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Resveratrol (RES) is a polyphenol with diverse beneficial biological and pharmacological activities, and our previous results have demonstrated its neuroprotective effects in several metabolic diseases, including non-alcoholic fatty liver disease. The aim of the present study is to investigate the potential effect of RES against oleic acid (OA)-induced cell injuries in SH-SY5Y cells and explore the possible mechanism. Based on the dose- and time-dependent effects of OA on cell proliferation and LDH release, SH-SY5Y cells were challenged with OA and incubated with or without RES (10-5-10-9 mM) or sitagliptin (STG, 10-7 mM). Lipid accumulation, SREBP1 and PPARα protein expression, glucose consumption and IRS1, AKT, ERK phosphorylation under insulin stimulation, and ROS production were detected. The protein expression of brain-derived neurotrophic factor (BDNF), Copine 6, and key molecules in the Wnt/β-catenin signalling pathway were measured via western blot. The expression of Wnt 1 was also measured via immunofluorescence staining. The results showed that RES treatment could alleviate the neurotoxicity induced by OA, as indicated by the increased cell proliferation and the decreased concentration of LDH in the supernatant. The increased lipid deposition and protein expression of SREBP1 and PPARα induced by OA was also reversed by treatment with RES. Moreover, RES could upregulate glucose consumption and the protein expression of phosphorylated IRS1, AKT, ERK and reduced ROS production in OA-induced SH-SY5Y cells. Furthermore, RES treatment reversed the imbalanced protein expression of BDNF, Copine 6, p-β-catenin, and Wnt 1 in SH-SY5Y cells induced by OA and decreased the hyperexpression of p-GSK3β. However, these effects were suppressed by DKK1, which is a specific antagonist of the Wnt signalling pathway. These results suggested that RES has a neuroprotective effect against OA-induced cell injury and dysfunctional glucolipid metabolism, and the mechanism might involve its ability to regulate oxidative stress and insulin resistance via the Wnt/β-catenin signalling pathway.

The specimens (two pairs of part and counterpart) of coniferalean branched leafy shoots were collected from the Jiulongshan Formation (Middle Jurassic) at the village of Daohugou, Ningcheng, Inner Mongolia, China. The fossil material displays helical phyllotaxy, dorsiventrally flattened linear, sessile leaves with decurrent base and prominent and single mid-vein. The foliate shoots are assigned to Sequoia jeholensis by comparing those of the genera Yanliaoa, Sequoia, Metasequoia, Taxodium, and Glyptostrobus, the basal members of the Cupressaceae sensu lato. Sequoia jeholensis is the oldest Sequoia species to date. It has coriaceous, dimorphic, helically arranged linear and scale leaves, with entire margins, attached obliquely to the axis by their decurrent bases. The leaf cuticle of S. jeholensis is described here for the first time. Leaves are hypostomatic, with stomata only on the abaxial surface. Anticlinal walls are straight, with single or more often paired pits. The epidermal structures of Sequoia are one of the key characters to distinguish it from similar genera, but they usually could not be used to distinguish the species within Sequoia. The Middle Jurassic of Daohugou represents a lacustrine environment with a warm and humid climate reflected by the species assemblage. So, the extinct Sequoia probably had similar climatic requirements to those of extant Sequoia sempervirens.

Background Quercetin (QUE) is a flavonol reported with anti-inflammatory and antioxidant activities, and previous results from the group of this study have demonstrated its neuroprotective effect against lipopolysaccharide-induced neuropsychiatric injuries. However, little is known about its potential effect on neuropsychiatric injuries induced or accompanied by metabolic dysfunction of glucose and lipids. Methods A nonalcoholic fatty liver disease (NAFLD) rat model was induced via a high-fat diet (HFD), and glucolipid parameters and liver function were measured. Behavioral performance was observed via the open field test (OFT) and the Morris water maze (MWM). The plasma levels of triggering receptor expressed on myeloid cells-1 (TREM1) and TREM2 were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of Synapsin-1 (Syn-1), Synaptatogmin-1 (Syt-1), TREM1 and TREM2 in the hippocampus were detected using western blotting. Morphological changes in the liver and hippocampus were detected by HE and Oil red or silver staining. Results Compared with the control rats, HFD-induced NAFLD model rats presented significant metabolic dysfunction, hepatocyte steatosis, and impaired learning and memory ability, as indicated by the increased plasma concentrations of total cholesterol (TC) and triglyceride (TG), the impaired glucose tolerance, the accumulated fat droplets and balloon-like changes in the liver, and the increased escaping latency but decreased duration in the target quadrant in the Morris water maze. All these changes were reversed in QUE-treated rats. Moreover, apart from improving the morphological injuries in the hippocampus, treatment with QUE could increase the decreased plasma concentration and hippocampal protein expression of TREM1 in NAFLD rats and increase the decreased expression of Syn-1 and Syt-1 in the hippocampus. Conclusions These results suggested the therapeutic potential of QUE against NAFLD-associated impairment of learning and memory, and the mechanism might involve regulating the metabolic dysfunction of glucose and lipids and balancing the protein expression of synaptic plasticity markers and TREM1/2 in the hippocampus.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive ability. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) are extracellular vesicles that can execute the function of bone marrow mesenchymal stem cells (BMSCs). Given the versatile therapeutic potential of BMSC and BMSC-exos, especially the neuroprotective effect, the aim of this study is to investigate the potential effect of BMSC-exos on the AD-like behavioral dysfunction in mice and explore the possible molecular mechanism.Methods: BMSCs were isolated from the femur and tibia of adult C57BL/6 mice, purified and sorted via flow cytometry technology, and cultured in vitro. The BMSC-exos were extracted and identified via transmission electron microscopy, and Western Blot was used to detect exosomes labeled proteins. A sporadic AD mouse model was established by intracerebroventricular injection of streptozotocin (STZ). 6 weeks later, BMSC-exos were given via lateral ventricle injection or caudal vein injection lasting for five consecutive days, and the control mice were intracerebroventricular given equal volume of solvent. The behavioral performance were observed via the Open field test (OFT), elevated plus maze test (EPM), novel object recognition test (NOR), Y maze test (Y-maze), and tail suspension test (TST). The mRNA and protein expressions of IL-1β, IL-6, and TNF-α in the hippocampus were measured via quantitative polymerase chain reaction (QPCR) and Western Blot, respectively. Meanwhile, the protein expression of Aβ1-42, BACE, p-Tau (Ser396), Synaptotagmin-1, Synapsin-1, and brain-derived neurotrophic factor (BDNF) in the hippocampus was detected using Western blot, and the expression of GFAP, IBA1, and DCX in the hippocampus was measured via immunofluorescence staining.Results: Lateral ventricle administration, but not caudal vein injection of BMSC-exos could improve the AD-like behaviors in STZ-injected mice model, as indicated by the increased number of rearing, increased frequency to the central area, and increased duration and moving distance in the central area in the OFT, together with improved preference index of the novel object in the NOR. Moreover, the hyper-activation of microglia and astrocytes in the hippocampus of the model mice were inhibited after treatment with BMSC-exos via lateral ventricle administration, accompanied by the reduced expression of IL-1β, IL-6, TNF-α, Aβ1-42, and p-Tau, and upregulated protein expression of synapse-related proteins and BDNF. Furthermore, results of Pearson test showed that the preference index of the novel object in the NOR was positively correlated to the hippocampal expression of BDNF, but negatively correlated with the expression of GFAP, IBA1, and IL-1β. Apart from a positive correlation between the hippocampal expression of BDNF and Syt-1, BDNF abundance was found negatively correlated with the markers of glial activation and the expression of inflammatory cytokines, Aβ, and p-tau, which were characteristic neuropathological features of AD.Conclusions: Lateral ventricle administration, but not caudal vein injection of BMSC-exos can improve the AD-like behavioral performance in STZ-injected mice, the mechanism of which might be involved with regulating glial activation and its associated neuroinflammation and BDNF-related neuropathological changes in the hippocampus.

// Ying Zhou 1, 2, 3 , Nan Song 1, 2 , Xin Li 1, 2, 4 , Ying Han 1, 2, 5 , Zihan Ren 1, 2 , Jing-xian Xu 6 , Yu-chen Han 1, 2 , Fang Li 1, 2, 7 , Xinshan Jia 1, 2 1 Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China 2 Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, 110001, China 3 Department of Emergency, First Affiliated Hospital of China Medical University, Shenyang, 110001, China 4 Department of Physiology, College of Life Science and Biopharmaceutics of Shenyang Pharmaceutical University, Shenyang, 110016, China 5 Department of Pathology, Shenyang Medical College, Shenyang, 110001, China 6 Department of Ophthalmology, The 4th Affiliated Hospital, Eye Institute, China Medical University, The Key Laboratory of Lens Research, Shenyang 110005, China 7 IVF Michigan, Bloomfield Hills, MI, 48304, USA Correspondence to: Xinshan Jia, email: xinshanjia@126.com Keywords: tracheal epithelium, stem cell, Oct3/4, methylation, silent gene Received: February 25, 2016 Accepted: November 21, 2016 Published: December 07, 2016 ABSTRACT We investigated the relationship between promoter methylation and tracheal stem cell activation. We developed a model of rat tracheal epithelium regeneration after 5-fluorouracil (5-FU)-induced injury. Using immunohistochemistry and Western blotting, the expression levels of the stem cell pluripotency regulator Oct3/4 and differentiation marker CK14 were measured after 5-FU treatment. The methylation status of the Oct3/4 , Nanog , and Sox2 promoters was investigated using methylation-specific PCR. Additionally, the effects of 5-azacytidine (5-azaC), a demethylating agent, on Oct3/4 , Nanog , and Sox2 mRNA and protein expression were evaluated. Finally, we measured the activity of the maintenance and de novo DNA methyltransferases DNMT1, DNMT3a, and DNMT3b. Our data indicate that Oct3/4 , Sox2 , and Nanog are transiently expressed in response to 5-FU-induced injury, and then they are gradually silenced as the cells differentiate. DNA methylation can result in silencing of gene expression, and it can determine whether tracheal stem cells are in an active or dormant state. Treatment with 5-FU reversed the methylation of the Oct3/4 , Nanog , and Sox2 promoters, which corresponded to increases in Oct3/4, Nanog, and Sox2 mRNA and protein. Thus, both maintenance and de novo methyltransferases are involved in regulating tracheal stem cell dormancy and activation.

Sugarcane is a multifunctional crop mainly used for sugar and renewable bioenergy production. Accurate and timely estimation of the sugarcane yield before harvest plays a particularly important role in the management of agroecosystems. The rapid development of remote sensing technologies, especially Light Detecting and Ranging (LiDAR), significantly enhances aboveground fresh weight (AFW) estimations. In our study, we evaluated the capability of LiDAR mounted on an Unmanned Aerial Vehicle (UAV) in estimating the sugarcane AFW in Fusui county, Chongzuo city of Guangxi province, China. We measured the height and the fresh weight of sugarcane plants in 105 sampling plots, and eight variables were extracted from the field-based measurements. Six regression algorithms were used to build the sugarcane AFW model: multiple linear regression (MLR), stepwise multiple regression (SMR), generalized linear model (GLM), generalized boosted model (GBM), kernel-based regularized least squares (KRLS), and random forest regression (RFR). The results demonstrate that RFR (R2 = 0.96, RMSE = 1.27 kg m−2) performs better than other models in terms of prediction accuracy. The final fitted sugarcane AFW distribution maps exhibited good agreement with the observed values (R2 = 0.97, RMSE = 1.33 kg m−2). Canopy cover, the distance to the road, and tillage methods all have an impact on sugarcane AFW. Our study provides guidance for calculating the optimum planting density, reducing the negative impact of human activities, and selecting suitable tillage methods in actual cultivation and production.

Resin-derived carbon foams with closed hollow spherical structure were prepared from mixtures of hollow phenolic microspheres and phenolic resin, followed by curing and carbonization. The resultant carbon foam had a bulk density of 0.45 g·cm-3. Effects of hollow microsphere on the on the compressive property and thermal conductivity of carbon foams were investigated. The results revealed that the hollow microspheres played an important role in improving compressive fracture toughness and lowering the thermal conductivity of carbon foams. The compressive fracture characteristics of carbon foam exhibited gradient brittle fracture, and the compressive strength was 10.93 MPa. The thermal conductivity of the carbon foam was 0.907 W·m-1·K-1 at room temperature, which was lowered by 49.67 % in comparison with phenolic-based vitreous carbon.

An aeropalynological study was preformed in Chongwen district of Beijing, China during one year (from 21, March 2006 to 20, March 2007). A total of 1670 pollen grains from 37 taxa were identified. Two separate peaks of airborne pollen occurred during one year: one was related to the presence of the trees/shrubs pollen (Cupressus L., Pinus L., Populus L., Betula L., Corylus L., Salix L., Juglans regia L., Fraxinus L., Anacardiaceae and Livistona chinensis (Jacq.) R.Br.) in March, the other was attributed to herbaceous pollen (Artemisia L., Chenopodiaceae, Gramineae, Humulus L. and Labiatae) in September. Only a few pollen grains were found from December to next January. Results indicated that airborne pollen composition was consistent with the vegetation components and the pollination periods of the plants in the sampling site. The variations of pollen numbers were affected positively by temperature, negatively by relative humidity and precipitation. Stable wind speed seemed to have little effect on the fluctuation of the pollen number during the study period.

// Xin Li 1, 2, 3 , Jing-xian Xu 4 , Xin-Shan Jia 2, 3 , Wen-ya Li 5 , Yi-chen Han 2, 3 , En-hua Wang 2, 3 , Fang Li 6 1 Department of Physiology, College of Life Science and Biopharmaceutics of Shenyang Pharmaceutical University, Shenyang, China 2 Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China 3 Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang, China 4 Department of Ophthalmology, The 4th Affiliated Hospital, Eye Institute, China Medical University, The Key Laboratory of Lens Research, Shenyang, China 5 Department of Thoracic Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China 6 IVF Michigan, Bloomfield Hills, MI, USA Correspondence to: Xin-Shan Jia, e-mail: xinshanjia@126.com Keywords: methylation, stem cell, dormancy, Sox2 expression Received: December 17, 2015 Accepted: March 02, 2016 Published: March 18, 2016 ABSTRACT Accurate markers and molecular mechanisms of stem cell dormancy and activation are poorly understood. In this study, the anti-cancer drug, 5-fluorouracil, was used to selectively kill proliferating cells of human bronchial epithelial (HBE) cell line. This method can enrich and purify stem cell population. The dormant versus active status of stem cells was determined by phosphorylation of RNAp II Ser2. The surviving stem cells were cultured to form stem cell spheres expressing stem cell markers and transplanted into nude mice to form a teratoma. The results demonstrated the properties of stem cells and potential for multi-directional differentiation. Bisulfite sequencing polymerase chain reaction showed that demethylation of the Sox2 promoter by 5-FU resulted in Sox2 expression in the dormant stem cells. This study shows that the dormancy and activation of HBE stem cells is closely related to epigenetic modification.

Two Schiff bases of chitosan (CTS) were synthesized from 4-methoxylbenzylaldehyde (CH3O-CTS) and 4-methylbenzylaldehyde(CH3-CTS). The Schiff bases were characterized by FTIR, DSC-TGA, solid13C CP-Mas NMR, and elemental analysis. Antibacterial activities of the Schiff bases against Escherichia coli and Staphylococcus aureus were measured by the optical density method. The antibacterial activity of the Schiff bases is better than that of the original CTS. The IC50of CH3O-CTS and CH3-CTS againstEscherichia coliis respectively 40.3 ppm and 43 ppm, which being 38.5 ppm and 39.5 ppm against Staphylococcus aureus, lower than IC50of chitosan, being 59.5 ppm and 52 ppm againstEscherichia coliand Staphylococcus aureus, respectively.

A three-year aeropalynological study was carried out in the month of August for each of the three years 2005, 2006 and 2007 in the Beijing Olympic Park. A total of 19550 pollen grains were counted (15057 grains in 2005, 2717 in 2006 and 1776 in 2007) for the following taxa: Gramineae, Chenopodiaceae, Humulus L., Artemisia L., Ambrosia L. and Pinus L. The analysis indicated that in the three consecutive years of 2005–2007, airborne pollen types and daily number of pollen in August in the Beijing Olympic Park were closely related to environmental change and vegetation composition. The daily variations of airborne pollen displayed similar patterns in August in each of the three years, which were affected positively by periods of daily sunshine, negatively by daily relative humidity and daily precipitation. Continuously high daily temperatures and stable daily wind speeds seemed to have little effect on the fluctuation of airborne pollen.

Copper nanoparticles embedded in soda-lime glass were fabricated by ion exchange followed by thermal treatment in hydrogen. The ultrafast dynamics of the embedded Cu nanoparticles formed under different fabrication conditions were investigated by applying femtosecond pump-probe technique. Non-Fermi electrons were suggested to be dominant in the transient behavior of the nanocomposites far from surface plasmon resonance of Cu. The long ion-exchange processing time was found to benefit and improve the ultrafast response of the fabricated nanocomposites.

Effects of thermal treatment on the third-order optical nonlinearity and ultrafast dynamics of Ag nanoparticles embedded in glasses were investigated by femtosecond time-resolved OKE and femtosecond pump–probe techniques. The results indicate that the third-order susceptibility increases from 1.1 × 10−11 esu to 1.48 × 10−9 esu with increasing the annealing temperature. The fast decay process is accelerated and its amplitude ratio increases with the thermal treatment, which could be attributed to an increase of the electron–phonon coupling through the process of treelike Ag nanoparticle aggregation. The slow relaxation time ranges from 25 ps to 140 ps, depending on the thermal conductivity of the matrix material.

The Luhe coalmine (25°10′N, 101°22′E) is located in Chuxiong County of Yunnan Province, southwestern China. Its Late Miocene palynoflora consists of 48 sporomorphs that are assigned to 35 natural families, including angiosperms (72.9%), gymnosperms (12.5%) and ferns (14.6%). Three pollen zones are recognized: The assemblages of Zone I are dominated by evergreen oaks, alder and hazel, while pine is present in comparatively low percentages. Zone II is characterized by smaller percentages of oak and hazel and more pine. In Zone III there is an expansion in the number of conifers at the expense of the broad-leaved trees and shrubs. Following the Coexistence Approach, seven palaeoclimatic parameters (Late Miocene) of Luhe are estimated. The mean annual temperature ranged from 13.3 to 20.9°C, the mean temperature of the warmest month from 22.5 to 27.5°C, the mean temperature of the coldest month from 2.5 to 12.6°C, the difference in temperatures of coldest and warmest month from 12.1 to 24.8°C, the mean annual precipitation from 803.6 to 1254.7mm, the mean maximum monthly precipitation from 179.4 to 249.6mm and the mean minimum monthly precipitation from 10.2 to 18.5mm. Comparison with the modern meteorological records indicates that the Luhe area had a warmer subtropical climate with more precipitation during Late Miocene; these data could indicate that extensive uplift of the western Yunnan Plateau had not yet occurred.

Cancer stem cells are supposed to be resistant to apoptosis, but information for this is quite limited. Cancer stem cells are usually isolated as dye-effluxing cells with Hoechst 33342 staining, called side-population (SP) cells. Because Hoechst 33342 dye itself induces apoptosis, the SP cells isolated by such method are not suitable for evaluation of apoptosis. For accurate assessment, SP cells must be isolated without Hoechst 33342. Here, we found that CD55 was highly expressed in SP cells of two mammary gland carcinoma cell lines. Then, the high expression of CD55 was used for isolation of cancer stem cells among mammary carcinoma cell lines as a surrogate character. Cells expressing high level of CD55 (CD55(hi)) were resistant to apoptosis induced by serum depletion as in the case of SP cells. In ceramide-inducing apoptosis, CD55(hi) cells showed high tolerance. Anti-apoptotic molecules such as Bcl-2 were abundantly expressed in both SP cells and CD55(hi) cells. These findings indicated that SP cells as revealed to be CD55(hi) cells were tolerant to apoptosis. The high expression of CD55 may be a useful character for SP cells in evaluating their functions.

The Eryuan palynoflora from the Late Pliocene of western Yunnan, China is described in this paper, and is compared with two contemporary palynofloras from Yangyi and Longling. The palynological data of the three locations are analyzed to reconstruct the climatic parameters of these areas at that time by using the Coexistence Approach. The Late Pliocene climatic parameters of Eryuan are estimated, i.e., the mean annual temperature ranged from 13.3 to 18.6 ◦ C, the mean temperature of the warmest month from 24.6 to 27.5 ◦ C, the mean temperature of the coldest month from 1.9 to 12.1 ◦ C, the difference in temperatures of coldest and warmest month from 14.2 to 16.6 ◦ C, the mean annual precipitation from 619.9 to 1484.3 mm, the mean maximum monthly precipitation from 143.8 to 245.6 mm, and the mean minimum monthly precipitation from 12.7 to 16.4 mm. Both paleovegetation and paleoclimate of the three localities are compared with the modern data at each location. The present study suggests a MAT decrease accompanied by a doubling of the MAP in the Longling area between the Late Pliocene and the present. This seems to be related to the uplift of Gaoligong Mountain in Longling which is now part of the eastern portion (Western Yunnan) of the Tibetan Plateau.

Objectives: To investigate whether mutations of the TP53 tumor suppressor gene are associated with a poor prognosis in lymphoproliferative disorders (LPD) developing in patients with a history of autoimmune disease (AID). Methods: Fifty patients, 15 males and 35 females ranging in age from 23 to 83 (median, 61) years, were examined. Rheumatoid arthritis (21 cases) is the commonest type of AID followed by systemic lupus erythematosus (10), dermatomyositis (9), progressive systemic sclerosis (4), and autoimmune hemolytic anemia (6). The interval between the diagnosis of AID and LPD ranged from 1 to 660 months (mean 42 months). Histological, immunohistological, and in situ hybridization studies revealed that 37 tumors were B cell lymphomas and 13 were T cell lymphomas with the Epstein-Barr virus genome present in the tumor cells in 24% of cases. Stage of disease was I in 15 cases, II in 5, III in 9, and IV in 21. Results: Polymerase chain reaction-single strand conformation polymorphism followed by direct sequencing revealed TP53 mutations in 45.9% of B cell and 53.8% of T cell lymphomas. The follow-up study revealed an unfavorable prognosis in cases with mutations compared with those without: the 1-year survival rate was 43.5 and 73.0% in B cell and 16.7 and 50% in T cell lymphoma, respectively. Conclusions: The occurrence of a TP53 mutation is an unfavorable prognostic factor not only in B cell but also in T cell LPD in AID.

The Longling Coal Mine (W. Yunnan) is situated in an area of substantial geotectonic activity. Its Late Pliocene palynoflora is of considerable interest, since the area represents a centre of biodiversity. Eighty-two palynomorphs belonging to 61 families were recovered from the lignite. The palynoflora is dominated by angiosperms (68.3%), with ferns (24.4%), gymnosperms (4.9%) and algae (2.4%). Comparisons indicate that most of the palynoflora was derived from the Montane Humid Evergreen Broad-leaved Forest, with lesser contributions from the Tsuga dumosa Forest and Evergreen Coniferous Broad-leaved Mixed Forest, as well as the Montane Mossy Evergreen Broad-leaved Forest. This indicates that the Late Pliocene climate was cooler than that of the present. In the course of the accumulation of the lignite, the climate underwent five major phases of warming and cooling.

The authors thank Dr. Masato Matsushita (Osaka Second Police Hospital) for providing clinical information.

Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA.We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD.Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%).The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.

Cases of nasal NK/T-cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life-style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000-2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74-9.87) for farmers, 2.81 (CI, 1.49-5.29) for producers of crops, 4.01 (CI, 1.99-8.09) for pesticide users, 11.65 (CI, 1.17-115.82) for residents near garbage burning plants, 2.95 (CI, 1.25-6.95) for former drinkers, and 0.49 (CI, 0.23-1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28-8.54), 1.18 (95% CI, 0.11-12.13) and 2.20 (95% CI, 0.88-5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life-style and environmental factors might be risk factors for NKTCL.

CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assay and si-RNA-mediated knockdown experiment revealed that zfp67, a zinc-finger protein, enhanced CDCP1 transcription. Amount of zfp67 in Jurkat was comparable with K562, but chromatin immunoprecipitation showed that zfp67 bound to CDCP1 promoter in K562 but not in Jurkat. There are CpG sequences around the promoter of CDCP1, which were heavily methylated in Jurkat but not in K562. Addition of demethylating reagent to Jurkat induced CDCP1 expression, and increased the zfp67 binding to CDCP1 promoter. Among normal hematopoietic cells such as CD34+CD38- cells, lymphocytes and granulocytes, inverse correlation between proportion of methylated CpG sequences and CDCP1 expression level was found. Demethylation of CpG sequences in lymphocytes, in which CpG sequences were heavily methylated, induced CDCP1 expression and its expression level further increased through zfp67 overexpression. The methylation of DNA appeared to regulate the cell-type-specific expression of CDCP1 through the control of interaction between chromatin DNA and transcription factors.

Individuals affected by rheumatoid arthritis (RA) occasionally develop lymphoproliferative disorders (RA-LPD). To study the molecular changes underscoring the RA-LPD, mutations of p53 and Bak gene were analyzed in RA-LPD with (MTX-LPD) or without methotrexate treatment for RA (non-MTX-LPD). Histology and immunophenotype were immunohistochemically examined in 32 cases of MTX-LPD and 21 of non-MTX-LPD. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing was employed to detect the mutations of p53 and Bak gene. Frequency of p53 mutations in non-MTX-LPD (47.6%) was significantly higher than that in MTX-LPD (15.6%) (P

To investigate whether mutations of the TP53 tumor suppressor gene are associated with a poor prognosis in lymphoproliferative disorders (LPD) developing in patients with a history of autoimmune disease (AID).Fifty patients, 15 males and 35 females ranging in age from 23 to 83 (median, 61) years, were examined. Rheumatoid arthritis (21 cases) is the commonest type of AID followed by systemic lupus erythematosus (10), dermatomyositis (9), progressive systemic sclerosis (4), and autoimmune hemolytic anemia (6). The interval between the diagnosis of AID and LPD ranged from 1 to 660 months (mean 42 months). Histological, immunohistological, and in situ hybridization studies revealed that 37 tumors were B cell lymphomas and 13 were T cell lymphomas with the Epstein-Barr virus genome present in the tumor cells in 24% of cases. Stage of disease was I in 15 cases, II in 5, III in 9, and IV in 21.Polymerase chain reaction-single strand conformation polymorphism followed by direct sequencing revealed TP53 mutations in 45.9% of B cell and 53.8% of T cell lymphomas. The follow-up study revealed an unfavorable prognosis in cases with mutations compared with those without: the 1-year survival rate was 43.5 and 73.0% in B cell and 16.7 and 50% in T cell lymphoma, respectively.The occurrence of a TP53 mutation is an unfavorable prognostic factor not only in B cell but also in T cell LPD in AID.