Imatinib mesylate has been commonly used in the treatment of patients with chronic myeloid leukemia (CML). However, a significant number of CML patients treated with imatinib developed thrombocytopenia, oligocythemia, granulocytopenia. It has been confirmed that imatinib not only inhibits BCR-ABL mutations, but also suppresses other tyrosine kinase receptor genes such as PDGFR, JAK2V617F and C-KIT mutations, providing an important potential of targeted therapy for myeloproliferative disease. As the PDGFR, JAK2 and C-KIT play important roles in the regulation of hematopoiesis, suggesting that imatinib may block the phosphorylation of PDGFR, JAK2V617F and C-KIT receptors, interrupt the signal transduction cascades, disrupt cell differentiation and proliferation. In this review, the application and the potential molecular mechanism of imatinib in the treatment of thrombocythemia and other myeloproliferative diseases are discussed.
Benzamides ; therapeutic use ; Humans ; Imatinib Mesylate ; Myeloproliferative Disorders ; drug therapy ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Thrombocytosis ; drug therapy

Since the outbreak of coronavirus disease 2019 (COVID-19) in the late 2019, a variety of antiviral drugs have been used in the first-line clinical trial. The Diagnostic and Treatment Protocol for COVID-19 (Trial Version 6) in China recommends chloroquine phosphate for the first time as an anti-coronavirus trial drug. As a classic drug for treatment of malaria and rheumatism, chloroquine phosphate has been used clinically for more than 80 years, and has also shown good results in the treatment of various viral infections. As the plasma drug concentration varies greatly among different races and individuals and due to its narrow treatment window, chloroquine in likely to accumulate in the body to cause toxicity. Among the treatment regimens recommended for COVID-19, reports concerning the safety of a short-term high-dose chloroquine regimen remain scarce. In this review, the authors summarize the current research findings of chloroquine phosphate in the treatment of COVID-19, and examine the pharmacokinetic characteristics, antiviral therapy, the therapeutic mechanism and safety of chloroquine.
Antiviral Agents ; Betacoronavirus ; drug effects ; China ; Chloroquine ; analogs & derivatives ; therapeutic use ; Coronavirus Infections ; drug therapy ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy

The properties of polyethyleneimine-cholesterol cationic lipopolymer (PEI-Chol) as gene carries and its gene transfer efficiency in vitro with lipid microbubbles were presented in this paper. PEI-Chol lipopolymer was synthesized by linking cholesterol chloroformate to the amino groups of branched poly(ethyleneimine) (PEI) of 1 800. The structure and molecular weight of PEI-Chol were confirmed by IR, 1H NMR and MADI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry), respectively. The average molecular weight of PEI-Chol was approximately 2 000. The gene delivery system of bubble/PEI-Chol/DNA was constructed by mixed PEI-Chol/pDNA (N/P 10:1) complexes with lipid microbubbles (2-8 microm) which were prepared by DPPC, DSPE-PEG2000 and perfluoropropane with the reverse phase evaporation technique. pEGFP-Cl (enhanced green fluorescent protein) was used as report gene to investigate the DNA condensing ability of PEI-Chol lipopolymer by agarose gel electrophoresis. And their cytotoxicity and in vitro transfer efficiency of different complexes were compared with each other in A549 and MCF-7. The results indicated PEI-Chol lipopolymer can condense plasmid DNA when N/P ratio upto 4, PEI-Chol complexes and bubble/PEI-Chol/DNA complexes were nontoxic to A549 and MCF-7 when formulated at the N/P ratio of 10/1 as determined by MTT assay. This bubble/PEI-Chol/DNA delivery system provided good transfer efficiency with other desirable characteristics such as against-precipitation of plasma proteins. In conclusion, bubble/PEI-Chol/DNA complex is a novel non-viral gene delivery system.
1,2-Dipalmitoylphosphatidylcholine ; chemistry ; Breast Neoplasms ; pathology ; Cell Line, Tumor ; Cell Survival ; Cholesterol ; chemistry ; Contrast Media ; DNA ; chemistry ; genetics ; Female ; Fluorocarbons ; chemistry ; Gene Transfer Techniques ; Genetic Vectors ; Green Fluorescent Proteins ; metabolism ; Humans ; Lipids ; chemistry ; Lung Neoplasms ; pathology ; Microbubbles ; Phosphatidylethanolamines ; chemistry ; Plasmids ; Polyethylene Glycols ; chemistry ; Polyethyleneimine ; chemistry ; Transfection ; methods

OBJECTIVE: To investigate the anti-apoptotic effect of Angelica polysaccharide (APS) on cryopreservated platelets and its mechanism. METHODS: The platelets were divided into 4 group: control group(4 ℃ stored platelets),APS group (APS-treated platelets stored at 4 ℃), LY294002 group (LY294002-treated platelets stored at 4 ℃) and LY294002+APS group(LY294002+APS treated platelets stored at 4 ℃ ). The expression of platelet membrane glycoprotein CD41 and CD61, as well as the platelet apoptotic rate, Caspase 3 expression and mitochondrial membrane potential (MMP) were detected by flow cytometry; the anti-apoptotic mechanism of APS by PI3K /AKT signaling pathway was analyzed by Western blot assay. RESULTS: The apoptosis rate of platelets in LY294002 group obviously increased, the activity of CD41 and CD61 expression gradually decreased along with the enhancement of LY294002 concentrations (r=-0.953)； compared with control group, the apoptosis rate of platelets in LY294002 group was enhanced significantly(P<0.05)，while the apoptosis rate of platelets in LY294002+APS group significantly was reduced(P<0.05) as compare with LY294002 group, which suggest that APS has an anti-apoptotic effect on the cryopreserved platelets. APS decreased the expression of Caspase-3 and inhibited the reduction of mitochondrial membrane potential induced by LY294002, moreover, APS could increase the activation of PI3K /AKT pathway in Plt. CONCLUSION APS has an anti-apoptotic effect on the cryopreserved platelets through activating the PI3K /AKT pathway, decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.
Angelica ; Apoptosis ; Blood Platelets ; Chromones ; Morpholines ; Phosphatidylinositol 3-Kinases ; Polysaccharides ; Proto-Oncogene Proteins c-akt

OBJECTIVETo investigate the effect of small interfering RNA (siRNA)-mediated COX-2 gene silencing in enhancing the chemosensitivity of KB/VCR cell lines.

METHODSKB/VCR cells were trasnfected with COX-2 siRNA were examined for expressions of COX-2 and MDR-1 mRNAs with RT-PCR and for Rho-123 accumulation using flow cytometry. MTT assay was used to analyze the proliferation of the transfected KB/VCR cells.

RESULTSCompared with the negative and blank control groups, COX-2 siRNA transfection resulted in significant growth inhibition of KB/VCR cells exposed to vincristine (P<0.01), down-regulated the expressions of COX-2 and MDR-1 mRNAs, and obviously increased Rho-123 accumulation in KB/VCR cells.

CONCLUSIONCOX-2 gene silencing can enhance the chemosensitivity of KB/VCR cells to vincristine, the mechanism of which may involve down-regulated MDR-1 gene expression and inhibition of P-glycoprotein activity.

ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; Cyclooxygenase 2 ; genetics ; metabolism ; Drug Resistance, Neoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; KB Cells ; RNA, Messenger ; RNA, Small Interfering ; Transfection ; Vincristine

OBJECTIVETo investigate the correlation between blood concentrations of tacrolimus (FK506) and cystatin C (Cys C) and the effect of FK506 on glycolipid metabolism in renal transplant recipients.

METHODSA total of 325 patients receiving renal transplantation between August, 2014 and September, 2015 in Nanfang Hospital were divided into 4 groups according to the postoperative time (1 month group, 1-3 months group, 4-6 months group, and 7-12 months group). FK506 blood trough concentration was measured at the time of postoperative follow-up, and creatinine (Scr) and Cys C levels were also detected. Results Plasma FK506 concentration decreased with age in the recipients and showed a positive correlation with Cys C (r=0.985, P=0.015) but no obvious correlation with Scr (r=0.259, P=0.741). FK506 had no effect on blood glucose (5.53-5.59 mmol

CONCLUSIONFK506 does not affect the level of glycolipid metabolism in patients after renal transplantation. Cys C is positively related to blood concentration of FK506 in the renal transplantation recipients. The rational use of FK506 can improve the effectiveness and safety of the treatment in the recipients.

OBJECTIVETo observe the effect of compound Huang Gan in delaying chronic renal failure in rats after 5/6 nephrectomy and explore the possible mechanisms.

METHODSHigh-performance liquid chromatography was used to was used identify the components of compound Huang Gan extract. Rat models of 5/6 nephrectomy received a 12-week treatment with intragastric administration of Niaoduqing, Cozaar, or compound Huang Gan at low, moderate or high doses (n=10). After the treatments, the rats were sacrificed for detecting Scr, BUN, Ucr and 24h UPr , pathological examination of the renal tissues, and determination of FN, MCP-1, and ICAM-1 expression levels in the renal tissues using RT-PCR and immunohistochemistry.

RESULTSThe major chemical components of compound Huang Gan extract included glycyrrhizin (0.61%), paeonol (1.2%), aloe emodin (0.72%), rhein (0.85%), emodin (0.87%), chrysophanol (0.79%) and physcion (0.8%). Treatment with compound Huang Gan at low, moderate and high doses significantly reduced Scr, BUN, Ucr , Ccr and 24 h UPr levels (P(P<0.05), improved interstitial fibrosis and glomerulosclerosis, and reduced FN and ICAM-1 expressions (P(P<0.05) in rats following nephrectomy.

CONCLUSIONSCompound Huang Gan can improve the renal function and lessen glomerulosclerosis and renal interstitial fibrosis to delay the progression of chronic renal failure in rat models of 5/6 nephrectomy.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Fibronectins ; metabolism ; Fibrosis ; Intercellular Adhesion Molecule-1 ; metabolism ; Kidney ; pathology ; Kidney Failure, Chronic ; drug therapy ; Nephrectomy ; Rats

PCR is an enabling and preferred technology for the detection of DNA or mRNA in genomic age, and has been widely used in molecular medicine, biotechnology, microbiology and diagnostics. PCR has many excellent traits, such as high specificity and sensitivity, short handle time, reliable and effective results, low demand for sample. In recent years, real-time reverse transcription PCR (qRT-PCR) has acquired an impressive improvement in the detection of mRNA, it has a perfect sensitivity and can quantify some rare mRNA copies as low as less ten. The progress in PCR results in a more strict demand for sample, so it is necessary to take the potential PCR-inhibitory components in peripheral blood and bone marrow samples into account again. This review explores the potential PCR-inhibitory components in peripheral blood and bone marrow samples, and discusses the possible mechanism and solutions for the inhibition effect, also emphasizes the potent effect of the frequently-used anticoagulant heparin sodium in PCR. This article will be helpful to assess the PCR detection results (especially qRT-PCR ) in some degree, for example, can use it to decide whether the PCR detection results are reasonable for some low-expression genes, or use it to eliminate the false negative results generated by PCR-inhibitory components in sample.
Bone Marrow Examination ; Hematologic Tests ; Humans ; Polymerase Chain Reaction

Objective: To study the clinical efficacy of biological ceramics (iRoot BP Plus ) and mineral trioxide aggregate (MTA) in direct pulp capping of mature permanent teeth, to provide referrence for clinical application. Methods : Seventy-four patients with pulp exposure due to deep caries or reversible pulpitis in 75 mature permanent teeth were selected and were randomly divided into two groups. iRoot BP Plus were used as pulp capping agents in the treatment group and MTA were used as pulp capping agents in the control group respectively. The clinical efficacy and imaging analysis were performed at 1, 3, 6 and 12 months after operation. Treatment success rate of the two groups were calculated, and the influence of various factors including gender, age, tooth position, cavity, number and size of pulp exposure on the efficacy of direct pulp capping were analyzed. Results : Sixty patients with 61 mature permanent teeth were selected. Twelve mouths after treatment, 61 teeth of 60 patents were completely investigated (iRoot group: 31 teeth 30 patients; MTA group: 30 teeth 30 patients). The success rates of the 2 groups were 90.3% (iRoot BP Plus) and 90.0% (MTA), respectively. There was no statistical difference between 2 groups (P>0.05). Statistical analysis also showed that gender, age, tooth position, cavity, number and size of pulp exposure had no significant difference between the two groups (P>0.05). Conclusion Both iRoot BP Plus and MTA are effective in direct pulp capping of mature permanent teeth with carious pulp exposure, while the operation of iRoot is simple and convenient.

OBJECTIVETo establish allo-transplantation model by using mRFP⁺ to eGFP⁺ transgenic mice and to observe the distribution of donor cells and donor-recipient cellular interaction in the bone marrow after semi-solid decalcification (SSD).

METHODSAfter myeloablative irradiation, C57BL/6 female eGFP⁺ transgenic mice were infused with (5 × 10⁶) bone marrow cells from FVB male donor mice through tail vein. The control group was infused with PBS. Then the general conditions, engraftment level, hematopoietic recovery, incidence of GVHD and survival of recipients were evaluated after transplantation. In the recovery process, SSD was used to treat the femora before observing the cells distribution, morphology and interaction by confocal microscopy directly or after making frozen section.

RESULTSWBC of recipient eGFP⁺ mice was recovered on (20 ± 3.07) d, (93.94 ± 1.59)% in peripheral cells were RFP⁺ cells (n = 10), GVHD happened in 4 of 10 mice within 1 month. During SSD, the hard components were replaced gradually and RFP⁺ cells could be seen mainly in the bone trabecula and surrounded by eGFP⁺ cells under confocal microscope, their interactions could be further observed clearly in bone marrow microenvironment in three-dimensional reconstruction.

CONCLUSIONThe double fluorescent allo-transplantation mouse model successfully established, by means of our novel protocol named SSD, the donor and recipient cell location and their interaction can be visually observed, which provides the basis for clinical studies on the distribution and homing of donor cells, and some related explorations after transplantation.

Animals ; Bone Marrow Cells ; Bone Marrow Transplantation ; Disease Models, Animal ; Female ; Graft vs Host Disease ; Green Fluorescent Proteins ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic