COL4A5 genotypes and clinical characteristics of children with Alport syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS).@*METHODS@#A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations.@*RESULTS@#Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset.@*CONCLUSIONS@#This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.

In vitro functional similarity assessment of a proposed biosimilar BAT1706 to bevacizumab / 药学学报

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin®. BAT1706 and Avastin® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin® are highly similar in terms of in vitro functional activities.

Comparison of TaqMan and Allglo probe in fluorescence quantitative RT-PCR detection of simian immunodeficiency virus / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the sensitivity and reproducibility of Allglo and TaqMan probe in the detection of simian immunodeficiency virus (SIV) using fluorescence quantitative RT-PCR (QPCR).</p><p><b>METHODS</b>The reference sample of SIV was diluted to 6 gradient concentrations; at each concentration 12 samples were tested to analyze the variations within batches, and each sample was tested for 12 times for analysis of variations between batches by QRT-PCR using TaqMan probe and Allglo probe. The results of QPCR using the two probes were analyzed with ABI7300 PCR system software.</p><p><b>RESULTS</b>In QPCR using TaqMan and Allglo probe, the lower limit of sensitivity for SIV detection was both 50 copies/mL. Assessment of the reproducibility of the tests showed that the maximum and minimum coefficients of variation between batches were 0.63% and 0.33% with Allglo probe, respectively, as compared with 1.33% and 0.2% with TaqMan probe. The maximum and minimum coefficients of inter-batch variation was 1.77% and 0.95% with Allglo probe, respectively, as compared with 1.86% and 1.03% with TaqMan probe.</p><p><b>CONCLUSION</b>Allglo probe shows a better performance then TaqMan probe in detection of SIV QPCR.</p>

Insights into battles between Mycobacterium tuberculosis and macrophages

As the first line of immune defense for Mycobacterium tuberculosis (Mtb), macrophages also provide a major habitat for Mtb to reside in the host for years. The battles between Mtb and macrophages have been constant since ancient times. Triggered upon Mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. Toll-like receptors (TLRs) expressed on macrophages can recognize pathogen-associated-molecular patterns (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as tumor necrosis factor (TNF) and type I Interferons (IFNs). In addition, Vitamin D receptor (VDR) and Vitamin D-1-hydroxylase are up-regulated in Mtb-infected macrophages, by which Vitamin D participates in innate immune responses. The signaling pathways that involve TNF, type I IFNs and Vitamin D are inter-connected, which play critical roles in the regulation of necroptosis, apoptosis, and autophagy of the infected macrophages. This review article summarizes current knowledge about the interactions between Mtb and macrophages, focusing on cellular fates of the Mtb-infected macrophages and the regulatory molecules and cellular pathways involved in those processes.

Phenotypic analysis of luxS gene deletion mutants and its application in virulence regulation research in group B Streptococcus / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the mechanism of virulence regulation in group B streptococcus (BGS) by studying LuxS-related AI-2 quorum-sensing pathway in GBS.</p><p><b>METHODS</b>luxS gene deletion mutants of GBS (Delta lusX) were characterized by reverse transcription (RT)-PCR, colony immunoblot analysis, growth curve measurement, and cAMP determination. Functional analysis of luxS in the deletion mutants was conducted by bioluminescence assay.</p><p><b>RESULTS</b>Genetic analysis results showed that the luxS deletion in the mutant 515-Delta lusX caused upregulation of scpB gene expression. Phenotypic analysis revealed that, in comparison with the wild strain, 515-Delta lusX mutant grew slowly in DCM media but quickly in THY media. An approximately two-fold decrement in bioluminescence was detected in the luxS deletion mutants as compared with the wild strain.</p><p><b>CONCLUSION</b>This study confirms the importance of LuxS molecule in the AI-2 quorum-sensing pathway in GBS and provides new insights into the virulence regulation mechanism of GBS.</p>

Protective Effect of Heparin on Kidneys of Children with Henoch-Schonlein Purpura / 实用儿科临床杂志

Objective To explore protective effect of heparin on renal of children with Henoch-Schonlein purpura(HSP).Methods Two hundred and fifteen cases with HSP were divided into heparin-treated group(110 cases,male 64,female 46) and control group (105 cases,male 61,female 44).Serum IL-6 and IL-8 levels were examined by using radioimmunoassay respectively.These patients were followed up for more than 6 months.Results 1.The level of IL-6,IL-8 did not show significant difference between heparin-treated group and control group before treatment.The serum concentrations of IL-6,IL-8 in heparin-treated group were obviously lower than those in control group,after treatment,there was significantly different[IL-6(116.50?19.45)vs(123.88?22.55)ng /L,t=2.573 P=0.011;IL-8(0.161?0.043)vs(0.173?0.048)?g/L,t=2.024 P=0.044].2.During more than 6 months follow-up there were 26 cases suffering from purpura nephritis in heparin-treated group, the morbidity was 25%; the morbidity in control group was 39.8%,the morbidity in treatment group was significant lower than that in control group(?2=5.061 P=0.024).The time of renal injury was significantly delay in treatment group(35.0?13.2)d compared with that of control group (26.0?12.1)d(t=2.659 P=0.010).Conclusions The serum IL-6 and IL-8 concentrations in HSP obviously decrease after heparin treatment.Heparin therapy can decrease the morbidity of renal injury in children with HSP and delay the time of renal injury effectively.