BACKGROUND: Mesenchymal stem cells are a kind of adult stem cells with self-renewal and multi-directional differentiation potential. These cells have the functions of immunoregulation, regulation of cell growth and repair of injury. In recent years, it has been found that when inflammatory injury occurs, mesenchymal stem cells can regulate the secretion of inflammatory factors, and function on the damaged region, thereby repairing and improving tissue damage caused by inflammation. OBJECTIVE: To review the immunoregulatory effects of mesenchymal stem cells on T lymphocytes, B lymphocytes, dendritic cells and natural killer cells when the body is in an inflammatory state. METHODS: A computer-based search of PubMed and CNKI was performed for articles published from 2000 to 2018 using the keywords of"inflammatory microenvironment, mesenchymal stem cell, immune response, T cell, B cell, DC, NK cell" in English and Chinese, respectively. Seventy-six articles related to the topic and with reliable arguments were finally included in result analysis. RESULTS AND CONCLUSION: The interaction between mesenchymal stem cells and inflammatory cells determines the result of tissue damage repair. In an inflammatory state, the biological characteristics of mesenchymal stem cells will undergo certain changes, but mesenchymal stem cells can still exert immunomodulatory effects by secretion of various soluble cytokines or via cell contact. There are still many problems to be further explored to facilitate better clinical application of mesenchymal stem cells.

Carnosic acid (CA) is the main phenolic diterpenoid active ingredient in plants such as rosemary and sage, and has antiviral, antioxidant, anti-inflammatory effects and so on, however, its antiviral activity against influenza virus infections was not reported. In this study, antiviral activities against influenza A virus infections of three main bioactive ingredients from rosemary, including rosmarinic acid, CA and ursolic acid, were evaluated using virus titer titration assay, and CA showed remarkable inhibition on influenza H5N1 replication in A549 cells. The antiviral activity of CA was further confirmed and its mechanism of action was investigated using the indirect immunofluorescence assay (IFA), Western blot and real-time fluorescence quantification polymerase chain reaction (qRT-PCR). The results showed that the 50% effective concentration (EC₅₀) of CA against influenza H5N1 in A549 cells and MDCK cells were 4.30 and 3.64 μmol·L^-1, respectively. Meanwhile, CA also showed inhibition on influenza virus 2009panH1N1 (EC₅₀: 10.1 μmol·L^-1) and H3N2 (EC₅₀: 12.8 μmol·L^-1) replications in A549 cells. Mechanistic studies showed that antiviral activity of CA is related to its induction of heme oxygenase-1 (HO-1) in A549 cells and suppression on production of reactive oxygen in H5N1-infected cells.

OBJECTIVETo evaluate the association between polymorphism of transforming growth factor-β1 (TGF-β1)-509C/T and radiochemotherapy response and survival in esophageal squamous cell carcinoma (ESCC) patients.

METHODSThe genotype of TGF-β1-509C/T was detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 230 ESCC patients receiving radiotherapy alone or in combination with chemotherapy. Unconditional multivariate logistic regression analysis was done to estimate adjusted odds ratios (ORs) along with the corresponding 95% confidence intervals (CIs) for the polymorphism and radiochemotherapy response. The associations between overall survival time or hazard ratio (HR) of ESCC patients and genetic variation or the clinical data were estimated by applying univariate and multivariate Cox-regression analyses.

RESULTSAmong 208 patients with upper gastrointestinal contrast assessment, 87 cases were susceptible to radiochemotherapy treatment and the TGF-β1-509CC, CT and TT genotype patients were 17 (19.5%), 48 (55.2%) and 22 (25.3%), respectively. Among the patients who were insensitive to radiochemotherapy treatment (n = 121), the TGF-β1-509CC, CT and TT genotype patients were 39 (32.2%), 54 (44.6%) and 28 (23.2%), respectively. Compared with TGF-β1-509CC genotype, the CT and TT genotype carriers had a significantly better treatment response (adjusted OR = 2.07, 95%CI, 1.05 - 4.09, P = 0.036). The median survival time of CC genotype patients was 17.0 (95%CI, 12.0 - 23.0) months, CT genotype patients was 22.0 (95%CI, 16.0 - 33.0) months and TT genotype patients was 25.0 (95%CI, 15.0 - 41.0) months. Compared to CC genotype patients, the survival time difference of CT and TT group was close to the statistical break point (P = 0.063). Our data showed that the subjects with CT or TT genotype had an decreased HR respectively as compared with those with CC genotype (CT, adjusted HR = 0.81, 95%CI, 0.52 - 1.24; TT, adjusted HR = 0.86, 95%CI, 0.65 - 1.12), but the difference was not statistically significant (P > 0.05). However, tumor location, clinical stage and radiochemotherapy response affected the overall survival time of the patient significantly (adjusted HR = 1.28, 95%CI: 1.01 - 1.61, P = 0.040; 1.49, 95%CI, 1.17 - 1.88, P = 0.001; 1.55, 95%CI, 1.06 - 2.26, P = 0.023, respectively).

CONCLUSIONThese results suggest that TGF-β1-509C/T polymorphisms were associated with radiochemotherapy for esophageal squamous cell carcinoma which might be genetic markers for prediction of the radiochemotherapy response in ESCC patients.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; radiotherapy ; Esophageal Neoplasms ; drug therapy ; genetics ; radiotherapy ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Survival Rate ; Transforming Growth Factor beta1 ; genetics ; Treatment Outcome

IMM0306 is a recombinant human signal regulatory protein α-anti-CD20 mouse chimeric antibody fusion protein, intended to treat refractory or recurrent CD20 positive B-cell non-Hodgkin lymphoma (B-NHL) in clinical. In this study, an ELISA method was established to evaluate the pharmacokinetics of IMM0306 in human serum. The experiment was approved by the Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences (No. CTR20192612). Recombinant human CD47 protein was coated with the plate overnight, blocking the plate with 5% skin milk for 2 h. After washing, 100 μL per well standard and unknown samples were added, and incubated for 1.5 h. After washing, the detection antibody Anti-IMM0306-Biotin was added and incubated for 1 h, and then HRP-labeled streptavidin was added for 1 h, and the color was detected. The optimal concentration of coating reagent was 2 μg·mL^-1 by ELISA method, and the optimal dilution of anti-IMM0306-biotin and SA-HRP were 1∶500 and 1∶5 000, respectively. The lower limit of quantitation was 4 ng·mL^-1, and the standard curve range was 4-100 ng·mL^-1. The verification results of the method meets the corresponding acceptance criteria, and can be used in IMM0306 clinical pharmacokinetic studies.

The differences of transitional components and metabolic processes of Huatan Jiangqi Capsules(HTJQ) in rats under normal physiological and pathological conditions of COPD were analyzed by UPLC-Q-TOF-MS. The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. After the normal and COPD model rats were douched with HTJQ, the blood was collected from hepatic portal vein and the drug-containing serum samples were prepared by methanol precipitation of protein. Then, 10 batches of drug-containing serum samples of HTJQ were prepared and analyzed by UPLC serum fingerprint to evaluate the quality and stability of drug-containing serum samples. UPLC-Q-TOF-MS was used to collect the mass spectrometric information of the transitional components. Twenty-eight transitional components of HTJQ in normal rats and 25 transitional components of HTJQ in COPD model rats were identified by UPLC-Q-TOF-MS. Under pathological and physiological conditions, there were not only the same transitional components in rat serum, but also corresponding differences. Further studies showed that there were also differences in the metabolic process of transitional components between the two conditions. In normal rats, most of the metabolic types of transitional components were phase I reactions. In COPD model rats, phase Ⅰ reactions decreased and phase Ⅱ reactions increased correspondingly. With UPLC-Q-TOF-MS technology, the differences of transitional components and the metabolism process of HTJQ in rats under normal physiological and pathological conditions were analyzed. The results showed that types of transitional components and the activity of some metabolic enzymes would be changed in COPD pathological state, which would affect the metabolic process of bioactive components in vivo. It laid a foundation for further elucidating the metabolic process and pharmacodynamic substance basis of HTJQ.
Animals ; Capsules ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacokinetics* ; Mass Spectrometry ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Rats ; Serum/chemistry*

OBJECTIVES: To construct a cell line that can stably express human phospholamban(PLN) and initially explore its application in the study of myocardial toxicity mechanism. METHODS: FastCloning method was used to insert the open reading frame sequence of target gene PLN into eukaryotic expression vector pcDNA5/FRT/TO(hereinafter referred to as pDFT) to construct the pDFT-PLN-Flag plasmid. The Flp-In^TM T-REx^TM 293 cells were generated by cotransfection of the constructed plasmid and pOG44 plasmid to express the target gene. Successfully recombined monoclonal cell lines were screened by hygromycin B resistance. Western blot and indirect immunofluorescence (IFA) were used to examine the expression of the target protein in recombinant cells. After the cell line was exposed to aconitine, it was verified by Western blot to detect changes in PLN protein phosphorylation. RESULTS: After PCR amplification of the recombinant plasmid and DNA electrophoresis, the length of the amplified product is the same as the known PLN gene fragment, which is consistent with the open reading frame (ORF) sequence of the human PLN gene after sequencing. IFA and Western blot showed that the constructed proliferation cell line can stably express high levels of human PLN under induction and regulation. Preliminary results showed that the phosphorylation level of Thr17-PLN decreased after two hours of exposure to 1 μmol/L aconitine. CONCLUSIONS This human cell line can stably express PLN and can be used to study the mechanism of action of aconitine on the cell at molecular level.
Calcium-Binding Proteins/metabolism* ; Cell Line ; Humans ; Myocardium/metabolism* ; Phosphorylation