LC-MS/MS analysis reveals plasma protein signatures associated with lymph node metastasis in colorectal cancer.

Objectives: Colorectal cancer (CRC) is a major global health concern, ranking as the third most common cancer and the fourth leading cause of cancer-related deaths worldwide. Currently, the diagnostic accuracy of Lymph node metastasis (LNM) is currently unsatisfactory. Therefore, there is an urgent need to develop a reliable tool that can accurately predict lymph node metastasis (LNM) in patients diagnosed with CRC.

CircCDR1as orchestrates the advancement of asthma triggered by PM through the modulation of ferroptosis.

Exposure to fine particulate matter (PM) in the ambient environment augments susceptibility to respiratory ailments. Circular RNAs, a distinctive subclass of endogenous non-coding RNAs, have been acknowledged as pivotal regulators of pathological conditions. Ferroptosis, an innovative iron-dependent form of cellular demise, has emerged as a consequential participant in numerous maladies.

Scorpion venom heat-resistant peptide alleviates mitochondrial dynamics imbalance induced by PM exposure by downregulating the PGC-1α/SIRT3 signaling pathway.

Background: Epidemiological inquiry reveals that neuroinflammation and mitochondrial dysfunction caused by PM exposure are associated with Alzheimer's disease. Nevertheless, the molecular mechanisms of mitochondrial dynamics and neuroinflammation induced by PM exposure remain elusive. In this study, our objective was to explore the impact of PM on mitochondrial dynamics and neuroinflammation, while also examining the reparative potential of scorpion venom heat-resistant synthetic peptide (SVHRSP).

The tumor suppressor OVCA1 is a short half-life protein degraded by the ubiquitin-proteasome pathway.

Ovarian cancer gene 1 () is a tumor suppressor associated with ovarian cancer, which is involved in cell proliferation regulation, embryonic development and tumorigenesis. Loss of heterozygosity in the gene occurs in 50-86% of cases of ovarian cancer; however, the physiological and biochemical functions of OVCA1 are not yet clear. In the present study, the stability and degradation of OVCA1 were investigated in A2780, Hela and 293 cells.

Cell Recognition Molecule L1 Regulates Cell Surface Glycosylation to Modulate Cell Survival and Migration.

Cell recognition molecule L1 (L1) plays an important role in cancer cell differentiation, proliferation, migration and survival, but its mechanism remains unclear. Our previous study has demonstrated that L1 enhanced cell survival and migration in neural cells by regulating cell surface glycosylation. In the present study, we show that L1 affected cell migration and survival in CHO (Chinese hamster ovary) cell line by modulation of sialylation and fucosylation at the cell surface via the PI3K (phosphoinositide 3-kinase) and Erk (extracellularsignal-regulated kinase) signaling pathways.

Development and validation of an UPLC-Q/TOF-MS assay for the quantitation of neopanaxadiol in beagle dog plasma: Application to a pharmacokinetic study.

Neopanaxadiol (NPD), the main panaxadiol constituent of Panax ginseng C. A. Meyer (Araliaceae), has been regarded as the active component for the treatment of Alzheimer's disease.

Fucosyltransferase IV (FUT4) as an effective biomarker for the diagnosis of breast cancer.

Specific enzymes are involved in altered glycosylation of cancer. Fucosyltransferase IV (FUT4) is associated with the proliferation and metastasis of breast cancer. The application of FUT4 assay in the serum has not been reported yet.

Pim1 serine/threonine kinase regulates the number and functions of murine hematopoietic stem cells.

The genes and pathways that govern the functions and expansion of hematopoietic stem cells (HSC) are not completely understood. In this study, we investigated the roles of serine/threonine Pim kinases in hematopoiesis in mice. We generated PIM1 transgenic mice (Pim1-Tx) overexpressing human PIM1 driven by vav hematopoietic promoter/regulatory elements.

The Pim protein kinases regulate energy metabolism and cell growth.

The serine/threonine Pim kinases are overexpressed in solid cancers and hematologic malignancies and promote cell growth and survival. Here, we find that a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the rapamycin-sensitive mammalian target of rapamycin (mTORC1) activity by stimulating the phosphorylation and thus activating the mTORC1 negative regulator AMP-dependent protein kinase (AMPK). Mouse embryonic fibroblasts (MEFs) deficient for all three Pim kinases [triple knockout (TKO) MEFs] demonstrated activated AMPK driven by elevated ratios of AMPATP relative to wild-type MEFs.

The BH3 mimetic ABT-737 induces cancer cell senescence.

ABT-737, a small molecule cell-permeable Bcl-2 antagonist that acts by mimicking BH3 proteins, induces apoptotic cell death in multiple cancer types. However, when incubated with this agent many solid tumor cell lines do not undergo apoptosis. The current study reveals a novel mechanism whereby ABT-737 when added to apoptosis-resistant cancer cells has profound biologic effects.

Regulation of Skp2 levels by the Pim-1 protein kinase.

The Pim-1 protein kinase plays an important role in regulating both cell growth and survival and enhancing transformation by multiple oncogenes. The ability of Pim-1 to regulate cell growth is mediated, in part, by the capacity of this protein kinase to control the levels of the p27, a protein that is a critical regulator of cyclin-dependent kinases that mediate cell cycle progression. To understand how Pim-1 is capable of regulating p27 protein levels, we focused our attention on the SCF(Skp2) ubiquitin ligase complex that controls the rate of degradation of this protein.

p53-dependent induction of prostate cancer cell senescence by the PIM1 protein kinase.

The PIM family of serine threonine protein kinases plays an important role in regulating both the growth and transformation of malignant cells. However, in a cell line-dependent manner, overexpression of PIM1 can inhibit cell and tumor growth. In 22Rv1 human prostate cells, but not in Du145 or RWPE-2, PIM1 overexpression was associated with marked increases in cellular senescence, as shown by changes in the levels of beta-galactosidase (SA-beta-Gal), p21, interleukin (IL)-6 and IL-8 mRNA and protein.

A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma.

The serine/threonine Pim kinases are up-regulated in specific hematologic neoplasms, and play an important role in key signal transduction pathways, including those regulated by MYC, MYCN, FLT3-ITD, BCR-ABL, HOXA9, and EWS fusions. We demonstrate that SMI-4a, a novel benzylidene-thiazolidine-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymphoid cell lines with precursor T-cell lymphoblastic leukemia/lymphoma (pre-T-LBL/T-ALL) being highly sensitive. Incubation of pre-T-LBL cells with SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme.

The high-mobility group A1a/signal transducer and activator of transcription-3 axis: an achilles heel for hematopoietic malignancies?

Although HMGA1 (high-mobility group A1; formerly HMG-I/Y) is an oncogene that is widely overexpressed in aggressive cancers, the molecular mechanisms underlying transformation by HMGA1 are only beginning to emerge. HMGA1 encodes the HMGA1a and HMGA1b protein isoforms, which function in regulating gene expression. To determine how HMGA1 leads to neoplastic transformation, we looked for genes regulated by HMGA1 using gene expression profile analysis.

[Dynamic changes of microtubule in parthenogenetic and in vitro fertilized preimplantation embryos in mouse.].

In this study we detected dynamic changes and function of beta-tubulin, a subtype of microtubule, during the first cleavage period in mouse parthenogenetic and in vitro fertilized embryos. Firstly, we compared the developmental potential of in vitro fertilized, parthenogenetic, and in vivo fertilized embryos in culture. Then, the dynamic changes of beta-tubulin and nucleus in parthenogenetic and in vitro fertilized preimplantation embryos were detected by immunofluorescence and confocal microscopy to analyze the role of microtubules in meiotic division and embryonic development.

Retroviral insertional mutagenesis identifies genes that collaborate with NUP98-HOXD13 during leukemic transformation.

The t(2;11)(q31;p15) chromosomal translocation results in a fusion between the NUP98 and HOXD13 genes and has been observed in patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia. We previously showed that expression of the NUP98-HOXD13 (NHD13) fusion gene in transgenic mice results in an invariably fatal MDS; approximately one third of mice die due to complications of severe pancytopenia, and about two thirds progress to a fatal acute leukemia. In the present study, we used retroviral insertional mutagenesis to identify genes that might collaborate with NHD13 as the MDS transformed to an acute leukemia.

Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma.

NOTCH1 is frequently mutated in human precursor T-cell lymphoblastic leukemia/lymphoma (pre-T LBL). In the current study, we found that 13 of 19 cell lines and 29 of 49 primary tumors from SCL/LMO1, OLIG2/LMO1, OLIG2, LMO1, NUP98/HOXD13, and p27(-/-)/SMAD3(+/-) mice had Notch1 mutations in either the heterodimerization (HD) or the glutamic acid/serine/threonine (PEST) domain but not both. Thymocytes from clinically healthy SCL/LMO1 mice aged 5 weeks did not have Notch1 mutations, whereas thymocytes from clinically healthy SCL/LMO1 mice aged 8 to 12 weeks did have Notch1 mutations and formed tumors upon transplantation into nude mice.

OLIG2 (BHLHB1), a bHLH transcription factor, contributes to leukemogenesis in concert with LMO1.

OLIG2 (originally designated BHLHB1) encodes a transcription factor that contains the basic helix-loop-helix motif. Although expression of OLIG2 is normally restricted to neural tissues, overexpression of OLIG2 has been shown in patients with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T LBL). In the current study, we found that overexpression of OLIG2 was not only found in oligodendroglioma samples and normal neural tissue but also in a wide spectrum of malignant cell lines including leukemia, non-small cell lung carcinoma, melanoma, and breast cancer cell lines.

NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia.

The myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis and dysplasia. A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene. Using a NUP98-HOXD13 fusion gene, we have developed a mouse model that faithfully recapitulates all of the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia, and apoptosis, and transformation to acute leukemia.

Distinct mechanisms lead to HPRT gene mutations in leukemic cells.

Leukemias are considered malignant clonal disorders arising from the accumulation of mutations in hematopoietic cells; the majority of these mutations are thought to be acquired somatically. Measurement of mutation frequency (Mf) at the hypoxanthine phosphoribosyltransferase (HPRT) locus has been developed as a method for estimating genomic instability. We investigated the Mf in 16 leukemic cell lines to determine whether these cell lines showed evidence of genomic instability.

Leukemic transformation.

Leukemia results from the uncontrolled accumulation of primitive, poorly differentiated blood cells, and is a consequence of the accumulation of mutations in hematopoietic precursor cells. These mutations include point mutations (single base pair insertions, deletions, or substitutions), gross chromosomal rearrangements such as deletions, insertions, amplifications, and translocations, and epigenetic changes. It seems likely that mutations affecting at least two pathways are required for the development of leukemia.

Serial granulocyte transfusions as a treatment for sepsis due to multidrug-resistant Pseudomonas aeruginosa in a neutropenic patient.

The emergence of multidrug-resistant Pseudomonas aeruginosa (MRPA) has become a major clinical problem. We successfully treated MRPA sepsis in a neutropenic patient undergoing peripheral blood stem cell transplantation with serial granulocyte transfusions. Granulocyte transfusion should be considered as a treatment for severe infection in patients with neutropenia.

A successful liver transplantation for refractory hepatic veno-occlusive disease originating from cord blood transplantation.

An 11-month-old boy with acute lymphoblastic leukemia (ALL) underwent umbilical cord blood transplantation (CBT) from an unrelated donor after a first complete remission. Despite the prophylactic use of low molecular weight heparin, prostaglandin E1 and ursodeoxycholic acid, hepatic veno-occlusive disease (VOD) occurred on the 29th day after CBT. Furthermore, neither defibrotide nor antithrombin-III improved the hepatic coma and coagulopathy due to the hepatic VOD.

Somatic cell mutation in pediatric patients undergoing allogeneic bone marrow transplantation.

In order to examine whether bone marrow transplantation (BMT) has genotoxic effects in vivo, mutant frequencies (Mfs) at the hypoxanthine-guanine phosphoribosyl transferase (Hprt) locus were evaluated. Thirty-seven pediatric patients who had received allogeneic BMT for various hematologic or immunologic disorders were enrolled. Nine out of the 37 patients (24.