Photodynamic therapy ( PDT ) is a new technique to diagnose and treat diseases with photodynamic effect produced by photosensitizer and light, and is now a main method of treating exudative age - related macular degeneration ( AMD ) . ln recent years, with the development of science and technology, combinations of PDT have become a research hot spot. ln this paper, we reviewed the research status of treatments on exudative AMD with PDT combined anti-VEGF drugs.

OBJECTIVETo investigate the effects of α3 neuronal nicotinic acetylcholine receptor (nAChR) on apoptosis and p38 signal transduction pathway in SH-SY5Y cells and to assess the roles of α3 nAChR in the pathogenesis of Alzheimer's disease (AD).

METHODSThe levels of α3 nAChR mRNA and protein were measured by real-time PCR and Western blot, respectively, in SH-SY5Y cells transfected with α3 nAChR siRNA. The mRNA level of bcl-2 and bax was measured by the real-time PCR. The siRNA transfected SH-SY5Y cells and control were then treated with 10 µmol/L Aβ25-35 for another 48 h, and the change in apoptotic rate and the levels of p-p38 and p38 were measured by flow cytometry and Western blot. Subsequently these SH-SY5Y cells were exposed to a blocker of p38 protein, and the apoptotic rate was measured again.

RESULTSCompared to the controls, the expression of α3 nAChR at mRNA and protein levels in the SH-SY5Y cells transfected with α3 nAChR siRNA decreased by 95% and 86%, respectively; the mRNA levels of bax increased 2.11 times and that for bcl-2 decreased 0.53 times. The apoptotic rate was unaffected (3.40% ± 0.20%); but it increased after Aβ25-35 treatment (24.52% ± 1.59%); the level of p-p38 protein also increased by 178% in the α3 nAChR inhibited cells treated with Aβ25-35. Compared to controls, the Aβ25-35-treated SH-SY5Y cells and the Aβ25-35-treated and siRNA-transfected cells both showed a reduction in apoptosis after treatment with p38 blocker, especially in the former.

CONCLUSIONThe siRNA silencing of α3 nAChR mRNA may enhance the effect of Aβ25-35 on the cell apoptosis by increasing the levels of p38 protein and bax mRNA and decreasing the level of bcl-2 mRNA, which may play a role in the pathogenesis of AD.

Alzheimer Disease ; etiology ; Amyloid beta-Peptides ; metabolism ; Apoptosis ; Cell Line, Tumor ; Gene Silencing ; Humans ; Neuroblastoma ; metabolism ; pathology ; Peptide Fragments ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, Nicotinic ; genetics ; metabolism ; Signal Transduction ; Transfection ; bcl-2-Associated X Protein ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

A high proportion of modified nucleotides has been found in mitochondrial tRNA. Such modification can promote accurate folding of tRNA and its stability, while unmodified mitochondrial tRNA may fold into various 2D-structures with impaired functions. Therefore, modification of mitochondrial tRNA is closely related to mitochondrial diseases. Particularly, positions 9, 34, 37, 54 and 55 of the mitochondrial tRNA are critical for such modification. Mutations at these positions are important cause for mitochondrial dysfunction and have been associated with various mitochondrial diseases.
DNA, Mitochondrial ; chemistry ; genetics ; Humans ; Mitochondrial Diseases ; genetics ; Mutation ; Nucleic Acid Conformation ; RNA, Transfer ; chemistry ; genetics

To have a better understanding on the evolution of Metallosphaera sedula-mediated precipitation and the properties of the precipitate synthesized by this species，a newly identified extremely thermophilic strain (YN23) of Metallosphaera sedula was cultured in the medium containing Fe2+ as energy resouTce under optimal condidons (pH1.5，65℃,0.2g·1-1 yeast extract,30g·1-1 Fe2SO4·7H2O and 170rpm)．XRD，EDS，ETIR and SEM reveal the precipitate obtained from YN23-inoculated flasks to be a mixture of potassium jarosite and ammoniojarosite，with morphological features similar to the latter．Precipitation Was first detected once over 90％ of Fe2+ was oxidized at hour 25 with a peak pH value of 1.92，and was ended when precipitate reached the highest point of 7.9g·1-1 at hour 95 with the lowest pH value of 1.32 in solution．Microbial density underwent a rapid increase along with Fe2+ oxidation and a gradual decrease with precipitate piling up.

BACKGROUNDMycoplasma pneumoniae (M. pneumoniae) is one of the common pathogens causing atypical pneumonia. In recent years, resistance to macrolides has become more common, especially in China. Previous studies have confirmed that the mutation at position 2063 in domain V of the 23S rRNA is the most prevalent, followed by the mutation at position 2064. Reported molecular detection methods for the identification of these mutations include direct sequencing, restriction fragment length polymorphism analysis, real-time polymerase chain reaction (PCR) with high-resolution melt analysis, and nested PCR-linked with capillary electrophoresis, etc. The most commonly used method for monitoring resistance-conferring mutations in M. pneumoniae is direct DNA sequencing of PCR or nested PCR products. However, these methods are time-consuming, labor-intensive or need expensive equipments. Therefore the development of rapid and sensitive methods is very important for monitoring the resistance globally.

METHODSIn this study, we reported a fast and cost-effective method for detecting 2063 and/or 2064 macrolide resistant mutations from specimens using a modified allele-specific PCR analysis, and all results were compared with the sequencing data. We also analyzed the clinical courses of these samples to confirm the modified allele-specific PCR results.

RESULTSAmong 97 M. pneumoniae specimens, 88 were found to possess mutations by this method, and all modified allele-specific PCR analysis results were consistent with the sequencing data. The data of the clinical courses of these 97 cases showed that they suffered from severe pneumonia. Erythromycin showed better efficacy on cases from which no macrolide resistance mutation was found on their specimens. However, in some cases from which mutations were detected, erythromycin monotherapy had poor efficacy, and on these patients severe symptoms improved only when azithromycin was added to the treatment.

CONCLUSIONSThe drug-resistant M. pneumoniae is very common in Beijing, China. Our modified allele-specific PCR analysis can identify erythromycin resistant mutations more rapidly from specimens than any other method currently available. Erythromycin is still effective for treating patients infected with the mutation negative M. pneumoniae, but this treatment fails to work on mutant organisms. This method can facilitate clinicians in selecting appropriate therapy within short timescales.

Alleles ; Anti-Bacterial Agents ; pharmacology ; China ; Drug Resistance, Bacterial ; genetics ; Erythromycin ; pharmacology ; Mycoplasma pneumoniae ; drug effects ; genetics ; Polymerase Chain Reaction ; methods

The objective of study was to investigate the expressions of CD80, CD86 and its ligand CD28 on peripheral lymphocytes in patients with idiopathic thrombocytopenic purpura (ITP), to explore the effect of interleukin 18 (IL-18) and its clinical significance in ITP. The expressions of co-stimulatory molecules (CD80, CD86 and its ligand CD28) on peripheral lymphocytes from 34 ITP patients and 34 normal humans were detected by immunofluorescence and flow cytometry. The IL-18 in the plasma was detected by using enzyme linked immunosorbent assay (ELISA). The results showed that the expressions of CD80 and CD86 on peripheral lymphocytes from ITP patients were higher than that of the normal control (4.21 +/- 2.27%, 7.19 +/- 5.16% vs 2.34 +/- 0.87%, 4.08 +/- 1.96%) (P < 0.01); the concentration of IL-18 in plasma of ITP patients was (538.31 +/- 111.33) pg/ml, but the concentration of IL-18 in plasma of controls was (489.44 +/- 49.07) pg/ml. The level of IL-18 negatively correlated with the platelet counts in peripheral blood (r = -0.395, P < 0.05). It is concluded that the CD28/CD80 and CD28/CD86 costimulatory molecules are overexpressed, when the IL-18 level in ITP patients is obviously higher than that in normal controls. When ITP occurred, and the co-stimulatory molecules CD80 and CD86 are closely associated with ITP, it seems that IL-18 may play an important role in ITP pathogenesis.
B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; CD28 Antigens ; metabolism ; Humans ; Interleukin-18 ; blood ; Lymphocytes ; metabolism ; Purpura, Thrombocytopenic, Idiopathic ; blood ; immunology

OBJECTIVETo investigate the relationship between the distribution of mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA-DRB1*11 gene episodes and the therapeutic effects of alpha-IFN treatment in chronic hepatitis B patients.

METHODSOne hundred seven chronic hepatitis patients from Nanjing Second Hospital who were treated by alpha-IFN for 12 months and then followed at least six months without the treatment were randomly selected for this regressive analysis. They were grouped into a continuous responsive group and a non-continuous responsive group. Hepatitis B virus X interacting protein gene locus was searched in NCBI. Single nucleotide polymorphism (SNP) gene locus was detected based on a pooling sequencing method. Primer and TaqMan-MGB probes referring to different mononucleotide loci were designed respectively to detect SNP in five regulation regions of alpha-IFN. Then gene sequencing differences between the two groups were analyzed.

RESULTSAmong the 107 cases there were 30 cases (28.0%) in the continuous responsive group and 77 cases (71.9%) in the non-continuous responsive group. CT occupation rate in five regulation regions of IFN reached 18.0% in the continuous responsive group and 23.8% in the non-continuous responsive group. AG occupation rate reached 10.8% in the former group and 15.8% in the latter group. The differences in CT and AG between the two groups were significant.

CONCLUSIONSThe distribution of mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA-DRB1*11 gene episodes affects the IFN anti-virus treatment. Detecting the gene distribution of mononucleotide in five regulation regions of alpha-IFN helps in predicting the therapeutic effects of alpha-IFN.

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; Genotype ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; genetics ; Humans ; Interferon-alpha ; therapeutic use ; Polymorphism, Single Nucleotide ; Regression Analysis ; Treatment Outcome ; Young Adult

Invasion and metastasis are key factors contributing to the high mortality rate of patients with hepatocellular carcinoma (HCC) involving a complex mechanism. In the invasion and metastasis of HCC, miRNAs can serve as either oncogenes or tumor suppressor genes to regulate the differentiation and proliferation of tumor cells being and play important roles in tumorigenesis, angiogenesis, invasion and metastasis. This review summarizes the recent progress in research of the molecular mechanisms by which miRNAs targeting GSK-3β regulate HCC invasion and metastasis and examines the roles of miRNAs in hepatocellular carcinoma cell proliferation, apoptosis, invasion, metastasis, and GSK-3β regulation.

OBJECTIVETo compare the knee osteoarthritis (OA) models in rabbits by different concentrations of papain and provide data for exploring pathogenesis and treatments of this disease.

METHODSSixty New Zealand white rabbits were randomly divided into four groups of 15 each and given injections into the right knee on days 1, 3 and 5 including intra-articular injections of 2%, 5% or 10% (w/v) papain and 0.03 mol/L L-cysteine at the dose of 0.1 ml/kg (experimental groups). The 0.9% NaCl (w/v) with a dose of 0.1 ml/kg were injected intra-articularly into the right knees of rabbits in the control group. The rabbits were sacrificed at 2, 4, 6 weeks respectively after the initiation of papain injection and these OA models were evaluated through recording the width of knee joint, performing the morphological observation and histological evaluation of articular cartilage and synovium.

RESULTSThe degenerative changes were demonstrated in knee joints of rabbit in all experimental groups, such as thinner articular cartilage, fibrillation and destroyed cartilage matrix, and inflammation, proliferation, and degeneration of the synovial tissue. All these changes were much worse with increased concentration and prolonged observation time.

CONCLUSIONDifferent severity of OA are established through intra-articular injections of 2%, 5% or 10% papain and 0.03 mol/L L-cysteine at the dose of 0.1 ml/kg. These models are of the characters of short period and a good reproducibility.

Animals ; Disease Models, Animal ; Male ; Osteoarthritis, Knee ; chemically induced ; pathology ; Papain ; toxicity ; Rabbits

Mitochondrial tRNAgene mutation is closely related to acoustic nerve deafness. Some mutations can affect the structure and transcriptional processing of tRNA, for instance m.7444G>A mutation in tRNAprecursor 3' side, m.7472 insC as well as m.7511T>C mutations in the stem and ring of tRNA, may influence tRNAstability, thus affect the synthesis of mitochondrial peptides, reduce the production of ATP and cause deafness. This article focuses on mitochondrial tRNAgene mutations as well as the mechanism underlying hearing loss.
Amino Acid Sequence ; Base Sequence ; Genetic Predisposition to Disease ; genetics ; Hearing Loss ; genetics ; Humans ; Mitochondrial Proteins ; biosynthesis ; genetics ; Mutation ; Nucleic Acid Conformation ; RNA ; chemistry ; genetics ; RNA, Transfer, Ser ; chemistry ; genetics