Demethylenetetrahydroberberine protects dopaminergic neurons in a mouse model of Parkinson's disease / 中国天然药物

Parkinson's disease (PD) is a multifactorial disorder of the nervous system where a progressive loss of dopaminergic neurons exist. However, the pathogenesis of PD remains undefined, which becomes the main limitation for the development of clinical PD treatment. Demethylenetetrahydroberberine (DMTHB) is a novel derivative of natural product berberine. This study was aimed to explore the neuroprotective effects and pharmacological mechanism of DMTHB on Parkinson's disease using C57BL/6 mice. A PD model of mice was induced by administration of MPTP (20 mg·kg-1) and probenecid (200 mg·kg-1) twice per week for five weeks. The mice were administered with DMTHB daily by gavage at the dose of 5 and 50 mg·kg-1 for one- week prophylactic treatment and five-week theraputic treatment. The therapeutic effects of DMTHB were evaluated by behavior tests (the open field, rotarod and pole tests), immunohistochemical staining of tyrosine hydroxylase (TH), Nissl staining and biochemical assays. The molecular mechanisms of DMTHB on the key biomarkers of PD pathological states were analyzed by Western blot (WB) and qRT-PCR. DMTHB treatment alleviated the behavioral disorder induced by MPTP-probenecid. Nissl staining and TH staining showed that the damage of dopaminergic neurons in the substantia nigra was remarkably suppressed by DMTHB treatment. Western blot results showed that the ratio of Bcl-2/Bax and TH increased, but the level of α-synuclein (α-syn) was remarkably reduced, which indicated that the apoptosis of dopaminergic neurons in mice was significantly reduced. The protein phosphorylation of p-PI3K, p-AKT and p-mTOR also increased about 2-fold, compared with the model group. Furthermore, qRT-PCR results demonstrated that the mRNA levels of pro-inflammatory cytokines, IL-1β and TNF-α, were reduced, but the level of anti-inflammatory cytokine IL-10 increased after DMTHB treatment. Finally, the cellular assay displayed that DMTHB was also a strong antioxidant to protect neuron cell line PC12 by scavenging ROS. In this study, we demonstrated DMTHB alleviates the behavioral disorder and protects dopaminergic neurons through multiple-target effects includubg anti-apoptotic, anti-inflammatory and antioxidant effects.

Bofutsushosan ameliorates obesity in mice through modulating PGC-1α expression in brown adipose tissues and inhibiting inflammation in white adipose tissues / 中国天然药物

The inducible co-activator PGC-1α plays a crucial role in adaptive thermogenesis and increases energy expenditure in brown adipose tissue (BAT). Meanwhile, chronic inflammation caused by infiltrated-macrophage in the white adipose tissue (WAT) is a target for the treatment of obesity. Bofutsushosan (BF), a traditional Chinese medicine composed of 17 crude drugs, has been widely used to treat obesity in China, Japan, and other Asia countries. However, the mechanism underlying anti-obesity remains to be elucidated. In the present study, we demonstrated that BF oral administration reduced the body weight of obese mice induced by high-fat diet (HFD) and alleviated the level of biochemical markers (P < 0.05), including blood glucose (Glu), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C) and insulin. Our further results also indicated that oral BF administration increased the expression of PGC-1α and UCP1 in BAT. Moreover, BF also reduced the expression of inflammatory cytokines in WAT, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These findings suggested that the mechanism of BF against obesity was at least partially through increasing gene expression of PGC-1α and UCP1 for energy consumption in BAT and inhibiting inflammation in WAT.

Role of Wnt/β-catenin signaling in aging of mesenchymal stem cells of rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the role of Wnt/β-catenin signaling in aging of mesenchymal stem cells (MSCs) of rats.</p><p><b>METHODS</b>Serum samples were collected from young (8 ≈ 12 w) and aged (64 ≈ 72 w) SD rat. Four experiment groups were assigned: young rat serum (YRS), YRS+Wnt 3a, old rat serum (ORS) and ORS+DKK1 groups. Immunofluorescence and Western blotting were used to detect the expression of intracellular β-catenin. The senescence-associated changes were examined with SA-β-galactosidase staining. The proliferation ability was tested by MTT assays. The survived and apoptotic cells were determined by AO/EB staining. The expressions of γ-H2A. X and p53 protein were detected by immunofluorescence and Western blotting. RT-PCR was used to detect the expression of p53 and p21 mRNA.</p><p><b>RESULTS</b>Compared with the YRS group, the intracellular expression of β-catenin in the ORS group was significantly increased,especially in the nuclei of MSCs. After treatment of DKK1 in ORS, the γ-catenin expression was reduced. The number of SA-β-galactosidase positive MSCs was significantly higher in the YRS+Wnt 3a group than that in the YRS group (P<0.01), and the proliferative and survival ability of MSCs was significantly decreased in the YRS+Wnt 3a group. The number of SA-β-galactosidase positive MSCs in the ORS+DKK1 group was significantly decreased compared with that in ORS group (P <0.01), and the proliferative and survival ability of MSCs was significantly increased in the ORS+DKK1 group. The expression of γ-H2A.X, p53 and p21 was markedly increased in the ORS group than that in YRS group, however, after treatment with Wnt/β-catenin signaling inhibitor DKK1, the expression of γ-H2A.X, p53 and p21 was significantly decreased compared with that in the ORS group.</p><p><b>CONCLUSION</b>Results suggest that the Wnt/β-catenin signaling is activated in the MSCs cultured with ORS and excessive activation of Wnt/β-catenin signaling can promote MSCs aging. The DNA damage response and p53/p21 pathway may be main mediators of MSC aging induced by excessive activation of Wnt/β-catenin signaling.</p>

In vitro evaluation of cutaneous allergic reaction induced by chemicals using dendritic cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the use of dendritic cells derived from mice bone marrow to evaluate the cutaneous allergic reaction induced by chemical sensitizers.</p><p><b>METHODS</b>Dendritic cells derived from mice bone marrow were cultured and administrated with 2, 4-dinitrochlorobenzene (DNCB), nickel sulfate (NiSO4), sodium dodecyl sulfate (SDS) and hexyl cinnamic aldehyde (HCA), respectively. Cell membrane molecule CD86 and extracellular IL-1 beta, IL-6 and IL-12 were detected after 0, 1, 6, 12, 24, 36, 48 hour's administration, respectively.</p><p><b>RESULTS</b>CD86 expression reached the highest level after exposure to DNCB for 48 h, and increased by about 279% compared with the control (P < 0.05), while it was lower than that of control after administrated with NiSO4 and HCA for 1 h and 6 h, and SDS for 36 h, respectively (P < 0.05). Extracellular IL-1 beta increased greatly after exposure to NiSO4 just for 1 h, with the maximum at 48 h (298 pg/ml, P < 0.05), and after exposure to HCA for 6 h, with maximum at 48 h (84 pg/ml, P < 0.05). However, it didn't fluctuate significantly after administrated with DNCB and SDS respectively, compared with the control. Extracellular IL-6 increased significantly after exposure to NiSO4 for 1 h, with the maximum at 24 h (2152 pg/ml, P < 0.05). After exposure to HCA, extracellular IL-6 reached the maximum at 1 h (1403 pg/ml), and then it was decreased quickly, but still higher than the control (P < 0.05), while it didn't change significantly after treatment with DNCB and SDS, compared with the control (P > 0.05). Extracellular IL-12 was not detected out among all the groups.</p><p><b>CONCLUSION</b>Chemical sensitizer DNCB could induce the high expression of CD86 on DC membrane, and NiSO4 and HCA could induce DC to release IL-1 beta and IL-6. However, the irritant SDS had no such effect.</p>

Study on maternal-fetal status of Pb, As, Cd, Mn and Zn elements and the influence factors / 中华预防医学杂志

<p><b>OBJECTIVE</b>Trace and toxic elements have great influences on the fetus growth during the pregnancy. The status of Pb, As, Cd, Mn and Zn in maternal and umbilical cord blood and influence factors were analyzed.</p><p><b>METHODS</b>From September 2006 to April 2007, 130 pairs of maternal blood and cord blood in total were collected at the time of spontaneous delivery or cesarean section. At the same time, the development of newborn was measured immediately. The concentrations of elements were determined by inductively coupled plasma mass spectrometry, the relationship of these elements between maternal and cord blood were also analyzed.</p><p><b>RESULTS</b>The median (microg/L) concentration of blood Pb, As, Cd, Mn and Zn in maternal blood were 64.32, 3.81, 0.84, 54.26 and 6312.50. And the median (microg/L) of those elements in cord blood were 35.72, 2.84, 0.32, 78.99 and 2250. The levels of Cd (r=0.341, P=0.000) and As (r=0.552, P=0.000) in maternal blood were positively correlated with the elements in the cord blood. From the questionnaire we conclude that the occupational hazardous factors and room decorated were the risk factors for the blood As and Zn levels. After multilinear regression analysis we also found mother weight, occupational hazardous factors and mother systolic pressure might affect the levels of blood Mn, Zn, As and Cd.</p><p><b>CONCLUSIONS</b>The levels of these elements were affected by environmental and maternal factors. In this study, although the levels of all heavy metals in pregnant women were below those considered hazardous, however, they were still higher than those in the developed countries. The effects of heavy metals of maternal exposure on developing fetuses should deserve attention further.</p>

Intervention of nicotinamide on skin melanin genesis after UVA exposed / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the interference effect of nicotinamide on UVA-induced melanin genesis and melanin transport in human skin melanocyte.</p><p><b>METHODS</b>The optimum UVA dose expected to cause cell proliferation: 0.2 J/cm(2), nicotinamide was added immediately after the 0.2 J/cm(2) UVA exposure and the melanin content, cell cycles, cell apoptosis and mRNA express level were measured respectively.</p><p><b>RESULTS</b>Melanin content in melanocytes was increased significantly after exposed to 0.2 J/cm(2) UVA. Melanin content in melanocytes was decreased after treatment with 10.0 mmol/ml nicotinamide following UVA exposure, but the cell cycles and the cell apoptosis rate were not significantly altered. mRNA express levels of TYR, TRP-1 were modulated by nicotinamide.</p><p><b>CONCLUSION</b>Nicotinamide has more effect on decreasing melanin genesis after UVA exposure, nicotinamide also plays a role in modulating the mRNA express of TYR, TRP-1 gene. It is possible to consider nicotinamide as an efficient and safe sun screen to provide a certain level of protection for UVA exposed skin.</p>

Low back pain prevalence of female workers in flat-grained veneer wood industry / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the low back pain(LBP) and its cause on female workers in flat-grained veneer wood industry.</p><p><b>METHODS</b>Bending posture was analyzed by observation and the prevalence of low back pain was investigated by physical examination and questionnaire among 299 female workers.</p><p><b>RESULTS</b>The prevalence of fatigue compliant in selecting, remending and sticking workers was 68.8%, 66.7% and 59.0%, respectively, which mainly involved in the part of low back. The prevalence of low back pain in selection (53.8%) and remending (58.7%) workers was higher than that in sticking workers (30.1%), which was in accordance with the tenderness between L4/L5 or L5/L6 and on the psoas major. Posture analysis indicated that the biggest bending range of selecting and remending workers (80 degrees ) was larger than that of sticking workers (60 degrees ), as well as the daily bending times[(4396+/-817), (1696+/-286), (1094+/-476)] and the time they kept bending[(6.5+/-0.6), (6.2+/-1.3), 4.5+/-0.9) h].</p><p><b>CONCLUSION</b>Bending posture is common among female workers especially those who work in selecting and remending and might be the major causes for the high prevalence of LBP in flat-grained veneer wood industry.</p>