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Background and Purpose Neurodegenerative diseases present progressive neurological disorder induced by cell death or apoptosis. Catalpol, an iridoid glucoside isolated from the root of Rehmannia glutinosa Libosch, is present in a wide range of plant families. Although catalpol is an effective anti‐apoptotic agent in LPS‐induced neurodegeneration, the underlying mechanism has not been established. Here we have identified some of the mechanisms involved the prevention by catalpol of apoptosis induced by LPS in an experimental model of neurodegeneration in vitro. Experimental Approach Apoptosis was induced by adding LPS (80 ng·mL−1) to pheochromocytoma (PC12) cells, pretreated with catalpol for 12 h. We measured intracellular reactive oxygen species (ROS), apoptosis and intracellular calcium concentration ( [Ca2+]i) by flow cytometry or laser confocal scanning microscopy. We also analysed the protein expression of Bcl‐2, Bax and Ca2+‐calmodulin‐dependent protein kinase II (CaMKII)‐dependent apoptosis signal‐regulating kinase‐1 (ASK‐1)/JNK/p38 signalling pathway in PC12 cells by Western blot. Key Results Catalpol stimulated expression of Bcl‐2 and inhibited the expression of Bax. Catalpol also attenuated the increase in Ca2+ concentration induced by LPS in PC12 cells and down‐regulated CaMK phosphorylation. The CaMKII‐dependent ASK‐1/JNK/p38 signalling cascade was blocked by catalpol. All these changes were accompanied by a decrease of apoptosis induced by LPS in PC12 cells. Conclusions and Implications The data presented here provide new mechanistic insights into the links between the CaMKII‐dependent ASK‐1/JNK/p38 signalling pathway and the protective effect of catalpol on apoptosis induced by LPS in PC12 cells.

In this study, the immunomodulatory effect of Seabuckthorn (SBT) pulp oil was elucidated in immunosuppressed Balb/c mice induced by cyclophosphamide (CTX). The results showed that SBT pulp oil could reverse...

Norepinephrine (NE) can regulate natural killer (NK) cell activity, but the mechanism remains unclear. In the present study the roles of adrenergic receptors (ARs) in inhibiting NK92‑MI cells‑mediated cytotoxicity by NE were investigated. To examine the effect of NE on NK92‑MI cytotoxicity, a lactate dehydrogenase‑release cytotoxicity assay was used to determine the cytotoxicity of NK92‑MI cells against K562 cells. To evaluate the possible function of the α, β1 and β2 AR in mediating NE‑induced effects, NK92‑MI cells were pre‑incubated with phenol‑amine, CGP20712A and ICI118551 prior to stimulation by NE. To evaluate the role of cyclic adenosine monophosphate (cAMP)‑protein kinase A (PKA) signaling pathway in the inhibitory effect on cytotoxicity of NK92‑MI cell by NE, NK92‑MI cells were pre‑incubated with PKA inhibitor Rp‑8‑Br‑cAMP prior to stimulation by NE. It was demonstrated that NE decreased cytotoxicity and downregulated the expression of perforin, granzyme B and interferon (IFN)‑γ of NK92‑MI cells in a dose‑dependent manner. Blocking NE functional receptors by ARs antagonists, particularly of β2 AR antagonist, suppressed the inhibitory effect of NE on cytotoxicity and expression of perforin, granzyme B, IFN‑γ of NK92‑MI cells significantly. Blockade of β2 AR in NE treated NK92‑MI cells resulted in a reduction of the expression of phosphorylated (p)‑cAMP‑responsive element‑binding protein (CREB) and intracellular cAMP concentration. Inhibiting the activity of PKA by Rp‑8‑Br‑cAMP in NE treated NK92‑MI cells resulted in increased cytotoxicity. The results of the present study suggest that NE can inhibit cytotoxicity and expression of perforin, granzyme B, IFN‑γ of NK92‑MI cell mainly via the β2‑AR/cAMP/PKA/p‑CREB signaling pathway.

Hyperthermia has shown clinical potency as a single agent or as adjuvant to other therapies in cancer treatment. However, thermotolerance induced by thermosensitive genes such as the heat shock proteins can limit the efficacy of hyperthermic treatment. In the present study, we identified HSPB1 (HSP27) is hyperthermically inducible or endogenously highly expressed in both murine and human melanoma cell lines. We used a siRNA strategy to reduce HSPB1 levels and showed increased intolerance to hyperthermia via reduced cell viability and/or proliferation of cells. In the investigation of underlying mechanisms, we found knock down of HSPB1 further increased the proportion of apoptotic cells in hyperthermic treated melanoma cells when compared with either single agent alone, and both agents leaded to cell cycle arrest at G0/G1 or G2/M phases. We concluded that hyperthermia combined with silencing of HSPB1 enhanced cell death and resulted in failure to thrive in melanoma cell lines, implying the potential clinical utility of hyperthermia in combination with HSPB1 inhibition in cancer treatment.

The immune system can be damaged by chronic stress. However, for this process, the involved molecular alterations and their regulatory roles played in immunosuppression still remain unclear. This study was aimed to identify the differences in serum protein expressions that are closely associated with the effect of chronic stress on immune function. Serum protein levels of rats in control group and chronic stress group were measured by iTRAQ analysis. Subsequently, among the 121 differentially expressed proteins screened between the two groups, 46 proteins were upregulated (>1.5-fold, P < 0.05), while 75 proteins were downregulated (<0.67-fold, P < 0.05). Bioinformatics analysis revealed that most of the differentially expressed proteins were in relation with the metabolic, cellular, response stimulus and immune system processes. The significantly differential expression of ceruloplasmin, haptoglobin, catalase and peroxiredoxin-1 were picked out for reconfirmation by ELISA analysis. The results were consistent with those obtained by iTRAQ. What is more, the roles of above-mentioned four proteins, apolipoprotein B-100 and heat-shock protein 90 in immunosuppression induced by chronic stress were discussed. Taken together, these findings may provide a new insight into better understanding the molecular mechanisms of immunosuppression induced by chronic stress.

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The efforts focused on discovering potential hepatoprotective drugs are critical for relieving the burdens caused by liver diseases. Traditional Chinese medicine (TCM) is an important resource for discovering hepatoprotective agents. Currently, there are hundreds of hepatoprotective products derived from TCM available in the literature, providing crucial clues to discover novel potential hepatoprotectants from TCMs based on predictive research. In the current study, a large-scale dataset focused on TCM-induced hepatoprotection was established, including 676 hepatoprotective ingredients and 205 hepatoprotective TCMs. Then, a comprehensive analysis based on the structure–activity relationship, molecular network, and machine learning techniques was performed at molecular and holistic TCM levels, respectively. As a result, we developed an in silico model for predicting the hepatoprotective activity of ingredients derived from TCMs, in which the accuracy exceeded 85%. In addition, we originally proposed a material basis and a drug property-based approach to identify potential hepatoprotective TCMs. Consequently, a total of 12 TCMs were predicted to hold potential hepatoprotective activity, nine of which have been proven to be beneficial to the liver in previous publications. The high rate of consistency between our predictive results and the literature reports demonstrated that our methods were technically sound and reliable. In summary, systematical predictive research focused on the hepatoprotection of TCM was conducted in this work, which would not only assist screening of potential hepatoprotectants from TCMs but also provide a novel research mode for discovering the potential activities of TCMs.