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Background: Blood count reference intervals are important to diagnose diseases and assess overall health, especially for young children. Although, in 2021, the National Health Commission of the People's Republic of China issued "Reference intervals of blood cell analysis for children (WS/T 779-2021)", these RIs may not suitable for small children all over the country due to racial, lifestyle, and geographical differences. The aim of this study was to establish and validate locally determined hematological reference intervals among young children in Nantong district and compare them with WS/T 779-2021 and American data. Methods: The reference sample consisted of 4,758 apparently healthy small children aged from age 28 days to 3 years according to the EP28-A3c guideline issued by the Clinical and Laboratory Standards Institute (CLSI). Capillary blood samples collected in K2-EDTA anticoagulant tubes analyzed by standard procedures. Statistical analysis was based on the guidelines of the CLSI. Results: Pediatric reference intervals for 18 capillary complete blood count (CCBC) parameters were established for young children. WBC and differentials did not differ by gender in the combined analysis of all data, but showed some variations among different age groups, especially for NE and LYM. RIs of RBC value, MCV, and MCH were established, especially with regard to the difference among different age and gender groups. An overall increasing trend of PLT value was observed in children with no obvious difference between boys and girls. Further validation with 1,136 healthy subjects demonstrated that the verified proportions of our study were within 90.11% - 100%. RIs determined in the present study were more concentrated than WS/T 779-2021, with slight differences in the upper and bottom boundaries. Conclusions: Establishing appropriate region-specific reference intervals for pediatrics is essential. This study offers local reference intervals of CCBC values for young children and could be used as a benchmark for similar populations in the Yangtze River Delta economic region. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) have been identified as promising novel biomarkers for cancer diagnosis and prognosis, especially for hepatocellular carcinoma (HCC). Nowadays, the expression level of miR-21 in serum samples is a diagnostic indicator for HCC diagnosis. Thus, the quantitative determination of miRNA concentration is of significance in clinical practice. It is particularly important to establish an analytical detection method for miR-21 in patient serum. Methods: The signal readout for miR-21 was based on the mass response of a reporter peptide using an isotope dilution mass spectrometry (MS) method in this work. To be more specific, miR-21 was biotinylated before being coupled with streptavidin (SA) agarose and then hybridized with a newly synthesized DNA-peptide probe. The release and purification of the sample was based on the method including trypsin digestion, solid-phase extraction, and drying, and the detection of the reporter peptide was carried out by UHPLC/MS/MS. The miR-21 in the corresponding samples was quantified by the ratio of the chromatographic peak area of the redissolved polypeptide to that of the isotope-labeled polypeptide. Additionally, within the calibration range, the performance of the method (including precision, accuracy, linearity, and recovery) was evaluated. Results: The concentration of miR-21 was determined using the ratio of relative peak area of stable isotope-labeled internal standard and reporter peptide, yielding a linear range of 0.1~30.0 nM (y = 0.0818x + 0.7554, R² = 0.9586, P < 0.01). The limit of detection (LOD) for miR-21 was 10 pM. For y5, the recoveries (n = 3) were 91.36 ± 2.19%, 93.64 ± 3.55%, and 96.04 ± 2.02% for the levels of three miR-21 samples including RL, RM, and RH, respectively. Conclusions: Overall, this research provides a novel analytical approach for quantitative detection of miRNAs in clinical serum samples. [ABSTRACT FROM AUTHOR]

Most small non-coding RNAs (sncRNAs) with regulatory functions are encoded by majority sequences in the human genome, and the emergence of high-throughput sequencing technology has greatly expanded our understanding of sncRNAs. sncRNAs are composed of a variety of RNAs, including tRNA-derived small RNA (tsRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), PIWI-interacting RNA (piRNA), etc. While for some, sncRNAs' implication in several pathologies is now well established, the potential involvement of tsRNA, snoRNA, snRNA and piRNA in human diseases is only beginning to emerge. Recently, accumulating pieces of evidence demonstrate that tsRNA, snoRNA, snRNA and piRNA play an important role in many biological processes, and their dysregulation is closely related to the progression of cancer. Abnormal expression of tsRNA, snoRNA, snRNA and piRNA participates in the occurrence and development of tumours through different mechanisms, such as transcriptional inhibition and post-transcriptional regulation. In this review, we describe the research progress in the classification, biogenesis and biological function of tsRNA, snoRNA, snRNA and piRNA. Moreover, we emphasised their dysregulation and mechanism of action in cancer and discussed their potential as diagnostic and prognostic biomarkers or therapeutic targets. [ABSTRACT FROM AUTHOR]

TIPE1 is a gene in the TNFAIP8 family involved in immune regulation and tumorigenesis. Although previous studies demonstrated that TIPE1 might play different roles in different tumors, its expression and role in lymphoma are unclear. Here we observed TIPE1 expression in diffuse large B cell lymphoma (DLBCL). Two microarrays containing 96 tumor tissue specimens were obtained from the Affiliated Hospital of Nantong University biobank. All specimens came from patients with a clear pathological diagnosis of lymphoma, lymphadenitis, breast cancer, or bladder cancer, and we performed immunohistochemical experiments on these tissue specimens. GEPIA and TIMER platforms were used for bioinformatic analyses. We found higher TIPE1 expression in tumor tissues from patients with lymphoma compared with those with lymphadenitis, breast cancer, or bladder cancer. The GEPIA and TIMER analyses revealed that TIPE1 was upregulated in DLBCL tissues but not in invasive breast carcinoma, urothelial bladder carcinoma, or liver hepatocellular carcinoma tissues. TIPE1 expression was irrelevant for pathological stage, overall survival, or DLBCL immune infiltration levels. However, TIPE1 expression was correlated with MKI67 expression in DLBCL. Overall, TIPE1’s high expression levels in DLBCL may contribute to tumor growth in DLBCL. [ABSTRACT FROM AUTHOR]

Background: Systematic performance verification is required before a laboratory can introduce a new measurement procedure for reporting results of patient testing. The aim of this study was to explore the basic performance and clinical application value of KU-F10 Feces analyzer. Methods: We collected 530 fecal specimens in our hospital from October 2019 to February 2020, using manual methods as the gold standard. Then we made a comprehensive evaluation from repeatability, carried pollution rate, coincidence rate of formed element, and coincidence rate of fecal occult blood test. Results: The sensitivity of white blood cells was 90.3%, the specificity was 99.2%, and the coincidence rate with microscopy was 98.7%; the sensitivity of the instrument to detect red blood cells was 90.3%, the specificity was 98.2%, and the coincidence rate with microscopy was 97.7%, The sensitivity of the instrument to detect fungi is 100.0%, the specificity is 98.7%, and the coincidence rate with the microscopy is 98.7%. The sensitivity of the instrument to detect fat globules is 94.7%, the specificity is 99.0%, the coincidence rate with the microscopy is 98.9%. Comparison of instrumental fecal occult blood test and reagent B fecal occult blood result: On the 387 cases tested fecal samples, the sensitivity of the instrument was 83.8%, the specificity was 96.5%, and the coincidence rate with the results of microscopy was 92.3%. FOB minimum detection limit is 0.1 µg/mL and detection range is 0.1 to 2,000 µg/mL. Conclusions: The KU-F10 feces analyzer has an advantage of a high degree of automation, simple operation procedures, fast detection speed, improved working environment, improved work efficiency, and higher clinical application value. [ABSTRACT FROM AUTHOR]

Background: Glucose is an important material in human metabolism. The establishment of glucose reference measurement procedures and to study the uncertainties of measurement is of great significance. Linear fitting and dilution of reference material were used in the measurement of glucose concentration and they are common operations in daily work. Investigation of the measurement uncertainty of these operations will be of important significance to clinical laboratory medicine. However, in the field of laboratory medicine, related research was rarely reported. Methods: The spectrometric quantification of glucose is an application of the enzymatic reference method with hexokinase. The sources of uncertainty in the measurement process were analyzed. The measurement uncertainties in the study were evaluated according to GUF method and the method introduced by Quantifying Uncertainty in Analytical Measurement (QUAM) was also applied in the evaluation of the measurement of linear fitting. Results: The standard curve was built successfully according to the measurement procedure recommended by the CDC and the linear equation was y = 0.000807x + 0.001213 (R² = 0.999179). The measurement uncertainty of glucose in the sample was 0.450,408 mmol/L. Conclusions: The method for the determination of serum glucose concentration by hexokinase in our laboratory has been successfully established. The measurement uncertainty was consistent with the GUF method and the method introduced by Quantifying Uncertainty in Analytical Measurement (QUAM) in the process of linear fitting when the glucose concentration was measured by the reference method (hexokinase method). [ABSTRACT FROM AUTHOR]

Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most commonly used tumor markers in gastric cancer (GC). The purpose of this study was to dynamically monitor the preoperative and postoperative CEA and/or CA19-9 levels in GC patients to determine their value in efficacy monitoring and prognosis. Methods: The preoperative and postoperative CEA and/or CA19-9 were measured in 397 GC patients and correlated to pathology and the overall survival (OS). Results: We found the depth of invasion, lymph node metastasis, and pTNM stage were the most important factors affecting the elevated levels of CEA and CA19-9 in GC patients (all p < 0.001). There were significant differences between preoperative CEA or CA19-9 and postoperative values (p < 0.001). Multivariate analyses revealed that postoperative CEA and the presence of lymph node metastasis were independently associated with shorter OS (p = 0.041; p = 0.030). Conclusions: Dynamic monitoring of CEA and CA19-9 before and after surgery can be used to determine tumor burden. Postoperative rather than preoperative tumor markers, especially postoperative CEA, are good indicators for judging the prognosis of GC patients. [ABSTRACT FROM AUTHOR]

Alu elements are one of most ubiquitous repetitive sequences in human genome, which were considered as the junk DNA in the past. Alu elements have been found to be associated with human diseases including cancers via events such as amplification, insertion, recombination or RNA editing, which provide a new perspective of oncogenesis at both DNA and RNA levels. Due to the prevalent distribution, Alu elements are widely used as target molecule of liquid biopsy. Alu-based cell-free DNA shows feasible application value in tumour diagnosis, postoperative monitoring and adjuvant therapy. In this review, the special tumourigenesis mechanism of Alu elements in human cancers is discussed, and the application of Alu elements in various tumour liquid biopsy is summarised. [ABSTRACT FROM AUTHOR]

Significant challenges to develop selective and effective pharmacological inhibitors for important oncoproteins like RAS continue impeding the success to treat cancers driven by such mutations. In the present study, the ABT263 and axitinib combination imposed synergistic effects on RAS-mutant colon cancer cells. The combination inhibited in vitro and in vivo growth of the cancer cells by enhancing apoptosis. Furthermore, AKT and Wnt/ß-catenin signaling pathways were slightly down-regulated by the combination in KRAS-mutant colon cancer cells. The current results indicate that oncogene addiction can be targeted for therapy in colon cancer cells harboring the RAS-mutant. Therefore, targeting oncogene addiction can be a viable strategy for treating refractory cancers driven by important oncogenes, such as KRAS, which are otherwise difficult to be targeted by small molecules. [ABSTRACT FROM AUTHOR]

Autophagy is an important process in endogenous substrate degradation by lysosomes within cells, with a degree of evolutionary conservation. Like apoptosis and cell senescence, cell autophagy is a very important biological phenomenon involving the development and growth of biological processes. Abnormal autophagy may lead to tumorigenesis. In recent years, increasing studies have demonstrated that long non-coding RNAs (lncRNAs) and miRNAs can regulate cell autophagy by modulating targetting gene expression. In this review, we will provide an overview of lncRNAs and miRNAs in autophagy modulation and new insights into the underlying mechanisms, as well as their potential utilization in disease diagnosis, prognosis, and therapy. [ABSTRACT FROM AUTHOR]

Background: Systematic performance verification is required before a laboratory can introduce a new measurement procedure for reporting results of patient testing. The aim of this study was to determine whether a new Iris iQ200 Sprint automated urine microscopy analyzer (iQ200 Sprint) could be incorporated into our routine laboratory. Methods: A total of 421 fresh urine samples were selected from the Affiliated Hospital of Nantong University, including those from healthy individuals and those with a variety of abnormalities to ensure a wide range of results. Precision, recovery, carry-over, linearity and reference interval were verified according to well-established protocols. Results: The repeatability studies found coefficients of variability (CVs) in the range of 10.53% - 20.28% for red blood cells, white blood cells, and squamous epithelial cells, while the CV for the iQ Positive Control sample was 3.23%. The relative bias was 0.5% for the iQ Positive Control sample and no carry-over was detected. Linearity was observed at concentrations of 10 - 2069.5 particles/µL (y = 0.989x + 9.1, R² = 0.999). The manufacturer's claimed reference interval meets the requirements for medical usefulness. Conclusions: Performance verification is needed before a clinical laboratory can introduce a new measurement procedure. The iQ200 Sprint is sufficiently precise and reliable to be applied in our clinical laboratory. [ABSTRACT FROM AUTHOR]

Background: miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer. Methods: We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR. Results: Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U = 8, p = 0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U = 374, p < 0.0001) and was significantly correlated with β2M, λ light and к light chain concentration (r = 0.480, p = 0.0003; r = 0.560, p < 0.0001; r = 0.560, p < 0.0001), but not correlated with the lactate dehydrogenase (LDH) concentration (r = 0.247, p = 0.0611). The area under the curve (AUC) of the receiver-operating characteristics (ROC) curve of serum miR-4449 was 0.885 (95% CI, 0.826-0.945), which is higher than for other markers. Combining miR- 4449, λ light chain, and β2M together, the sensitivity was highest compared with λ light chain or β2M alone, or combined.Conclusions: The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to explore serum PCAT-1 expression in multiple myeloma (MM) and examine the potential usefulness of this molecule as a biomarker for diagnosis in MM. METHODS: Serum samples were collected from 60 newly diagnosed untreated MM patients, and 48 healthy controls. Serum PCAT-1 expression levels were detected by RT-qPCR. In addition, correlations between the relative expression of serum PCAT-1 and the concentrations of lactic acid dehydrogenase (LDH), β2M, λ light chain and κ light chain were assessed. RESULTS: It was found that the relative expression of serum PCAT-1 in MM patients (81.02 ± 136.9) was higher than that in healthy controls (3.17 ± 5.75) (U = 307.0,P <0.0001) and was significantly correlated with β2M concentration (r = 0.461, P = 0.0002), but not with LDH, κ light and λ light chain concentration (r = 0.061, P = 0.641; r = 0.007, P = 0.956; r = -0.090, P = 0.499 respectively). Additionally, it was significantly correlated with different isotype of MM (H = 7.464, P = 0.024). The AUC of the ROC curve of serum PCAT-1 was 0.892 (95% CI 0.833--0.950), which was higher than other markers. Combining PCAT-1 and β2M together, the sensitivity was highest compared with other markers alone, or combined. CONCLUSION: The expression levels of serum PCAT-1 in MM patients were significantly higher than that in healthy controls, suggesting that it may be useful in the auxiliary diagnosis of MM. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the diagnostic value of combined detection of plasma miR-127-3p and HE4 for breast cancer (BC). METHODS: Included in this study were 102 patients with pathologically confirmed BC who received treatment in the affiliated hospital of Nantong University between March 2015 and April 2016, 87 patients with benign breast tumors, and 90 healthy volunteers as control. Plasma miR-127-3p was detected by SYBR Green RT-qPCR, and plasma HE4 was detected by chemiluminescent immunoassay. The diagnostic efficacy of miR-127-3p alone, HE4 alone and combined detection of miR-127-3p and HE4 in BC women patients was evaluated by ROC curve analysis. RESULTS: The relative expression quantity (RQ) of plasma miR-127-3p and HE4 in BC patients was 13.561 (3.345~18.281) pmol/L and 105.42 (40.28~156.31) pmol/L. The RQ of plasma miR-127-3p in BC patients was significantly higher than that in benign breast tumor patients and healthy individuals (bothP <0.001), and there was no significant difference between benign breast tumor patients and healthy individuals (P >0.05). There was no significant correlation between plasma miR-127-3p and HE4 levels (r2 = 0.086, P = 0.471). ROC curve analysis on the diagnostic efficacy of plasma miR-127-3p and HE4 in BC diagnosis showed that the cut-off value of miR-127-3p and HE4 in BC diagnosis was 3.471 and 63.21 pmol/L; AUC was 0.767 and 0.670; sensitivity was 78.2% and 64.6%; specificity was 79.1% and 69.3%; accuracy was 73.2% and 65.1%, respectively. Prediction probability (P) obtained from the miR-127-3p and HE4 model established by logistic regression was P = 1/[1 + exp (-0.142miR-127-3p-0.024HE4 + 2.875)]. AUC calculated from ROC was 0.825 and the sensitivity was increased to 87.4%. CONCLUSION: Combined detection of plasma miR-127-3p and HE4 greatly improved the sensitivity of BC diagnosis and may prove to be a candidate biomarker for early detection and diagnosis of BC. [ABSTRACT FROM AUTHOR]

Growth-related oncogene (GRO)-β, or chemokine (C-X-C motif) ligand 2 (CXCL2), is a member of the CXC chemokine family that may mediate various functions, including attracting neutrophils to sites of inflammation, and participating in tumorigenesis and progression. However, the expression of GRO-β in colorectal cancer (CRC) and the association with the clinical outcome of the disease remains poorly understood. In the present study, CXCL2 mRNA expression in CRC was analyzed using six independent datasets from the Oncomine microarray database. The immunohistochemical analysis of tissue microarrays (TMA) was used to characterize the expression of the GRO-β protein in CRC. The association between GRO-β expression and the clinicopathological features and prognosis of patients was determined by statistical analysis. The results indicated that GRO-β was highly expressed in CRC tissues, and that high GRO-β cytoplasmic expression was associated with the tumor location, extent of the primary tumor, and lymph node metastasis. Kaplan-Meier survival and Cox regression analysis revealed that high GRO-β expression was an independent indicator of poor prognosis for CRC patients. The results indicate that high GRO-β expression in CRC may correlate with an unfavorable outcome and facilitate cancer cell invasion and metastasis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association between cell-free DNA (cf-DNA) levels and clinicopathological characteristics of patients with ovarian cancer using a branched DNA (bDNA) technique, and to determine the value of quantitative cf-DNA detection in assisting with the diagnosis of ovarian cancer. Serum specimens were collected from 36 patients with ovarian cancer on days 1, 3 and 7 following surgery, and additional serum samples were also collected from 22 benign ovarian tumor cases, and 19 healthy, non-cancerous ovaries. bDNA techniques were used to detect serum cf-DNA concentrations. All data were analyzed using SPSS version 18.0. The cf-DNA levels were significantly increased in the ovarian cancer group compared with those of the benign ovarian tumor group and healthy ovarian group (P<0.01). Furthermore, cf-DNA levels were significantly increased in stage III and IV ovarian cancer compared with those of stages I and II (P<0.01). In addition, cf-DNA levels were significantly increased on the first day post-surgery (P<0.01), and subsequently demonstrated a gradual decrease. In the ovarian cancer group, the area under the receiver operating characteristic curve of cf-DNA and the sensitivity were 0.917 and 88.9%, respectively, which was higher than those of cancer antigen 125 (0.724, 75%) and human epididymis protein 4 (0.743, 80.6%). There was a correlation between the levels of serum cf-DNA and the occurrence and development of ovarian cancer in the patients evaluated. bDNA techniques possessed higher sensitivity and specificity than other methods for the detection of serum cf-DNA in patients exhibiting ovarian cancer, and bDNA techniques are more useful for detecting cf-DNA than other factors. Thus, the present study demonstrated the potential value for the use of bDNA as an adjuvant diagnostic method for ovarian cancer. [ABSTRACT FROM AUTHOR]

The receptor for advanced-glycation end products (RAGE) is upregulated in various cancers and has been associated with tumor progression, but little is known about its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and investigate the biological role of miR-185 in ESCC. In this study, we found that the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues was correlated positively with the depth of invasion by immunohistochemistry, suggesting that RAGE was involved in ESCC. We used bioinformatics searches and luciferase reporter assays to investigate the prediction that RAGE was regulated directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect was further confirmed in RAGE protein by immunofluorescence in both cell lines. The effects were reversed following cotransfection with miR-185 and high-level expression of the RAGE vector. Furthermore, the biological role of miR-185 in ESCC cell lines was investigated using assays of cell viability, Ki-67 staining, and cell migration and invasion, as well as in a xenograft model. We found that overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro and reduced their capacity to develop distal pulmonary metastases in vivo partly through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical specimens, the level of plasma miR-185 expression was decreased significantly (P 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248- 1.676] compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855). In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker in ESCC. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, C-reactive protein (CRP), and the erythrocyte sedimentation rate (ESR) in the diagnosis of rheumatoid arthritis (RA). Methods: Using rate nephelometry, chemiluminescence microparticle immunoassay (CMIA), and Westergren sedimentation rate testing, we detected RF, anti-CCP antibody, CRP, and ESR in 134 patients with RA and 50 healthy control individuals. Results: We observed significant differences in RF, anti-CCP antibody, CRP, and ESR concentrations between the RA and control groups (P <.01). The sensitivity, specificity and accuracy in the diagnosis of RA were 91.0%, 74.4%, and 87.0%, respectively, for RF; 88.0%, 90.4%, and 88.1%, respectively, for anti-CCP antibody; and 90.2%, 83.3%, and 89.5%, respectively, for the detection of RA via the combination of RF and anti-CCP antibody. Conclusion: Anti-CCP is more specific than the other parameters we reviewed for the diagnosis of RA. Combined detection of the 4 parameters is beneficial when confirming a diagnosis of RA. [ABSTRACT FROM AUTHOR]

Cancerous inhibitor of protein phosphatase 2A (CIP2A) has been identified as an oncoprotein that is able to promote the proliferation of cancer cells. The role of CIP2A in the anticancer activity of bortezomib in colon cancer remains to be elucidated. In the present study, the antitumor effect of bortezomib was investigated and the role of CIP2A in determining the effect on colon cancer cells was identified. In the present study, bortezomib demonstrated an antitumor effect, as observed by WST-1 assay and flow cytometry. In addition, the mRNA and protein level of CIP2A was inhibited in a dose-dependent manner by bortezomib with quantitative PCR (qPCR) and western blotting. Furthermore, the inhibition of CIP2A with small interfering RNA by treatment with bortezomib inhibited proliferation, increased apoptosis and attenuated the invasion of the cells. Finally, the in vivo data demonstrated that bortezomib was able to decrease the growth of tumors, and that CIP2A was downregulated in the LoVo tumors treated with bortezomib. Therefore, CIP2A was shown to be important in the bortezomib-induced inhibitory effect on colon cancer. [ABSTRACT FROM AUTHOR]

Circulating DNA is an emerging biomarker in various types of cancer. It is generally believed that DNA released from apoptotic cells is uniformly truncated to small DNA fragments with 185 - 200 base pair (bp), whereas DNA produced by malignant cells varies in size (most of these are longer DNA fragments). Recently, the application of circulating DNA integrity indexes, represented by the ratio of the longer DNA fragments concentration to the shorter ones, has been reported in different cancers. This review will summarize the recently reported assays for detection of the circulating cell-free DNA (ccf-DNA) integrity and their clinical utility. [ABSTRACT FROM AUTHOR]

The nontoxic, targeted and effective delivery of nucleic acid drugs remains an important challenge for clinical development. Here, we describe a novel negative lipidoid nanoparticle delivery system, providing entrapment-based transfection agents for local delivery of siRNA to the colorectal cancer focus. The delivery system was synthesized with lipidoid material 98N12-5(1), mPEG2000-C12/C14 glyceride and cholesterol at a desired molar ratio to realize the anionic surface charge of particles, which could alleviate to a larger degree the inflammatory response and immune stimulation of the organism, embodying dramatic biocompatibility. In particular, mPEG2000-C12/C14 glyceride was selected to ameliorate the stability of the delivery system and protection of nucleic acids by extending the tail length of the carbons, crucial also to neutralize the positive charge of 98N12-5(1) to form a resultant anionic particle. In vivo experiments revealed that a particle size of 90 nm perfectly realized a passive target in a size-dependent manner and did not affect the function of the liver and kidneys by a local delivery method, enema. We clarified that the uptake of negative lipidoid nanoparticles internalized through a lipid raft endocytotic pathway with low cytotoxicity, strong biocompatibility and high efficacy. This study suggests that negative lipidoid nanoparticles with enema delivery costitute, uniquely and appropriately, a local anti-colorectal cancer nucleic acid drug delivery platform, and the application of similar modes may be feasible in other therapeutic settings. [ABSTRACT FROM AUTHOR]

A proliferation-inducing ligand (April) is highly expressed in colorectal cancer (CRC) tissues and cell lines. However, the biological functions and precise signals elicited by April in CRC have not been fully understood. Here, we used small interfering RNA to selectively deplete April and to determine its tumorigenic effects in a CRC cell line SW480 both in vitro and in vivo. Knockdown of April in SW480 cells was associated with modulation of cell proliferation as well as reduction of cell migration and invasion in vitro. Moreover APRIL-knockdown SW480 cells displayed markedly inhibited tumor growth and decreased metastasis to the liver in immunodeficient mice upon subcutaneous injection. Importantly, we observed that downregulation of APRIL in SW480 cells resulted in greatly decreased activity of phosphoinositide 3-kinase (PI3K)/Akt pathway. In addition, we observed that recombinant human APRIL mediated activation of the PI3K/Akt pathway in CRC cells resulting in induced expression of important cell cycle proteins and matrix metalloproteinases in a PI3K/Akt dependent manner. This was concurrent with marked cell growth viability as well as increased cell migration and invasion. Together, these compelling data suggest that APRIL-induced tumorigenesis and metastasis of CRC cells may be accomplished through activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of APRIL and may provide clues for identifying novel therapeutic and preventive molecular markers for CRC. [ABSTRACT FROM AUTHOR]

B-cell activating factor (BAFF) is critical for maintaining the development and homeostasis of B cells. Overexpression of BAFF is associated with autoimmune diseases and malignant B lymphoma. BAFF receptor (BAFF-R) was found to be a specific receptor of BAFF. It not only plays a significant role in splenic B-cell maturation but also works as a major mediator in BAFF-dependent costimulatory response in peripheral B and T cells. Previous studies have demonstrated that BAFF-R is related to several diseases; however, the molecular mechanism of BAFF-R genic transcription has not been clearly defined. The aim of this study was to investigate the transcriptional regulation of the BAFF-R gene. This study was designed to clone and characterize the 5′-regulatory region of the human BAFF-R gene and determine the mechanisms involved in its transcriptional regulation. In addition, the effects of interferon (IFN)-γ and BAY11-7082 (inhibitor of nuclear factor [NF]-κB) on the expression and promoter activity of BAFF-R were examined. The results showed that the sequence between −1420 and +261 could be a core promoter region, and −1562 and −1420 bp harbored a transcriptive silencer. IFN-γ promoted BAFF-R promoter activity and upregulated BAFF-R mRNA expression. BAY11-7082 (inhibitor of NF-κB) exhibited an inhibitory effect on BAFF-R promoter activity and downregulated BAFF-R mRNA expression. Our data provided novel evidence to clarify the mechanism of transcriptional regulation of BAFF-R and illustrated that IFN-γ and NF-κB pathway were involved in regulating BAFF-R expression. Thus some BAFF-R-related diseases might be cured by blocking transcriptional regulation of BAFF-R and reducing its expression. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggested that early B-cell factor 3 (EBF3) might be a tumor suppressor.Methods: To explore the biological function of EBF3 in hepatocellular carcinoma (HCC) tissues, we measured the expression of EBF3 at mRNA level in 20 cases of HCC using real-time polymerase chain reaction (PCR) and the expression of EBF3 at protein level in nuclear extracts in 5 cases of HCC using Western blot.Results: The results showed that EBF3 mRNA was expressed in all HCC tissues, and only in 10 whole paired distant noncancerous tissues. The ratio of EBF3 mRNA to β2M mRNA in HCC tissues was significantly higher than that in distant liver noncancerous tissues (0.55 ± 0.12 versus 0.22 ± 0.23, t=5.69, Pt=2.52, P=0.036). We also successfully constructed a eukaryotic expression vector for human EBF3 fused with enhanced green fluorescent protein (EGFP) and expressed EBF3-EGFP fusion protein in HepG2 cells. It was found that expression of EBF3-EGFP fusion protein in HepG2 induced cell proliferation by increasing the number of cells in S phase.Conclusion: These findings suggested that the expression of EBF3 at both mRNA and protein levels was up-regulated in HCC tissues, and that EBF3 may play a critical pathological role in HCC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the possible association between allelic polymorphism of tumor necrosis factor β (TNFβ) in 1069 locus and severe post-trauma sepsis in the Han Chinese of Jiangsu Province, China. Methods: We studied the polymorphism of single-base mutation of the TNFβ gene in 58 patients with severe post-trauma sepsis and 88 healthy controls, using polymerase chain reaction (PCR) amplification and polyacrylamide gel electrophoresis (PAGE) analyses. Results: The frequency of the TNFβ*2 allele in patients complicated with post-trauma sepsis was significantly higher than that in healthy controls (68.9% vs 55.1%, P=0.015, RR=1.73). Conclusion: Our results implied an association between an allelic polymorphism of TNFβ in 1069 locus and severe post-trauma sepsis susceptibility in a Chinese population. [ABSTRACT FROM AUTHOR]

Objective: To investigate the possible association between allelic polymorphism of tumor necrosis factor β (TNFβ) in 1069 locus and severe post-trauma sepsis in the Han Chinese of Jiangsu Province, China. Methods: We studied the polymorphism of single-base mutation of the TNFβ gene in 58 patients with severe post-trauma sepsis and 88 healthy controls, using polymerase chain reaction (PCR) amplification and polyacrylamide gel electrophoresis (PAGE) analyses. Results: The frequency of the TNFβ*2 allele in patients complicated with post-trauma sepsis was significantly higher than that in healthy controls (68.9% vs 55.1%, P=0.015, RR=1.73). Conclusion: Our results implied an association between an allelic polymorphism of TNFβ in 1069 locus and severe post-trauma sepsis susceptibility in a Chinese population. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about the attribution of falsely elevated troponin I to examine its inadequate centrifugation using Vitros ECiQ immunodianostic system.