Objective:To study the anti proliferation and inducing apoptosis effects of cytokine induced killer cells CIK cells on MGC 803 gastric cancer cell lines and to probe its underlying mechanism.Methods:To detect the anti proliferation and the cytotoxicity of CIK cells on MGC 803 gastric cancer line by MTT assay.The morphological changes of the apoptosis cell were observed by HE stain, scanning and transmission electron microscope. The positive expression of p53, p16,C myc were determined by immunocytochemistry (ICC).Results:MTT assay showed that the inhibitive rate inhanced obviously with the addition of Effect/Target rate and extension of time ( P

Objective To investigate the effect of parthenolide ( PTL) and PKC inhibitor on human gastrointestinal stromal tumor (GIST) cell proliferation and apoptosis and the mechanism involved .Methods Human GIST cell lines were cultured in vitro, and the cell proliferation rate of GIST , was determinate by MTT;flow cytometry was used to test the early apoptosis rate of GIST;Western blot assay was applied to detect the expression of endoplasmic reticulum stress-related proteins , GRP78 and GADD153.There were four groups: control group , PTL group, PKC inhibitor group , combine PTL and PKC inhibitor group .Results PTL and PKC inhibitor combination therapy for GIST was sig-nificantly more effective than a single-drug therapy (P<0.05);as for the early apoptosis rate , the combination ther-apy for GIST cells was significantly higher than that medication alone group (P<0.05).the expression of endoplas-mic reticulum stress-associated protein GRP 78 and GADD153 was obviously higher in PTL and PKC inhibitor combi-nation group than that in medication alone group (P<0.05).Conclusions PTL and PKC inhibitor combination therapy for GIST cells can induce apoptosis , which is possibly mediated via endoplasmic reticulum stress pathway .

Purpose To study the clinicopathologic features, immunophenotype and differential diagnosis of solid papillary carcinoma (SPC) of breast.Methods 73 cases of breast SPC with or without invasive carcinoma were collected, and the clinical data and histopathologic features were analyzed with further investigation of transmission electron microscopy and immunohistochemical staining (EnVision method). Selected antibodies included cytokeratin (CK), myoepithelial markers, neuroendocrine markers, proliferation marker Ki-67 and ER,PR,c-erbB-2,etc.Results All the patients were females with mean age of 64.7 years.The presenting symptoms were either a palpable breast mass or nipple discharge.Metastasis was observed in 43 cases who had undergone axillary lymph node dissection. Histologically, the tumor displayed a solid-papillary growth pattern, with mucin production demonstrated in 25 cases. Intraductal papilloma was not uncommon at the peripheral area of the tumor. The tumor cells were polygonal, oval, spindled or signet ring-like and contained abundant eosinophilic to granular cytoplasm and mildly to moderately pleomorphic nuclei. More than 5 mitotic figures/10 HPF were observed in 51 cases. 43 cases contained foci of invasive carcinoma which showed similar cytologic features as those of in-situ component. Immunohistochemical study showed that the tumor cells were negative for basal cell cytokeratin; positivity for smooth muscle actin-alpha and p63 were demonstrated in the myoepithelial layers of fibrovascular cores, as well as around the expanded ductolobular units.Most cases also showed cytoplasmic positivity for chromogranin A (89.0%), synaptophysin (86.3%) and neuron-specific enolase (95.9%).The proliferatiing index, as highlighted by Ki-67 imnunostaining, was 9.2%.The tumor mainly expressed estrogen receptor and progesterone receptor. The staining for c-erbB-2 oncoprotein was negative in the most cases. Neuroendocrine granules were seen under transmission electron microscope in the cytoplasm.Conclusions SPC represents a subgroup of low-grade ductal carcinoma in situ.SPC predilection in older women is associated with mucinous and neuroendocrine components. Follow-up data suggest that SPC has a good prognosis.

To establish the HPLC fingerprints of Eucommia ulmoides at different ages of different varieties with pi-noresinol diglucoside as the reference material to provide the basis for the HPLC fingerprints in the enterprise quality standards of Eu-commia ulmoides from the GAP base of Chenzhou Dacheng Chinese Herbal Medicine Co. Ltd. . Methods: A column of ZORBAX E-clipse XDB-C18 (250 mm × 4. 6 mm, 5μm) was used. The mobile phase consisted of methanol-0. 1% phosphoric acid with gradient e-lusion. The detection wavelength was 277 nm, the column temperature was 25℃,the flow rate was 1. 0 ml·min-1 , and the injection volume was 5 μl. Results:The Eucommia ulmoides HPLC fingerprints including 14 common peaks were established with pinoresinol diglucoside as the reference material. The similarity of the HPLC fingerprints of 10 samples was over 0. 939. Conclusion:The method is accurate and reliable. The HPLC fingerprints can be used as the enterprise quality standards of Eucommia ulmoides for Chenzhou Dacheng Chinese Herbal Medicine Co. Ltd. .

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-kB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-kB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-kB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-kB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-kB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-kB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

Objective To compare the difference in the microstructure of gray matter nucleus in basal ganglia of different movement subtypes of Parkinson's disease (PD) by diffusion kurtosis imaging (DKI) technique,and to analyze its clinical significance in the process of disease occurrence and development.Methods A total of 44 PD patients and 20 healthy controls (HC) admitted to the First Hospital of Shanxi Medical University from July 2017 to October 2018 were recruited into the study.The PD patients were classified into tremor dominant (TD) and non-tremor dominant (NTD) subtypes according to motor symptoms.All participants were scanned for DKI sequence.Fractional anisotropy (FA),mean kurtosis (MK),and mean diffusivity (MD) were obtained from bilateral red nucleus,substantia nigra,caudate nucleus,globus pallidus,putamen,and thalamus.The DKI of the deep brain nucleus in TD,NTD,HC groups was compared,and relationships between DKI and clinical measures were tested.Results Comparing the two substypes of PD with the HC group,the TD group had lower FA value (0.346±0.006 vs 0.389±0.009,U=-3.052,P=0.007),higher MK value (1.101±0.008 vs 0.981±0.006,U=-5.577,P=0.000) and higher MD value (1.005(0.919,1.082) vs 0.934 (0.899,0.970),U=2.493,P=0.038) in the substantia nigra ipsilateral to the more affected side than the HC group.The NTD group had higher MK value in the bilateral substantia nigra than the HC group (less affected side:1.090±0.022 vs 0.990±0.008,U=-4.102,P=0.000;more affected side:1.071±0.020 vs 0.981±0.006,U=-3.728,P=0.001).In the PD patients,the MK value in the substantia nigra ipsilateral to the more affected side showed a negative correlation with the Hoehn-Yahr (H-Y) grade,Unified Parkinson's Disease Rating Scale (UPDRS) Ⅲ scores,and non-tremor scores (r=-0.299,P=0.048;r=-0.366,P=0.015;r=-0.402,P=0.007).The FA values of the bilateral putamen of the TD group and the NTD group were lower than those of the HC group.The FA value in putamen contralateral to the more affected side was positively correlated with H-Y grade,UPDRS Ⅲ scores,and non-tremor scores (r=0.331,P=0.028;r=0.403,P=0.007;r=0.376,P=0.012).Compared with the HC group,the FA value of the bilateral globus pallidus was lower in the TD group.Comparing different subtypes of PD,only the FA and MK values of the bilateral thalamus were different.The tremor scores of PD patients were negatively correlated with the FA value of bilateral thalamus (less affected side:r=-0.371,P=0.013;more affected side:r=-0.402,P=0.007),and positively correlated with MK value (less affected side:r=0.547,P＜0.01;more affected side:r=0.532,P＜0.01).Conclusions The microstructure of the deep brain nucleus of PD is changed,while the TD and NTD patients have only differences in the microstructure changes of the thalamus.The changes in the microstructure of the thalamus are related to the severity of tremor in PD patients.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.