Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-kB pathway

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.

Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-kB pathway

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 induces A549 cell mitophagy and mitochondrial apoptosis via a reactive oxygen species-mediated reduction in mitochondrial membrane potential

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.

Sesamin induces A549 cell mitophagy and mitochondrial apoptosis via a reactive oxygen species-mediated reduction in mitochondrial membrane potential

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.

Parthenolide enhances the apoptosis induced by PKC inhibitor in human gastrointestinal stromal tumors cell lines / 基础医学与临床

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 .

Solid papillary carcinoma of breast: a clinicopathologic study of 73 case / 临床与实验病理学杂志

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.

Studies on anti proliferation and inducing apoptosis effects of CIK cells against MGC 803 gastric cancer cell lines / 中国免疫学杂志

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