Combining inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment improves motor function by modulating GABA in acute ischemic stroke patients.

BACKGROUND: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. OBJECTIVES: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. METHODS: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. RESULTS: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). CONCLUSIONS: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.

Effect of the Nrf2-ARE signaling pathway on biological characteristics and sensitivity to sunitinib in renal cell carcinoma.

The aim of the present study was to examine the effects of the nuclear factor erythroid-2 related factor 2-antioxidant-responsive element (Nrf2-ARE) signaling pathway on the biological characteristics and sensitivity to targeted therapy in human renal cell carcinoma (RCC) cells. RCC tissues and adjacent tissues were collected and assessed by immunohistochemistry to determine the expression of Nrf2, NAD(P)H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) to analyze the clinicopathological features of RCC. A series of in vitro experiments were conducted to analyze the biological characteristics of Nrf2-ARE signaling in RCC. The renal cancer cell line, 786-0 was used, and cells was divided into a mock group, negative control group and small hairpin (sh)RNA-Nrf2 group. A Cell Counting Kit-8 assay was performed alongside flow cytometry to detect cell viability, cell cycle stage and apoptosis following treatment with sunitinib. The results demonstrated that Nrf2, NQO1 and HO-1 were significantly upregulated in RCC tissues compared with adjacent tissues and were associated with tumor node metastasis stage, Fuhrman classification and lymph node metastasis. Following shRNA-Nrf2 transfection, the 786-0 cells demonstrated a significant decrease in viability, cell invasion and scratch healing rate, and the mRNA and protein expression levels of Nrf2, NQO1, HO-1 and glutathione transferase were significantly decreased, which enhanced the sensitivity to sunitinib, arrested cells in the G0/G1 phase and increased apoptosis. In conclusion, Nrf2-ARE signaling is important for RCC progression, and its inhibition may increase sensitivity to targeted drugs to provide novel developments for RCC treatment.

Homocysteine level in patients with obstructive sleep apnea/hypopnea syndrome and the impact of continuous positive airway pressure treatment.

BACKGROUND: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a common disorder in the general population. OBJECTIVES: The aim of this study was to investigate the homocysteine (Hcy) level in the patients with OSAHS of varying degrees and the effect of continuous positive airway pressure (CPAP) treatment on OSAHS patients. MATERIAL AND METHODS: A total of 117 OSAHS patients were recruited and divided into 3 groups (mild OSAHS, moderate OSAHS and severe OSAHS), while 33 non-OSAHS people were selected as control group. For all cases, polysomnography (PSG) variables and the concentrations of Hcy, methane dicarboxylic aldehyde (MDA) and glutathione (GSH) were recorded. Serum Hcy was measured by cyclophorase. The values of MDA and GSH were measured by a spectrophotometer. In the severe OSAHS group, a total of 30 patients received CPAP for more than 4 h every night and were re-examined 6 months later. RESULTS: The serum levels of Hcy, MDA and GSH showed a significant difference in OSAHS patients and controls. The Hcy and GSH concentrations of OSAHS patients with CPAP treatment showed no apparent change compared with the prior treatment, but the MDA level was obviously lower after CPAP treatment. In controls and the mild/moderate OSAHS groups, multi-element linear regression analysis results indicated that there was a statistically significant relationship between the Hcy concentration and various independent variables (age, MDA, GSH, and the apnea-hypopnea index - AHI). CONCLUSIONS: The change of the Hcy level was not proportional to the severity of the disease in different groups of OSAHS patients, and CPAP did not affect the Hcy levels.

[Integrity of multilayer of human periodontal ligament fibroblasts and human gingival fibroblasts grown on filter membrane of Transwell].

OBJECTIVE: To investigate the integrity of multilayer of human periodontal ligament fibroblasts (HPDLF) and human gingival fibroblasts (HGF) on filter membrane of Transwell and to provide basis for the drug transcellular transport by the HPDLF and HGF in the hypothesis of delivering medicine to the periodontium and whole body through the root canal. METHODS: HPDLF and HGF derived from the primary culture were seeded on polycarbonate filter membrane of transwell respectively. After 1, 2, 3 and 4 weeks of culture, transepithelial electrical resistance (TEER) was detected and the growth of HPDLF and HGF observed by light microscope. After 2 weeks of culture, section of filter membrane where HPDLF and HGF lived was observed with light microscope and transmission electron microscope (TEM), and the permeability of the drug transport cell models was measured with fluorescein sodium. RESULTS: HPDLF and HGF converged 1 week after inoculation, and the cells connected each other tightly and completely 2 weeks later. Observation of section of filter membrane by light microscope and TEM revealed a stratified cell growth of HPDLF and HGF 2 weeks after inoculation, and TEER of HPDLF and HGF were (56.14 +/- 7.43) and (57.34 +/- 7.62) ohm.cm(-2) respectively. The values of TEER remained the same level until 4 weeks later. Two weeks after inoculation, the paracellular transport of fluorescein sodium was less than 1% after the cell models were incubated for 30 min. CONCLUSIONS: Stratified cell layers of HPDLF and HGF grown on filter membrane of Transwell are analogous to periodontal membrane and gingiva 2 weeks after inoculation, the test results of permeability and TEER were consistent with the demands of development of cell models. HPDLF and HGF grown on filter membrane of Transwell could be used to study drug transcellular transport by HPDLF and HGF in vitro.

Resistin levels of serum and follicular fluid in non-obese patients with polycystic ovary syndrome during IVF cycles / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVES</b>To measure serum and follicular resistin, steroids hormone levels in women with PCOS (polycystic ovary syndrome) (BMI (body mass index)<25 kg/m(2)), to assess possible correlations of resistin to hormonal and metabolic parameters and to analyze the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with PCOS and tubal infertility.</p><p><b>STUDY DESIGN</b>We analyzed the clinical outcomes of IVF-ET in women with PCOS (BMI<25 kg/m(2)) and tubal infertility during the years 2002 to 2004 and compared the serum and follicular fluid resistin levels, estradiol (E(2)), progesterone (P), testosterone (T) levels in 20 PCOS and 20 healthy, age-matched women without PCOS during IVF-stimulated cycles. The correlations between the resistin levels and the outcomes of IVF-ET were evaluated.</p><p><b>RESULTS</b>No significant differences in resistin levels of either serum or follicular fluid between PCOS and control group were found. However, resistin levels in serum were higher than that in follicular fluid in both groups. Multiple regression analysis showed that resistin levels in serum did not correlate with BMI, estradiol, LH (luteinizing hormone) and insulin level in fasting blood. No significant correlations were found between follicular fluid reisistin levels and fertilization rate, implantation rate, clinical pregnancy rate or early miscarriage rate in both PCOS and control groups.</p><p><b>CONCLUSION</b>Our results show that resistin does not have correlation with the hormonal and metabolic parameters as well as the outcomes of IVF. These data suggest that resistin is unlikely to be a local determinant factor in steroidogenesis and growth and maturation of oocytes during IVF-ET in lean women with PCOS.</p>