Prostatic stromal tumor of uncertain malignant potential: a case report and literature review.

Prostatic stromal tumors, encompassing prostatic sarcoma and stromal tumors of uncertain malignant potential (STUMP), represent an exceedingly rare category of prostatic diseases, with a prevalence of less than 1%. We present a rare case involving a man in his early 40s diagnosed with STUMP. Despite presenting with normal prostate-specific antigen (PSA) concentrations, the patient experienced persistent dysuria and gross hematuria for >7 months, leading to an initial misdiagnosis of benign prostatic hyperplasia. Persistent symptoms prompted further investigation, with magnetic resonance imaging (MRI) revealing a suspicious lesion on the left side of the prostate, initially thought to be malignant. Transrectal prostatic biopsy subsequently confirmed the presence of mucinous liposarcoma, with no medical history of diabetes, coronary heart disease, or hypertension. The treatment approach comprised robot-assisted laparoscopic radical prostatectomy, culminating in a postoperative pathological definitive diagnosis of STUMP. This case underscores the indispensable role of early MRI in the diagnostic process, highlighting the necessity of detailed pathological examination for a conclusive diagnosis. Our report aims to illuminate the diagnostic challenges and potential treatment pathways for STUMP, emphasizing its consideration in the differential diagnosis of prostatic tumors to advance clinical outcomes in this rare but important condition.

Large-scale uterine myoma MRI dataset covering all FIGO types with pixel-level annotations.

Uterine myomas are the most common pelvic tumors in women, which can lead to abnormal uterine bleeding, abdominal pain, pelvic compression symptoms, infertility, or adverse pregnancy. In this article, we provide a dataset named uterine myoma MRI dataset (UMD), which can be used for clinical research on uterine myoma imaging. The UMD is the largest publicly available uterine MRI dataset to date including 300 cases of uterine myoma T2-weighted imaging (T2WI) sagittal patient images and their corresponding annotation files. The UMD covers 9 types of uterine myomas classified by the International Federation of Obstetrics and Gynecology (FIGO), which were annotated and reviewed by 11 experienced doctors to ensure the authority of the annotated data. The UMD is helpful for uterine myomas classification and uterine 3D reconstruction tasks, which has important implications for clinical research on uterine myomas.

Bladder Cancer in Exosomal Perspective: Unraveling New Regulatory Mechanisms.

Bladder cancer, a prevalent malignant neoplasm of the urinary tract, exhibits escalating morbidity and mortality rates. Current diagnosis standards rely on invasive and costly cystoscopy and histopathology, underscoring the urgency for non-invasive, high-throughput, and cost-effective novel diagnostic techniques to ensure timely detection and standardized treatment. Recent years have witnessed the rise of exosome research in bladder cancer studies. Exosomes contain abundant bioactive molecules that can help elucidate the intricate mechanisms underlying bladder cancer pathogenesis and metastasis. Exosomes hold potential as biomarkers for early bladder cancer diagnosis while also serving as targeted drug delivery vehicles to enhance treatment efficacy and mitigate adverse effects. Furthermore, exosome analyses offer insights into the complex molecular signaling networks implicated in bladder cancer progression, revealing novel therapeutic targets. This review provides a comprehensive overview of prevalent exosome isolation techniques and highlights the promising clinical utility of exosomes in both diagnostic and therapeutic applications in bladder cancer management.

Multi-omics reveals the testosterone promotion effect mechanism of Cordyceps Sobolifera on Leydig cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sobolifera (CS) has been traditionally utilized as an ethnic remedy for various health conditions, including chronic kidney diseases, anti-fatigue interventions, and management of chronic inflammation. Notably, CS is recognized for its substantial content of bioactive compounds, among which nucleosides prominently feature as constituents with diverse therapeutic advantages. AIM OF THE STUDY: This study aims to investigate the effects of CS on testosterone secretion in Leydig cells and explore the underlying mechanism. MATERIALS AND METHODS: Leydig cells were isolated from rat testes to establish a primary rat Leydig cells model. Cell proliferation and testosterone secretion were assessed via the methyl-piperidino-pyrazole (MTT) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Samples earmarked for RNA sequencing (RNA-Seq) analysis facilitated the identification of significantly differentially expressed genes (DEGs), and we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and enrichment analyses. The veracity of our findings was validated through quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. RESULTS: The results showed that CS and guanosine could promote Leydig cell proliferation and bolster testosterone secretion. Our integrative analysis of metabolomics and transcriptomics has unveiled the potential mechanisms governing testosterone synthesis. Specifically, metabolomics has illuminated striking correlations within cholesterol metabolism, and bile secretion. Concurrently, transcriptomics has underscored the pivotal roles played by the cyclic adenosine monophosphate (cAMP) signaling pathway and steroid hormone biosynthesis. Furthermore, our investigation has demonstrated CS's aptitude in elevating the expression of proteins and genes. Notably, our findings have elucidated that these effects can be mitigated by protein kinase A (PKA) and adenylate cyclase (AC) specific inhibitors. CONCLUSION: This study delineates the cAMP-PKA pathways as plausible mechanisms underpinning the testosterone-enhancing properties of CS, with guanosine emerging as a fundamental bioactive constituent.

Revolutionizing hysteroscopy outcomes: AI-powered uterine myoma diagnosis algorithm shortens operation time and reduces blood loss.

Background: The application of artificial intelligence (AI) powered algorithm in clinical decision-making is globally popular among clinicians and medical scientists. In this research endeavor, we harnessed the capabilities of AI to enhance the precision of hysteroscopic myomectomy procedures. Methods: Our multidisciplinary team developed a comprehensive suite of algorithms, rooted in deep learning technology, addressing myomas segmentation tasks. We assembled a cohort comprising 56 patients diagnosed with submucosal myomas, each of whom underwent magnetic resonance imaging (MRI) examinations. Subsequently, half of the participants were randomly designated to undergo AI-augmented procedures. Our AI system exhibited remarkable proficiency in elucidating the precise spatial localization of submucosal myomas. Results: The results of our study showcased a statistically significant reduction in both operative duration (41.32 ± 17.83 minutes vs. 32.11 ± 11.86 minutes, p=0.03) and intraoperative blood loss (10.00 (6.25-15.00) ml vs. 10.00 (5.00-15.00) ml, p=0.04) in procedures assisted by AI. Conclusion: This work stands as a pioneering achievement, marking the inaugural deployment of an AI-powered diagnostic model in the domain of hysteroscopic surgery. Consequently, our findings substantiate the potential of AI-driven interventions within the field of gynecological surgery.

Case report: Two rare new cases of diaphragmatic bronchogenic cysts.

The bronchogenic cyst (BC) is a type of congenital anomaly that is most usually found in the mediastinum and lung, and rarely in the diaphragm. We report two cases of bronchogenic cysts originating from the left diaphragm. Case 1 involved a 50-year-old man who underwent computed tomography (CT) of the adrenal glands for hypertension, showing left adrenal changes. An adrenal CT at our hospital showed a space-occupying lesion above the left diaphragm. We performed a left-sided thoracotomy in the seventh intercostal space and found that the mass was entirely located in the diaphragm. Case 2 was a 58-year-old woman who underwent chest CT under a standard health check-up, and a subpleural lesion of approximately 4 cm was found in the posterior basal segment of the left inferior lung lobe. During thoracoscopic surgery, the mass was found to originate from the surface of the diaphragm, having no correlation with the lung tissue. The two cases of diaphragmatic bronchogenic cysts were confirmed by surgical pathology. Ectopic bronchogenic cysts arising from the diaphragm are very uncommon, and diaphragmatic bronchogenic cysts typically occur on the left side, in women, and in the angle between the vertebral column and the diaphragm. As far as we know, there are no relevant reports of intradiaphragmatic BCs similar to case 1, which was entirely located within the diaphragm. Most diaphragmatic BCs are located on the surface of the diaphragm and project toward the thoracic or abdominal cavities. Moreover, bilocular diaphragmatic bronchogenic cysts, similar to case 2, have not yet been reported.

Identification of ATP6V0A4 as a potential biomarker in renal cell carcinoma using integrated bioinformatics analysis.

Clear cell renal cell carcinoma (ccRCC) is the most common pathological type of renal cancer, and is associated with a high mortality rate, which is related to high rates of tumor recurrence and metastasis. The aim of the present study was to identify reliable molecular biomarkers with high specificity and sensitivity for ccRCC. A total of eight ccRCC-related expression profiles were downloaded from Gene Expression Omnibus for integrated bioinformatics analysis to screen for significantly differentially expressed genes (DEGs). Reverse transcription-quantitative (RT-q)PCR, western blotting and immunohistochemistry staining assays were performed to evaluate the expression levels of candidate biomarkers in ccRCC tissues and cell lines. In total, 255 ccRCC specimens and 165 adjacent normal kidney specimens were analyzed, and 344 significant DEGs, consisting of 115 upregulated DEGs and 229 downregulated DEGs, were identified. The results of Gene Ontology analysis suggested a significant enrichment of DEGs in 'organic anion transport' and 'small molecule catabolic process' in biological processes, in 'apical plasma membrane' and 'apical part of the cell' in cell components, and in 'anion transmembrane transporter activity' and 'active transmembrane transporter activity' in molecular functions. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were significantly enriched in the 'phagosome', the 'PPAR signaling pathway', 'complement and coagulation cascades', the 'HIF-1 signaling pathway' and 'carbon metabolism'. Next, 7 hub genes (SUCNR1, CXCR4, VCAN, CASR, ATP6V0A4, VEGFA and SERPINE1) were identified and validated using The Cancer Genome Atlas database. Survival analysis showed that low expression of ATP6V0A4 was associated with a poor prognosis in patients with ccRCC. Additionally, received operating characteristic curves indicated that ATP6V0A4 could distinguish ccRCC samples from normal kidney samples. Furthermore, RT-qPCR, western blotting and immunohistochemistry staining results showed that ATP6V0A4 was significantly downregulated in ccRCC tissues and cell lines. In conclusion, ATP6V0A4 may be involved in tumor progression and regarded as a potential therapeutic target for the recurrence and metastasis of ccRCC.

WA-ResUNet: A Focused Tail Class MRI Medical Image Segmentation Algorithm.

Medical image segmentation can effectively identify lesions in medicine, but some small and rare lesions cannot be well identified. Existing studies do not take into account the uncertainty of the occurrence of diseased tissue, and the problem of long-tailed distribution of medical data. Meanwhile, the grayscale image obtained from Magnetic Resonance Imaging (MRI) detection has problems, such as the features being difficult to extract and invalid features being difficult to distinguish. In order to solve these problems, we propose a new weighted attention ResUNet (WA-ResUNet) and a class weight formula based on the number of images contained in the class, which improves the performance of the model in the low-frequency class and the overall effect of the model by improving the degree of attention paid to the valid features and invalid ones and rebalancing the learning efficiency among the classes. We evaluated our method on an uterine MRI dataset and compared it with the ResUNet. WA-ResUNet increased Intersection over Union (IoU) in the low-frequency class (Nabothian cysts) by 21.87%, and the overall mIoU increased by more than 6.5%.

A special polysaccharide hydrogel coated on Brasenia schreberi: preventive effects against ulcerative colitis via modulation of gut microbiota.

Ulcerative colitis (UC) is a growing health concern in humans, but it can be prevented by using special dietary strategies. Young stems and leaves of Brasenia schreberi (BS) are coated with a special polysaccharide hydrogel (BS mucilage) which can be beneficial for colon health. The aim of this study was to investigate the preventive effects of BS mucilage against UC in a DSS-treated mouse model. Although containing only 0.3% solid content, our research showed that BS mucilage effectively attenuated the disease activity index (DAI) and the spleen index and downregulated IL-1ß, IL-18, IL-6 and CAT mRNA levels in DSS-treated mice, which is a promising UC alleviation function. Additionally, BS mucilage also improved the propionate and butyrate levels in mouse feces and alleviated the imbalanced gut microbiota induced by DSS. The abundance of pro-inflammatory and colorectal cancer related bacteria, such as Prevotella, Ruminococcus, Acutalibacter and Christensenella, was decreased by BS mucilage feeding, whereas the abundance of anti-inflammatory and SCFA-producing bacteria including Alistipes and Odoribacter was increased. In conclusion, the current study shows that the daily consumption of BS mucilage could be an effective way to prevent UC in mice, via modulation of gut microbiota.

Renal pseudoaneurysm after holmium laser lithotripsy with flexible ureteroscopy: an unusual case report and literature review.

Pseudoaneurysms of the renal arteries are caused by focal rupture or perforation of the arterial wall, resulting in local bleeding. Such pseudoaneurysms can be observed in conditions such as nodular polyarteritis, penetrating or closed renal injury, and medically induced injuries (such as renal puncture biopsy, percutaneous nephrostomy, or partial nephrectomy). Flexible ureteroscopy (FURS) is performed entirely through the urethra to prevent potentially severe kidney damage. Because of this, almost no renal parenchymal hemorrhage occurs after FURS laser lithotripsy. Only four cases had been documented in the literature as of December 2022. In this report, we describe a 53-year-old man with a history of recurrent kidney stones who underwent FURS laser lithotripsy for bilateral kidney stones. The procedure was smoothly performed, and no active bleeding occurred. However, the patient developed recurrent macroscopic hematuria after discharge from the hospital, and renal angiography revealed a pseudoaneurysm in the distal right kidney. The pseudoaneurysm was treated with selective arterial embolization. Serious complications of FURS surgery are rare, particularly the formation of pseudoaneurysms. We report the present case to bring this potential complication to the attention of urologists.

Improving the Segmentation Accuracy of Ovarian-Tumor Ultrasound Images Using Image Inpainting.

Diagnostic results can be radically influenced by the quality of 2D ovarian-tumor ultrasound images. However, clinically processed 2D ovarian-tumor ultrasound images contain many artificially recognized symbols, such as fingers, crosses, dashed lines, and letters which assist artificial intelligence (AI) in image recognition. These symbols are widely distributed within the lesion's boundary, which can also affect the useful feature-extraction-utilizing networks and thus decrease the accuracy of lesion classification and segmentation. Image inpainting techniques are used for noise and object elimination from images. To solve this problem, we observed the MMOTU dataset and built a 2D ovarian-tumor ultrasound image inpainting dataset by finely annotating the various symbols in the images. A novel framework called mask-guided generative adversarial network (MGGAN) is presented in this paper for 2D ovarian-tumor ultrasound images to remove various symbols from the images. The MGGAN performs to a high standard in corrupted regions by using an attention mechanism in the generator to pay more attention to valid information and ignore symbol information, making lesion boundaries more realistic. Moreover, fast Fourier convolutions (FFCs) and residual networks are used to increase the global field of perception; thus, our model can be applied to high-resolution ultrasound images. The greatest benefit of this algorithm is that it achieves pixel-level inpainting of distorted regions without clean images. Compared with other models, our model achieveed better results with only one stage in terms of objective and subjective evaluations. Our model obtained the best results for 256 × 256 and 512 × 512 resolutions. At a resolution of 256 × 256, our model achieved 0.9246 for SSIM, 22.66 for FID, and 0.07806 for LPIPS. At a resolution of 512 × 512, our model achieved 0.9208 for SSIM, 25.52 for FID, and 0.08300 for LPIPS. Our method can considerably improve the accuracy of computerized ovarian tumor diagnosis. The segmentation accuracy was improved from 71.51% to 76.06% for the Unet model and from 61.13% to 66.65% for the PSPnet model in clean images.

ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a major worldwide health problem due to its high prevalence and mortality rate. A disintegrin and metalloproteinase 12 (ADAM12) is aberrantly expressed in various cancers and plays an important role in tumor progression. However, its explicit effect and molecular mechanism in ccRCC remain unclear. METHODS: We investigated the dysregulation of ADAM12 in ccRCC through public databases and bioinformatics analyses. The expression of ADAM12 was further verified in ccRCC tissues by RT-qPCR and immunohistochemistry (IHC). The relationship between ADAM12 expression and clinicopathological characteristics was analyzed statistically. The effects of ADAM12 on the proliferation, migration and invasion of ccRCC cells were examined by in vitro and in vivo experiments. RESULTS: ADAM12 was significantly upregulated in ccRCC tissues and associated with poor prognosis in ccRCC patients. ADAM12 promoted ccRCC cell proliferation, migration and invasion in vitro and the growth of subcutaneous tumors in vivo. Knockdown of ADAM12 successfully suppressed its oncogenic function. Mechanistically, its overexpression induced epithelial-mesenchymal transition (EMT) by downregulating E-cadherin and upregulating N-cadherin and Snail. Moreover, ADAM12 participated in the epidermal growth factor receptor (EGFR) pathway and activated the downstream signal ERK1/2 by shedding the EGFR ligand, thereby upregulating target genes including c-Myc, enhancing cell survival and invasion ability, and promoting tumor progression, metastasis and the induction of EMT. CONCLUSIONS: High expression of ADAM12 induced EMT and promoted cell proliferation, migration, and invasion by activating the EGFR/ERK signaling pathway in ccRCC.

Short-term Outcomes of Laparoscopy-Assisted vs Open Surgery for Patients With Low Rectal Cancer: The LASRE Randomized Clinical Trial.

Importance: The efficacy of laparoscopic vs open surgery for patients with low rectal cancer has not been established. Objective: To compare the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer. Design, Setting, and Participants: This multicenter, noninferiority randomized clinical trial was conducted in 22 tertiary hospitals across China. Patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery. Between November 2013 and June 2018, 1070 patients were randomized to laparoscopic (n = 712) or open (n = 358) surgery. The planned follow-up was 5 years. Data analysis was performed from April 2021 to March 2022. Interventions: Eligible patients were randomized to receive either laparoscopic or open surgery. Main Outcomes and Measures: The short-term outcomes included pathologic outcomes, surgical outcomes, postoperative recovery, and 30-day postoperative complications and mortality. Results: A total of 1039 patients (685 in laparoscopic and 354 in open surgery) were included in the modified intention-to-treat analysis (median [range] age, 57 [20-75] years; 620 men [59.7%]; clinical TNM stage II/III disease in 659 patients). The rate of complete mesorectal excision was 85.3% (521 of 685) in the laparoscopic group vs 85.8% (266 of 354) in the open group (difference, -0.5%; 95% CI, -5.1% to 4.5%; P = .78). The rate of negative circumferential and distal resection margins was 98.2% (673 of 685) vs 99.7% (353 of 354) (difference, -1.5%; 95% CI, -2.8% to 0.0%; P = .09) and 99.4% (681 of 685) vs 100% (354 of 354) (difference, -0.6%; 95% CI, -1.5% to 0.5%; P = .36), respectively. The median number of retrieved lymph nodes was 13.0 vs 12.0 (difference, 1.0; 95% CI, 0.1-1.9; P = .39). The laparoscopic group had a higher rate of sphincter preservation (491 of 685 [71.7%] vs 230 of 354 [65.0%]; difference, 6.7%; 95% CI, 0.8%-12.8%; P = .03) and shorter duration of hospitalization (8.0 vs 9.0 days; difference, -1.0; 95% CI, -1.7 to -0.3; P = .008). There was no significant difference in postoperative complications rate between the 2 groups (89 of 685 [13.0%] vs 61 of 354 [17.2%]; difference, -4.2%; 95% CI, -9.1% to -0.3%; P = .07). No patient died within 30 days. Conclusions and Relevance: In this randomized clinical trial of patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons was shown to provide pathologic outcomes comparable to open surgery, with a higher sphincter preservation rate and favorable postoperative recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT01899547.

Antitumor Effects of Evodiamine in Mice Model Experiments: A Systematic Review and Meta-Analysis.

BACKGROUND: Evodiamine (EVO), an alkaloid extracted from the traditional Chinese medicine Euodia rutaecarpa, plays an important role in the treatment of cancer. This study was performed to clarify the effects of evodiamine in mice tumor model studies. METHODS: Electronic databases and search engines involved China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, and ClinicalTrials.gov databases, which were searched for literature related to the antitumor effects of evodiamine in animal tumor models (all until 1 October 2021). The evodiamine effects on the tumor volume and tumor weight were compared between the treatment and control groups using the standardized mean difference (SMD). RESULTS: Evodiamine significantly inhibited tumor growth in mice, as was assessed with tumor volume [13 studies, n=267; 138 for EVO and 129 for control; standard mean difference (SMD)= -5.99; 95% (CI): -8.89 to -3.10; I2 = 97.69%, p ≤ 0.00], tumor weight [6 studies, n=89; 49 for EVO and 40 for control; standard mean difference (SMD)= -3.51; 95% (CI): -5.13 to -3.90; I2 = 83.02%, p ≤ 0.00]. CONCLUSION: EVO significantly suppresses tumor growth in mice models, which would be beneficial for clinical transformation. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether EVO can be used in the adjuvant treatment of clinical tumor patients.

Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2.

Hypoxanthine (Hx), an intermediate metabolite of the purine metabolism pathway which is dramatically increased in blood and skeletal muscle during muscle contraction and metabolism, is characterized as a marker of exercise exhaustion. However, the physiological effects of Hx on skeletal muscle remain unknown. Herein, we demonstrate that chronic treatment with Hx through dietary supplementation resulted in skeletal muscle fatigue and impaired the exercise performance of mice without affecting their growth and skeletal muscle development. Hx increased the uncoupling protein 2 (UCP2) expression in the skeletal muscle, which led to decreased energy substrate storage and enhanced glycolysis. These effects could also be verified in acute treatment with Hx through intraperitoneal injection. In addition, muscular specifically knockout of UCP2 through intra-muscle tissue injection of adenovirus-associated virus reversed the effects of Hx. In conclusion, we identified a novel role of Hx in the skeletal muscular fatigue mediated by UCP2-dependent mitochondrial uncoupling. This finding may shed light on the pathological mechanism of clinical muscle dysfunctions due to abnormal metabolism, such as muscle fatigue and weakness.

Emulsified blend film based on konjac glucomannan/carrageenan/ camellia oil: Physical, structural, and water barrier properties.

The objective of this study was to develop a new hydrophobic film based on konjac glucomannan and kappa-carrageenan (KGM-KC) incorporating camellia oil (CO) (2, 4, and 6 %). CO was directly emulsified as a dispersed phase into KGM-KC matrix. The physical, structural, and water barrier properties of the film were studied. The results of Fourier transform infrared and scanning electron microscopy suggested that CO was successfully distributed in KGM-KC matrix by emulsification. Contact angle of the film indicated that addition of CO increased the hydrophobicity and water-resistance properties of film, which corresponding to the moisture content, total soluble mass, water vapor permeability, water vapor adsorption kinetics and water vapor adsorption isotherms. Addition of CO by emulsification improved thermal stability of film, optical properties, and mechanical properties. In conclusion, the incorporation of CO by emulsification is an effective and promising pathway to improve the properties of polysaccharide-based film.

Mice with miR-146a deficiency develop severe gouty arthritis via dysregulation of TRAF 6, IRAK 1 and NALP3 inflammasome.

BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of inflammatory and immune responses and are implicated in several immune disorders including gouty arthritis. The expression of miR-146a is upregulated in the peripheral blood mononuclear cells of patients with inter-critical gout when compared to normouricemic and hyperuricemic controls and those patients with acute gout flares. However, the role of miR-146a in the development of gout remains unknown. Here, we used miR-146a knockout (KO) mice to test miR-146a function in a monosodium urate (MSU)-induced gouty arthritis model. METHODS: The footpad or ankle joint of miR-146a KO and wild-type (WT) mice were injected with an MSU suspension to induce acute gouty arthritis. Bone marrow-derived macrophages (BMDMs) were stimulated with MSU and the gene expression of miR-146a; interleukin 1 beta (IL-1ß); tumor necrosis factor-α (TNF-α); and the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome was evaluated. TNF-α and IL-1ß protein levels in BMDMs were assessed by fluorescence-activated cell sorting and western blot analyses. Gene and protein levels of TNF receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase (IRAK1), the targets of miR-146a, were also measured. RESULTS: Significantly increased paw swelling and index and ankle joint swelling were observed in miR-146a KO mice compared to WT controls after MSU treatment. MiR-146a expression in BMDMs from WT mice was dramatically upregulated at 4 h following MSU stimulation. Additionally, the expression of IL-1ß, TNF-α, and NALP3 was higher in BMDMs from miR-146a KO mice after exposure to MSU crystals compared to those from WT mice. Consistent with the observed gene expression, the IL-1ß and TNF-α proteins were upregulated in miR-146a KO mice. Additionally quantitative RT-PCR and western blot demonstrated that TRAF6 and IRAK1 were dramatically upregulated in BMDMs from miR-146 KO mice compared to those from WT mice. CONCLUSIONS: Collectively, these observations suggest that miR-146a provides negative feedback regulation of gouty arthritis development and lack of miR-146a enhances gouty arthritis via upregulation of TRAK6, IRAK-1, and the NALP3 inflammasome function.

MiR-20a and miR-106b negatively regulate autophagy induced by leucine deprivation via suppression of ULK1 expression in C2C12 myoblasts.

Autophagy is an evolutionarily conserved process responsible for degradation and recycling of cytoplasmic components through the lysosomal machinery. It has been proved to play pivotal roles in cellular homeostasis, cell growth and organism development. Moreover, abnormalities of autophagy have been linked to numerous human pathophysiologies. Emerging evidence has linked leucine deprivation induced protein breakdown to autophagy, but the underlying mechanisms controlling autophagic activity in this process are not fully understood. Here, we demonstrate that two members of the miR-17 microRNA family, miR-20a and miR-106b, may participate in regulating leucine deprivation induced autophagy via suppression of ULK1 expression in C2C12 myoblasts. We showed that leucine deprivation downregulated miR-20a and miR-106b expression via suppression of their transcription factor c-Myc. We discovered the essential autophagy gene ULK1 as cellular target of miR-20a and miR-106b. Treatment of C2C12 cells with the miR-20a or miR-106b mimic decreased the endogenous ULK1 protein levels. Dual luciferase reporter assay confirmed that the miRNA binding sequences in the 3' UTR of ULK1 contribute to the modulation of ULK1 expression by miR-20a and miR-106b. Furthermore, inhibition of ULK1 expression by the miR-20a or miR-106b mimic blunted activation of autophagy induced by leucine deprivation, while suppression of endogenous miR-20a or miR-106b by specific antagomir in C2C12 cells showed normal autophagic activity. Altogether, our data demonstrated that miR-20a and miR-106b regulated autophagy induced by leucine deprivation in C2C12 cells via targeting ULK1.

Automatic segmentation on cell image fusing gray and gradient information.

To develop an automatic classifying and diagnostic system for the hematopoietic cells from the blood and bone marrow smears stained with Wright-Giemsa, an automated segmentation algorithm fusing gray level, colorful information and mathematical morphological gradient is proposed for segmentation of the nucleated hematopoietic cells (including nucleus and cytoplasm). For the accurate segmentation of the nucleus, the conventional iterative threshold segmentation has been improved. Color information and prior knowledge are fully used by transaction of color spaces for the purpose of cytoplasm segmentation. In order to prevent over-segmentation, the morphological gradient information is used to mark the background, nucleus and cytoplasm. The edge detection is implemented in gray gradient image since the morphological gradient can detect the contour better than other conventional edge detection operators. The success rate is 95.5 % for nucleus and 92.6 % for cytoplasm. The results show that the method is valid and efficient to segment color images from blood and bone marrow smears.