A novel therapeutic strategy for hepatocellular carcinoma: Immunomodulatory mechanisms of selenium and/or selenoproteins on a shift towards anti-cancer.

Selenium (Se) is an essential trace chemical element that is widely distributed worldwide. Se exerts its immunomodulatory and nutritional activities in the human body in the form of selenoproteins. Se has increasingly appeared as a potential trace element associated with many human diseases, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that Se and selenoproteins exert their immunomodulatory effects on HCC by regulating the molecules of oxidative stress, inflammation, immune response, cell proliferation and growth, angiogenesis, signaling pathways, apoptosis, and other processes in vitro cell studies and in vivo animal studies. Se concentrations are generally low in tissues of patients with HCC, such as blood, serum, scalp hair, and toenail. However, Se concentrations were higher in HCC patient tissues after Se supplementation than before supplementation. This review summarizes the significant relationship between Se and HCC, and details the role of Se as a novel immunomodulatory or immunotherapeutic approach against HCC.

919 syrup inhibits ROS-mediated leptin-induced anorexia by activating PPARγ and improves gut flora abnormalities.

BACKGROUND: Women with postpartum psychiatric disorders are prone to severe anorexia. Clinical studies have revealed the efficacy of 919 syrup, a traditional Chinese medicine mixture against postpartum illnesses, such as in regulating maternal mood and improving postpartum anorexia. AIM: This study investigated the mechanisms through which 919 syrup improved anorexia induced by postpartum stress, focussing on the combined peroxisome proliferator-activated receptor gamma (PPARγ) and leptin signalling pathway, and its effects on the structure of the gut flora. METHODS: Mice were randomly divided into five groups-control group, immobilisation stressed (IS) group (normal saline), pioglitazone (Piog; western medicine control) group, 919 syrup low-dose (TJD; 13.5 g/kg) group, and 919 syrup high-dose (TJG; 27.0 g/kg) group. The control group was housed normally. The other groups received IS for 3 h daily for 21 days. The treatments were initiated following the first postnatal day and were administered by gastric gavage. All mice were sacrificed under anaesthesia on postnatal day 22. Blood, hypothalamus, stomach, and faecal specimens were collected. Gene and protein expression levels of components of the PPARγ-leptin signalling pathway in the serum, hypothalamus, and stomach were determined. Immunofluorescence staining for proopiomelanocortin (POMC), phosphorylated signal transducer and activator of transcription 3 (pSTAT3), and leptin was performed to observe their spatial distributions in the hypothalamus and stomach. 16s rRNA gene sequencing and bioinformatics analysis of fecal specimens were performed. RESULTS: After IS, postpartum mice showed significantly reduced appetite and body weight, accompanied by abnormalities in the structure of the gut flora. Treatment with 919 syrup (27.0 g/kg) downregulated malondialdehyde and upregulated catalase, glutathione peroxidase, and superoxide dismutase by activating PPARγ, thereby affecting the expression of leptin signalling pathway components (leptin, leptin receptor, pSTAT3, POMC, and cocaine and amphetamine-related transcript and neuropeptide Y), and modulated the gut flora in stressed mice. CONCLUSION: 919 syrup improved appetite in mice with postnatal stress by activating PPARγ to induce crosstalk with the leptin signalling pathway, this mechanism was similar to that of PPARγ agonists. 919 syrup also improved gut flora structure, and the changes in the relative abundances of the gut flora strongly correlated with the expression levels of PPARγ and leptin pathway components.

Nicotinamide Ameliorates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice through Its Anti-Inflammatory Properties and Modulates the Gut Microbiota.

Vitamin B (nicotinamide (NAM)), one of the most important nutritional components for humans, exerts anti-inflammatory activity. This study was aimed at investigating the effect of NAM on the gut microbiota and short-chain fatty acids (SCFAs) in mice with chronic colitis. Colitis was induced in C57BL/6 male mice by administration of 1.5% dextran sulfate sodium (DSS), and the mice were intraperitoneally injected with normal saline (NS) or NAM. NAM treatment ameliorated weight loss and changes in colon length, disease activity index (DAI) score, and histologic scores. Moreover, enzyme-linked immunosorbent assay (ELISA) analysis of LPL cells revealed that the level of interleukin- (IL-) 6, IL-12p70, IL-1ß, tumor necrosis factor- (TNF-) α, interferon- (IFN-) γ, IL-21, and IL-17A was increased, while IL-10 was reduced, in the chronic colitis group compared to the control group, but the levels of all these factors were restored after NAM treatment. Then, 16S rRNA sequencing of the large intestinal content was performed, and analysis of alpha diversity and beta diversity showed that the richness of the gut microbiota was decreased in the DSS group compared to the control group and restored after NAM treatment. In addition, NAM modulated specific bacteria, including Odoribacter, Flexispira, and Bifidobacterium, in the NAM+chronic colitis group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that NAM treatment restored disruptions in the functions of the gut microbiota (replication and repair, cell motility) in mice with DSS-induced colitis. Furthermore, NAM also restored the reduction in valeric acid in mice with DSS-induced chronic colitis. Our results suggest that NAM treatment could alleviate DSS-induced chronic colitis in mice by inhibiting inflammation and regulating the composition and function of gut microbiota.

Expression patterns of clock genes in the hypothalamus and eye of two Lasiopodomys species.

To investigate the relationship between light sensing systems in the eye and circadian oscillators in the hypothalamus of subterranean rodents, we studied subterranean Mandarin voles (Lasiopodomys mandarinus) that spend their entire lives under dark conditions with degenerated eyes, and compared oscillatory expression patterns of clock genes in the hypothalamus and eye between Mandarin voles and their aboveground relatives, Brandt's voles (L. brandtii). Individuals of both vole species were kept under a 12-h light/12-h dark condition or continuous dark condition for 4 weeks. In both species, the expressions of most genes showed significant cosine rhythmicity in the hypothalamus but relatively weak rhythmicity in the eye. The number of rhythmic genes in the eye of Mandarin voles increased under the dark condition, but the opposite trend was observed in the eye of Brandt's voles. The expression levels of most clock genes in the hypothalamus of both vole species did not significantly differ between the two conditions, but unlike in Mandarin voles, these expression levels significantly decreased in the eye of Brandt's voles kept under the dark condition. In both vole species, the peak phase of most clock genes exhibited advanced or invariant change in the hypothalamus under the dark condition, and the peak phase of most clock genes showed consistent changes between the eye and hypothalamus of Mandarin voles. However, most clock genes in the eye showed a delayed phase in Brandt's voles kept under the dark condition. In conclusion, the hypothalamus plays an important role in both vole species irrespective of the light condition. However, the expression patterns of clock genes in the eye differed between the vole species, indicating that each species adapted differently to their environments.

Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer.

Colorectal cancer (CRC), a multifactorial disease, is usually induced and developed through complex mechanisms, including impact of diet and lifestyle, genomic abnormalities, change of signaling pathways, inflammatory response, oxidation stress, dysbiosis, and so on. As natural polyphenolic phytochemicals that exist primarily in tea, tea polyphenols (TPs) have been shown to have many clinical applications, especially as anticancer agents. Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC. TPs can inhibit the growth and metastasis of CRC by exerting the anti-inflammatory, anti-oxidative or pro-oxidative, and pro-apoptotic effects, which are achieved by modulations at multiple levels. Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells, including the mitogen-activated protein kinase pathway, phosphatidylinositol-3 kinase/Akt pathway, Wnt/ß-catenin pathway, and 67 kDa laminin receptor pathway, to inhibit proliferation and promote cell apoptosis. In addition, novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses. Molecular pathological epidemiology, a novel multidisciplinary investigation, has made great progress on CRC, and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC. This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.

Administration of chlorogenic acid alleviates spinal cord injury via TLR4/NF­κB and p38 signaling pathway anti­inflammatory activity.

Chlorogenic acid, as a secondary metabolite of plants, exhibits a variety of effects including free radical scavenging, antiseptic, anti­inflammatory and anti­viral, in addition to its ability to reduce blood glucose, protect the liver and act as an anti­hyperlipidemic agent and cholagogue. The present study demonstrated that administration of chlorogenic acid alleviated spinal cord injury (SCI) via anti­inflammatory activity mediated by nuclear factor (NF)­κB and p38 signaling pathways. Wistar rats were used to structure a SCI model rat to explore the effects of administration of chlorogenic acid on SCI. The Basso, Beattie and Bresnahan test was executed for assessment of neuronal functional recovery and then spinal cord tissue wet/dry weight ratio was recorded. The present study demonstrated that chlorogenic acid increased SCI­inhibition of BBB scores and decreased SCI­induction of spinal cord wet/dry weight ratio in rats. In addition, chlorogenic acid suppressed SCI­induced inflammatory activity, inducible nitric oxide synthase activity and cyclooxygenase­2 protein expression in the SCI rat. Furthermore, chlorogenic acid suppressed Toll like receptor (TLR)­4/myeloid differentiation primary response 88 (MyD88)/NF­κB/IκB signaling pathways and downregulated p38 mitogen activated protein kinase protein expression in SCI rats. The findings suggest that administration of chlorogenic acid alleviates SCI via anti­inflammatory activity mediated by TLR4/MyD88/NF­κB and p38 signaling pathways.

Association of Individual Characteristics with Teleoperation Performance.

BACKGROUND: A number of space activities (e.g., extravehicular astronaut rescue, cooperation in satellite services, space station supplies, and assembly) are implemented directly or assisted by remote robotic arms. Our study aimed to reveal those individual characteristics which could positively influence or even predict teleoperation performance of such a space robotic arm. METHODS: There were 64 male volunteers without robot operation experience recruited for the study. Their individual characteristics were assessed, including spatial cognitive ability, cognitive style, and personality traits. The experimental tasks were three abstracted teleoperation tasks of a simulated space robotic arm: point aiming, line alignment, and obstacle avoidance. Teleoperation performance was measured from two aspects: task performance (completion time, extra distance moved, operation slips) and safety performance (collisions, joint limitations reached). The Pearson coefficients between individual characteristics and teleoperation performance were examined along with performance prediction models. RESULTS: It was found that the subjects with relatively high mental rotation ability or low neuroticism had both better task and safety performance (|r| = 0.212 ∼ 0.381). Subjects with relatively high perspective taking ability or high agreeableness had better task performance (r = -0.253; r = -0.249). Imagery subjects performed better than verbal subjects regarding both task and safety performance (|r| = 0.236 ∼ 0.290). Compared with analytic subjects, wholist subjects had better safety performance (r = 0.300). Additionally, extraverted subjects had better task performance (r = -0.259), but worse safety performance (r = 0.230). CONCLUSIONS: Those with high spatial cognitive ability, imagery and wholist cognitive style, low neuroticism, and high agreeableness were seen to have more advantages in working with the remote robotic arm. These results could be helpful to astronaut selection and training for space station missions. Pan D, Zhang Y, Li Z, Tian Z. Association of individual characteristics with teleoperation performance. Aerosp Med Hum Perform. 2016; 87(9):772-780.

[Preliminary study on efficacy and mechanism of Atractylodes Macrocephelae Rhizoma extracts in metabolic hyperlipidemia rats].

Hyperlipidemia is a major factor causing coronary heart disease and atherosclerosis. The high-density lipoprotein cholesterol (HDL-C) is a major indicator for measuring lipid levels. However, there is no an effective medicine that can obviously increase HDL-C at present. According to previous laboratory studies, atractylodes macrocephalae extracts could significantly increase HDL-C level. In this study, the metabolic hyperlipidemia rat model was established by feeding high-sugar and fat diets and alcohol-drinking to explore the effect and mechanism of atractylodes macrocephalae extracts on hyperlipidemia rats. According to the findingins, different doses of atractylodes macrocephalae extracts could reduce the levels of TC, TG, LDL-C, ACAT and increase the contents of LCAT, HDL-C. Particularly, the atractylodes macrocephalae extracts (100 mg · kg(-1) group showed increase in HDL-C by about 50% and significant declines in HMG-CoA reductase, TC, TG. In conclusion, Atractylodes Macrocephelae Rhizoma extracts could effectively regulate the dyslipidemia of hyperlipidemia rats, especially on HDL-C. Its mechanism may be related to reduction in cholesterol synthesis by inhibiting HMG-CoA reductase in livers and increase in lipid metabolism and transport by regulating LCAT and ACAT levels.

[Effect of improper diets on blood viscosity in SD rats in high-salt and fat diet and alcohol abuse simulation model].

OBJECTIVE: To observe the effect of composite factors, like long-term high-salt & fat diet and alcohol abuse on blood viscosity and blood pressure in rats, and compare with a model induced by high molecular dextran, in order to build a chronic hyperviscosity aminal model which is similar to human hyperviscosity in clinic and lay a foundation for efficacy evaluation on traditional Chinese medicines. METHOD: Male SD rats were randomly divided into the normal group, the high molecular dextran (HMD) group and the high salt & fat and alcohol (HSFA) group. The HMD group was given normal diet and water for 23 day and then 10% HMD through tail vein for 5 days. The HSFA group was fed with high salt and high fat diets every day and alcohol for 20 h x d(-1) for 13 weeks. After the modeling, whole blood viscosity and plasma viscosity were measured in the 5th, 8th and 11th week. Blood pressure was measured in the 5d, 7h, and 10th week. Red cell count (RBC) and hematocrit (HCT) were measured in the 11th week. PAgT, Fb, ET-1, NO, PGI, TXA2 contents of the normal group and the HSFA group were measured in the 13th week, and IECa21 content was measured with flow cytometry. Result: After the modeling, the HMD group was in good conditions with glossy hairs and active behaviors. The HSFA group was depressed with withered hairs and less activities. During the 5th-11th weeks, the HMD group and the HSFA group showed higher values in high and low shear whole blood viscosity (WBV) than the normal control group. The plasma viscosity (PV) of HMD rats was significantly increased only in the 5th week, and that of HSFA rats significantly increased in the 8"' and 11th week, particularly in the 11'h week. In the 111h week, the HSFA group showed significant increases in RBC and HCT. After the modeling, the blood pressure of HMD rats showed no significant changes, but the blood pressure of HSFA rats significantly increased during 7' and 101h weeks, particularly in the 10"' week. In the 13th week, PAgT, IECa2+, Fb, ET-1 of HSFA rats significantly increased, but with decreases in NO and PGI2. CONCLUSION: Long-term high salt & fat and alcohol diets can cause abnormal blood viscosity in rats. WBV significantly increased since the 5th week in rats, and PV increased since the 8th week. The mechanism for increasing BV may be: (1) increases in RBC, HCT, and IECa2+, (2) PAgT increase, (3) Fb content increase, or (4) TXA2/PGI2, ET-1/NO imbalance. Although the modeling time with the method is longer than that with the HMD method, the model is more stable and moderate, and could lead to abnormal increases in WBV and PV; Whereas the HMD method only induced transient increase in plasma viscosity and abnormal increase in SBP. The model is more similar to traditional Chinese medicine syndromes and pathogenesis, with higher value for studies on efficacy of traditional Chinese medicines.