Identification and validation of sialyltransferase ST3Gal5 in bladder cancer through bioinformatics and experimental analysis.

BACKGROUND: Bladder cancer (BLCA) is one of the top ten most common cancers in the world. Aberrant sialylation is a common feature in tumorigenesis and tumor immunity. This study seeks to explore the potential impact of sialyltransferase ST3Gal5 on BLCA. METHODS: Initially, glycosyltransferase-related DEGs (GRDEGs) were identified using multiple bioinformatics approaches in TCGA-BLCA cohort and validated using GEO databases. Clinical prognosis integration facilitated the determination of ST3Gal5 as an independent prognostic factor in BLCA, employing univariate and multivariate Cox regression analyses. Immune cell infiltration was assessed via CIBERSORT and ssGSEA analyses, while HLA and immune checkpoint genes' levels, along with drug sensitivity, were evaluated in low- and high-ST3Gal5 groups. The TIDE and IPS scores were used to gauge the immune checkpoint blockade (ICB) response. Furthermore, functional experiments, both in vivo and in vitro, were conducted to elucidate the biological roles of ST3Gal5. RESULTS: In agreement with bioinformatics findings, ST3Gal5 expression was down-regulated in BLCA tissues and cells, correlating with poorer prognostic outcomes. The StromalScore, ImmuneScore, and ESTIMATEScore were significantly elevated in low-ST3Gal5 group. Moreover, the levels of HLA and immune checkpoint genes were upregulated in low-ST3Gal5 group. Down-regulated ST3Gal5 promoted the proliferation, migration, and invasion of BLCA cells in vivo and in vitro. CONCLUSION: Our findings demonstrated that low ST3Gal5 level promoted tumorigenesis and progression of BLCA, implying its potential as a predictive biomarker and therapeutic target.

SUMOylation regulation of ribosome biogenesis: Emerging roles for USP36.

Ribosome biogenesis is essential for cell growth, proliferation, and animal development. Its deregulation leads to various human disorders such as ribosomopathies and cancer. Thus, tight regulation of ribosome biogenesis is crucial for normal cell homeostasis. Emerging evidence suggests that posttranslational modifications such as ubiquitination and SUMOylation play a crucial role in regulating ribosome biogenesis. Our recent studies reveal that USP36, a nucleolar deubiquitinating enzyme (DUB), acts also as a SUMO ligase to regulate nucleolar protein group SUMOylation, thereby being essential for ribosome biogenesis. Here, we provide an overview of the current understanding of the SUMOylation regulation of ribosome biogenesis and discuss the role of USP36 in nucleolar SUMOylation.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/ß-catenin signaling pathways in clear cell renal cell carcinoma.

BACKGROUND: CD56 has been observed in malignant tumours exhibiting neuronal or neuroendocrine differentiation, such as breast cancer, small-cell lung cancer, and neuroblastoma. Abnormal glycosylation modifications are thought to play a role in regulating tumour cell proliferation, migration, and invasion. Nevertheless, the exact roles and molecular mechanisms of CD56 and polysialylated CD56 (PSA-CD56) in the development and progression of clear cell renal cell carcinoma (ccRCC) remain elusive. Here we unveil the biological significance of CD56 and PSA-CD56 in ccRCC. METHODS: In this study, we employed various techniques, including immunohistochemistry (IHC), RT-qPCR, and western blot, to examine the mRNA and protein expression levels in both human ccRCC tissue and cell lines. Lentivirus infection and CRISPR/Cas9 system were utilized to generate overexpression and knockout cell lines of CD56. Additionally, we conducted several functional assays, such as CCK-8, colony formation, cell scratch, and transwell assays to evaluate cell growth, proliferation, migration, and invasion. Furthermore, we established a xenograft tumor model to investigate the role of CD56 in ccRCC in vivo. To gain further insights into the molecular mechanisms associated with CD56, we employed the Hedgehog inhibitor JK184 and the ß-catenin inhibitor Prodigiosin. RESULTS: CD56 was significantly overexpressed in both human ccRCC tissues and renal cancer cell lines compared to adjacent normal tissues and normal renal epithelial cells. In vitro and in vivo experiments revealed that the knockout of CD56 inhibited the proliferation, migration, and invasion capabilities of ccRCC cells, whereas the overexpression of PSA-CD56 promoted these capacities. Finally, PSA-CD56 overexpression was found to activate both the Hedgehog and Wnt/ß-catenin signaling pathways. CONCLUSION: Our findings demonstrate that the oncogenic function of CD56 polysialylation plays a vital role in the tumorigenesis and progression of ccRCC, implying that targeting PSA-CD56 might be a feasible treatment target for ccRCC.

Impacts of reclamation marsh restoration on greenhouse gas emission in the Sanjiang Plain, China.

To understand the variations in greenhouse gas fluxes during the process of returning cropland to wetland in the Sanjiang Plain, we selected naturally restored wetlands of 4, 7, 11, 16 and 20 years as research objects to compare with a cultivated site (soybean plantation for 13 years) and an uncultivated marsh dominated by Deyeuxia purpurea and Carex schmidtii. We measured carbon dioxide (CO2) and methane (CH4) fluxes using a static chamber-gas chromatography and explored the main influencing factors. The results showed that there were seasonal variations in growing-season CO2 and CH4 fluxes of the restored wetlands, with the seasonal trends in greenhouse gases becoming gradually similar to that of natural marsh with increasing restoration time. The mean growing-season CO2 fluxes increased during the early stage of restoration, but then decreased during the late stage, which decreased from 893.4 mg·m-2·h-1 to 494.0 mg·m-2·h-1 in the 4-year and 20-year sites, respectively. Mean CH4 fluxes increased with restoration time, ranging from a weak CH4 sink (soybean fields, -0.6 mg·m-2·h-1) to a CH4 source of 87.8 mg·m-2·h-1(20-year restored site). The CH4 fluxes of experimental plots were consistently lower than that of natural marsh (96.4 mg·m-2·h-1). Increases in water level and soil conductivity resulting from restoration were the main driving factors for the decrease in CO2 fluxes. The increases in water level and soil dissolved organic carbon resulting from restoration were the primary drivers for the increase of CH4 fluxes in the restored wetlands. The global warming potentials increased with restoration time, ranging from 27.8 t·CO2-eq·hm-2(soybean fields) to 130.8 t·CO2-eq·hm-2(plot of 20-year restoration), which gradually approached that of natural marsh (156.3 t·CO2-eq·hm-2). The emission of GHGs from restored wetlands in the Sanjiang Plain gradually approached those of natural marsh. Further monitoring is required to identify the maturity of restored wetlands for achieving greenhouse gas emissions equivalent to that of natural marshland.

Multiple cardiac myxofibrosarcomas with complete right pulmonary artery occlusion: a case report.

Primary cardiac myxofibrosarcoma is a rare form of cardiac malignant tumors. MFS usually involves the left atrium and presents as a unicentric or multicentric tumor mass. We reported on a 37-year-old female who presented with chest tightness and dyspnea for a month, dry cough, and occasionally having blood streak sputum for half a month. Echocardiography, cardiac computed tomography and cardiac positron emission tomography revealed multiple tumors in the heart. The right ventricle and right pulmonary artery were involved, with occlusion of the right pulmonary artery. Cardiac tumors were surgically resected and were consistent with low-grade MFS. No recurrence or metastasis occurred at 20 months of follow-up.

Artificial cells delivering itaconic acid induce anti-inflammatory memory-like macrophages to reverse acute liver failure and prevent reinjury.

Hepatic macrophages represent a key cellular component of the liver and are essential for the progression of acute liver failure (ALF). We construct artificial apoptotic cells loaded with itaconic acid (AI-Cells), wherein the compositions of the synthetic plasma membrane and surface topology are rationally engineered. AI-Cells are predominantly localized to the liver and further transport to hepatic macrophages. Intravenous administration of AI-Cells modulates macrophage inflammation to protect the liver from acetaminophen-induced ALF. Mechanistically, AI-Cells act on caspase-1 to suppress NLRP3 inflammasome-mediated cleavage of pro-IL-1ß into its active form in macrophages. Notably, AI-Cells specifically induce anti-inflammatory memory-like hepatic macrophages in ALF mice, which prevent constitutive overproduction of IL-1ß when liver reinjury occurs. In light of AI-Cells' precise delivery and training of memory-like hepatic macrophages, they offer promising therapeutic potential in reversing ALF by finely controlling inflammatory responses and orchestrating liver homeostasis, which potentially affect the treatment of various types of liver failure.

Utility of Contrast Echocardiography in the Diagnosis of a Primary Nonfunctioning Cardiac Paraganglioma with a Coronary Aneurysm.

Cardiac paragangliomas (PGLs) are rare neuroendocrine tumors, and data regarding the features of nonfunctioning PGLs are limited. These tumors are extensively vascularized and have high risk of hemorrhage for surgery and even biopsy. Differential diagnosis including biochemical analysis of these PGLs is important for further management. In this case report, we present the clinical, laboratory, imaging, and radionuclide presentations of a rare primary nonfunctioning cardiac PGL with a coronary aneurysm. Echocardiography initially showed a large echogenic mass in the left atrioventricular groove. The mass presented a diffuse hyperenhancement pattern with a central perfusion defect on contrast echocardiography. The tumor enclosed the left coronary artery from the coronary orifice, and an aneurysm was found in the left circumflex artery, with significantly increased flow velocity. These echocardiographic features and its susceptible location are indicative of the presence of a cardiac PGL. Although all biochemical evaluations of catecholamines from blood and urine samples were negative, positron emission tomography and scintigraphy finally confirmed the diagnosis of a primary cardiac PGL. Therefore, when imaging features are indicative of the presence of PGLs, the implementation of radionuclide imaging for final diagnosis is required even if the biochemical results are negative. Recognizing these uncommon Doppler and contrast echocardiographic characteristics is important for early diagnosing these nonfunctioning PGLs.

The Ubiquitin-specific Protease USP36 Associates with the Microprocessor Complex and Regulates miRNA Biogenesis by SUMOylating DGCR8.

miRNA biogenesis is a cellular process that produces mature miRNAs from their primary transcripts, pri-miRNAs, via two RNAse III enzyme complexes: the Drosha-DGCR8 microprocessor complex in the nucleus and the Dicer-TRBP complex in the cytoplasm. Emerging evidence suggests that miRNA biogenesis is tightly regulated by posttranscriptional and posttranslational modifications and aberrant miRNA biogenesis is associated with various human diseases including cancer. DGCR8 has been shown to be modified by SUMOylation. Yet, the SUMO ligase mediating DGCR8 SUMOylation is currently unknown. Here, we report that USP36, a nucleolar ubiquitin-specific protease essential for ribosome biogenesis, is a novel regulator of DGCR8. USP36 interacts with the microprocessor complex and promotes DGCR8 SUMOylation, specifically modified by SUMO2. USP36-mediated SUMOylation does not affect the levels of DGCR8 and the formation of the Drosha-DGCR8 complex, but promotes the binding of DGCR8 to pri-miRNAs. Consistently, abolishing DGCR8 SUMOylation significantly attenuates its binding to pri-miRNAs and knockdown of USP36 attenuates pri-miRNA processing, resulting in marked reduction of tested mature miRNAs. Induced expression of a SUMOylation-defective mutant of DGCR8 inhibits cell proliferation. Together, these results suggest that USP36 plays an important role in regulating miRNA biogenesis by SUMOylating DGCR8. Significance: This study identifies that USP36 mediates DGCR8 SUMOylation by SUMO2 and is critical for miRNA biogenesis. As USP36 is frequently overexpressed in various human cancers, our study suggests that deregulated USP36-miRNA biogenesis pathway may contribute to tumorigenesis.

An Integrative Multi-Omics Analysis Based on Nomogram for Predicting Prostate Cancer Bone Metastasis Incidence.

Background: The most common site of prostate cancer metastasis is bone tissue with many recent studies having conducted genomic and clinical research regarding bone metastatic prostate cancer. However, further work is needed to better define those patients that are at an elevated risk of such metastasis. Methods: SEER and TCGA databases were searched to develop a nomogram for predicting prostate cancer bone metastasis. Results: Herein, we leveraged the Surveillance, Epidemiology, and End Results (SEER) database to construct a predictive nomogram capable of readily and accurately predicted the odds of bone metastasis in prostate cancer patients. This nomogram was utilized to assign patients with prostate cancer included in The Cancer Genome Atlas (TCGA) to cohorts at a high or low risk of bone metastasis (HRBM and LRBM, respectively). Comparisons of these LRBM and HRBM cohorts revealed marked differences in mutational landscapes between these patient cohorts, with increased frequencies of gene fusions, somatic copy number variations (CNVs), and single nucleotide variations (SNVs), particularly in the P53 gene, being evident in the HRBM cohort. We additionally identified lncRNAs, miRNAs, and mRNAs that were differentially expressed between these two patient cohorts and used them to construct a competing endogenous RNA (ceRNA) network. Moreover, three weighted gene co-expression network analysis (WGCNA) modules were constructed from the results of these analyses, with KIF14, MYH7, and COL10A1 being identified as hub genes within these modules. We further found immune response activity levels in the HRBM cohort to be elevated relative to that in the LRBM cohort, with single sample gene enrichment analysis (ssGSEA) scores for the immune checkpoint signature being increased in HRBM patient samples relative to those from LRBM patients. Conclusion: We successfully developed a nomogram capable of readily detecting patients with prostate cancer at an elevated risk of bone metastasis.

Clinical features, etiology, and prognosis of hand knob stroke: a case series.

BACKGROUND: Hand knob stroke is a rare clinical disorder frequently misdiagnosed as peripheral neuropathy. The purpose of this study is to recognize this particular type of stroke by analyzing clinical features, etiology, and prognosis. METHODS: We enrolled 19 patients with acute hand knob stroke in the Department of Neurology of the Beijing Geriatric Hospital from January 2018 to January 2022, and the clinical and imaging data of the patients during hospitalization and follow-up were collected and summarized. RESULTS: Acute hand knob stroke accounted for 0.9% of all acute stroke, and ischemic stroke (17 cases, 89.5%) was more than hemorrhagic stroke (2 cases, 10.5%). All patients presented sudden contralateral hand paresis, 12 (63.2%) of them had only isolated hand paralysis, and the location of the lesion corresponded to different finger weakness. The cause of hand knob hemorrhage was hypertension, while the causes of hand knob infarction were mainly small-vessel occlusion (SVO) (35.3%) and large-artery atherosclerosis (LAA) (35.3%), and the rare causes include carotid artery dissection and carotid body tumor. After a median follow-up 13.5 months, the prognosis of 94.7% patients was good, and one patient (5.3%) had recurrent stroke. CONCLUSIONS: Hand knob stroke is a rare stroke with a good prognosis and a low stroke recurrence rate. Ischemic stroke is the predominant type and the main clinical manifestation is hand paresis. The cause of hand knob hemorrhage is hypertensive, while SVO and LAA are the main causes of hand knob infarction, but there are some rare etiologies.

Finite element study of a partial meniscectomy of a complete discoid lateral meniscus in adults.

BACKGROUND: Incidence of osteoarthritis and genu valgus is higher after partial meniscectomy of the discoid lateral meniscus. We aimed to provide a biomechanical reference for slowing the development of osteoarthritis and genu valgus after complete discoid lateral meniscus (CDLM) surgery. METHODS: Computed tomography and magnetic resonance images of the knee were used to establish a finite element model of the knee. The discoid lateral meniscus model was cut at 2-mm intervals to obtain 10 lateral meniscus models of different widths (2-20 mm). The instantaneous stress peak and knee valgus angle were obtained by finite element analysis under the same coaxial load. FINDINGS: When the residual width of the lateral meniscus was greater than 12 mm, the peak stress of the knee joint and angle of genu valgus did not significantly change from preoperative levels. The contact stress peak increased slightly as the width decreased from 12 to 8 mm. When the width was reduced from 8 to 0 mm, the contact stress peak increased significantly. INTERPRETATION: For partial meniscectomy in CDLM patients, meniscus width of 8-10 mm provides a better biomechanical environment. This may reduce risk of early knee degeneration and valgus from excessive meniscectomy in conventional surgery.

Glycosylation in Renal Cell Carcinoma: Mechanisms and Clinical Implications.

Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors of the urinary system, accounting for around 2% of all cancer diagnoses and deaths worldwide. Clear cell RCC (ccRCC) is the most prevalent and aggressive histology with an unfavorable prognosis and inadequate treatment. Patients' progression-free survival is considerably improved by surgery; however, 30% of patients develop metastases following surgery. Identifying novel targets and molecular markers for RCC prognostic detection is crucial for more accurate clinical diagnosis and therapy. Glycosylation is a critical post-translational modification (PMT) for cancer cell growth, migration, and invasion, involving the transfer of glycosyl moieties to specific amino acid residues in proteins to form glycosidic bonds through the activity of glycosyltransferases. Most cancers, including RCC, undergo glycosylation changes such as branching, sialylation, and fucosylation. In this review, we discuss the latest findings on the significance of aberrant glycans in the initiation, development, and progression of RCC. The potential biomarkers of altered glycans for the diagnosis and their implications in RCC have been further highlighted.

Sex-specific reference limits of left ventricular ejection fraction and volumes estimated by gated myocardial perfusion imaging for low-risk patients in China: a comparison between three quantitative algorithms.

BACKGROUND: Establishing appropriate reference value limits of left ventricular (LV) functional parameters is fundamental for the assessment of cardiac function. At present, there are no reports aimed at establishing reference limits using gated myocardial perfusion imaging (MPI) in mainland China. METHODS: A total of 175 consecutive patients who were defined as low-risk coronary artery disease patients underwent stress Technetium-99m sestamibi (99mTc-MIBI)-gated myocardial perfusion single-photon emission computed tomography (SPECT) imaging. The LV ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV) were obtained by 3 quantitative algorithms: quantitative-gated SPECT, emory cardiac toolbox, and 4-dimensional model SPECT, respectively. The threshold values were obtained using Gaussian distribution or percentiles. The influence of gender, age, and weight on cardiac functional parameters was analyzed by multiple regressions for linear models. RESULTS: For males, the lower reference limits of EF were 52%, 63%, and 58%, respectively; and the upper limits of EDV/ESV were 106/45, 152/55, and 135/55 mL, respectively. For females, the lower reference limits of EF were 58%, 66%, and 65%, respectively; and the upper limits of EDV/ESV were 73/27, 105/31, and 88/29 mL, respectively. Compared to females, males had greater cardiac volume values and lower mean EF values. Bland-Altman plots revealed that the cardiac function parameters calculated by the three quantitative algorithms were in high agreement. CONCLUSIONS: In this study, the reference limits of cardiac parameters calculated by the 3 methods based on single-center data in China were preliminarily established. The threshold values determined by three quantitative algorithms were not interchangeable but were highly correlated.

Characterization of Volatile Compounds of Rosa roxburghii Tratt by Gas Chromatography-Olfactometry, Quantitative Measurements, Odor Activity Value, and Aroma Intensity.

Rosa roxburghii tratt (RRT), widely distributed in the southwest of China, is favored by consumers for its good taste and healthy functions. In this study, thirty-seven compounds of Rosa roxburghii Tratt (RRT) were identified and quantified by gas chromatography-olfactometry (G-O) and gas chromatography-mass spectrometry (GC-MS) analysis. Furthermore, ethyl 2-methylpropanoate, ethyl butanoate, ethyl 2-methylbutyrate, and ethyl hexanoate were present with much higher odor activity values (OAVs) than other compounds. The key notes were confirmed by omission tests. Possible interaction among key notes was investigated through odor intensity determination and sensory analysis. It showed fruity and woody notes had synergistic effects. Full factorial design was used to evaluate the notes contribution to the whole odor. One important finding is the major effect of order interactions, fruity note (X1) and woody note (X4) especially, emphasizing the existence of complex interactions occurring between odor notes. The interaction X1X4 was further investigated. The woody note has a positive effect when the fruity note is also in the mixture but tends to show a negative effect otherwise.

Multiparametric Cardiovascular Magnetic Resonance in Acute Myocarditis: Comparison of 2009 and 2018 Lake Louise Criteria With Endomyocardial Biopsy Confirmation.

Background: Cardiac magnetic resonance (CMR) has been shown to improve the diagnosis of myocarditis, but no systematic comparison of this technique is currently available. The purpose of this study was to compare the 2009 and 2018 Lake Louise Criteria (LLC) for the diagnosis of acute myocarditis using 3.0 T MRI with endomyocardial biopsy (EMB) as a reference and to provide the cutoff values for multiparametric CMR techniques. Methods: A total of 73 patients (32 ± 14 years, 71.2% men) with clinically suspected myocarditis undergoing EMB and CMR with 3.0 T were enrolled in the study. Patients were divided into two groups according to EMB results (EMB-positive and -negative groups). The CMR protocol consisted of cine-SSFP, T2 STIR, T2 mapping, early and late gadolinium enhancement (EGE, LGE), and pre- and post-contrast T1 mapping. Their potential diagnostic ability was assessed with receiver operating characteristic curves. Results: The myocardial T1 and T2 relaxation times were significantly higher in the EMB-positive group than in the EMB-negative group. Optimal cutoff values were 1,228 ms for T1 relaxation times and 58.5 ms for T2 relaxation times with sensitivities of 86.0 and 83.7% and specificities of 93.3 and 93.3%, respectively. The 2018 LLC had a better diagnostic performance than the 2009 LLC in terms of sensitivity, specificity, positive predictive value, and negative predictive value. T1 mapping + T2 mapping had the largest area under the curve (0.95) compared to other single or combined parameters (2018 LLC: 0.91; 2009 LLC: 0.76; T2 ratio: 0.71; EGEr: 0.67; LGE: 0.73; ). The diagnostic accuracy for the 2018 LLC was the highest (91.8%), followed by T1 mapping (89.0%) and T2 mapping (87.7%). Conclusion: Emerging technologies such as T1/ T2 mapping have significantly improved the diagnostic performance of CMR for the diagnosis of acute myocarditis. The 2018 LLC provided the overall best diagnostic performance in acute myocarditis compared to other single standard CMR parameters or combined parameters. There was no significant gain when 2018LLC is combined with the EGE sequence.

ST8SIA1 inhibits the proliferation, migration and invasion of bladder cancer cells by blocking the JAK/STAT signaling pathway.

Bladder cancer (BLCA) is the most common malignant tumor of the urinary system, with distant metastasis of the tumor being the main cause of death. The identification of an effective biomarker may provide a novel direction for BLCA diagnosis and treatment. The aim of the present study was to screen the BLCA-related genes involved in sialyl transferase (ST) dysregulation and to investigate the functional mechanisms of α-2,8-ST1 (ST8SIA1) in BLCA cells. Data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases suggested that the mRNA expression levels of ST8SIA1 were decreased in BLCA tissues compared with normal tissues, which was also demonstrated using immunohistochemistry and western blot analysis. The expression levels of ST8SIA1 were negatively associated with the pathological grade and invasiveness of BLCA. Western blot analysis revealed that the expression levels of ST8SIA1 were lower in BLCA cell lines than in a normal urothelial cell line. CCK-8, flow cytometry, wound healing, colony formation and Transwell assays indicated that ST8SIA1 overexpression attenuated the proliferation, migration and invasion of T24 and 5637 BLCA cells. Further experiments revealed that ST8SIA1 could inhibit the phosphorylation of Janus kinase (JAK)2 and STAT3, as well as decrease the expression levels of JAK/STAT pathway-targeting signal molecules, including MMP2, proliferating cell nuclear antigen, cyclin D1 and Bcl2 in two BLCA cell lines. In conclusion, to the best of our knowledge, the present study was the first to indicate that the antitumor effect of ST8SIA1 in BLCA cells was mediated by the JAK/STAT signaling pathway, and the results provided a novel target for the diagnosis and treatment of BLCA.

Conditioned Medium from Mesenchymal Stem Cells Alleviates Endothelial Dysfunction of Vascular Grafts Submitted to Ischemia/Reperfusion Injury in 15-Month-Old Rats.

In patients undergoing coronary artery bypass grafting (CABG), ischemia/reperfusion injury (IRI) is the main contributor to organ dysfunction. Aging-induced vascular damage may be further aggravated during CABG. Favorable effects of conditioned medium (CM) from mesenchymal stem cells (MSCs) have been suggested against IRI. We hypothesized that adding CM to saline protects vascular grafts from IRI in rats. We found that CM contains 28 factors involved in apoptosis, inflammation, and oxidative stress. Thoracic aortic rings from 15-month-old rats were explanted and immediately mounted in organ bath chambers (aged group) or underwent 24 h of cold ischemic preservation in saline-supplemented either with vehicle (aged-IR group) or CM (aged-IR+CM group), prior to mounting. Three-month-old rats were used as referent young animals. Aging was associated with an increase in intima-to-media thickness, an increase in collagen content, higher caspase-12 mRNA levels, and immunoreactivity compared to young rats. Impaired endothelium-dependent vasorelaxation to acetylcholine in the aged-IR group compared to the aged-aorta was improved by CM (aged 61 ± 2% vs. aged-IR 38 ± 2% vs. aged-IR+CM 50 ± 3%, p < 0.05). In the aged-IR group, the already high mRNA levels of caspase-12 were decreased by CM. CM alleviates endothelial dysfunction following IRI in 15-month-old rats. The protective effect may be related to the inhibition of caspase-12 expression.

Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy.

Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated via diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation. In addition, MYC is also regulated by SUMOylation which crosstalks with the ubiquitination pathway and controls MYC protein stability and activity. In this mini-review, we will summarize current updates regarding MYC ubiquitination and provide perspectives about these MYC regulators as potential therapeutic targets in cancer.

The Regulating Effect of Autophagy-Related MiRNAs in Kidney, Bladder, and Prostate Cancer.

Autophagy is a treatment target for many disorders, including cancer, and its specific role is becoming increasingly well known. In tumors, researchers pay attention to microribonucleic acids (miRNAs) with regulatory effects to develop more effective therapeutic drugs for autophagy and find new therapeutic targets. Various studies have shown that autophagy-related miRNAs play an irreplaceable role in different tumors, such as miR-495, miR-30, and miR-101. These miRNAs are associated with autophagy resistance in gastric cancer, non-small cell lung cancer, and cervical cancer. In recent years, autophagy-related miRNAs have also been reported to play a role in autophagy in urinary system tumors. This article reviews the regulatory effects of autophagy-related miRNAs in kidney, bladder, and prostate cancer and provides new ideas for targeted therapy of the three major tumors of the urinary system.