ABSTRACT
Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC50) was 13.8 μmol·L-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC50: 41.99 μmol·L-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.
ABSTRACT
Compared with the racemate of chiral drugs, enantiopure chiral drugs have been the hot spot of drug research because of their higher selectivity and lower side-effects. Although remarkable progress of asymmetric synthesis has been achieved in the last decades, chiral resolution is regarded as an important approach to obtain chiral drugs. Recent research advancements in the field of chiral resolution of racemic drugs and intermediates are reviewed here. It is clear that combination of chiral separation and racemization to improve the resolution efficiency has become a trend of chiral resolution. In addition, we also introduce some novel resolution methods, such as chiral extraction, membrane resolution, and resolution using nanoparticles.
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<p><b>OBJECTIVE</b>To compare the efficacy between synchronized intermittent mandatory ventilation (SIMV) and pressure support ventilation with volume guarantee (PSV+VG) in the weaning phase of preterm infants with respiratory distress syndrome (RDS).</p><p><b>METHODS</b>Forty preterm infants with RDS who were admitted to the neonatal intensive care unit between March 2016 and May 2017 were enrolled as subjects. All infants were born at less than 32 weeks' gestation and received mechanical ventilation. These patients were randomly and equally divided into SIMV group and PSV+VG group in the weaning phase. Ventilator parameters, arterial blood gas, weaning duration (from onset of weaning to extubation), duration of nasal continuous positive airway pressure (NCPAP) after extubation, extubation failure rate, the incidence rates of pneumothorax, patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD), and the mortality rate were compared between the two groups.</p><p><b>RESULTS</b>The PSV+VG group had significantly decreased mean airway pressure, weaning duration, duration of NCPAP after extubation, and extubation failure rate compared with the SIMV group (P<0.05). There were no significant differences in arterial blood gas, mortality, or incidence rates of pneumothorax, PDA and BPD between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>For preterm infants with RDS, the PSV+VG mode may be a relatively safe and effective mode in the weaning phase. However, multi-center clinical trials with large sample sizes are needed to confirm the conclusion.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the percentages of peripheral blood γδ T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-β1 (TGF-β1), in infants with human cytomegalovirus (HCMV) infection.</p><p><b>METHODS</b>Twenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood γδ T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-β1 in plasma were measured using ELISA.</p><p><b>RESULTS</b>Compared with the control group, the HCMV group had significantly higher percentage of γδ T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-β1 level (P<0.01). In the HCMV group, the percentage of γδ T cells was negatively correlated with the percentage of Treg cells and TGF-β1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-β1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-β1 level (P>0.05).</p><p><b>CONCLUSIONS</b>There is an imbalance between γδ T cells and Treg cells in the peripheral blood of infants with HCMV infection, and γδ T cells may be involved in the secretion of IL-17.</p>
Subject(s)
Female , Humans , Infant , Male , Cytokines , Blood , Cytomegalovirus Infections , Allergy and Immunology , Interleukin-17 , Blood , Receptors, Antigen, T-Cell, gamma-delta , T-Lymphocytes, Regulatory , Allergy and Immunology , Transforming Growth Factor beta1 , BloodABSTRACT
@#AIM: To investigate the detrimental effect of glucocorticoid(GC)on the retinal neurons of diabetes mellitus(DM)rats.<p>METHODS: The DM model was induced by intraperitoneal injection(IP)of streptozotocin in adult male rats, and the solution of RU486 was configured with dimethyl sulfoxide(DMSO). RU486 treatment group with glucocorticoid receptor antagonist RU486 and diabetic group with DMSO by intraperitoneal injection was in successful DM model. Naive rats were injected with DMSO as control group. Three months later, we detected the body weight and blood glucose and GC concentration of serum. The changes of retinal ganglion cell(RGC)density was investigated by HE staining. The expression of growth associated protein-43(GAP-43, a marker of neuronal axon regeneration)and synaptophysin(SYN, a marker of synaptic number)were semi-quantity analyzed by the optical density of immunofluorescence and Western blot.<p>RESULTS:Compared with the control group, the body weight and density of RGC and expression of SYN in diabetic group were significantly lower(<i>P</i><0.01), the blood glucose and GC concentration of serum and expression of GAP-43 in diabetic group were significantly higher(<i>P</i><0.01). Compared with the diabetic group, the density of RGC and expression of GAP-43, SYN in RU486 group were significantly higher(<i>P</i><0.01).<p>CONCLUSION: Inhibition of GC could ameliorate the axonal degeneration of retinal neurons in diabetic rats, and loss of the number of synapses, and restore the RGC density of retina. The results suggest that long-term elevation of GC may be involved in the occurrence and development of diabetic retinopathy.
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<p><b>OBJECTIVE</b>To examine the expression of calreticulin (CRT) and the changes of intracellular free calcium and neuronal apoptosis in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage (HIBD), and to investigate the intervention effects of Shenfu injection.</p><p><b>METHODS</b>Seven-day-old rats were randomly assigned to three groups: control, hypoxic-ischemia (HI) and Shenfu-treated. Each group (n=50) was subdivided into 5 groups sacrificed at 3, 6, 12, 24 and 72 hours. Rat models of HIBD were prepared according to the Rice's method. Rats in the control group only underwent the separation of right common carotidartery. Shenfu injection was administered by intraperitoneal injections right after HI insults and then once daily at a dosage of 10 mL/kg for 3 days in the Shenfu-treated group. The expression of CRT in the cerebral cortex was detected by RT-PCR and Western blot. The free calcium concentrations were determined under a fluorescent microscope. The apoptosis rate was measured by the flow cytometry.</p><p><b>RESULTS</b>Compared with the control group, the expression levels of CRT in the HI and the Shenfu-treated groups were obviously up-regulated (P<0.05), and the expression levels of CRT in the Shenfu-treated group were notably higher than those in the HI group (P<0.05) at all time points. The concentrations of intracellular free calcium and the apoptosis rate of neurons in the cerebral cortex in the Shenfu-treated group were significantly reduced compared with those in the HI group (P<0.05), but increased significantly compared with those in the control group at all time points (P<0.05).</p><p><b>CONCLUSIONS</b>Shenfu injection may have neuroprotective effects against HIBD by up-regulation of CRT expression and relief of calcium overload.</p>