Positive effect of microvascular proliferation on functional recovery in experimental cervical spondylotic myelopathy.

Background and purpose: Cervical Spondylotic Myelopathy (CSM), the most common cause of spinal cord dysfunction globally, is a degenerative disease that results in non-violent, gradual, and long-lasting compression of the cervical spinal cord. The objective of this study was to investigate whether microvascular proliferation could positively affect neural function recovery in experimental cervical spondylotic myelopathy (CSM). Methods: A total of 60 male adult Sprague-Dawley (SD) were randomly divided into four groups: Control (CON), Compression (COM), Angiostasis (AS), and Angiogenesis (A G),with 15 rats in each group. Rats in the AS group received SU5416 to inhibit angiogenesis, while rats in the AG group received Deferoxamine (DFO) to promote angiogenesis. Motor and sensory functions were assessed using the Basso Beattie Bresnahan (BBB) scale and somatosensory evoked potential (SEP) examination. Neuropathological degeneration was evaluated by the number of neurons, Nissl bodies (NB), and the de-myelination of white matter detected by Hematoxylin & Eosin(HE), Toluidine Blue (TB), and Luxol Fast Blue (LFB) staining. Immunohistochemical (IHC) staining was used to observe the Neurovascular Unit (NVU). Results: Rats in the CON group exhibited normal locomotor function with full BBB score, normal SEP latency and amplitude. Among the other three groups, the AG group had the highest BBB score and the shortest SEP latency, while the AS group had the lowest BBB score and the most prolonged SEP latency. The SEP amplitude showed an opposite performance to the latency. Compared to the COM and AS groups, the AG group demonstrated significant neuronal restoration in gray matter and axonal remyelination in white matter. DFO promoted microvascular proliferation, especially in gray matter, and improved the survival of neuroglial cells. In contrast, SU-5416 inhibited the viability of neuroglial cells by reducing micro vessels. Conclusion: The microvascular status was closely related to NVU remodeling an-d functional recovery. Therefore, proliferation of micro vessels contributed to function -al recovery in experimental CSM, which may be associated with NVU remodeling.

Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy.

The progression and remission of cervical spondylotic myelopathy (CSM) are quite unpredictable due to the ambiguous pathomechanisms. Spontaneous functional recovery (SFR) has been commonly implicated in the natural course of incomplete acute spinal cord injury (SCI), while the evidence and underlying pathomechanisms of neurovascular unit (NVU) compensation involved in SFR remains poorly understood in CSM. In this study, we investigate whether compensatory change of NVU, in particular in the adjacent level of the compressive epicenter, is involved in the natural course of SFR, using an established experimental CSM model. Chronic compression was created by an expandable water-absorbing polyurethane polymer at C5 level. Neurological function was dynamically assessed by BBB scoring and somatosensory evoked potential (SEP) up to 2 months. (Ultra)pathological features of NVUs were presented by histopathological and TEM examination. Quantitative analysis of regional vascular profile area/number (RVPA/RVPN) and neuroglial cells numbers were based on the specific EBA immunoreactivity and neuroglial biomarkers, respectively. Functional integrity of blood spinal cord barrier (BSCB) was detected by Evan blue extravasation test. Although destruction of the NVU, including disruption of the BSCB, neuronal degeneration and axon demyelination, as well as dramatic neuroglia reaction, were found in the compressive epicenter and spontaneous locomotor and sensory function recovery were verified in the modeling rats. In particular, restoration of BSCB permeability and an evident increase in RVPA with wrapping proliferated astrocytic endfeet in gray matter and neuron survival and synaptic plasticity were confirmed in the adjacent level. TEM findings also proved ultrastructural restoration of the NVU. Thus, NVU compensation changes in the adjacent level may be one of the essential pathomechanisms of SFR in CSM, which could be a promising endogenous target for neurorestoration.

Ultrastructural destruction of neurovascular unit in experimental cervical spondylotic myelopathy.

Background and purpose: The pathogenesis of cervical spondylotic myelopathy (CSM) remains unclear. This study aimed to explore the ultrastructural pathology of neurovascular unit (NVU) during natural development of CSM. Methods: A total of 24 rats were randomly allocated to the control group and the CSM group. Basso-Beattie-Bresnahan (BBB) scoring and somatosensory evoked potentials (SEP) were used as functional assessments. Hematoxylin-eosin (HE), toluidine blue (TB), and Luxol fast blue (LFB) stains were used for general structure observation. Transmission electron microscopy (TEM) was applied for investigating ultrastructural characteristics. Results: The evident compression caused significant neurological dysfunction, which was confirmed by the decrease in BBB score and SEP amplitude, as well as the prolongation of SEP latency (P < 0.05). The histopathological findings verified a significant decrease in the amount of Nissl body and myelin area and an increase in vacuolation compared with the control group (P < 0.05). The TEM results revealed ultrastructural destruction of NVU in several forms, including: neuronal degeneration and apoptosis; disruption of axonal cytoskeleton (neurofilaments) and myelin sheath and dystrophy of axonal terminal with dysfunction mitochondria; degenerative oligodendrocyte, astrocyte, and microglial cell inclusions with degenerating axon and dystrophic dendrite; swollen microvascular endothelium and loss of tight junction integrity; corroded basement membrane and collapsed microvascular wall; and proliferated pericyte and perivascular astrocytic endfeet. In the CSM group, reduction was observed in the amount of mitochondria with normal appearance and the number of cristae per mitochondria (P < 0.05), while no substantial drop of synaptic vesicle number was seen (P > 0.05). Significant narrowing of microvascular lumen size was also observed, accompanied by growth in the vascular wall area, endothelial area, basement membrane thickness, astrocytic endfeet area, and pericyte coverage area (rate) (P < 0.05). Conclusion: Altogether, the findings of this study demonstrated ultrastructural destruction of NVU in an experimental CSM model with dorsal-lateral compression, revealing one of the crucial pathophysiological mechanisms of CSM.

Associated factors for HIV stigma among the patients on antiretroviral therapy in Wenshan Prefecture / 预防医学

Objective@#To learn HIV related stigma and its associated factors among the patients on antiretroviral therapy ( ART ) in Wenshan Prefecture, Yunnan Province, so as to provide evidence for eliminating HIV discrimination.@*Methods@#A total of 419 subjects were recruited by convenience sampling from three ART clinics in Wenshan City and Maguan County between October 2017 and January 2018. HIV/AIDS Related Stigma and Discrimination Scale developed by Li Xianhong et al was employed. The multivariate linear regression model were used to explore the influencing factors for HIV stigma. @*Results@#The median scores of disclosure concern, public rejection, family stigma, internalized stigma, health service providers＇ stigma were 24.00, 6.00, 10.00, 20.00, 2.00, respectively, and the overall was 68.00. The multivariate linear regression analysis showed that female patients ( standardized β=0.135 ) , patients with opportunistic infection ( standardized β=0.120 ), patients had no HIV infected family member ( standardized β=-0.128 ) , patients without family support ( standardized β=-0.175 ) , patients received gift from ART clinics ( standardized β=0.124 ) , patients scored lower in ART knowledge ( standardized β=-0.117 ) were likely to scored higher in HIV stigma. @*Conclusions@#The stigma on disclosure concern and internalized stigma dimensions are grievous among ART patients in Wenshan Prefecture. Gender, opportunistic infection, HIV infection in family, family support, receiving incentive gifts from clinics and awareness of ART are associated with HIV stigma.

[Identification and evaluation of Citrus grandis based on DNA barcode,UPLC and chromaticity method].

In order to identify the source of Citrus grandis and evaluate its quality originate from two areas comprehensively,DNA barcode was used to identify 26 samples of C. grandis. The content of naringin,rhoifolin,naringenin and apigenin was determined by UPLC method,and the color difference was numerically studied by color difference analyzer,which was related to the effective components of C. grandis. The results showed that samples was the source of C. grandis in both regions. The ITS2 sequence length was about400-500 bp,and the sequence similarity reached 99. 82%. There was only one base deletion in the two groups. There was one base A in some medicinal materials of Guangdong at 330 bp,but no base in Chongqing. The contents of naringin and rhoifolin in Chongqing samples were higher than those in Guangdong samples,and there were statistical differences between naringenin and apigenin. The chroma value showed that L*value of Guangdong was larger,a*value was smaller,L*value of Chongqing was smaller,and a*value was larger,while the b*value of both was not significantly different; The results of correlation analysis showed that naringin,rhoifolin,naringenin were positively correlated with L*,b*value,negatively correlated with a*value,and apigenin had no correlation with L*,a*,b*value. In this study,the scientific identification and evaluation of C. grandis was carried out to provide a new idea for the further study of the rapid identification and evaluation of C. grandis.

Limb remote ischemic postconditioning protects integrity of the blood-brain barrier after stroke.

Integrity of the blood-brain barrier structure is essential for maintaining the internal environment of the brain. Development of cerebral infarction and brain edema is strongly associated with blood-brain barrier leakage. Therefore, studies have suggested that protecting the blood-brain barrier may be an effective method for treating acute stroke. To examine this possibility, stroke model rats were established by middle cerebral artery occlusion and reperfusion. Remote ischemic postconditioning was immediately induced by three cycles of 10-minute ischemia/10-minute reperfusion of bilateral hind limbs at the beginning of middle cerebral artery occlusion reperfusion. Neurological function of rat models was evaluated using Zea Longa's method. Permeability of the blood-brain barrier was assessed by Evans blue leakage. Infarct volume and brain edema were evaluated using 2,3,5-triphenyltetrazolium chloride staining. Expression of matrix metalloproteinase-9 and claudin-5 mRNA was determined by real-time quantitative reverse transcription-polymerase chain reaction. Expression of matrix metalloproteinase-9 and claudin-5 protein was measured by western blot assay. The number of matrix metalloproteinase-9- and claudin-5-positive cells was analyzed using immunohistochemistry. Our results showed that remote ischemic postconditioning alleviated disruption of the blood-brain barrier, reduced infarct volume and edema, decreased expression of matrix metalloproteinase-9 mRNA and protein and the number of positive cells, increased expression of claudin-5 mRNA and protein and the number of positive cells, and remarkably improved neurological function. These findings confirm that by suppressing expression of matrix metalloproteinase-9 and claudin-5 induced by acute ischemia/reperfusion, remote ischemic postconditioning reduces blood-brain barrier injury, mitigates ischemic injury, and exerts protective effects on the brain.

[Mechanisms of Hirudo in promoting blood circulation and removing stasis based on network pharmacology].

The study aims to analyze the mechanisms of Hirudo in promoting blood circulation and removing blood stasis based on network pharmacology. A database of chemical components of Hirudo was established through literature retrieval. The targets were predicted by using the reverse pharmacophore matching method and screened according to the antithrombotic and anticoagulant drug targets approved by FDA in the DrugBank database. Then, the targets were analyzed by KEGG pathway analysis, the protein interactions were analyzed by using BioGrid database, and the active constituents-target-pathway network model of Hirudo was established to study the mechanisms of Hirudo in promoting blood circulation and removing blood stasis. This study collected 49 chemical components of Hirudo, including amino acid, polypeptide, fatty acid ester, alkaloid, glycosides, and steroid. Totally 376 targets were predicted, and 5 critical targets related to the effects of Hirudo in promoting blood circulation and removing blood stasis were screened, including fibrinogen gamma chain, plasminogen, prothrombin, Urokinase-type plasminogen activator and coagulation factor X. The potential regulatory pathways included complement and coagulation cascades, platelet activation, VEGF signaling pathway, focal adhesion. This study reflects the multi-component, multi-target and multi-pathway features of Hirudo, and provides a scientific basis for elucidating the mechanisms of action of Hirudo in promoting blood circulation and removing blood stasis, as well as a reference for the study of mechanisms of traditional Chinese medicine.

Effect of acrylamide-induced neurotoxicity in a primary astrocytes/microglial co-culture model.

Acrylamide (AA), is a common food contaminant generated by heat processing. Astrocytes and microglia are the two major glial cell types in the brain that play pivotal but different roles in maintaining optimal brain function. The objective of this study is to investigate the neurotoxicity of AA, using a primary astrocytes/microglia co-culture model. Co-cultural cells obtained from Balb/c mice were cultured and treated with 0-1.0mM AA for 24-96h. Cell viability, reactive oxygen species (ROS) generation, oxidative end produces formation and glutathione (GSH) levels were measured. The expression of nuclear-E2-related factor 2(Nrf2), and nuclear factor kappa-beta (NF-κB) and selected down-stream genes were measured. Results showed that AA treatment led toa dose-dependent toxicity. Oxidative stress was induced as indicated by an increase of ROS, a decrease of GSH levels, and an increase in the formation of 4-hydroxynonenal-adduct and 8-hydroxy-2-deoxyguanosine-adduct. Both Nrf2 and NF-κB pathway contributed to the initiation of oxidative stress but the timing of two factors was different. Nrf2 and its related downstream genes were activated earlier than that in NF-κB pathway. In conclusion, AA-induced neurotoxicity attribute to oxidative stress via Nrf2 and NF-κB pathway. Moreover, the co-culture cell model was proven to be a viable model to study AA neurotoxicity.

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) improves brain ischemia-induced pulmonary injury in rats associated to TNF-α expression.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. This study explores the effects of transplantation of BMSCs on acute lung injury induced by focal cerebral ischemia and investigates the underlying mechanism. METHODS: Acute lung injury model was induced by middle cerebral artery occlusion (MCAO). BMSCs (with concentration of 1 × 10(6)/ml) were transplanted into host through tail vein 1 day after MCAO. Then, the survival, proliferation and migration of BMSCs in lung were observed at 4 days after transplantation, and histology observation and lung function were assessed for 7 days. Meanwhile, in situ hybridization (ISH), qRT-PCR and western blotting were employed to detect the expression of TNF-α in lung. RESULTS: Neurobehavioral deficits and acute lung injury could be seen in brain ischemia rats. Implanted BMSCs could survive in the lung, and relieve pulmonary edema, improve lung function, as well as down regulate TNF-α expression. CONCLUSIONS: The grafted BMSCs can survive and migrate widespread in lung and ameliorate lung injury induced by focal cerebral ischemia in the MCAO rat models. The underlying molecular mechanism, at least partially, is related to the suppression of TNF-α.

Physico-chemical and antioxidant properties of four mango (Mangifera indica L.) cultivars in China.

Four principal mango cultivars (Tainong No.1, Irwin, JinHwang and Keitt) grown in southern China were selected, and their physico-chemical and antioxidant properties were characterized and compared. Of all the four cultivars, Tainong No.1 had highest content of total phenols, ρ-coumaric acid, sinapic acid, quercetin, titratable acidity, citric acid, malic acid, fructose, higher antioxidant activities (DPPH, FRAP) and L(*), lower pH, PPO activity and individual weight. Keitt mangoes showed significantly (p<0.05) higher contents of ß-carotene, ρ-hydroxybenzoic acid, sucrose, total sugar, total soluble solid, catechin, succinic acid and higher PPO activity. JinHwang mangoes exhibited significantly (p<0.05) higher individual weight and PPO activity, but had lower content of total phenols, ß-carotene and lower antioxidant activity. Principal component analysis (PCA) allowed the four mango cultivars to be differentiated clearly based on all these physico-chemical and antioxidant properties determined in the study.

Inactivation of polyphenol oxidase from watermelon juice by high pressure carbon dioxide treatment.

The inactivation of polyphenol oxidase from watermelon juice with high pressure carbon dioxide (HPCD) treatment was investigated. The maximum reduction of polyphenol oxidase (PPO) activity inactivated by HPCD treatment was 95.8% at 30 MPa and 50 °C for 30 min, which was far higher than 50.9% of control treatment at 50 °C for 30 min. The inactivation of PPO was adequately described by a two-fraction model, which indicated that a labile and stable fraction might present in PPO from watermelon juice. The kinetic rate constants kL and kS of labile and stable fractions were 1.976 and 0.041 min(-1) by HPCD treatment of 30 MPa and 50 °C. And the labile fraction was easier to be inactivated by kinetic analysis. HPCD treatment with the combined effects of pressure, temperature, pH reduction, and time was stronger to inactivate PPO from watermelon juice than control treatment at the same temperature.

Membrane Damage Induced by Supercritical Carbon Dioxide in Rhodotorula mucilaginosa.

To clarify the mechanism of microbial inactivation by supercritical carbon dioxide (SCCO2), membrane damage of Rhodotorula mucilaginosa was investigated within specific pressure (10 Mpa), temperature (37 °C), and treatment time (10-70 min) ranges, including cell morphological structure, membrane permeability and fluidity. SEM and TEM observations showed morphological changes in the cell envelope and intracellular organization after SCCO2 treatment. Increase of membrane permeability was measured as increased uptake of the trypan blue dye with microscopy, and leakage of intracellular substances such as UV-absorbing materials and ions by determining the change of protein and electrical conductivity. The SCCO2 mediated reduction in CFU ml(-1) was 0.5-1 log higher at 37 °C and 10 MPa for 60 min in Rose Bengal Medium containing 4 % sodium than a similar treatment in Rose Bengal Medium. Membrane fluidity analyzed by fluorescence polarization method using 1,6-diphenyl-1,3,5-hexatriene showed that the florescence polarization and florescence anisotropy of the SCCO2-treated cells were increased slightly and gently compared with the untreated cells. The correlation between membrane damage and death of cells under SCCO2 was clear, and the membrane damage was a key factor induced the inactivation of cells.

[X-ray diffraction study of high hydrostatic pressure on crystalline structure of different type starches].

Crystalline changes of different type starches after high hydrostatic pressure treated under 300, 450, 600 MPa were studied by X-ray diffraction. Waxy maize (A type, 100% amylopectin), hylon VII (B type, 30% amylopectin) and tapioca starch (C type, 83% amylopectin) were chosen. The results indicated that for waxy maize starch, annealing effect was observed at 300 MPa, disappearance of crystalline structure happened at 450 MPa and retrogradation at 600 MPa. The results proved that the granule under high hydrostatic pressure processing experiences "three development stages" including annealling effect, disappearance of crystalline structure and recrystalline after granule disintegration.

[Study on the effect of high hydrostatic pressure treatment on the secondary structure of mushroom polyphenoloxidase by SRCD and FTIR].

The secondary structure of the mushroom polyphenoloxidase treated by the high hydrostatic pressure (HHP) was analyzed by the synchrotron radiation circular dichroism (SRCD) and Fourier transform infrared spectroscopy (FTIR). The alpha-helix content of mushroom PPO was decreased after HHP treatment, which indicated that the secondary structure of PPO was changed. There was a discrepancy of the result of the secondary structure content between untreated or HHP-treated mushroom PPO analyzed by SRCD and FTIR spectra, and this discrepancy may be due to the different determination temperature, the concentration of the PPO solution and the spectra analysis method etc. The fluorescence spectra showed that the fluorescence intensity of the mushroom PPO was decreased after HHP treatment, and a red shift was observed after HHP treatment, which indicated that the tertiary structure of the enzyme molecule has been modified.

[Analysis of the extraction of red pellicle of walnut (Juglans regia L.) by ultraviolet-visible spectra and HPLC-ESI-MS(n)].

The extraction of the red pellicle of walnut (Juglans regia L.) was analyzed by UV-visible spectra and HPLC-ESI-MS(n) (high-performance-liquid-chromatography coupled with electrospray ionization mass spectrometry). The extraction in ethanol-HCl showed two absorption peaks at 560 and 591 nm respectively in the UV-Vis spectrum; after purified by lead acetate and thin-layer-chromatography, the extraction in ethanol-HCl showed 4 absorption peaks at 340, 370, 552 and 585 nm respectively. These results testified that the anthocyanin was in the extraction. Six molecular ion peaks (m/z) occurred on MS: 301, 481, 633, 783, 785 and 950, which was identified as ellagic acid, Hexahydroxydiphenoyl(HHDP)-glucose, Galloyl-HHDP-glucose, Di-HHDP-glucose, Di-Galloyl-HHDP-glucose, and HHDP-Valoneoyl-glucose respectively.

[Effects of high pulsed electric field on the secondary and tertiary structure of lipoxygenase].

The effect of pulsed electric field (PEF) on the secondary and tertiary structure of lipoxygenase (LOX) in a buffer solution was analyzed using far UV-circular dichroism (CD) and fluorescence spectrophotometry, respectively. The secondary and tertiary structure of LOX changed after PEF treatment. The CD spectra of LOX also changed, with the intensity of two negative peaks and the content of alpha-helix significantly decreased (p < 0.05). The decrease in alpha-helix content in LOX showed a good linear correlation with the electric field strength. The fluorescence intensity of LOX increased, and the relative fluorescence intensity of the two characteristic peaks of LOX emission spectra at 337 nm and 583 nm also showed a good linear correlation with the electric field strength. These results showed that the activity inactivation of LOX may be due to the alteration in secondary structure, and both had a good relation.

[Determination of mineral elements in eight pear varieties by ICP-MS after microwave-assisted digestion].

A study was carried out on the contents of mineral elements such as Na, K, Ca, Mg, Zn, Cu, Fe, Mn and B in eight different pear varieties by ICP-MS after microwave-assisted digestion. The results indicated that the main elements of the eight pears are similar, but the content of each element is different. The content of K is the highest in the detected pears, followed by Mg, Ca and Na. Compared with the reference value of AIJN (Association of Industry of Juices and Nectars from fruits and vegetables of the European Union), the range scale of K, Mg, and Ca was higher than that of the AIJN, while the content of Na element was lower than that of the AIJN, and other elements content was consistent with it.

[The characteristic analysis of several mineral contents in Chinese orange juice].

A study was carried out on the contents of mineral elements such as K, Ca, Na, and Mg in seven different orange varieties, namely Pineapple orange, Hamlin, Trovita, Jincheng, 1,232 Tangor, Olinda Valencia and Delta Valencia, by flame atomic absorption spectrometry. The results indicated that the content sequence of different nutritional elements was K > Mg > Ca > Na, with a range of 1,233.75-1,866.23, 77.51-167.15, 49.32-125.29 and 1.22-9.26 mg x L(-1) respectively. The range scale of the four elements was largely consistent with the reference value of AIJN (Association of the Industry of Juices and Nectars from Fruits and Vegetables of the European Union). The samples can be clustered into 2 groups by factor analysis, and lower Na content would be the characteristic of the Valencia varieties. All these data would offer important information for orange juice adulteration determination and quality evaluation.

Biological properties of different protein extracts from selenium-enriched Ganoderma lucidum.

Our previous studies showed that Ganoderma lucidum bio-transformed 20-30% of inorganic selenium from substrate to organic forms by preferentially incorporating selenium into proteins. In the present study, four kinds of protein extracts from selenium-enriched G. lucidum were prepared with different extracting solvents, which contain water-soluble, alkaline-soluble, salt-soluble and alcohol-soluble protein extracts, and the effects on antioxidant activity of characterizations of protein extracts were studied. Results showed that water-soluble extract showed strongest antioxidant properties among all extracts as suggested by spin trapping experiment due to its characterizations, followed by the alkaline-soluble > the salt-soluble > the alcohol-soluble protein extracts, a result demonstrating that selenium content and amino acids composition of the protein extracts play important and direct roles in enhancing their antioxidant activities, and the protein distribution and sugar content have an indirect effect by influencing the characters and structures. The activity of water-soluble crude protein was verified by CuSO4 Phen-Vc-H2O2-DNA chemiluminescent analysis, and it should be selected as the subject to be studied and purified further.

Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells.

AIM: To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS: [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells. RESULTS: C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERK1/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARgamma was upregulated. Addition of GW9662, which is a PPARgamma specific antagonist, could reserve the modulation action on CDK7. CONCLUSION: Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARgamma activation. The ERK signaling pathway was involved in this process.