Objective In order to study the value of drug treatment for leukemia, quercetin was delivered to the cultured NB4 cell line. MethodsUsing RT- PCR and western blot, we studied the expression of mutant p53 gene and protein after inducing 24, 48, 72, 96 and 120h by the quercetin with different concentrations (30, 60, 90μmol/L). Results We verified the results that quercetin with concentration of 30 ～90μmol/L could successfully inhibit the expression of mutant p53 protein, but the mutant p53 gene did not have. ConclusionThat data suggested that quercetin would be an effective method for the therapy of leukemia.

The author introduces the basic concepts of microsatellite and population genetics and its characteristics, expounds the application of these theories for population genetic structure and genetic diversity, gene flow and evolutionary significant unit ESU division research. This paper discuss its applicationin study of genetic causes, origin of cultivation, different regional origins of geoherbs, aiming at providing a new theory and method for geoherbs.
Drugs, Chinese Herbal ; Evolution, Molecular ; Genetic Markers ; genetics ; Genetic Techniques ; Geography ; Microsatellite Repeats ; genetics

Adult ; Ambroxol ; administration & dosage ; therapeutic use ; Expectorants ; administration & dosage ; therapeutic use ; Female ; Glycoproteins ; therapeutic use ; Humans ; Lung ; pathology ; Lung Injury ; drug therapy ; pathology ; Male ; Paraquat ; poisoning ; Respiratory Distress Syndrome, Adult ; drug therapy ; etiology ; Retrospective Studies ; Young Adult

ObjectiveTo observe the effects of mild hypothermia on post-resuscitation myocardial dysfunction in rabbits in order to elucidate the underlying mechanism of hypothermia.Methods After setting up rabbit model of cardiopulmonary resuscitation,20 rabbits were randomly ( random number)divided into two groups,namely normothermic resuscitation group (group A,n =10 ) and post-ROSC hypothermia group ( group B,n =10).In the group A,animals wore treated with standard CPR after cardiac arrest.In post-ROSC hypothermia group,the body temperature of animals was cooled to 32 ～ 34°C after successful ROSC.The left ventricular end-diastolic pressure (LVEDP),left ventricular pressure rise and fall rates ( ± dp/dtmax,serum concentrations of heart-type fatty acid-binding protein (H-FABP) and 8-isoprostaglandin F2a (8-iso-PGF2a) and Cyclooxygenase-2 (COX-2) were observed. Results Compared with the A group,the B group had significantly better hemodynamics,and lower serum H-FABP,8-isoPGF2a and COX-2 levels in the early stage of post-resuscitation ( both P ＜ 0.05 ).ConclusionsMild hypothermia attenuated post-resuscitation myocardial dysfunction during the early period of postresuscitation.The cryoprotective effect on myooardium is likely associated with the reduction of 8-iso-PGF2a and COX-2.

Objective To evaluate the effect of propofol on noise-induced hearing loss in guinea pigs.Methods Forty-eight healthy adult male guinea pigs,aged 3 months,weighing 400-500 g,were randomly divided into 4 groups (n =12 each) using a random number table:control grotup (C group),propofol group (P group),noise-induced hearing loss group (N group),and propofol + noise-induced hearing loss group (P + N group).A loading dose of propofol 5 mg/kg was infused intravenously over 5 min,followed by infusion at 20 mg· kg-1 · h-1 for 115 min in P and P + N groups,while the equal volume of normal saline was given in N group.N and P+ N groups were exposed to the noise of 4 kHz center frequency and 118-122 dB sound pressure level for 120 min.Distortion product otoacoustic emission (DPOAE) was measured before noise exposure (T1) and at 1 h after the end of noise exposure (T2) and the amplitudes were recorded at the frequencies of 2,4,6 and 8 kHz.After the second measurement of DPOAE,all the animals were sacrificed and organs of Corti were harvested for determination of cochlear 8-isoprostaglandin F(2alpha) (8-iso-PGF2α) content (by ELISA assay) and out hair cell (OHC) count.The rate of OHC lesions was calculated.Results The DPOAE amplitude was significantly lower at frequencies of 4,6 and 8 kHz at T2 than at T1 in N and P + N groups (P ＜ 0.05).Compared with C group,the DPOAE amplitude was significantly decreased at frequencies of 4,6 and 8 kHz at T2,while the cochlear 8-isoPGF2α content and rate of OHC lesions were increased in N and P + N groups (P ＜ 0.05).Compared with N group,the DPOAE amplitude was significantly increased at frequencies of 4,6 and 8 kHz at T2,while the cochlear 8-iso-PGF2α content and rate of OHC lesion were decreased in P + N group (P ＜ 0.05).Conclusion Propofol can reduce noise-induced hearing loss in guinea pigs possibility through decreasing oxidative stress response-induced damage to cochlear OHCs.

0.05).The abrupt onset of the inflammatory arteriopathy group was 10 cases(31.2%),the abrupt onset of the noninflammatory arteriopathy group was 38 cases(58.5%),there was significant difference for the mode of onset between the 2 groups(?2=6.352 P

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Objective To investigate whether mesenchymal stem cells can promote the recovery of acute renal tubular damage induced by mercuric chloride and to explore its possible mechanism.Methods Acute renal failure rat model was established by intraperitoneal injection of mercuric chloride.SD rats were randomly divided into three groups which were MSCs injection group, saline infusion group and normal control group.Seven days later,the changes of rat weight,survival,renal function and pathology were observed;PCNA,ED-1 and GFP were detected by immunohistochemistry; The expression of cytokines in kidney and the distribution of GFP plasmid-transfected MSCs in kidney were examined by RT-PCR.Results MSCs infusion ameliorated the decline of rat weight,survival, renal function,and pathological changes.PCNA and ED-1 positive cells in MSCs group were fewer than those in saline group.Expression of growth factors EGF,PDGF,HGF were obviously up- regulated and pre-inflammatory cytokines TNF-?was significantly reduced in MSCs-treated kidneys. GFP-labelled MSCs occurred occasionally in renal interstitium of MSCs-treated rats,but not in renal tubules.Conclusions Bone marrow mesenchymal stem cells can promote the recovery of acute renal tubular epithelial cells damage caused by mercuric chloride.The mechanism may partly depend on regulating the excretion of cytokines in renal microenvironment rather than completely depend on their differentiation to tubular cells.

Objective To investigate the relationship between the promoter of IL-12B gene polymorphism and the susceptibility and clinical features of chronic gastritis and duodenal ulcer with or without Helicobacter pylori(Hp) infection in children and adolescent.Methods Mucosal biopsies were obtained from 132 children and adolescent (patient group),including 100 children with chronic gastritis and 32 children with duodenal ulcer,undergoing an upper gastrointestinal endoscopy for dyspeptic symptoms.Biopsy specimens were stained with hematoxilin and eosin (HE),and gastritis was graded according to the Sydney system.Serology,urease test and histology were taken to assess Hp status.Genomic DNA was obtained from peripheral blood or gastric biopsies of patients and 102 healthy children as normal control group.The promoter of IL-12B +1188A/G gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing.The genotype distributions and allele frequencies were compared between the study group and the normal control group,and the association of genotypes with clinicopathological features was studied.IL-12B mRNA level expressions in gastric mucosa were confirmed by reverse transcription PCR biopsy-based tests.Results The genotype distributions and allele frequencies of IL-12B +1188A/G gene polymorphisms were similar in gastric upper gastrointestinal diseases and healthy subjects.The IL-12B +1188A/G gene polymorphisms were not associated with Hp status.IL-12B+1188A/G gene polymorphisms did not affect IL-12B mRNA level expressions and were not associated with the degree of antrum chronic inflammation.Conclusions These data suggest that IL-12B+1188A/G gene polymorphisms are not associated with susceptibility to chronic gastritis and duodenal ulcer in children and adolescent.

According to the designed specific primers of gene fragment based on the Salvia miltiorrhiza transcriptome data, with the method of reverse transcription polymerase chain reaction (RT-PCR), this study cloned full-length cDNA sequence of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase gene from Salvia miltiorrhiza bge.f.alba, this sequence is named as SmHDS and its GenBank registration number is KJ746807. SmHDS, 2 529 bp long, contains an ORF of 2 229 bp, encodes 742 amino acids, including 5' UTR 170 bp and 3' UTR 130 bp. Using bioinformatics software, having made a homology analysis of the obtained sequence, we can have a conclusion that SmHDS have a close genetic relationship with HDS of Salvia miltiorrhiza. Analysis result of prokaryotic expression revealed that in Escherichia coli, SmHDS expressed target proteins which in size are comparable with the protein predicted. Meanwhile, the 4 factors which can influence the protein expression were optimized, the 4 factors are inducing temperature, inducing time, IPTG concentrations and density of inducing host bacterium (A600). The optimal expression conditions of SmHDS were 30 degrees C until the A600 is 0.6, and add IPTG to a final concentration of 0.2 mmol x L(-1), and the induction time of 20 h. It provides theoretical basis for the further study of the function of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase in the biosynthesis of tanshinone compounds.
Cloning, Molecular ; DNA, Complementary ; genetics ; Diterpenes, Abietane ; biosynthesis ; Enzymes ; biosynthesis ; genetics ; Escherichia coli ; metabolism ; Plant Proteins ; biosynthesis ; genetics ; Salvia miltiorrhiza ; enzymology ; genetics