The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy.

With the continuous improvement of human technology, the medical field has gradually moved from molecular therapy to cellular therapy. As a safe and effective therapeutic tool, cell therapy has successfully created a research boom in the modern medical field. Mesenchymal stem cells (MSCs) are derived from early mesoderm and have high self-renewal and multidirectional differentiation ability, and have become one of the important cores of cell therapy research by virtue of their immunomodulatory and tissue repair capabilities. In recent years, the application of MSCs in various diseases has received widespread attention, but there are still various problems in the treatment of MSCs, among which the heterogeneity of MSCs may be one of the causes of the problem. In this paper, we review the correlation of MSCs heterogeneity to provide a basis for further reduction of MSCs heterogeneity and standardization of MSCs and hope to provide a reference for cell therapy.

Indoxacarb resistance-associated mutation of Liriomyza trifolii in Hainan, China.

Liriomyza trifolii, which has been recently prevalent in China, harms more than 300 plant species, especially cowpea in Hainan. This pest also affects the quality and production of vegetables in winter. Indoxacarb is the first commercial oxadiazine pesticide, which is a new efficient insecticide used to control pests of Diptera, including L. trifolii. The unique mechanism of indoxacarb is that indenyl is transformed into N-demethoxycarbonyl metabolite (DCJW) in insects and acts on inactivated sodium channel; DCJW could then destroy the conduction of nerve impulses, which leads to movement disorders, feeding stoppage, paralysis, and eventually the death of pests. The field population of L. trifolii developed resistance by 769 times higher than the sensitive population in Sanya, Hainan. Results revealed the existence of a mutation (i.e., V1848I) in the sixth transmembrane segment of Domain IV of the sodium channel in the field population. The homozygous resistant genotype frequency for the V1848I mutation was 10-15% among the three field-collected populations. This paper reports for the first time the presence of the kdr mutation V1848I in resistant populations of L. trifolii to indoxacarb. The present study will contribute to the understanding of the evolution of indoxacarb resistance and contribute to the development of resistance management practices for winter vegetables in Hainan.

Correlation between Th17 and nTreg cell frequencies and the stages of progression in chronic hepatitis B.

Several studies have suggested that the balance of T helper 17 (Th17) and natural regulatory T (nTreg) cells in the Th17­mediated immune response are critical in the pathogenesis of viral hepatitis. The aim of the present study was to examine the role of circulating Th17 and nTreg cells in the disease progression of hepatitis B virus (HBV) infection. A total of 40 patients with chronic HBV (CHB), 27 patients with HBV­associated cirrhosis, 20 patients with HBV­associated liver failure and 20 healthy controls were enrolled in the present study. The frequencies of Th17 and nTreg cells in the peripheral blood were examined using flow cytometry. Th17­associated serum cytokine levels were measured using an enzyme­linked immunosorbent assay. The results revealed a significantly higher frequency of circulating Th17 cells in the patients with CHB, cirrhosis and liver failure compared, with the normal controls, particularly in the patients with liver failure. The same trend was observed in the serum levels of interleukin (IL)­17. The frequency of Th17 cells and the serum levels of IL­17 were positively correlated with the levels of alanine aminotransferase and the prothrombin times. There was a significantly higher frequency of circulating nTreg cells in the patients with CHB, compared with the normal controls. The nTreg cell frequencies were significantly and positively correlated with plasma HBV DNA load, and were negatively correlated with Th17 frequencies in the cohort of patients with HBV. Taken together, the results suggested that Th17 cell­mediated inflammation is associated with progression from CHB to cirrhosis, and to liver failure. Peripheral Th17 cell frequency and serum levels of IL­17 may assisting in predicting the severity of liver damage and fibrosis.

Relationship between adhesion molecules and virological response to pegylated interferon-alpha-2a treatment in patients with chronic hepatitis B: A pilot study.

AIM: We performed a clinical study to investigate potential association between serum levels of soluble adhesion molecules and virological response to pegylated interferon-alpha-2a (PEG IFN-α-2a) treatment in patients with chronic hepatitis B (CHB). METHODS: Thirty-two patients with chronic hepatitis B virus genotype B were recruited in this study, who were treated with PEG IFN-α-2a 180 µg every week and then followed up for 24 weeks. Thirty healthy control subjects were recruited from volunteer blood donors. Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble L-selectin (sL-selectin) in patients were investigated by enzyme-linked immunoassay before and after treatment. RESULTS: Serum concentrations of sICAM-1, sVCAM-1, sE-selectin and sL-selectin in CHB patients were significantly higher compared to the control group before treatment (P < 0.00001, respectively). In CHB patients responding to the PEG IFN-α-2a treatment, serum levels of sICAM-1, sVCAM-1, sE-selectin and sL-selectin were higher than those in non-responders before treatment (PI = 0.001, PV = 0.002, PE = 0.02, PL = 0.004). The levels of sICAM-1, sVCAM-1, sE-selectin and sL-selectin decreased in virological responders of treatment at 12 and 24 weeks (PI = 0.0001, PV = 0.00004, PE = 0.002, PL = 0.0004; PI = 0.00007, PV = 0.00001, PE = 0.0003, PL = 0.00003), while no obvious changes were observed in non-responders (P > 0.05, respectively). CONCLUSION: Results obtained indicated increased levels of sICAM-1, sVCAM-1, sE-selectin and sL-selectin could be related to virological response to PEG IFN-α-2a treatment in CHB patients, and have a prognostic effect on virological response.

Differential expression of ISG20 in chronic hepatitis B patients and relation to interferon-alpha therapy response.

The 20 kDa exonuclease encoded by the interferon-stimulated gene, ISG20, can inhibit the replication of hepatitis B virus (HBV), and may represent a clinically useful prognostic marker for response to interferon-alpha (IFN-α) antiviral therapy. The present study was designed to investigate the differential expression patterns of ISG20 in liver biopsy samples from treatment-naive patients with chronic hepatitis B and non-HBV infected controls and to determine the relation between the differential expression and IFN-α treatment outcome (responders vs. non-responders). HBV infection status was determined by measuring levels of hepatitis B surface antigen (HBsAg) by chemoluminescence immunoassay and of HBV DNA by real-time quantitative (q)PCR. ISG20 protein and mRNA expressions were assessed by immunohistochemistry and qPCR, respectively. Chronic hepatitis B responders showed significantly higher levels of ISG20 protein and mRNA expressions than either the chronic hepatitis B non-responders or the controls. Moreover, increased expression of ISG20 in both the nucleus and cytoplasm was correlated with positive response to IFN-α treatment. Thus, active transcription and translation of ISG20 may represent a marker to identify chronic hepatitis B patients likely to respond to IFN-α therapy. Prognostic clinical strategies based upon this marker may include genomic screening methods and immunohistochemical staining of liver biopsies.

Prediction of response to interferon α-1b in HBeAg-positive chronic hepatitis B: a clue from HBsAg levels.

BACKGROUND: Quantification of hepatitis B surface antigen (HBsAg) in serum may be of clinical importance in predicting treatment response towards interferon α (IFNα). AIMS: To explore the predictive role of serum quantitative HBsAg in predicting treatment response towards IFNα-1b in hepatitis B e antigen-positive chronic hepatitis B patients. METHODS: Seventy patients received 5 MU of IFNα-1b three times weekly for 48 weeks; the quantification of HBsAg was carried out at baseline, weeks 12, 24, 36, and 48 during treatment. At the end of treatment, the predictive role of quantitative HBsAg in predicting treatment response towards IFNα-1b was evaluated. RESULTS: From weeks 12 to 48, the serum hepatitis B virus DNA and HBsAg levels were positively correlated; the HBsAg levels were lower in responders than those in nonresponders and the difference was statistically significant (P<0.05). The HBsAg cutoff of 6109.01 IU/ml in serum at week 24 had a positive predictive value of 37.5% and a negative predictive value of 94.7%, and with an area under the receiver operating characteristic curve of 0.816. CONCLUSION: On-treatment, serum HBsAg had a high predictive value to predict treatment response towards IFNα-1b.