Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice.     

Affective and inflammatory responses among orchestra musicians in performance situation

A number of studies have shown that mental challenge under controlled experimental conditions is associated with elevations in inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). However, relatively little work has been done on the effects of ‘naturalistic’ stressors on acute changes in inflammatory markers. The present study examined whether perceived arousal, valence and dominance in musicians are associated with pro-inflammatory and oxidative responses to a concert situation. Blood and salivary samples obtained from 48 members of a symphony orchestra on the day of rehearsal (i.e. control situation) and on the following day of premiere concert (i.e. test situation) were used to determine changes in salivary cortisol, pro-inflammatory markers (plasma myeloperoxidase, serum CRP, plasma IL-6), oxidative stress markers (paraoxonase1 activity and malondialdehyde), and homocysteine, a risk factor for vascular disease. Results of regression analyses showed a significant trend to increased myeloperoxidase (MPO) response in individuals with low valence score. Both affective states, valence and arousal, were identified as significant predictors of cortisol response during concert. In addition, control levels of plasma malondialdehyde were positively correlated with differences in IL-6 levels between premiere and rehearsal (r = .38, p = .012), pointing to higher oxidative stress in individuals with pronounced IL-6 response. Our results indicate that stress of public performance leads to increased concentrations of plasma MPO (20%), IL-6 (27%) and salivary cortisol (44%) in musicians. The decreasing effect of pleasantness on the MPO response was highly pronounced in non-smokers (r = −.60, p < .001), suggesting a significant role of emotional valence in stress-induced secretion of MPO. Additional studies are needed to assess the generalizability of these findings to other ’naturalistic’ stress situations.     

Inhibition of phosphodiesterase-4 suppresses HMGB1/RAGE signaling pathway and NLRP3 inflammasome activation in mice exposed to chronic unpredictable mild stress

Inhibition of phosphodiesterase-4 (PDE4) produces robust anti-inflammatory and antidepressant-like effects in multiple animal models. However, the detailed mechanisms have not been well studied. Receptor for advanced glycation endproducts (RAGE) and inflammasome activation are implicated in the etiology of depression. Here, we aimed to investigate the involvement of RAGE and nucleotide-binding domain (NOD)–like receptor protein 3 (NLRP3) inflammasome in the antidepressant-like effects of PDE4 inhibition in mice. We found that inhibition of PDE4 by roflupram (ROF, 0.5, and 1.0 mg/kg, i.g.) exerted antidepressant-like effects in mice subjected to chronic unpredictable mild stress (CUMS). Simultaneously, ROF inhibited CUMS-induced microglial activation and restored the morphology of microglial cells in the hippocampus, as evidenced by reduced total process length, area, volume, number of branching points, number of terminal points and total sholl intersections of microglia. ROF also decreased the expression of ionized calcium-binding adapter molecule-1 and the level of interleukin-1β. Western blot analysis showed that PDE4 inhibition suppressed the high-mobility group box 1 protein (HMGB1)/RAGE signaling pathway, as the levels of HMGB1, RAGE, toll-like receptor 4, phosphorylated p38 mitogen-activated protein kinase, and nuclear factor κ-B were decreased in both hippocampus and cortex in mice after treatment with ROF. Moreover, ROF also attenuated the protein levels of NLRP3, the apoptosis-associated speck-like protein containing (ASC), and cysteine-requiring aspartate protease-1 (Caspase-1), which are key proteins in the NLRP3-mediated inflammasome signaling pathway. In summary, these results demonstrate that the down-regulation of HMGB1/RAGE signaling pathway and inflammasome suppression possibly contribute to the antidepressant-like effects of PDE4 inhibitors. And, ROF has potential as a candidate drug in the treatment of depression.     

Effect of Ethanol Content on Carbon Dioxide Extraction of Polyphenols from Tea

This study presents a novel packed-column extractor coupled with an absorption system to improve the quality of oleoresin oils for Oolong and green teas, extracted by using carbon dioxide. The effect of various co-solvents on the extract is also examined. In addition, gravimetrical measurement and HPLC chromatographic analysis individually determine the amount of oleoresin oil and the concentration of four major catechins. According to those results, the mean contents in the extract are 7.0- and 10.0-fold higher in an addition of 95% ethanol than in no addition for green tea and Oolong tea, respectively. The ratio of four major catechins to caffeine is the highest in Soxhlet ethanol extraction for both green and Oolong teas.     

Deterioration of nuclear morphology and architecture: A hallmark of senescence and aging

The metazoan nucleus is a highly structured organelle containing several well-defined sub-organelles. It is the largest organelle inside a cell taking up from one tenth to half of entire cell volume. This makes it one of the easiest organelles to identify and study under the microscope. Abnormalities in the nuclear morphology and architecture are commonly observed in an aged and senescent cell. For example, the nuclei enlarge, loose their shape, appear lobulated, harbour nuclear membrane invaginations, carry enlarged/fragmented nucleolus, loose heterochromatin, etc. In this review we discuss about the age-related changes in nuclear features and elaborate upon the molecular reasons driving the change. Many of these changes can be easily imaged under a microscope and analysed in silico. Thus, computational image analysis of nuclear features appears to be a promising tool to evaluate physiological age of a cell and offers to be a legitimate biomarker. It can be used to examine progression of age-related diseases and evaluate therapies.     

Methotrexate-mediated inhibition of RAD51 expression and homologous recombination in cancer cells

Background  

Methotrexate is an inhibitor of folic acid metabolism. Homologous recombination is one of the most important ways to repair double-stranded breaks in DNA and influence the radio- and chemosensitivity of tumor cells. But the relationship between methotrexate and homologous recombination repair has not been elucidated.     

肠道菌群对肿瘤治疗的影响

肠道菌群是寄居在人体肠道内的正常微生物群落,维持着宿主肠道微生态的稳态,肠道微生态失调促进肿瘤的发生,但特异的肠道共生菌及其代谢产物可能抑制肿瘤的发生。肠道菌群对宿主固有免疫和适应性免疫系统的成熟与调节具有重要作用,其可增强烷化剂、Toll 样受体（Toll-like receptor,TLR ）激动剂、免疫检验点抑制剂、过继性细胞免疫治疗等的抗肿瘤作用。肠道菌群主要通过调节肿瘤浸润髓源细胞的分化和功能影响抗肿瘤免疫反应,重新编程肿瘤浸润髓源细胞可能是一种理想的肿瘤治疗方法。肠道菌群为肿瘤治疗提供了新的策略,但其临床应用还面临着较多问题。本文就肠道菌群对肿瘤的发生和肿瘤治疗的有益影响进行综述。      

A novel TSHR gene mutation (Ile691Phe) in a Chinese family causing autosomal dominant non-autoimmune hyperthyroidism

Familial non-autoimmune hyperthyroidism is a rare autosomal dominant genetic disease resulting from activating mutations in the thyroid-stimulating hormone receptor (TSHR) gene. In this work a Chinese family with autosomal dominant non-autoimmune hyperthyroidism across four generations was collected. The strongest evidence for linkage in this study occurred on chromosome 14q24.2–31.3. By mutation scan of the TSHR gene located within the region of interest, a heterozygote substitution (A > T) at position 2071 of the TSHR was found, changing isoleucine 691 to phenylalanine. Our study identified the first germline mutation in the intracellular C-terminal domain of TSHR. Zheng Liu and Yuanming Sun contribute to this work equally.     

In vitro the differences of inflammatory and oxidative reactions due to sulfur mustard induced acute pulmonary injury underlying intraperitoneal injection and intratracheal instillation in rats

This study was to investigate the differences of inflammatory reaction and oxidative stress due to sulfur mustard (SM)-induced acute pulmonary injury via two ways in rats. In intraperitoneal and tracheal SM groups, injected intraperitoneally and instilled intratracheally with 0.1 mL diluted SM (0.96 LD₅₀ = 8 mg/kg) and SM (0.98 LD₅₀ = 2 mg/kg) were administered in rats. In bronchoalveolar lavage fluid, serum, and alveolar septum, lactate dehydrogenase, glutathione peroxidase, tumor necrosis factor-α, interleukin-1β, interleukin-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, l-selectin, r-glutamyl transpeptidase, thiobarbituric acid reactive substances levels as well as the expression of CD4, CD20, CD68, 8-hydroxy deoxyguanosine, nuclear factor-E2-related factor 2, and heme oxygenase-1 measured by ELISA, immune scatter turbidimetry and immunohistochemical method in the intraperitoneal SM group were increased at each time-point compared with the tracheal SM groups, respectively. These data demonstrated an increased inflammatory reaction and oxidative stress indices in rat via intraperitoneal injection under similar SM LD₅₀ doses.