Blocking Posttranslational Core Fucosylation Ameliorates Rat Peritoneal Mesothelial Cell Epithelial-Mesenchymal Transition / 中华医学杂志(英文版)

<p><b>Background:</b>Core fucosylation (CF), catalyzed by α-1,6 fucosyltransferase (Fut8) in mammals, plays an important role in pathological processes through posttranslational modification of key signaling receptor proteins, including transforming growth factor (TGF)-β receptors and platelet-derived growth factor (PDGF) receptors. However, its effect on peritoneal fibrosis is unknown. Here, we investigated its influence on epithelial-mesenchymal transition (EMT) of rat peritoneal mesothelial cells (PMCs) in vitro induced by a high-glucose (HG) culture solution.</p><p><b>Methods:</b>Rat PMCs were first cultured in a HG (2.5%) culture solution to observe the CF expression level (fluorescein isothiocyanate-lens culinaris agglutinin), we next established a knockdown model of rat PMCs in vitro with Fut8 small interfering RNA (siRNA) to observe whether inhibiting CF decreases the messenger RNA (mRNA) expression and protein expression of Fut8 and reverses EMT status. Rat PMCs were randomly divided into control group, mock group (transfected with scrambled siRNA), Fut8 siRNA group, HG group, HG + mock group, and HG + Fut8 siRNA group. Finally, we examined the activation of TGF-β/Smad2/3 signaling and PDGF/extracellular signal-regulated kinase (ERK) signaling to observe the influence of CF on them.</p><p><b>Results:</b>CF, Fut8 mRNA, and protein expression were all significantly upregulated in HG- induced EMT model than those in the control rat PMCs (P < 0.05). Fut8 siRNA successfully blocked CF of TGF-β receptors and PDGF receptors and attenuated the EMT status (E-cadherin and α-SMA and phenotypic changes) in HG-induced rat PMCs. In TGF-β/Smad2/3 signaling, Fut8 siRNA did not suppress the protein expression of TGF-β receptors and Smad2/3; however, it significantly suppressed the phosphorylation of Smad2/3 (relative expression folds of HG + Fut8 group vs. HG group: 7.6 ± 0.4 vs. 15.1 ± 0.6, respectively, P < 0.05). In PDGF/ERK signaling, Fut8 siRNA did not suppress the protein expression of PDGF receptors and ERK, but it significantly suppressed the phosphorylation of ERK (relative expression folds of HG + Fut8 group vs. HG group: 8.7 ± 0.9 vs. 15.6 ± 1.2, respectively, P < 0.05). Blocking CF inactivated the activities of TGF-β and PDGF signaling pathways, and subsequently blocked EMT.</p><p><b>Conclusions:</b>These results demonstrate that CF contributes to rat PMC EMT, and that blocking it attenuates EMT. CF regulation is a potential therapeutic target of peritoneal fibrosis.</p>

Impact of chronic kidney disease on serum tumor markers concentrations / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Serum tumor markers have always been of clinical importance in the diagnosis, monitoring disease progression and therapy efficacy for patients with malignant diseases. However, elevated serum tumor markers are found in some benign conditions, especially in chronic kidney disease (CKD). The elevation of them in CKD might cause confusion and misuse of these tumor markers. We conducted this retrospective study to investigate which of the five widely used tumor markers including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) are affected markedly by CKD, in order to use them more effectively.</p><p><b>METHODS</b>Serum tumor marker concentrations, biochemical, hematological parameters, and urinalysis were measured in CKD patients and healthy controls. The positive rate and median tumor markers' level in CKD patients and controls, and those in CKD patients stratified by CKD grade were compared using nonparametric rank tests. Correlation analysis of serum tumor markers and other parameters in CKD patients were performed using the Spearman correlation coefficient. Multivariate Logistic regression analysis was used to estimate the important variables that caused elevated serum concentrations of these markers in CKD patients.</p><p><b>RESULTS</b>The overall positive rates and serum concentrations of Cyfra21-1, SCC, CEA in CKD group were significantly higher than those in control group. Positive rate and serum concentrations of those tumor markers increased as kidney function decreased. Both univariate analysis and multivariate regression analysis showed that the elevations of those tumor markers were not only associated with kidney function, but also with nutritional status.</p><p><b>CONCLUSIONS</b>Serum concentrations of Cyfra21-1, SCC, CEA are significantly influenced by kidney function, as well as nutritional status. Therefore, in clinical work, the indices of kidney function and nutritional status could be simultaneously measured to improve interpretation of the results of those tumor marker concentrations.</p>

Changes of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the change of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients.</p><p><b>METHODS</b>Twenty-one peripheral blood lymphocyte subsets from 62 colorectal carcinoma patients before and after FOLFOX4(including oxaliplatin, 5-fluorouracil and leucovorin) , FOLFRI(including irinotecan, 5-fluorouracil and leucovorin) , or XELOX(including oxaliplatin and capecitabine) regimen chemotherapy were examined by flow cytometry.The differences of these lymphocyte subsets were analyzed.</p><p><b>RESULTS</b>After chemotherapy, the percentages of CD3(+), CD3(+)CD8(+), CD29(+), CD4(+)CD29(+), and CD4(+)CD25(+) cells in peripheral blood of colorectal carcinoma patients increased significantly, while the percentages of CD19(+) and human leukocyte antigen(locus) DR(HLA-DR) (+) cells decreased significantly(P<0.05) .The results of subgroup analysis showed that the patients' CD3(+)CD8(+) and CD4(+)CD25(+) cells increased significantly, CD19(+) and HLA-DR(+) cells decreased significantly after FOLFOX4 regimen chemotherapy(P<0.05) ;CD3(+)CD8(+) cells increased significantly and CD19(+) cells decreased significantly after XELOX regimen chemotherapy(P<0.05) ;while after FOLFRI regimen chemotherapy, there were no significant changes in all 21 lymphocyte subsets(P>0.05) . CD3(+), CD3(+)CD8(+), memory T lymphoctye(45RO(+)) , and CD4(+)CD45RO(+) cells increased significantly(P<0.05) in patients who received no more than 4 cycles of chemotherapy. However, in patients that received 5 to 8 cycles and more than 9 cycles chemotherapy, we only found significant decrease of HLADR(+) cells and significant increase of CD29(+) cells, respectively(P<0.05) .</p><p><b>CONCLUSIONS</b>The humoral immunity is attenuated after chemotherapy in colorectal carcinoma patients. FOLFOX4 may suppress the cellular immunity.Chemotherapy that is less than 4 cycles will strengthens the cellular immunity by modulating body immunity arrangement;however, along with the increase of chemotherapy cycles, the cellular immunity gradually declines in these patients.</p>

Feasibility of peptide mass fingerprinting for differential diagnosis of IgA and non-IgA nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the feasibility of peptide mass fingerprinting for non-invasive differential diagnosis of IgA nephropathy (IgAN) from the non-IgA nephropathy (IgAN).?</p><p><b>METHODS</b>According to the results of renal biopsy, 56 patients were divided into IgAN group (n=28) and non-IgAN group (n=28), and peptide mass fingerprints were acquired from these patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).</p><p><b>RESULTS</b>Nine different peptides were identified between IgAN and non-IgAN. The two most distinctive differentially expressed peptides, with peptide peak values of 4476.46 and 1968.10, showed area under curve values of 86.18% and 79.77%. Principal component analysis demonstrated that the accumulated explained variance of the first 8 differential peptides reached 95%, suggesting the feasibility of differential diagnosis of IgAN from non-IgAN. Comparison with the Matrix protein database identified the peptide with a relative molecular mass of 5338.08 as a fragment of mucin 4 inform and the 2082.77 peptide as fragment of α1-II type collagen inform.</p><p><b>CONCLUSION</b>MALDI-TOF MS is feasible for differential diagnosis of IgAN and non-IgAN and also has great potentials in the classification of the subtypes of other systemic diseases.</p>

Recent Advance in Anti-CD20 Monoclonal Antibody Therapy in B-Cell Lymphoma / 中国实验血液学杂志

Substantial advances in antigen-targeted lymphoma therapy have been achieved in recent years. Monoclonal antibodies targeting B-cell differential antigen CD20 have emerged as promising new treatments. CD20 is a 35 kD non-glycosylated transmembrane phosphoprotein. It is expressed on most mature B-lymphocytes and disappears from the surface of B lineage cells during terminal differentiation into plasma cells. The antigen appears to be involved in the regulation of B-cell development and differentiation and may mediate some of its effects by functioning as a calcium channel. Most importantly, CD20 is expressed on more than 95% of B-cell lymphomas and is not significantly internalized or shed. These features make it an ideal target for monoclonal antibody therapy for B-cell lymphomas. The results of clinical trials have showed that anti-CD20 monoclonal antibodies, which can be utilized in either unmodified form or as carrier for radioisotopes or cytotoxic agents, have significant effects and can be administrated safely with minimum side effects. Many studies have proposed several potential mechanisms to mediate the eradication of tumor cells targeted by anti-CD20 monoclonal antibodies. Ongoing prospective studies will establish some new therapeutic strategies with high anti-lymphoma specificity and low unspecific toxicity.