental mode operation over the wide wavelength range.

Knockdown of Myoferlin Suppresses Migration and Invasion in Clear-Cell Renal-Cell Carcinoma.

BACKGROUND/AIM: Myoferlin (MYOF) has emerged as an oncogenic protein in various human cancer types. This study was conducted to investigate comprehensively the expression and functional properties of MYOF in clear-cell renal-cell carcinoma (ccRCC) with respect to its value as diagnostic biomarker and therapeutic target. MATERIALS AND METHODS: mRNA and protein expression of MYOF were assessed by quantitative polymerase chain reaction and immunohistochemistry. siRNA-mediated knockdown of MYOF was performed in the RCC cell line ACHN followed by proliferation, migration and invasion assays. RESULTS: MYOF mRNA and protein expression were significantly up-regulated in ccRCC. Higher mRNA levels were measured in advanced tumors. MYOF protein expression was increased in tumors with higher histological grades, and those with positive lymph node and surgical margin status. MYOF knockdown led to reduction of migration and invasion in ACHN cells, whereas expression of angiogenesis-associated genes tyrosine-protein kinase receptor-2 (TIE2), angiopoietin 2 (ANG2) and caveolin-1 (CAV1) was up-regulated following knockdown. CONCLUSION: MYOF may serve as a diagnostic biomarker of tumor progression and a potential therapeutic target in ccRCC.

The contrasting roles of Dysferlin during tumor progression in renal cell carcinoma.

BACKGROUND: The vesicle fusion protein Dysferlin (DYSF) is mainly known as a membrane repair protein in muscle cells. Mutations of DYSF lead to muscular dystrophies and cardiomyopathies. In contrast to other members of the Ferlin protein family, few is known about its role in cancer. Our study was designed to investigate the expression and functional properties of DYSF in ccRCC and its association with clinicopathological parameters and survival. MATERIAL AND METHODS: TCGA cohort: mRNA expression data of DYSF were extracted from TCGA for patients with ccRCC (n = 603; ccRCC n = 522, benign n = 81). Study cohort: mRNA expression of DYSF in ccRCC was determined using qPCR (n = 126; ccRCC n = 82, benign n = 44). Immunohistochemical staining against DYSF was performed on tissue microarrays to validate protein expression (n = 172; ccRCC n = 142, benign n = 30). Correlations between mRNA/protein expression and clinicopathological data were statistically tested. Following siRNA-mediated knockdown of DYSF in ccRCC cell line ACHN, cell migration, invasion and proliferation were investigated. RESULTS: Both DYSF mRNA and protein expression are significantly up-regulated in ccRCC tissue. DYSF mRNA expression decreased during tumor progression: lower expression levels were measured in higher stage/grade and metastatic ccRCC with independent prognostic significance for overall and cancer-specific survival. In contrast, protein expression correlated positively with pathological parameters. Overexpression showed tendency toward poor survival. Accordingly, knockdown of DYSF suppressed migration and invasion of ccRCC cells. CONCLUSION: DYSF mRNA and protein expression are opposingly involved in tumor progression of ccRCC. DYSF could be used as a prognostic biomarker to predict survival of patients with ccRCC.

Spectral Modulation of Optofluidic Coupled-Microdisk Lasers in Aqueous Media.

We present the spectral modulation of an optofluidic microdisk device and investigate the mechanism and characteristics of the microdisk laser in aqueous media. The optofluidic microdisk device combines a solid-state dye-doped polymer microdisk with a microfluidic channel device, whose optical field can interact with the aqueous media. Interesting phenomena, such as mode splitting and single-mode lasing in the laser spectrum, can be observed in two coupled microdisks under the pump laser. We modulated the spectra by changing the gap of the two coupled microdisks, the refractive indices of the aqueous media, and the position of a pump light, namely, selective pumping schemes. This optofluidic microlaser provides a method to modulate the laser spectra precisely and flexibly, which will help to further understand spectral properties of coupled microcavity laser systems and develop potential applications in photobiology and photomedicine.

Hydroxycitric Acid Tripotassium Inhibits Calcium Oxalate Crystal Formation in the Drosophila Melanogaster Model of Hyperoxaluria.

BACKGROUND Hydroxycitric acid is a potential lithontriptic agent for calcium oxalate (CaOx) stones in the kidneys. This study aimed to evaluate the safety and efficiency of hydroxycitric acid tripotassium (K-HCA) against CaOx crystal formation using Drosophila melanogaster hyperoxaluria models. MATERIAL AND METHODS Wild-type D. melanogaster were fed standard medium with ethylene glycol or sodium oxalate added to induce hyperoxaluria. Their Malpighian tubules were dissected and observed under a microscope every 3 days. Crystal deposit score of each Malpighian tubule were evaluated under a magnification of ×200. Using hyperoxaluria Drosophila models, we investigated the inhibitory efficiency of hydroxycitrate acid tripotassium and citric acid tripotassium (K-CA) against CaOx crystal formation. The survival rate of each group was also assessed. RESULTS When fed with 0.05% NaOx, the CaOx formation in Malpighian tubules increased significantly, without reduction of life span. Therefore, we selected 0.05% NaOx-induced hyperoxaluria models for the further investigations. After treatment, the stone scores showed that K-CA and K-HCA both significantly inhibit the formation of CaOx crystals in a dose-dependent manner, and with smaller dosage (0.01%), K-HCA was more efficient than K-CA. Moreover, after treatment of K-CA or K-HCA, the life span in different groups did not change, reflecting the safety to life. CONCLUSIONS The hyperoxaluria Drosophila models fed on 0.05% NaOx diet might be a useful tool to screen novel agents for the management of CaOx stones. K-HCA may be a promising agent for the prevention CaOx stones, with satisfying efficiency and acceptable safety.

Mitochondrial PIWI-interacting RNAs are novel biomarkers for clear cell renal cell carcinoma.

PURPOSE: PIWI-interacting RNAs (piRNAs) have been suggested to serve as biomarkers in cancer. In this study, we validated the expression profile of two piRNAs derived from mitochondria, piR-34536 and piR-51810, in tissue and serum of a cohort of clear cell renal cell carcinoma (ccRCC) patients. METHODS: Tissue and serum samples of patients with ccRCC were collected prospectively in our biobank. Total RNA was isolated from 118 ccRCC tissues, 75 normal renal tissues as well as 30 serum samples from patients with ccRCC, and 15 serum samples from patients with non-malignant diseases. The expression of piRNAs was determined using quantitative real-time PCR. RESULTS: Both piR-34536 and piR-51810 were downregulated in ccRCC compared to non-malignant renal tissue. Decreased tissue piRNA levels were significant and independent predictors of shortened progression-free, cancer-specific and overall survival of ccRCC patients. The piRNA levels in serum did not differ in ccRCC patients and control subjects. CONCLUSIONS: The expression of piR-34536 and piR-51810 in ccRCC tissues may be used as prognostic biomarkers in ccRCC.

tRNA-halves are prognostic biomarkers for patients with prostate cancer.

OBJECTIVE: Noncoding RNAs play an important role in carcinogenesis; a number of tRNA-halves are expressed in response to androgen stimulation and are involved in prostate cancer (CaP) initiation and progression. In this study, we evaluated the expression profile of androgen-dependent tRNA-halves in CaP. MATERIALS AND METHODS: Total RNA was isolated from formalin-fixed paraffin-embedded 58 CaP, and 25 benign prostate hyperplasia tissues. We also studied the expression in serum from 49 localized and 21 metastatic castration-resistant CaP samples. The ligation of a RNA adaptor molecule to the tRNA-halves allowed the specific amplification of 3'/5'-tRNA-halves using quantitative TaqMan reverse transcription polymerase chain reaction. The expression levels were correlated with clinicopathological parameters as well as prostate-specific antigen recurrence free survival. RESULTS: 5'-tRNA-Asp-GUC-half and 3'-tRNA-Asp-GUC-half were up-regulated in CaP tissues compared with benign prostate hyperplasia tissues. An increased expression level of all the 5 candidate tRNA-halves was associated with adverse clinicopathological parameters (pT-stage, pN-stage, prostate-specific antigen, International Society of Urological Pathology /ISUP grade) and a shorter time to biochemical relapse. In serum, 5'-tRNA-Glu-CUC-half was circulating at a higher level in metastatic castration-resistant CaP patients compared to patients with localized CaP. CONCLUSIONS: The androgen-dependent tRNA-halves can potentially act as biomarkers to monitor and predict the progression of CaP.

Efficacy of Hydroxy-L-proline (HYP) analogs in the treatment of primary hyperoxaluria in Drosophila Melanogaster.

BACKGROUND: Substrate reduction therapy with analogs reduces the accumulation of substrates by inhibiting the metabolic pathways involved in their biosynthesis, providing new treatment options for patients with primary hyperoxalurias (PHs) that often progress to end-stage renal disease (ESRD). This research aims to evaluate the inhibition efficacy of Hydroxy-L-proline (HYP) analogs against calcium oxalate (CaOx) crystal formation in the Drosophila Melanogaster (D. Melanogaster) by comparing them with Pyridoxine (Vitamin B6). METHODS: Three stocks of Drosophila Melanogaster (W118, CG3926 RNAi, and Act5C-GAL4/CyO) were utilized. Two stocks (CG3926 RNAi and Act5C-GAL4 /CyO) were crossed to generate the Act5C > dAGXT RNAi recombinant line (F1 generation) of D. Melanogaster which was used to compare the efficacy of Hydroxy-L-proline (HYP) analogs inhibiting CaOx crystal formation with Vitamin B6 as the traditional therapy for primary hyperoxaluria. RESULTS: Nephrolithiasis model was successfully constructed by downregulating the function of the dAGXT gene in D. Melanogaster (P-Value = 0.0045). Furthermore, the efficacy of Hydroxy-L-proline (HYP) analogs against CaOx crystal formation was demonstrated in vivo using D. Melanogaster model; the results showed that these L-Proline analogs were better in inhibiting stone formation at very low concentrations than Vitamin B6 (IC50 = 0.6 and 1.8% for standard and dietary salt growth medium respectively) compared to N-acetyl-L-Hydroxyproline (IC50 = 0.1% for both standard and dietary salt growth medium) and Baclofen (IC50 = 0.06 and 0.1% for standard and dietary salt growth medium respectively). Analysis of variance (ANOVA) also showed that Hydroxy-L-proline (HYP) analogs were better alternatives for CaOx inhibition at very low concentration especially when both genetics and environmental factors are intertwined (p < 0.0008) for the dietary salt growth medium and (P < 0.063) for standard growth medium. CONCLUSION: Addition of Hydroxy-L-Proline analogs to growth medium resulted in the reduction of CaOx crystals formation. These analogs show promise as potential inhibitors for oxalate reduction in Primary Hyperoxaluria.

YRNA expression in prostate cancer patients: diagnostic and prognostic implications.

OBJECTIVE: To study the expression of YRNAs (Ro-associated Y), a novel class of non-coding RNAs, in prostate cancer (PCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival PCA (prostate adenocarcinoma, n = 56), normal (n = 36) and benign prostatic hyperplasia (BPH; n = 28) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for biochemical recurrence-free survival were analysed. RESULTS: All YRNAs were significantly downregulated in PCA tissue compared to normal tissue (all YRNAs) and to BPH tissue (RNY4 and RNY5; RNY1 and RNY3 as trend). Among tumor ISUP grade groups, the most prominent differences in the expression were evident between groups 1 and 2 (RNY1, RNY3 und RNY4; all p < 0.05). Discrimination ability for normal/BPH tissue versus tumor tissue in ROC analysis (area under curve) was ranging from 0.658 (RNY1) to 0.739 (RNY4). Higher RNY5 expression was associated with poor prognosis (biochemical recurrence-free survival). CONCLUSION: The expression of YRNAs is altered in PCA and associated with poor prognosis (RNY5). Possible diagnostic role of YRNAs in prostate cancer should be investigated in further studies.

5'-tRNA Halves are Dysregulated in Clear Cell Renal Cell Carcinoma.

PURPOSE: In various malignancies RNA fragments are dysregulated. Our study was designed to determine the expression of 4, 5'-tRNA halves in the tissue and serum of patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: Tissue and serum samples of patients with clear cell renal cell carcinoma and nonmalignant disease were collected prospectively in our biobank. We isolated total RNA from 95 clear cell renal cell carcinomas and 50 normal renal tissues as well as serum RNA from 27 patients with clear cell renal cell carcinoma and 13 with nonmalignant urological disease. To specifically determine the expression of 5'-tRNA halves we dephosphorylated and ligated an adaptor nucleotide to the 3' end of the tRNA halves. The expression levels of 4, 5'-tRNA halves (5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC, 5'-tRNA-Leu-CAG and 5'-tRNA-Lys-TTT) were then measured by TaqMan® based quantitative reverse transcription-polymerase chain reaction. RESULTS: All studied 5'-tRNA halves were down-regulated in clear cell renal cell carcinoma tissues, indicating a potential role as a tumor suppressor. Furthermore, we noted decreased expression of 5'-tRNA halves in patients with adverse clinicopathological parameters. All 5'-tRNA halves were expressed at lower levels in nonorgan confined clear cell renal cell carcinoma. The 5'-tRNA-Lys-TTT halves inversely correlated with ISUP (International Society of Urological Pathology) grade. In patients with clear cell renal cell carcinoma 5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC and 5'-tRNA-Lys-TTT halves circulated at lower levels than in control subjects, indicating relevance as noninvasive biomarkers. CONCLUSIONS: In patients with clear cell renal cell carcinoma 5'-tRNA halves have potential as diagnostic and prognostic biomarkers. The 5'-tRNA halves may act in a tumor suppressive manner, which requires further research to confirm.

Oxalate-Degrading Enzyme Recombined Lactic Acid Bacteria Strains Reduce Hyperoxaluria.

OBJECTIVE: To develop recombinant lactic acid bacteria (LAB) strains that express oxalate-degrading enzymes through biotechnology-based approach for the treatment of hyperoxaluria by oral administration. MATERIAL AND METHODS: The coding gene of oxalate decarboxylase (ODC) and oxalate oxidase (OxO) was transformed into Lactococcus lactis MG1363. The oxalate degradation ability in vitro was evaluated in media with high concentration of oxalate. Hyperoxaluria rat models through high oxalate diet were given recombinant LAB through oral administration. Twenty-four-hour urinary oxalate was measured, and kidney stone formation was investigated. RESULTS: LAB recombined with the coding gene of ODC could effectively decrease the amount of oxalate in the media and in the urine of rats. Moreover, the formation of calcium oxalate crystals in kidneys was also inhibited. The acid-induced promoter p170 significantly enhanced the reduction of hyperoxaluria. However, recombinant LAB expressing heterologous OxO showed less efficiency in oxalate degradation even in the presence of p170. CONCLUSION: LAB expressing ODC is more efficient in degradation of oxalate in vitro and in vivo than that expressing OxO. This present study provided novel recombinant probiotic strains as a potential treatment tool against oxalosis.

Urgent laparoscopic ureterolithotomy for proximal ureter stones accompanied with obstructive pyelonephritis: Is it safe and effective without preoperative drainage?

To evaluate the safety and efficacy of retroperitoneal laparoscopic ureterolithotomy (RLU) in the treatment of proximal ureteral stones accompanied with obstructive pyelonephritis without preoperative drainage.We retrospectively reviewed 21 cases of proximal ureteral stones with infected kidney undergoing RLU between July 2013 and September 2016. Stone-induced obstructive infected hydronephrosis was diagnosed using blood and urine tests and imaging modalities. Empirical effective broad spectrum antibiotic therapy was initiated immediately, and then urgent RLU was performed without preoperative drainage. During the surgical procedure, infected urine was also aspirated before stone was removed. Preoperative, intraoperative, and postoperative clinical data were collected.Operations were performed successfully without open conversion or blood transfusion. The mean operation time was 69.3 ±â€Š12.33 minutes. For all the patients, the level of plasma procalcitonin decreased after RLU. The mean hospital stay duration was 6.4 ±â€Š1.54 days. No septic shock or other severe complications occurred. By discharge, the body temperature and hemogram of each patient returned to normal. A 100% stone-free rate was achieved.Our study suggests that RLU is a potentially safe and effective method to treat proximal ureteral stones accompanied with obstructive pyelonephritis without any need of preoperative drainage.

YRNA expression predicts survival in bladder cancer patients.

BACKGROUND: Non-coding RNAs play an important role in human carcinogenesis. YRNAs (Ro-associated Y), a novel class of non-coding RNAs, have been identified as biomarker in various malignancies, but remain to be studied in urinary bladder cancer (BCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival BCA (urothelial carcinoma, n = 88) and normal urothelial bladder (n = 30) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for overall and cancer-specific survival were analysed. RESULTS: All YRNAs were significantly downregulated in BCA tissue. A low expression of RNY1, RNY3 and RNY4 was associated with muscle-invasive BCA, lymph node metastases and advanced grade. Furthermore, expression of RNY1 and RNY3 was predictive for BCA patients' overall (also RNY4) and cancer-specific survival as estimated using Kaplan-Meier and univariate (but not multivariate) Cox regression analyses. RNY1, RNY3 and RNY4 show good discriminative ability between tumor and normal tissue, as well as between muscle-invasive and non-muscle-invasive urothelial carcinoma. CONCLUSIONS: The expression of YRNAs is altered in BCA and associated with poor prognosis. Possible diagnostic role of YRNAs should be investigated in further studies.