Comparison of time-dependent resistance isometric exercise and active range of motion exercise in alleviating the sensitization of postoperative axial pain after cervical laminoplasty.

BACKGROUND: Postoperative axial pain (PAP) is a significant complication after cervical laminoplasty. OBJECTIVE: To investigate pain sensitization in PAP patients and effects of time-dependent resistance isometric exercise compared to active range-of-motion exercise on PAP. STUDY DESIGN: Retrospective cohort analysis. METHODS: 211 patients undergoing postoperative 12-week exercises were evaluated for pressure pain threshold (PPT), temporal summation (TS) and both cross-sectional area and fatty infiltration of paraspinal muscles preoperatively and 3 months postoperatively. There patients underwent Numeric rating pain scale (NRS) and neck disability index (NDI) 3 and 6 months postoperatively. RESULTS: At postoperative 3-month assessments, fewer patients undergoing isometric exercise showed PAP compared to range-of-motion exercise group (14/98 vs. 34/113; P = 0.006), and pain-related assessments in the former were lower than the latter (NRS at rest: 0.3 ± 0.8 vs. 0.7 ± 1.4, P = 0.014; NRS with movements: 0.4 ± 1.0 vs. 1.0 ± 1.7, P = 0.015; NDI: 2.4 ± 6.3 vs. 6.7 ± 10.9, P = 0.002). Postoperative cross-sectional area was smaller in isometric exercise group (603.5 ± 190.2) than in range-of-motion exercise group (678.7 ± 215.5) (P = 0.033), and the former showed higher local-area PPT and lower TS than the latter (PPT: 3.9 ± 1.8 vs. 3.1 ± 1.6, P = 0.002; TS: 1.8 ± 0.9 vs. 2.2 ± 1.0, P = 0.003). PAP patients showed lower local-area PPT and greater TS than those without PAP in both isometric (PPT: 2.8 ± 0.7 vs. 4.0 ± 1.9, P = 0.019; TS: 2.4 ± 0.6 vs. 1.7 ± 0.9, P = 0.011) and range-of-motion (PPT: 2.2 ± 0.9 vs. 3.6 ± 1.7, P < 0.001; TS: 2.8 ± 0.8 vs. 1.9 ± 0.9, P < 0.001) exercise groups. CONCLUSIONS: Both peripheral and central sensitization are involved in PAP. Time-dependent isometric exercise has more positive effects on PAP than range-of-motion exercise because of its advantages in improving pain sensitization.

Mechanism of dexamethasone in the context of Toxoplasma gondii infection.

Toxoplasmosis is a serious zoonoses disease and opportunistic, and can be life-threatening. Dexamethasone (DEX) is widely used in the clinic for treatment of inflammatory and autoimmune diseases. However, long-term use of DEX is often easy to lead to acute toxoplasmosis in patients, and the potential molecular mechanism is still not very clear. The aims of this study were to investigate the effect of DEX on proliferation of Toxoplasma and its molecular mechanisms, and to establish the corresponding control measures. All the results showed that dexamethasone could enhance the proliferation of Toxoplasma gondii tachyzoites. After 72 h of DEX treatment, 566 (±7) tachyzoites were found in 100 host cells, while only 86 (±8) tachyzoites were counted from the non-treated control cells (P < 0·01). Gas chromatography (GC) analysis showed changes in level and composition of fatty acids in DEX-treated host cells, and T. gondii. Fish oil was added as a modulator of lipid metabolism in experimental mice. It was found that mice fed with fish oil did not develop the disease after infection with T. gondii, and the structure of fatty acids in plasma changed significantly. The metabolism of fatty acid in the parasites was limited, and the desaturase gene expression was downregulated. These results indicate that the molecular mechanism of dexamethasone to promote the proliferation of T. gondii may be that dexamethasone induces the change of fatty acids composition of tachyzoites and host cells. Therefore, we recommend supplementation of fatty acid in immunosuppressive and immunocompromised patients in order to inhibit toxoplasmosis.

PLSCR1/IP3R1/Ca2+ axis contributes to differentiation of primary AML cells induced by wogonoside.

Multiple lines of evidence have demonstrated that increased expression of phospholipid scramblase 1 (PLSCR1) is involved in the differentiation of acute myeloid leukemia (AML) cells by several differentiation-inducing agents including ATRA and phorbol 12-myristate 13-acetate. However, none of these agents can achieve nonhomogenous subcellular distribution of PLSCR1. We have demonstrated that wogonoside possesses differentiation and anti-leukemic effects in AML cell lines by promoting PLSCR1 trafficking into nucleus. Here we report that wogonoside promotes the expression of PLSCR1 and enhances its nuclear translocation and binding to the 1, 4, 5-trisphosphate receptor 1 (IP3R1) promoter in AML patient-derived primary cells. Wogonoside activates IP3R1, in turn, promotes release of Ca2+ from endoplasmic reticulum, and eventually leads to cell differentiation. Our in vivo study further confirms that wogonoside can promote PLSCR1 and IP3R1 expression in primary AML cells and reduce the AML cell counts in engrafted nonobese diabetic/severe combined immunodeficient mice. Taken together, our findings provide new insight into the mechanism of wogonoside-induced differentiation and anti-leukemic effect on primary AML cells, suggesting the therapeutic potential of wogonoside for AML, especially for non-APL AML.

Downregulation of human epidermal growth factor receptor 2 by short hairpin RNA increases chemosensitivity of human ovarian cancer cells.

The aim of the current study was to investigate the suppressive effects of pSilencer T7-human epidermal growth factor receptor 2 (HER2)-short hairpin RNA (shRNA) recombinant plasmids on human SKOV3 ovarian cancer cell growth and sensitivity to carboplatin (CBP). Three different pairs of shRNAs (shRNAa, shRNAb and shRNAc), targeting the HER2 gene, were selected and transfected into human SKOV3 cells, respectively. The expression levels of HER2 were then detected by immunohistochemical (IHC), semi-quantitative reverse transcription-polymerase chain reaction and western blot analyses. In addition, cell cycle and cell growth were investigated using cell counting kit-8 (CCK-8). The results of the IHC and western blot analyses revealed that shRNAb significantly inhibited HER2 protein expression in SKOV3 cells. shRNAb exhibited an improved effect on HER2 expression compared with shRNAa (P<0.01), while shRNAc did not affect HER2 expression. Nontransfected and nonspecific shRNA groups were used as the negative controls. Knockdown of HER2 expression by shRNA was initiated at 24 h following transfection, achieving an optimum effect at 48 h and lasting for at least 72 h after the treatment. The CCK-8 cell growth assay indicated that the knockdown of HER2 expression in the SKOV3 cell line resulted in significant growth suppression and cell cycle arrest. In addition, inhibition of HER2 significantly increased SKOV3 cell sensitivity to CBP treatment. In conclusion, pSilencer T7-HER2-shRNA significantly inhibited HER2 expression in human ovarian cancer cells in vitro and induced chemotherapeutic sensitivity to CBP.

Exogenous soluble tumor necrosis factor receptor type I ameliorates murine experimental autoimmune neuritis.

Tumor necrosis factor (TNF) and its receptor (TNFR) have been strongly implicated in the pathogenesis of autoimmune disease. Soluble cytokine receptors may be shed naturally from cell membranes to inhibit cytokine activity. Experimental autoimmune neuritis (EAN) is a CD4 Th1 cell-mediated animal model of Guillain-Barré syndrome (GBS) in humans. In the present study, we investigated the effects of soluble TNFR type I (sTNFR I) in EAN induced in mice by P0 peptide 180-199 and Freund's complete adjuvant. Our data from two different therapeutic regimens indicate that the administration of sTNFR I effectively ameliorated the clinical and pathological signs of EAN, i.e., decreased its severity, shortened its duration, and reduced inflammatory cell infiltration into the peripheral nervous system. The suppression of clinical EAN was accompanied in vitro by a marked reduction in antigen-specific T-cell proliferation and IFN-gamma synthesis by spleen cells from sTNFR I-treated mice, compared to control mice treated with PBS. These data directly demonstrate a pivotal role for TNF in the development of EAN and also suggest that sTNFR I may have therapeutic potential for alleviating GBS in humans.