Spin Crossover in [Fe(qsal-5-Brq)2]+ Complexes with a Quinoline-Substituted Qsal Ligand.

Using a quinoline substituted Qsal ligand, Hqsal-5-Brq (Hqsal-5-Brq = N-(5-bromo-8-quinolyl)salicylaldimine), four FeIII complexes, [Fe(qsal-5-Brq)2]A·CH3OH (Y = NO3- (1NO3), BF4- (2BF4), PF6- (3PF6), OTf- (4OTf), were prepared and characterized. Structure analysis revealed that complex 2BF4 contained two species (2BF4(P1̅) and 2BF4(C2/c)). In these compounds except 3PF6, the [Fe(qsal-5-Brq)2]+ cations form 1D chains through π-π interactions and other weak interactions. Adjacent chains are connected to form the 2D "Chain Layer" structures and 3D structures through various supramolecular interactions. For 3PF6, a "Dimer Chain" structure is formed from the loosely connected dimers. Magnetic studies revealed that compounds 1NO3 and 2BF4(P1̅) displayed abrupt hysteretic SCO with the transition temperature T1/2↓ = 235 K, T1/2↑ = 240 K for 1NO3 and T1/2↓ = 230 K, T1/2↑ = 235 K for 2BF4(P1̅), while compounds 3PF6 and 4OTf are in the HS state. Desolvation of the complexes significantly modifies their SCO properties: the desolvated 1NO3 and 2BF4 show a gradual SCO, desolvated 3PF6 undergoes a two-step SCO, and desolvated 4OTf exhibits a hysteretic transition. Overall, this work reported the FeIII-SCO complexes of the quinoline-substituted Hqsal ligand and highlighted the potential of these ligands for the development of interesting FeIII-SCO materials.

Hysteretic Spin Crossover with High Transition Temperatures in Two Cobalt(II) Complexes.

Cooperative spin crossover transitions with thermal hysteresis loops are rarely observed in cobalt(II) complexes. Herein, two new mononuclear cobalt(II) complexes with hysteretic spin crossover at relatively high temperatures (from 320 to 400 K), namely, [Co(terpy-CH2OH)2]·X2 (terpy-CH2OH = 4'-(hydroxymethyl)-2,2';6',2″-terpyridine, X = SCN-(1) and SeCN- (2)), have been synthesized and characterized structurally and magnetically. Both compounds are mononuclear CoII complexes with two chelating terpy-CH2OH ligands. Magnetic measurements revealed the existence of the hysteretic SCO transitions for both complexes. For compound 1, a one-step transition with T1/2↑= 334.5 K was observed upon heating, while a two-step transition is observed upon cooling with T1/2↓(1) = 329.3 K and T1/2↓(2) = 324.1 K (at a temperature sweep rate of 5 K/min). As for compound 2, a hysteresis loop with a width of 5 K (T1/2↓ = 391.6 K and T1/2↑ = 396.6 K, at a sweep rate of 5 K/min) can be observed. Thanks to the absence of the crystallized lattice solvents, their single crystals are stable enough at high temperatures for the structure determination at both spin states, which reveals that the hysteretic SCO transitions in both complexes originate from the crystallographic phase transitions involving a thermally induced order-disorder transition of the dangling -CH2OH groups in the ligand. This work shows that the modification of the terpy ligand has an important effect on the magnetic properties of the resulting cobalt(II) complexes.

Modulating the Structures and Magnetic Properties of Dy(III) Single-Molecule Magnets through Acid-Base Regulation.

Chemical modulation on the structures and physical properties of the coordination complexes is of great interest for the preparation of new functional materials. By changing the acidity or basicity of the reaction medium, the deprotonation degree of a multidentate ligand with multiple active protons, H4daps (H4daps = N',N'″-((1E,1'E)-pyridine-2,6-diylbis(ethan-1-yl-1-ylidene))bis(2-hydroxybenzohydrazide)), can be regulated on purpose. With this ligand of different deprotonation and charges, three new DyIII complexes ([Dy(H3daps)(CH3COO)2(EtOH)]·CH3COOH (1Dy), [Dy2(H2daps)2(EtOH)2(H2O)2(MeOH)2](CF3SO3)2·(H2O)2 (2Dy), and [Dy3(H1daps)2(H2daps)(µ3-OH)(EtOH)(H2O)] (3Dy)) of different nuclearities (mono-, di-, and trinuclear for 1Dy to 3Dy, respectively) have been synthesized and characterized structurally and magnetically. Analyses on the related bond lengths and resulting hydrogen bond modes in the complexes provide the details of the deprotonation position and the charge of the ligands, which can be in the form of H3daps-, H2daps2-, and H1daps3-. Interestingly, the more deprotonated ligand can act as a bridging ligand between the DyIII centers using the phenol and/or carbonyl oxygen atoms, which leads to the multinuclear structures. Magnetic studies on these complexes revealed that complex 1Dy is a field-induced single-molecule magnet (SMM), while complexes 2Dy and 3Dy show SMM behavior under a zero dc field.

Activation of AMP-activated protein kinase by compound 991 protects osteoblasts from dexamethasone.

Dexamethasone (Dex) induces direct cytotoxicity to cultured osteoblasts. The benzimidazole derivative compound 991 ("C991") is a novel and highly-efficient AMP-activated protein kinase (AMPK) activator. Here, in both MC3T3-E1 osteoblastic cells and primary murine osteoblasts, treatment with C991 activated AMPK signaling, and significantly attenuated Dex-induced apoptotic and non-apoptotic cell death. AMPKα1 knockdown (by shRNA), complete knockout (by CRISPR/Cas9 method) or dominant negative mutation (T172A) not only blocked C991-mediated AMPK activation, but also abolished its pro-survival effect against Dex in osteoblasts. Further studies showed that C991 boosted nicotinamide adenine dinucleotide phosphate (NADPH) activity and induced mRNA expression of NF-E2-related factor 2 (Nrf2)-regulated genes (heme oxygenase-1 and NADPH quinone oxidoreductase 1). Additionally, C991 alleviated Dex-induced reactive oxygen species (ROS) production in osteoblasts. Notably, genetic AMPK inhibition reversed the anti-oxidant actions by C991 in Dex-treated osteoblasts. Together, we conclude that C991 activates AMPK signaling to protect osteoblasts from Dex.

Identification of Key Gene Modules in Human Osteosarcoma by Co-Expression Analysis Weighted Gene Co-Expression Network Analysis (WGCNA).

Osteosarcoma is the eighth-most common form of childhood cancer, comprising about 20% of all primary bone cancers. To date, systemic co-expression analysis for this cancer is still insufficient to explain the pathogenesis of poorly understood OC. The objective of this study was to construct a gene co-expression network to predict clusters of candidate genes involved in the pathogenesis of osteosarcoma. First, we contributed co-expression modules via weighted gene co-expression network analysis (WGCNA) and investigated the functional enrichment analysis of co-expression genes in terms of GO and KEGG. In result, seven co-expression modules were identified, containing 2,228 differentially expressed genes identified from the 22 human osteosarcoma samples. Subsequently, correlation study showed that the hub-genes between pair-wise modules displayed significant differences. Lastly, functional enrichment analysis of the co-expression modules showed that the module 5 enriched in progresses of immune response, antigen processing, and presentation. In conclusion, we identified essential genes in module 5 which were associated to human osteosarcoma. The key genes in our findings might provide the framework of co-expression gene modules of human osteosarcoma. Further, the functional analysis of these associated genes provides references to understand the mechanism of Osteosarcoma. J. Cell. Biochem. 118: 3953-3959, 2017. © 2017 Wiley Periodicals, Inc.

Two new alkaloids from the endophytic fungus Schizophyllum sp. HM230 isolated from Vincetoxicum mongolicum Maxim.

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M (1) and N (2), along with three known ones (3-5). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher's method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1-4 showed middle cytotoxicity against MCF-7 cells with IC50 values range of 68.1 ∼ 87.32 µM. Compounds 1-5 displayed obvious antioxidant activity with the IC50 values range of 0.86 ∼ 5.78 mg/mL.

microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1.

Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a ("miR-19a", -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a downregulated TSC1 in OB-6 osteoblastic cells and primary human osteoblasts. miR-19a activated mTORC1 and protected human osteoblasts from dexamethasone. mTORC1 inhibition, by RAD001 or Raptor shRNA, almost completely abolished miR-19a-induced osteoblast cytoprotection against dexamethasone. Knockdown of TSC1 by targeted shRNA similarly induced mTORC1 activation and protected osteoblasts. Moreover, miR-19a activated mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited dexamethasone-induced reactive oxygen species production in osteoblasts. Together, miR-19a protects human osteoblasts from dexamethasone possibly via targeting TSC1-mTORC1 signaling.

A panel study on the effect of atmospheric PM2.5 exposure on the gut microbiome in healthy elderly people aged 60-69 years old / 中华预防医学杂志

Objective: To analyze the short-term effect of individual atmospheric PM2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods: The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m2. There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) μg/m3. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM2.5 exposure were significantly associated with a lower gut α diversity index (FDR<0.05 after correction). Further analysis showed that PM2.5 exposure was significantly associated with changes in the abundances of Firmicutes (Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes (Alistipes) (FDR<0.05 after correction). Conclusion: Short-term PM2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.

Association of greenness, nitrogen dioxide with the prevalence of hypertension among the elderly over 65 years old in China / 中华预防医学杂志

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO2) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO2 was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO2 for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO2 as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO2 and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO2 concentration was (32.18±10.36) μg/cm3. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T1 group of NDVI, the risk of hypertension was lower in the T3 group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T1 group of NO2, the risk of hypertension was higher in the T2 and T3 groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO2 was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO2 had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO2 are associated with hypertension in older adults.

Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urine arsenic and urine creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urine arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urine arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/L and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction<0.05). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18-79 years.

Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes.

Vitamin D deficiency could cause insulin resistance. However, the underlying mechanisms are unclear. The 1α-Hydroxylase ["1α(OH)ase"] is a key enzyme for activate vitamin D3 synthesis. Here, we show that 1α(OH)ase stable knockdown by targeted shRNA led to vitamin D3 depletion in L02 hepatocytes. 1α(OH)ase silence also inhibited insulin-induced downstream signaling (IRS-1, ERK and AKT) transduction and glucose transporter 4 expression. Further, 1α(OH)ase shRNA in L02 hepatocytes led to significant reactive oxygen species production, p53-p21 activation and DNA damages. Such effects were almost completely reversed with co-treatment of n-acetylcysteine, which is an established anti-oxidant. Remarkably, insulin-induced downstream signaling transduction and glucose transporter 4 expression were recovered with n-acetylcysteine co-treatment in 1α(OH)ase-silenced L02 hepatocytes. Together, our results suggest that vitamin D deficiency-induced insulin resistance is possibly caused by oxidative stress in hepatocytes.

Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine.

Vitamin D deficiency will lead to insulin resistance. In the current study, vitamin D3 1α-Hydroxylase ["1α(OH)ase"] knockout mice were generated to mimic vitamin D deficiency in vivo. As compared to the wild-type mice, the liver tissues of the knockout mice showed impaired insulin signaling, decreased glucose transporter 4 expression and increased reactive oxygen species production. Meanwhile, p53-p21 activation, apoptosis intensity and pro-inflammatory cytokines (IL-6, IL-1 and MIP-1α) level were significantly increased in the knockout mice livers. Significantly, such effects in the knockout mice were largely attenuated by supplement with anti-oxidant n-acetylcysteine (NAC). Remarkably, insulin resistance and metabolic abnormalities in the knockout mice were largely alleviated after treatment of NAC. Therefore, inhibition of oxidative stress by NAC alleviated insulin resistance in vitamin D-deficient mice. Oxidative stress could be the primary cause of insulin resistance by vitamin D deficiency.

MicroRNA-200a activates Nrf2 signaling to protect osteoblasts from dexamethasone.

Treatment with dexamethasone in human osteoblasts leads to oxidative stress and cell injures. NF-E2-related factor 2 (Nrf2) is a key anti-oxidant signaling. We want to induce Nrf2 activation via microRNA-mediated silencing its suppressor Keap1. Our results show that microRNA-200a ("miR-200a") expression depleted Keap1, causing Nrf2 protein stabilization in OB-6 osteoblastic cells. Reversely, the miR-200a anti-sense led to Keap1 upregulation and Nrf2 degradation. miR-200a expression activated Nrf2 signaling, which inhibited dexamethasone-induced reactive oxygen species production and OB-6 cell death/apoptosis. Keap1 shRNA also activated Nrf2 and protected OB-6 cells from dexamethasone. Importantly, miR-200a was in-effective in Keap1-silenced (by shRNA) OB-6 cells. In the primary human osteoblasts, Keap1 silence by targeted-shRNA or miR-200a protected cells from dexamethasone. Significantly, miR-200a level was decreased in necrotic femoral head tissues, which was correlated with Keap1 mRNA upregulation. Together, miR-200a expression activates Nrf2 signaling and protects human osteoblasts from dexamethasone.

Activation of Nrf2 by MIND4-17 protects osteoblasts from hydrogen peroxide-induced oxidative stress.

MIND4-17 is a recently developed NF-E2-related factor 2 (Nrf2) activator, which uniquely causes Nrf2 disassociation from Keap1. Here, we showed that pretreatment with MIND4-17 significantly inhibited hydrogen peroxide (H2O2)-induced viability reduction of primary osteoblasts and OB-6 osteoblastic cells. Meanwhile, MIND4-17 inhibited both apoptotic and non-apoptotic osteoblast cell death by H2O2. MIND4-17 treatment induced Keap1-Nrf2 disassociation, causing Nrf2 stabilization, accumulation and nuclear translocation in osteoblasts, leading to transcription of several Nrf2-dependent genes, including heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase modifier subunit (GCLM) and catalytic subunit (GCLC). Additionally, MIND4-17 largely attenuated H2O2-reactive oxygen species (ROS) production, lipid peroxidation and DNA damages. Nrf2 knockdown by targeted short hairpin RNA (shRNA) exacerbated H2O2-induced cytotoxicity in OB-6 osteoblastic cells, and nullified MIND4-17-mediated cytoprotection against H2O2. Meanwhile, Keap1 shRNA took over MIND4-17's actions and protected OB-6 cells from H2O2. Together, MIND4-17 activates Nrf2 signaling and protects osteoblasts from H2O2.

Assessment of GSK1904529A as a promising anti-osteosarcoma agent.

The insulin growth factor-I receptor (IGF1R) signaling is a key mechanism for osteosarcoma (OS) cell proliferation. GSK1904529A is a novel small molecule IGF1R kinase inhibitor. Its activity against OS cells was tested. In both established OS cell lines (Saos-2 and MG-63) and primary human OS cells, treatment with GSK1904529A (at nM concentrations) significantly inhibited cell proliferation. At the molecular level, GSK1904529A almost completely blocked IGF1R activation in OS cells, and inhibited downstream AKT-ERK activation. IGF1R silence by targeted shRNA also inhibited AKT-ERK activation and Saos-2 cell proliferation. Significantly, GSK1904529A was unable to further inhibit proliferation of IGF1R-silenced Saos-2 cells. In vivo, GSK1904529A administration orally inhibited Saos-2 tumor growth in nude mice. Together, these results suggest that targeting IGF1R by GSK1904529A inhibits OS cell growth in vitro and in vivo.

B7-H3 protein expression in a murine model of osteosarcoma.

Osteosarcoma is an aggressive type of bone tumor that commonly occurs in pediatric age groups. The complete molecular mechanisms behind osteosarcoma formation and progression require elucidation. B7-H3 is a protein of the B7 family that acts as a co-stimulatory molecule with a significant role in adaptive immune responses. The link between B7-H3 expression and its role in different types of cancer remains unclear. B7-H3 protein exhibits different functional roles in in vivo and in vitro conditions that remain controversial. In the present study, a murine model of osteosarcoma was successfully established using a modified protocol so as to easily obtain a low grade and metastatic form of osteosarcoma tissue without complication. Histological data showed that a less organized and highly proliferative mass of cells was observed in the osteosarcoma tissue. A higher expression level of B7-H3 protein was also observed at each advanced stage of osteosarcoma, which indicated the contributory role of the protein in the development of the primary and metastatic forms of osteosarcoma. Immunohistochemistry was performed, which showed that the overexpression of B7-H3 protein in the metastatic form of osteosarcoma may be associated with its migration and invasion.

[Establishment of Human Acute B-Lymphoblastic Leukemia--NOD/SCID Xenotransplant Mouse Model].

OBJECTIVE: To establish human B-acute lymphoblastic leukemia NOD/SCID mouse model. METHODS: The unirradiated mice aged 4-5 weeks were injected with Nalm-6 cells via the tail vein. Successful transplantation was assessed by the general state, bone marrow smear and histopathologic examination. RESULTS: After 15 days of injection with Nalm-6 cells, the NOD/SCID mice displayed the morbidily with lethargy, hind limb paralysis, hunched back and lossing weight. The infiltration of leukemia cells could be observed in bone marrow and spleen sections. CONCLUSION: Systemic B lineage acute leukemia animal mode1 has been successfully established in the NOD/SCID mice, which is a useful tool for studying pathogenesis of leukemia and guiding clinical chemotherapy regimens.

Activation of astrocytes in the anterior cingulate cortex contributes to the affective component of pain in an inflammatory pain model.

The anterior cingulate cortex (ACC) has been implicated as a key structure in the affective component of pain (such as unpleasantness or aversion). Recent evidence suggests that activation of spinal astrocytes contributes to the development and maintenance of the sensory component of pain after peripheral inflammation. However, whether the astrocytes in the ACC contribute to the affective component of pain is unknown. In this study, we demonstrated that intraplantar administration of Complete Freund's Adjuvant (CFA) in rats induced mechanical allodynia and place escape/avoidance behavior, which reflects the aversion of mechanical nociceptive stimuli. A reverse transcriptase-polymerase chain reaction study showed a significant increase in the mRNA level of GFAP, an astrocytic marker in the bilateral ACC at 3 d and 14 d after CFA-induced peripheral inflammation. Similarly, Western blot also revealed enhanced expression of GFAP protein at 3 d and 14 d after CFA injection. Interestingly, intra-ACC injection of L-alpha-aminoadipate (L-α-AA), an astroglial toxin, inhibited the escape/avoidance behavior, but did not affect the paw withdrawal threshold at 3d following CFA injection. All together, our results suggest that the astrocytes activation in the ACC may contribute to the affective component of pain.