In recent years the interaction between host and gut microbiota has attracted increasing attention. However, intestinal flora dysbiosis may lead to many diseases, and there is increasing evidence that the intestinal microbiota in patients with chronic kidney disease (CKD) is associated with the pathophysiological status of the host. "Gut-kidney axis" provides a better explanation of the two-way communication between intestinal flora and CKD. Impaired kidney function leads to dysbiosis of intestinal flora and an altered intestinal flora can damage the intestinal mucosal barrier and facilitate the entry into the bloodstream of harmful bacteria, which can induce chronic inflammation and thus accelerate renal injury. In addition, the accumulation of nephrotoxic metabolites from an altered intestinal flora can aggravate CKD in the "gut-kidney axis". Among them, p-cresol sulfate, indoxyl sulfate and trimethylamine oxide are the most widely studied metabolites of nephrotoxicity, and their renal toxicity has been widely confirmed in basic research and clinical studies. Current studies show that the intestinal microbiota-metabolite network is closely related to the occurrence and development of chronic kidney disease. Thus, intervention in the intestinal microbiota may provide a new approach to the prevention and treatment of chronic kidney disease.

Benzene is classified as Group 1 carcinogen by IARC. It has been found that benzene induces hematotoxicity even in low dose exposure. The identification of key events during benzene induced hematotoxicty leads to adjustment of occupational exposure limits of benzene. In this review, we focus on the exposure, metabolism, target organs, key epigenetic changes, toxicty effects and end points of low-dose chronic benzene exposure induced hematotoxicity and finally discuss the perspectives on the future study of this area.
Benzene ; toxicity ; Carcinogens ; toxicity ; Epigenesis, Genetic ; Humans ; Occupational Exposure

Adenocarcinoma/surgery* ; Esophageal Neoplasms/surgery* ; Esophagogastric Junction/surgery* ; Gastrectomy ; Humans ; Margins of Excision ; Neoadjuvant Therapy ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVETo ascertain the frequency of prothrombin (FII) gene 3'-untranslated region (3'-UT) G20210A variant and to explore whether this mutation is related to arterial thrombosis in Chinese Zhuang population.

METHODSSeventy-six patients with cerebral thrombosis, 23 patients with myocardial infarction and 106 healthy Chinese Zhuang persons were studied. The G20210A mutant allele of the prothrombin gene in all blood specimens was investigated by DNA extraction, polymerase chain reaction amplification, Hind III digestion and polyacrylamide gel electrophoresis.

RESULTSThe patients and normal control subjects were all homozygous for the normal G20210G allele, and there was no FII G20210A variant.

CONCLUSIONFactor II gene 3'-UT G20210A mutant allele is absent in the 99 Chinese Zhuang ethnic patients with ischemic stroke and myocardial infarction and is absent in 106 normal healthy Zhuang people. FII G20210A mutation may not be a major risk factor for thrombogenesis in ethnic Chinese.

3' Untranslated Regions ; genetics ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; China ; DNA Mutational Analysis ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Humans ; Intracranial Thrombosis ; genetics ; Male ; Middle Aged ; Mutation ; Myocardial Infarction ; genetics ; Polymerase Chain Reaction ; Prothrombin ; genetics

BACKGROUNDA nonsteroidal anti-inflammatory drug, indomethacin, has been shown to have anti-leukemic activity and induce leukemic cell apoptosis. This study was to elucidate the mechanism of indomethacin-induced K562 cell apoptosis.

METHODSK562 cells were grown in RPMI 1640 medium and treated with different doses of indomethacin (0 micromol/L, 100 micromol/L, 200 micromol/L, 400 micromol/L, 800 micromol/L) for 72 hours. The cells were harvested, and cell viability or apoptosis was analyzed using MTT assay and AO/EB stain, combining laser scanning confocal microscopy (LSCM) technique separately. For the localization and distribution of intracellular caspase-3 or caspase-8 protein, immunofluorescence assay was carried out. To reveal the activation of caspase-3 or caspase-8 in indomethacin-treated cells, Western blot detection was used. The change in intracellular free calcium was determined by Fluo-3/Am probe labeling combined with LSCM.

RESULTSIndomethacin could lead to K562 cell apoptosis and inhibit cell viability in a concentration-dependent manner. An increased expression of intracellular caspase-3 or caspase-8 was observed at higher doses of indomethacin (400 - 800 micromol/L). Western blot results showed upregulation and activation in both caspase-3 and caspase-8 protein. Under indomethacin intervention, the levels of intracellular free calcium showed a significant increase. Blocking the activity of cyclooxygenase did not abolish the effects of indomethacin on K562 cell apoptosis.

CONCLUSIONSActivation and upregulation of caspase-3 or caspase-8 protein were responsible for Indomethacin-induced K562 cell apoptosis. Variation of intracellular free calcium might switch on the apoptotic pathway and the proapoptotic effect of indomethacin might be cyclooxygenase-independent.

Apoptosis ; drug effects ; Calcium ; metabolism ; Caspase 3 ; Caspase 8 ; Caspases ; genetics ; metabolism ; Cyclooxygenase Inhibitors ; pharmacology ; Enzyme Activation ; Gene Expression Regulation, Enzymologic ; drug effects ; Humans ; Indomethacin ; pharmacology ; K562 Cells

The study was purposed to detect BAFF/APRIL gene expression changes in bone marrow mononuclear cells (BMMNC) and myeloma cell line U266 after interference with glucocorticoid and bortezomib. After separation of BMMNC from 7 patients with multiple myeloma, BAFF/APRIL mRNA expression in BMMNC and U266 cell line was detected by real-time PCR after treated with dexamethasone 100, 200 µg/ml, methylprednisolone 100, 200 µg/ml, bortezomib 0.1 µg/ml alone and dexamethasone or methylprednisolone combined with bortezomib respectively for 48 hours. The results showed that U266 cells and BMMNC of untreated MM patients highly expressed BAFF/APRIL genes. When dexamethasone, methylprednisolone or bortezomib was added to U266 cells or BMMNC alone, BAFF/APRIL gene expression decreased as compared with the blank control (p < 0.01). The inhibiting effect of bortezomib to BAFF/APRIL expression was obviously strong(p < 0.05). When dexamethasone or methylprednisolone combined with bortezomib, the BAFF/APRIL gene expression further decreased compared with dexamethasone or methylprednisolone alone (p < 0.01). As compared with the group of methylprednisolone combined with bortezomib, BAFF/APRIL gene expression decreased in dexamethasone combined with bortezomib with a statistically significant difference (p < 0.05). It is concluded that the expression of BAFF/APRIL gene is down-regulated after bing treated with glucocorticoids and bortezomib, which suggests that besides the glucocorticoid receptor and proteasomes targets, BAFF/APRIL and their receptor sites may be new targets of glucocorticoids and bortezomib.
B-Cell Activating Factor ; genetics ; metabolism ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; drug effects ; Glucocorticoids ; pharmacology ; Humans ; Multiple Myeloma ; metabolism ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; genetics ; metabolism

This study was purposed to investigate the change of early hemostatic function in patients with myeloproliferative diseases (MPD) and to explore its significance in combination with clinical data. The platelet aggregative function was measured by using ristomycin, adenosine diphosphate, collagen and adrenine as inductors, the plasma von Willebrand factor-associated antigen (vWF: Ag) level was measured by enzyme-linked immunosorbent assay (ELISA), the plasma von Wellebrand factor-ristomycin cofactor (vWF: Rco) activity was measured in 6 patients with obviously low ristomycin induced platelet aggregation (RIPA). The results showed that the platelet aggregative function obviously decreased in 35 patients, there were distinct differences in maximal platelet aggregative rate between patients and normal controls induced by 4 inductors respectively (P < 0.001, P < 0.001, P = 0.002, P < 0.001). There was no obvious difference between patients with MPD and healthy controls in plasma vWF: Ag level (P > 0.50). Plasma vWF: Rco activity in all 6 patients with MPD chosen was in the normal range, except one patient with essential thrombocytosis (ET) whose plasma vWF: Rco activity was much lower than normal. No correlation was found between platelet count and plasma vWF: Ag level in the patients (r = -0.180). No correlation was found between platelet count and maximal platelet aggregative rate induced by 4 inductors respectively in patients. It is concluded that the occurrence of abnormal platelet aggregative function is high in patients with MPD. The RIPA and vWF: Rco activity decrease in one patient with ET. However, the shortage of vWF polymer existed in his plasma have needs for further research. No correlation was observed between hemostasis and clinical manifestations. However, because of the high occurrence of platelet dysfunction in MPD patients, the clinical application of anti-platelet drugs should be considered carefully.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Myeloproliferative Disorders ; blood ; physiopathology ; Platelet Aggregation ; Platelet Function Tests ; von Willebrand Factor ; analysis

Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; metabolism ; Th17 Cells ; metabolism

OBJECTIVETo screen phosphopeptide specific for acute leukemia.

METHODSMononuclear cells from bone marrow were collected from 16 newly diagnosed acute lymphoblastic leukemia (ALL) and 20 acute myeloid leukemia (AML) patients. Peptides were extracted and purified, analyzed by immunoprecipitation and liquid chromatography coupled with tandem mass spectrometry (LC-MS).

RESULTS(1) Non-receptor tyrosine kinase family members Fyn, Yes, Src widely expressed in acute leukemia; (2) Some phosphopeptides, including non-receptor tyrosine kinase family members Abl/iso1 and Abl, non-receptor Ser/Thr protein kinase family members Bcr, JNK2, JNK2 iso2, Adaptor/scaffold members Cas-L, Cbl, CrkL CENTD1 (Centaurin delta1) ZO2, transcriptor GFR-1 and phosphatase SHIP-2 were detected in Ph positive ALL, but not in other kinds of ALL. (3) Hck, Lyn and Fgr selectively expressed in AML (except AML-M(3)).

CONCLUSIONSome phosphopeptides were specific for ALL and AML, and may be useful for diagnosis and therapy of acute leukemia.

Chromatography, High Pressure Liquid ; Humans ; Immunoprecipitation ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Neoplasm Proteins ; analysis ; Phosphopeptides ; analysis ; Phosphorylation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; Proteomics ; Tandem Mass Spectrometry

This study was aimed to observe whether expressions of JAK2, STAT1, STAT5 proteins in indomethacin-treated CML cells involved in the proliferation inhibition of CML cells, and elucidate the pharmacological mechanism of indomethacin anti-leukemia. MTT assay and trypan blue dye exclusion test were used to detect the inhibitory effect of indomethacin on CML cells proliferation. JAK2, STAT1, STAT5 proteins were analyzed by Western blot; the subcellular distribution of STAT1, STAT5 were detected with indirect immunofluorescence technique. The results showed that indomethacin at >or= 400 micromol/L significantly inhibited the proliferation of CML cells and down-regulated the expression of STAT1, STAT5 protein, no JAK2 change was observed. STAT1 and STAT5 were located in cytoplasm. It is concluded that indomethacin inhibits the proliferation of CML cells and the mechanism may be related to down-regulated expression of STAT, or blockage of cells growth signals.
Antineoplastic Agents ; pharmacology ; Blotting, Western ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Fluorescent Antibody Technique ; Humans ; Indomethacin ; pharmacology ; Janus Kinase 2 ; metabolism ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; pathology ; STAT1 Transcription Factor ; metabolism ; STAT5 Transcription Factor ; metabolism ; Signal Transduction ; drug effects