Abbreviation Non-small-cell lung carcinoma (NSCLC) Tumor-initiating cells (TICs) circular RNAs (circRNAs) lung adenocarcinoma (LUAD) lung squamous cell carcinoma (LUSC) Quantitative real-time PCR (qRT-PCR) Cell Counting Kit-8 (CCK-8) Chromatin immunoprecipitation (ChIP) RNA Immunoprecipitation (RIP) Immunohistochemistry (IHC) genomic DNA (gDNA) Running heading: Circ-SOX4 regulates c-MYC. AbstractNon-small-cell lung carcinoma (NSCLC) accounts for the majority of lung cancer deaths, and thus there is a clinical need to understand the molecular mechanisms underlying this malignancy. Tumor-initiating cells (TICs) have been accepted to be closely related to tumor reoccurrence after surgery, and circular RNAs (circRNAs) play a crucial function in the tumorigenesis and development of human cancers.Here, we examined the role of the circular RNA hsa_circ_0131457 (circ-SOX4) in lung TICs. We report that circ-SOX4 is upregulated and exists as a covalently closed loop structure in CD133 + cancer cells. Subsequent functional assays showed that circ-SOX4 downregulation suppresses lung TIC proliferation, self-renewal, migration and invasion. Circ-SOX4 upregulation facilitates in vitro development of CD133cancer cells, and circ-SOX4 deficiency represses in vivo malignancy of CD133 + cells. Additionally, circ-SOX4 was shown to interact with c-MYC by activating the Wnt/β-catenin pathway in NSCLC. In summary, circ-SOX4 expedites NSCLC progression by activating the Wnt/β-catenin pathway, and this finding may facilitate the identification of effective therapeutic targets for NSCLC.
Adefovir dipivoxil (ADV) is one of the most important nucleostide analogues currently in use for the treatment of chronic hepatitis B virus (HBV) infection. Low-dose ADV-induced nephrotoxicity in most cases was reported to be reversible after the discontinuation of ADV or by decreasing the dose of ADV. In our study, we have 5 documented cases of low-dose ADV-induced hypophosphatemia osteomalacia with or without Fanconi syndrome which were diagnosed in our hospital between 2010 and 2017. Three patients were observed to have a full recovery after the discontinuation of ADV. Two patients had persistently elevated urine β 2 -microglobulin levels and out of these two patients, one patient had persistent hypophosphatemia after the cessation of ADV. These cases illustrated that the use of low-dose ADV increased the risk of nephrotoxicity, and in some patients, low-dose ADV-induced nephrotoxicity was not completely reversible. Patients of East Asian origin, especially those with a low body mass index, were prone to a relatively higher risk of developing low-dose ADV-induced nephrotoxicity; therefore, it was worth paying attention to the side effects caused by low-dose ADV.
Extracellular vesicle (EV) cargos with regular fluctuations hold the potential for providing chemical predictors toward clinical diagnosis and prognosis. A plasma sample is one of the most important sources of circulating EVs, yet the technical barrier and cost consumption in plasma-EV isolation still limit its application in disease diagnosis and biomarker discovery. Here, we introduced an easy-to-use strategy that allows selectively purifying small EVs (sEVs) from human plasma and detecting their metabolic alternations. Fe 3 O 4 @TiO 2 microbeads with a rough island-shaped surface have proven the capability of performing efficient and reversible sEV capture owing to the phospholipid affinity, enhanced binding sites, and size-exclusion-like effect of the rough TiO 2 shell. The proposed system can also shorten the separation procedure from hours to 20 min when compared with the ultracentrifugation method and yield approximately 10 8 sEV particles from 100 μL of plasma. Metabolome variations of sEVs among progressive diabetic retinopathy subjects were finally studied, observing a cluster of metabolites with elevated levels and suggesting potential roles of these sEV chemicals in diabetic retinopathy onset and progression. Such a scalable and flexible EV capture system can be seen as an effective analytical tool for facilitating plasma-based liquid biopsies.
Objective Early diagnosis of diabetic kidney disease (DKD) has long been a complex problem. This study aimed to analyze the metabolomic characteristics of plasma extracellular vesicles (EVs) at different stages of DKD in order to evaluate the metabolites of plasma EVs and select new biomarkers for the early diagnosis of DKD. Patients and methods A total of 78 plasma samples were collected, including samples from 20 healthy controls, 20 patients with type 2 diabetes mellitus (T2DM), 18 patients with DKD stage III, and 20 patients with DKD stage IV. In addition, EVs were isolated for metabolomics analysis. Results The results identified differences in EV metabolomic characteristics in DKD patients at different stages, as well as significant differences in EV metabolomics between T2DM patients without DKD and patients with DKD. Ten Significantly differential metabolites were associated with the occurrence and progression of DKD. Uracil, LPC(O-18:1/0:0), sphingosine 1-phosphate, and 4-acetamidobutyric acid were identified as potential early biomarkers for DKD, showing excellent predictive performance. Conclusion Uracil, LPC(O-18:1/0:0), sphingosine 1-phosphate, and 4-acetamidobutyric acid exhibited potential as suitable biomarkers for early DKD diagnosis. Unexpectedly, combining these four candidate metabolites resulted in enhanced predictive ability for DKD.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. We herein report a rare case of TIO in a 58-year-old Chinese man who presented with a large lump in the right palm. Clinical, biochemical, and radiological assessments were performed. Laboratory examination showed severe hypophosphatemia, phosphaturia, an elevated serum alkaline phosphatase level, and an elevated serum fibroblast growth factor 23 (FGF-23) level. Dual-energy X-ray absorptiometry showed low bone mineral density. Magnetic resonance imaging revealed an irregular mass located in the right palm and abnormal findings in several metacarpal bones. During the operation, the surgeons found that the tumor had penetrated the surrounding muscles. The tumor had unique characteristics of local tissue invasion. The patient’s symptoms fully resolved and his serum phosphorus level normalized, although his serum FGF-23 level remained slightly high in the postoperative phase. Our findings suggest that in some patients with TIO, the serum phosphorus level might return to the normal range despite a relatively high postoperative serum FGF-23 level. These patients should be kept under close observation and regularly surveyed for any evidence of a residual tumor.
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