Low dose short duration pulsed electromagnetic field effects on cultured human chondrocytes: An experimental study

Background:

Pulsed electromagnetic field (PEMF) is used to treat bone and joint disorders for over 30 years. Recent studies demonstrate a significant effect of PEMF on bone and cartilage proliferation, differentiation, synthesis of extracellular matrix (ECM) and production of growth factors. The aim of this study is to assess if PEMF of low frequency, ultralow field strength and short time exposure have beneficial effects on in-vitro cultured human chondrocytes.

Materials and Methods:

Primary human chondrocytes cultures were established using articular cartilage obtained from knee joint during joint replacement surgery. Post characterization, the cells were exposed to PEMF at frequencies ranging from 0.1 to 10 Hz and field intensities ranging from 0.65 to 1.95 μT for 60 min/day for 3 consecutive days to analyze the viability, ECM component synthesis, proliferation and morphology related changes post exposure. Association between exposure doses and cellular effects were analyzed with paired''t’ test.

Results:

In-vitro PEMF exposure of 0.1 Hz frequency, 1.95 μT and duration of 60 min/day for 3 consecutive days produced the most favorable response on chondrocytes viability (P < 0.001), ECM component production (P < 0.001) and multiplication. Exposure of identical chondrocyte cultures to PEMFs of 0.65 μT field intensity at 1 Hz frequency resulted in less significant response. Exposure to 1.3 μT PEMFs at 10 Hz frequency does not show any significant effects in different analytical parameters.

Conclusions:

Short duration PEMF exposure may represent a new therapy for patients with Osteoarthritis (OA).     

Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A

The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinib-resistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was enhanced by ectopic SK-1 expression. Conversely, siRNA-mediated SK-1 knockdown in K562/IMA-3 cells, or its genetic loss in SK-1(-/-) MEFs, significantly reduced Bcr-Abl1 stability. Regulation of Bcr-Abl1 by SK-1/S1P was dependent on S1P receptor 2 (S1P2) signaling, which prevented Bcr-Abl1 dephosphorylation, and degradation via inhibition of PP2A. Molecular or pharmacologic interference with SK-1/S1P2 restored PP2A-dependent Bcr-Abl1 dephosphorylation, and enhanced imatinib- or nilotinib-induced growth inhibition in primary CD34(+) mononuclear cells obtained from chronic phase and blast crisis CML patients, K562/IMA-3 or LAMA4/IMA cells, and 32Dcl3 murine progenitor cells, expressing the wild-type or mutant (Y253H or T315I) Bcr-Abl1 in situ. Accordingly, impaired SK-1/S1P2 signaling enhanced the growth-inhibitory effects of nilotinib against 32D/T315I-Bcr-Abl1-derived mouse allografts. Since SK-1/S1P/S1P2 signaling regulates Bcr-Abl1 stability via modulation of PP2A, inhibition of SK-1/S1P2 axis represents a novel approach to target wild-type- or mutant-Bcr-Abl1 thereby overcoming drug resistance.     

草药复方Bresol？抵抗化合物48/80诱导的肥大细胞脱颗粒及组胺释放：促使肥大细胞稳定的一种非免疫机制

目的：研究一种草药复方制剂Bresol？对于肥大细胞脱颗粒以及组胺释放的保护作用。 方法：使用大鼠腹膜内肥大细胞,在体外经化合物48/80诱导肥大细胞脱颗粒及组胺释放,评估Bresol？稳定肥大细胞的作用。 结果：显微镜下正常对照组涂片显示较多完整的肥大细胞,有极少量的脱颗粒肥大细胞和微量的组胺释放。阳性对照组中用化合物48/80培养的肥大细胞出现了显著的肥大细胞脱颗粒现象以及高浓度的组胺释放。而100 mg/L浓度的Bresol？明显抑制了化合物48/80诱导的肥大细胞脱颗粒。此外,Bresol？可有效抑制化合物48/80诱导的组胺释放,且抑制效果与剂量有关。 结论：Bresol？能够在体外抑制化合物48/80诱导的肥大细胞脱颗粒和组胺释放。本研究的发现可解释Bresol？对多种过敏疾病有效可能是通过一种非免疫机制。     

Antibacterial effect of novel synthesized sulfated β-cyclodextrin crosslinked cotton fabric and its improved antibacterial activities with ZnO, TiO2 and Ag nanoparticles coating

Sulfated β-cyclodextrin was synthesized from sulfonation of β-cyclodextrin and sulfated polymer was crosslinked with cotton fabric using ethylenediaminetetraacetic acid as crosslinker. ZnO, TiO(2) and Ag nanoparticles were prepared and characterized by XRD, UV, DLS, SEM and PSA. The prepared nanoparticles were coated on crosslinked cotton fabric. The crosslinking and nanoparticles coating effects of cotton fabrics were studied by FTIR and SEM analysis. The antibacterial test was done against gram positive Staphylococcus aureus and gram negative Escherichia coli bacterium.     

Human papillomavirus detection in dysplastic and malignant oral verrucous lesions

The role of human papillomaviruses (HPV) in dysplastic and malignant oral verrucous lesions is controversial since there is a wide range in the incidence of virus detection. This study used a multi-tiered method of HPV detection using DNA in-situ hybridisation (ISH) for low- and high-risk subtypes, consensus PCR, and HPV genotype analysis in archival tissue from 20 cases of dysplastic and malignant oral verrucous lesions. The biological significance of HPV DNA detection was assessed by p16 immunohistochemistry (IHC). While 1/7 carcinomas and 5/13 dysplasias contained HPV DNA by consensus PCR and genotype analysis, all specimens were negative for low- and high-risk HPV ISH and negative for p16 IHC. Results show that although high-risk HPV DNA is detectable in a subset of these lesions, the lack of p16 overexpression suggests that the oncogenic process is not driven by HPV oncoproteins.