OBJECTIVETo investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms.

METHODSNK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure. To clarify the mechanisms, phosphorylated ERK (p-ERK) was detected at 1 h after exposure. Moreover, microwave-induced cellular apoptosis and cell cycle regulation were analyzed after blockade of ERK signaling by using U0126.

RESULTSMicrowave-induced morphological and ultrastructural injury, dose-dependent apoptosis (P < 0.001) and cell cycle arrest (P < 0.001) were detected at 1 h after microwave exposure. Moreover, significant apoptosis was still detected at 24 h after 50 mW/cm2 microwave exposure (P < 0.01). In the 30 mW/cm2 microwave exposure model, microwaves impaired the cytotoxic activity of NK-92 cells at 1 h and down regulated perforin protein both at 1 h and 6 h after exposure (P < 0.05). Furthermore, p-ERK was down regulated at 1 h after exposure (P < 0.05), while ERK blockade significantly promoted microwave-induced apoptosis (P < 0.05) and downregulation of perforin (P < 0.01).

CONCLUSIONMicrowave dose-dependently induced morphological and functional injury in NK-92 cells, possibly through ERK-mediated regulation of apoptosis and perforin expression.

Apoptosis ; radiation effects ; Cell Cycle ; radiation effects ; Cell Line ; Dose-Response Relationship, Radiation ; Down-Regulation ; Humans ; Killer Cells, Natural ; radiation effects ; MAP Kinase Signaling System ; Microwaves ; adverse effects ; NK Cell Lectin-Like Receptor Subfamily K ; genetics ; metabolism ; Signal Transduction

OBJECTIVETo investigate the molecular mechanism of arsenic trioxide(ATO) inhibiting K562 cell proliferation, and explore the new targets for treating chronic myeloid leukemia(CML).

METHODShuman CML cell line K562 cells were cultured in vitro, and were treated with different concentrations of ATO; MTT was used to detect the cell proliferation; flow cytometry(FCM) was used to determine cell apoptosis, cell cycle and the expression of CD44; Transcriptional levels of β-catenin and cyclin D1 were assayed by RT-PCR.

RESULTS2 µmol/L ATO could inhibit the cell proliferation obviously in a time-and-dose-dependent manner. With drug concentration increasing and time prolonging, the expression rate of CD44 was declined gradrually. FCM with AnnexinV/PI double staining showed that K562 cells were induced to apoptosis after exposure to 2.5-10 µmol/L ATO for 48 hours and in dose-dependent manner. Treating with different concentration ATO for 48 hours, cell ratio of G/Gphase increased and cell ratio in S phase decreased gradually. RT-PCR showed that the expression of β-catenin and CyclinD1 decreased with increasing of drug concentration.

CONCLUSIONATO in certain concentration range can inhibit K562 cell proliferation, and induce the cell apotosis, the mechanismin influencing the Wnt/β-catenin pathway may be the downregulation of CD44 expression, arresting K562 cells in G/Gphase, and affecting the gene transcription, thus inhibiting K562 cell proliferation.

There is no gold diagnostic standard for BCR-ABL fusion gene negative chronic myeloproliterative neoplasm(cMPN). The following detection methods such as comprehensive bone marrow cell morphology, bone marrow pathology, genetic mutation, flow cytometry and immunohistochemical are needed to diagnose the BCR-ABL fusion gene positive cMPN. The JAK2 mutation can be used as a specific diagnostic criteria for polycythemia vera (PV), but there is no specific and sensitive indication for the JAK2 mutation-negative MPN. CALR mutation would be an indication in a certain extent. In this review, the CALR mutation detection, detection mean and its correlation with disease diagnosis and prognosis etc were summarized.
Bone Marrow ; Bone Marrow Cells ; Calreticulin ; Humans ; Mutation ; Myeloproliferative Disorders ; Prognosis

OBJECTIVEWhether statins can slow down the progression of chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to evaluate the effects of statin therapy on disease progression in adult patients with CKD who did not require dialysis therapy.

METHODSWe searched the electronic databases for relevant randomized controlled trials (RCTs) published by February 2015. Random-effects meta-analysis of RCTs was used to pool the renal outcomes of the patients.

RESULTSTwenty-eight studies (30 RCTs) involving a total of 45 688 participants were included in the analysis. Compared with the control groups, statins produced no effects in preventing end-stage renal disease (ESRD) [relative risks (RR) 0.98, 95% confidence intervals (CI): 0.91-1.05] and in reducing the risk of doubling of the serum creatinine level (RR 1.43, 95% CI: 0.26-7.79). Statin therapy was associated with a lowered risk of estimated glomerular filtration rate (eGFR) reduction by 25% or more (RR 0.91, 95% CI: 0.83-0.99) and delayed the reduction of eGFR [standardized mean differences (SMD) 0.04, 95% CI: 0.02-0.07]. In subgroup analyses, the benefit of statins on changes in eGFR was statistically significant in patients with moderate CKD (SMD 0.09, 95% CI 0.04-0.13). Among different statins, atorvastatin was associated with a beneficial effect on kidney function (SMD 0.10, 95% CI 0.03-0.17). Patients who received high-intensity statin therapy showed significant changes in eGFR (SMD 0.12, 95% CI: 0.02-0.21).

CONCLUSIONStatin therapies may not prevent ESRD or doubling of serum creatinine level, but can improve GFR or delay the reduction of GFR in CKD patients. The therapeutic effects are associated with the patients' baseline eGFR levels, statin types and therapy intensity.

Adult ; Disease Progression ; Glomerular Filtration Rate ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; Randomized Controlled Trials as Topic ; Renal Insufficiency, Chronic ; drug therapy

OBJECTIVETo investigate the effects of valproic acid(VPA) on the expression of intracellular domain of Notch1 (ICN1) and Hes1 in multiple myeloma RPMI 8226 cell line.

METHODSExperiments were divided into 4 group: blank control group and groups of cells treated with VPA of different concentration (2, 4, 8 mmol/L), the cell proliferation was detected by MTT method, RT-PCR was applied to detect the mRNA expression level of ICN1 and Hes1. Western blot was used to detect the protein expression of ICN1 and Hes1.

RESULTSThe proliferation of the RPMI 8226 cell was obviously inhibited by different concentration of VPA (2, 4, 8 mmol/L) at the same time. The same concentration of VPA was used to treat RPMI8226 cell for different time (24, 48, 72 h), the cell proliferation was obviously inhibited. Compared with control group, the mRNA and protein expression of ICN1 was significantly depressed at different concentration of VPA(2, 4, 8 mmol/L) for 48 h (P<0.05). Compared with control group, the mRNA and protein expression of Hes1 was depressed at different concentration 2, 4, 8 mmol/L)of VPA for 48 h (P<0.05).

CONCLUSIONVPA inhibits the proliferation of the RPMI 8226 cell in a time- and dose- dependent manner; VPA down-regulates the mRNA and protein expression level of ICN1 and Hes1 in RPMI8226 cell; thus VPA might inhibit cell proliferation possibly through the inhibition of Notch signaling pathway in multiple myeloma cells.

OBJECTIVETo explore the effect of anti-CD44 monoclonal antibody A3D8 on expression of transcription factor AP-1 in acute myeloid leukemia cells.

METHODSAfter acute leukemia cell line HL-60 was treated by different concentrations of A3D8, the proliferation and cell cycle were detected by MTT and FCM respectively. The expressions of c-JUN and c-FOS at mRNA and protein level were detected by RT-PCR and Western Blot respectively.

RESULTSThe proliferation of HL-60 was inhibited by A3D8. The A3D8 treatment increased the percentage of G/Gcells. The expressions of c-JUN at mRNA and protein level were both decreased in HL-60 cells treated with A3D8. The expressions of c-FOS at mRNA and protein level in rapamycin treatment groups showed no statistically significant difference as compared with that in control group.

CONCLUSIONSA3D8 can affect the activity of AP-1 through inhibiting the expressions of c-JUN at mRNA and protein level.

OBJECTIVE: To determine the efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of radiation-induced myocardial damage in beagles by comparing two pre-scan preparation protocols as well as to determine the correlation between abnormal myocardial FDG uptake and pathological findings. MATERIALS AND METHODS: The anterior myocardium of 12 beagles received radiotherapy locally with a single X-ray dose of 20 Gy. 18F-FDG cardiac PET/CT was performed at baseline and 3 months after radiation. Twelve beagles underwent two protocols before PET/CT: 12 hours of fasting (12H-F), 12H-F followed by a high-fat diet (F-HFD). Regions of interest were drawn on the irradiation and the non-irradiation fields to obtain their maximal standardized uptake values (SUVmax). Then the ratio of the SUV of the irradiation to the non-irradiation fields (INR) was computed. Histopathological changes were identified by light and electron microscopy. RESULTS: Using the 12H-F protocol, the average INRs were 1.18 +/- 0.10 and 1.41 +/- 0.18 before and after irradiation, respectively (p = 0.021). Using the F-HFD protocol, the average INRs were 0.99 +/- 0.15 and 2.54 +/- 0.43, respectively (p < 0.001). High FDG uptake in irradiation field was detected in 33.3% (4/12) of 12H-F protocol and 83.3% (10/12) of F-HFD protocol in visual analysis, respectively (p = 0.031). The pathology of the irradiated myocardium showed obvious perivascular fibrosis and changes in mitochondrial vacuoles. CONCLUSION: High FDG uptake in an irradiated field may be related with radiation-induced myocardial damage resulting from microvascular damage and mitochondrial injury. An F-HFD preparation protocol used before obtaining PET/CT can improve the sensitivity of the detection of cardiotoxicity associated with radiotherapy.
Animals ; Dogs ; Fasting ; Fluorodeoxyglucose F18/*metabolism ; Heart/*radiography ; Heart Injuries/*radiography ; Male ; Myocardium/metabolism/pathology ; Positron-Emission Tomography/*methods ; Radiation Injuries/diagnosis/*radiography ; Thoracic Neoplasms/radiotherapy ; Tomography, X-Ray Computed/*methods

OBJECTIVETo explore the effect of Compound Tongtu Granule (CTG) on intestinal permeability in elderly sepsis patients.

METHODSEighty elderly sepsis patients were randomly assigned to the experimental group and the control group by randomized double blinded method, 40 in each group. On the basis of conventional antiseptic treatment program, patients in the experimental group took CTG, while those in the control group took placebos. The dosage for CTG or placebos was 14.3 g each package, one package each time, twice daily for 14 successive days. Patients' abdominal symptoms and signs, levels of serum inflammatory factors (high-sensitivity C-reactive protein and procalcitonin), levels of plasma endotoxin, and the intestinal permeability (IP, represented by urinary lactulose/mannitol excretion rate) were compared between the two groups before and after treatment.

RESULTSAfter 14-day treatment, patients in the experimental group had improved abdominal symptoms, increased frequency of defecation, significantly decreased levels of plasma endotoxin and IP, when compared with the control group (P < 0.05).

CONCLUSIONCTG could improve the intestinal barrier function in elderly sepsis patients.

Aged ; C-Reactive Protein ; metabolism ; Calcitonin ; metabolism ; Calcitonin Gene-Related Peptide ; Defecation ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endotoxins ; metabolism ; Humans ; Intestines ; metabolism ; Permeability ; Protein Precursors ; metabolism ; Sepsis ; drug therapy ; physiopathology

Adult ; Aged ; Bevacizumab ; therapeutic use ; Brain Neoplasms ; drug therapy ; therapy ; Edema ; drug therapy ; etiology ; Female ; Humans ; Male ; Middle Aged ; Re-Irradiation ; adverse effects