LEPR/FOS/JUNB signaling pathway contributes to chronic restraint stress-induced tumor proliferation.

BACKGROUND & AIMS: Psychosocial stress has become an unavoidable part of life, which was reported to promote tumor development. Chronic stress significantly promotes the norepinephrine (NE) secretion and the expression of leptin receptor (LEPR), leading to tumor invasion, metastasis, and proliferation. However, the mechanism of chronic stress-induced tumor proliferation remains unclear. METHODS: To reveal the effect of chronic stress on tumor proliferation, subcutaneous tumor models combined with chronic restraint stress (CRS) were established. Combined with the transcript omics database of liver cancer patients, the target pathways were screened and further verified by in vitro experiments. RESULTS: The results showed that the CRS with subcutaneous tumor transplantation (CRS + tumor) group exhibited significantly larger tumor sizes than the subcutaneous tumor transplantation (tumor) group. Compared with the tumor group, CRS obviously increased the mRNA levels of LEPR, FOS, and JUNB of tumor tissues in the CRS + tumor group. Furthermore, the treatment with norepinephrine (NE) significantly elevated the survival rate of H22 cells and enhanced the expression of LEPR, FOS, and JUNB in vitro. Silencing LEPR significantly reduced the expression of FOS and JUNB, accompanied by a decrease in H22 cell viability. CONCLUSIONS: Our study demonstrated that CRS activates the LEPR-FOS-JUNB signaling pathway by NE, aggravating tumor development. These findings might provide a scientific foundation for investigating the underlying pathological mechanisms of tumors in response to chronic stress.

The hepatocyte-specific HNF4α/miR-122 pathway contributes to iron overload-mediated hepatic inflammation.

Hepatic iron overload (IO) is a major complication of transfusional therapy. It was generally thought that IO triggers substantial inflammatory responses by producing reactive oxygen species in hepatic macrophages. Recently, a decrease in microRNA-122 (miR-122) expression was observed in a genetic knockout (Hfe-/-) mouse model of IO. Because hepatocyte-enriched miR-122 is a key regulator of multiple hepatic pathways, including inflammation, it is of interest whether hepatocyte directly contributes to IO-mediated hepatic inflammation. Here, we report that IO induced similar inflammatory responses in human primary hepatocytes and Thp-1-derived macrophages. In the mouse liver, IO resulted in altered expression of not only inflammatory genes but also >230 genes that are known targets of miR-122. In addition, both iron-dextran injection and a 3% carbonyl iron-containing diet led to upregulation of hepatic inflammation, which was associated with a significant reduction in HNF4α expression and its downstream target, miR-122. Interestingly, the same signaling pathway was changed in macrophage-deficient mice, suggesting that macrophages are not the only target of IO. Most importantly, hepatocyte-specific overexpression of miR-122 rescued IO-mediated hepatic inflammation. Our findings indicate the direct involvement of hepatocytes in IO-induced hepatic inflammation and are informative for developing new molecular targets and preventative therapies for patients with major hemoglobinopathy.

Stress-Induced Mucus Secretion and Its Composition by a Combination of Proteomics and Metabolomics of the Jellyfish Aurelia coerulea.

BACKGROUND: Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood. METHODS: Aurelia coerulea jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and tissue samples were then collected within 60 min, and analyzed by a combination of proteomics and metabolomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), respectively. RESULTS: Two phases of sample collection displayed a quick decrease in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were identified in tissue homogenate and secreted mucus, respectively. Gene Ontology (GO) analysis showed that the mucus-enriched proteins are mainly located in extracellular or membrane-associated regions, while the tissue-enriched proteins are distributed throughout intracellular compartments. Tryptamine, among 16 different metabolites, increased with the largest-fold change value of 7.8 in mucus, which is consistent with its involvement in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway 'tryptophan metabolism'. We identified 11 metalloproteinases, four serpins, three superoxide dismutases and three complements, and their presence was speculated to be related to self-protective defense. CONCLUSIONS: Our results provide a composition profile of proteins and metabolites in stress-induced mucus and tissue homogenate of A. coerulea. This provides insight for the ongoing endeavors to discover novel bioactive compounds. The large increase of tryptamine in mucus may indicate a strong stress response when jellyfish were taken out of seawater and the active self-protective components such as enzymes, serpins and complements potentially play a key role in innate immunity of jellyfish.

HIF1α/miR-146α/TRAF6/NF-κB axis modulates hepatic iron overload-induced inflammation.

Transfusional therapy is used to cure anemia but raises the risk of hepatic iron overload (IO), which triggers oxidative stress damage, inflammation, and failure even fibrosis. microRNAs play a vital role in developing hepatic diseases. This study presented the mechanism by which IO induce hepatic inflammation through microRNAs. In this study, microRNA expression profiling in the liver was observed after IO for 2 weeks, in which the target microRNA will be found. IO activating the miR-146α/TRAF6/NF-κB pathway was validated, and the molecular mechanism of the IO-induced decrease of miR-146α in the liver was studied in vivo and in vitro. The expression of TRAF6/NF-κB (p65)-dependent inflammatory factors increased, whereas the expression of miR-146α decreased during the IO-induced inflammatory response in the liver. The reduced expression of HNF4α caused by HIF1α and miR-34α may decrease the expression of miR-146α. Overexpression of miR-146α alleviated the hepatic inflammatory response caused by IO. Our findings indicate that miR-146α is a key factor in inducing hepatic IO inflammation, which will be another potential target to prevent IO-induced hepatic damage.

Tryptophan metabolic pathway plays a key role in the stress-induced emotional eating.

Chronic stress disrupts the emotional and energetic balance, which may lead to abnormal behaviors such as binge eating. This overeating behavior alleviating the negative emotions is called emotional eating, which may exacerbate emotional instability and lead to obesity. It is a complex and multifaceted process that has not yet been fully understood. In this study, we constructed an animal model of chronic mild stress (CMS)-induced emotional eating. The emotional eating mice were treated with tryptophan for 21 days to reveal the key role of tryptophan. Furthermore, serum-targeted metabolomics, immunohistochemical staining, qPCR and ELISA were performed. The results showed that CMS led to the binge eating behavior, accompanied by the disturbed intestinal tryptophan-derived serotonin (5-hydroxytryptamine; 5-HT) metabolic pathways. Then we found that tryptophan supplementation improved depression and anxiety-like behaviors as well as abnormal eating behaviors. Tryptophan supplementation improved the abnormal expression of appetite regulators (e.g., AgRP, OX1R, MC4R), and tryptophan supplementation also increased the tryptophan hydroxylase 2 (tph2) and 5-HT receptors in the hypothalamus of CMS mice, which indicates that the 5-HT metabolic pathway influences feeding behavior. In vitro experiments confirmed that 5-HT supplementation ameliorated corticosterone-induced aberrant expression of appetite regulators, such as AgRP and OX1R, in the hypothalamic cell line. In conclusion, our findings revealed that the tryptophan-derived 5-HT pathway plays an important role in emotional eating, especially in providing targeted therapy for stress-induced obesity.

A magnetic graphene oxide and UiO-66 based homogeneous dual recognition electrochemical aptasensor for accurate and sensitive detection of aflatoxin B1.

Aflatoxin (AFs) contamination is one of the serious food safety issues. Aflatoxin B1 (AFB1) is the most common and toxic aflatoxin, which has been classified as a class 1 carcinogen by the International Agency for Research on Cancer (IARC). It is extremely destructive to liver tissue. Developing a convenient and sensitive detection technique is essential. In this paper, we developed a homogeneous dual recognition strategy based electrochemical aptasensor for accurate and sensitive detection of aflatoxin B1 (AFB1) based on the magnetic graphene oxide (MGO) and UiO-66. The MGO was synthesized for the recognition and magnetic separation of AFB1 from complex samples. UiO-66/ferrocenecarboxylic acid (Fc)/aptamer composites were constructed as both recognition and signal probes. The probes would specifically capture AFB1 enriched by MGO, which enables dual recognition in homogeneous solution, thus further improving the accuracy of AFB1 detection. The electrochemical aptasensor for AFB1 had a linear range from 0.005 to 500 ng mL-1. Additionally, the limit of detection was 1 pg mL-1. It shows a favorable potential for both sensitive and accurate detection of AFB1 in real samples.

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury.

Mild traumatic brain injury (mTBI)-induced post-traumatic headache (PTH) is a pressing public health concern and leading cause of disability worldwide. Although PTH is often accompanied by neurological disorders, the exact underlying mechanism remains largely unknown. Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH. In this study, a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery. Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage. Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum, temporal lobe/cortex, and hippocampal regions during the early stages of PTH. Additionally, variations in brain functional activities and connectivity were further detected in the early stage of PTH, particularly in the cerebellum and temporal cortex, suggesting that these regions play central roles in the mechanism underlying PTH. Moreover, our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH. Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex, with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

28-day repeated-dose toxicity of orally administered Jinmao Jiedu granule in Sprague-Dawley rats.

Jinmao Jiedu granule is a Chinese medicine preparation consisting of Actinidia valvata Dunn, Salvia chinensis Benth, Iphigenia indica Kunth, and chicken gizzard. For many years, it has been employed in adjuvant therapy for cancer, especially liver cancer. However, the potential toxicity of the granule has not been reported. The present study aimed to assess the repeated-dose toxicity of orally administered Jinmao Jiedu granules for Sprague-Dawley (SD) rats. SD rats were orally administered Jinmao Jiedu granules at doses of 2.85, 5.70, and 11.40 g/kg in a 28-day subchronic toxicity study. No adverse clinical signs associated with treatment were noted throughout the experiment. There were no treatment-related toxicity alterations in body weight, hematology, clinical biochemistry, urinalysis, necropsy, and histopathology in rats compared with the control group. The No Observed Adverse Effect Level (NOAEL) of the Jinmao Jiedu granule was higher than 11.40 g/kg/day in rats.

Rapid detection of foodborne pathogens in diverse foodstuffs by universal electrochemical aptasensor based on UiO-66 and methylene blue composites.

Rapid and sensitive detection of foodborne pathogens in complex environments is essential for food protection. A universal electrochemical aptasensor was fabricated for the detection of three common foodborne pathogens, including Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Salmonella typhimurium (S. typhimurium). The aptasensor was developed based on the homogeneous and membrane filtration strategy. Zirconium-based metal-organic framework (UiO-66)/methylene blue (MB)/aptamer composite was designed as a signal amplification and recognition probe. Bacteria were quantitatively detected by the current changes of MB. By simply changing the aptamer, different bacteria could be detected. The detection limits of E. coli, S. aureus and S. typhimurium were 5, 4 and 3 CFU·mL-1, respectively. In humidity and salt environments, the stability of the aptasensor was satisfactory. The aptasensor exhibited satisfactory detection performance in different real samples. This aptasensor has excellent potential for rapid detection of foodborne pathogens in complex environments.

Effects of Chinese herbal diet on hematopoiesis, immunity, and intestines of mice exposed to different doses of radiation.

Radiotherapy causes a series of side effects in patients with malignant tumors. Polygonati Rhizoma, Achyranthis Bidentatae Radix, and Epimedii Folium are all traditional Chinese herbs with varieties of functions such as anti-radiation and immune regulation. In this study, the above three herbs were used as a herbal diet to study their effects on the hematopoietic, immune, and intestinal systems of mice exposed to three doses of radiation. Our study showed that the diet had no radiation-protective effect on the hematopoietic and immune systems. However, at the radiation dose of 4 Gy and 8 Gy, the diet showed an obvious radiation-protective effect on intestinal crypts. At the dose of 8 Gy, we also found that the Chinese herbal diet had an anti-radiation effect on reducing the loss of the inhibitory nNOS+ neurons in the intestine. That provides a new diet for relieving the symptoms of hyperperistalsis and diarrhea in patients after radiotherapy.

Probiotics formulation and cancer nanovaccines show synergistic effect in immunotherapy and prevention of colon cancer.

Probiotics play essential roles in immune modulation. Combining probiotics with cancer vaccines potentially can achieve a synergistic effect. To maximize the efficacy of probiotics, proper probiotics formulation is necessary. Herein, Lactobacillus rhamnosus and Bifidobacterium longum are coated with lipid membrane to achieve the goal of losing less activity and bettering colonization in colon. In the subcutaneous transplanted colon cancer mouse model, probiotics formulation showed potent preventive and therapeutic efficacy, and the efficacy could be further improved by combining with cancer nanovaccines. Probiotics formulation can perform as immune adjuvants to enhance the innate immune response or as in-situ cancer vaccines. In the study of preventing chemical-induced orthotopic colon cancer model, probiotics formulation alone efficiently reduced tumor number in colon and the efficacy is improved by combining with cancer nanovaccines. All in all, the studies demonstrated that probiotics formulation can assist to maximize the efficacy of cancer nanovaccines.

miR-182 mediated the inhibitory effects of NF-κB on the GPR39/CREB/BDNF pathway in the hippocampus of mice with depressive-like behaviors.

BACKGROUND: Chronic stress is one of the most important causes of depression, accompanied by neuroinflammation and hippocampal injuries. Long-term elevation of glucocorticoid leads to activation of NF-κB and inhibition of GPR39/CREB/BDNF pathway, which is pivotal for neuroprotection and neurogenesis. The present study thus was designed to determine the relationship between NF-κB and GPR39/CREB/BDNF pathway. METHODS: Depressive-like behaviors were induced by chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) in mice. Corticosterone, inflammatory cytokines, and GPR39/CREB/BDNF pathway were determined by ELISA and Western Blot assays. The activation of NF-κB and inhibition of GPR39 were connected by bioinformatic analysis and experimentally validated in hippocampus cells by knock-in and knock-down techniques. RESULTS: CUMS and CRS led to an elevation of serum corticosterone and depressive-like behaviors in mice, with activation of NF-κB subunit p65 in the hippocampus and elevations of TNFα and IL-6. The expression of GPR39/CREB/BDNF pathway in the hippocampus was inhibited. Bioinformatic analysis revealed that four miRNAs, miR-96, miR-143, miR-150, and miR-182, were potentially transcribed by NF-κB and bound with GPR39 mRNA. NF-κB overexpression increased miR-182 expression and decreased GPR39 expression in hippocampus cells. Its inhibitor led to reverse effects. miR-182 mimics or inhibitors also regulated GPR39 expression in hippocampus cells and more importantly, blocked the regulation of NF-κB on GPR39. CONCLUSIONS: The results suggested that activation of NF-κB inhibited GPR39/CREB/BDNF pathway through increasing miR-182 in chronic stress-induced depressive-like behaviors. The negative-regulation features of miRNAs might be important for neuroinflammation-induced inhibition of neurofunction in depression.

[Relationships between constitutional types of traditional Chinese medicine and motion sickness in 145 ocean sailors].

OBJECTIVE: To investigate the relationships between constitutional types of traditional Chinese medicine (TCM) and motion sickness. METHODS: A survey of TCM constitutions in ocean sailors participating in a voyage was performed by using the TCM Constitution Questionnaire developed by Beijing University of Traditional Chinese Medicine, while the survey of motion sickness was operated by Graybiel's diagnostic criteria. The incidences of motion sickness among sailors with different types of constitutions were compared. RESULTS: Prior to the voyage, 50.3% of sailors exhibited a gentleness constitution, 14.5% were of dampness-heat constitution, 10.3% were of qi-stagnation constitution, whereas the percentages of qi-deficiency, yang-deficiency, yin-deficiency, blood-stasis and special diathesis constitutions were 6.2%, 7.6%, 6.2%, 4.1% and 0.7%, respectively. None exhibited a phlegm-dampness constitution. By the end of the 176-day voyage, the percentages of gentleness, dampness-heat, qi-depression, qi-deficiency, yang-deficiency, yin-deficiency, blood-stasis, special diathesis and phlegm-dampness constitutions were 33.8%, 13.8%, 13.1%, 11.0%, 6.9%, 9.7%, 4.1%, 0.7% and 6.9%, respectively. The incidence of motion sickness was 69.7% (101 sailors) during this voyage. The incidences of motion sickness among sailors with different types of constitutions before the voyage showed significant difference (P<0.001). The incidence of motion sickness was higher in the sailors with dampness-heat constitution than in those with gentleness constitution. CONCLUSION: Types of Chinese medical constitution can be related to susceptibility to motion sickness. Furthermore, ocean voyage may have an effect or influence on the type of Chinese medical constitution of sailors involved.

Pyruvate accumulation may contribute to acceleration-induced impairment of physical and cognitive abilities: an experimental study.

BACKGROUND: Fatigue can be induced after acceleration exposure, however its mechanism is still unclear. The aim of the present study was to examine whether metabolites' changes can decrease cognitive and physical function after acceleration. METHODS: Graybiel scale and Fatigue Self-rating scale were used to assess the seasickness and fatigue degrees of 87 male seafarers respectively after sailing. To test the effect of pyruvate on cognitive and physical functions, five different doses of pyruvate were administrated into rats. Insulin can reduce the accumulation of pyruvate. To observe the insulin effect on pyruvate, cognitive and physical functions after acceleration, insulin administration or treatment of promoting insulin secretion was used. Physical and cognitive functions were assessed using open field test (OFT), morris water maze (MWM) and loaded swimming test (LST) in animals. RESULTS: Physical and cognitive abilities were decreased obviously, and serum pyruvate increased mostly in human and rats after acceleration. Compared with vehicle group, physical and cognitive abilities were significantly decreased after pyruvate administration. Besides, we found a significant decline in adenosine triphosphate (ATP) concentration and pyruvate dehydrogenase (PDH) activity in the hippocampus, prefrontal cortex, liver, and muscle of rats treated with acceleration or pyruvate injection, while insulin administration or treatment of promoting insulin secretion markedly alleviated this decline and the impairment of physical and cognitive abilities, compared with the control group. CONCLUSION: Our results indicate that pyruvate has a negative effect on physical and cognitive abilities after acceleration. Insulin can inhibit pyruvate accumulation and cognitive and physical function after acceleration exposure.

Sesamol Attenuates Amyloid Peptide Accumulation and Cognitive Deficits in APP/PS1 Mice: The Mediating Role of the Gut-Brain Axis.

Alzheimer's disease (AD), a neurodegenerative disease, is the leading cause of dementia. Sesamol is a lignan extracted from sesame oil and has been found to exert neuroprotective effects. The present study aimed to investigate the neuroprotective effects of sesamol on APPswe/PS1dE9 transgenic AD mice. The AD mice were fed with a diet supplemented with sesamol (0.075 w/w %). Sesamol treatment improved spatial memory and learning ability in AD mice, improved neuronal damage, and decreased Aß accumulation. Sesamol protected the synaptic ultrastructure and inhibited neuroinflammatory responses in the brain of AD mice. Sesamol also significantly inhibited the overactivated microglia and reduced the overexpression of TNF-α and IL-1ß in the brain of AD mice. Notably, sesamol reshaped gut microbiota by significantly decreasing the relative abundance of Helicobacter hepaticus, Clostridium, and Bacillaceae, enhancing the relative abundance of Rikenellaceae and Bifidobacterium in AD mice. It has been found that sesamol protected the gut barrier integrity and prevented the LPS leakage into the serum. Importantly, sesamol remarkably enhanced the content of SCFAs, including acetate, propionate, isobutyrate, butyrate, and valerate, in AD mice. Correlation analysis indicated that there was a strong correlation between the levels of SCFAs and cognitive functions. These results demonstrated that sesamol attenuated AD-related cognitive dysfunction and neuroinflammatory responses, which could be partly explained by its role in mediating the gut microbe-SCFA-brain axis. Thus, sesamol is a promising nutritional intervention strategy to prevent AD via the microbiota-gut-brain axis.

Immunotherapy and Prevention of Cancer by Nanovaccines Loaded with Whole-Cell Components of Tumor Tissues or Cells.

Tumor tissues/cells are the best sources of antigens to prepare cancer vaccines. However, due to the difficulty of solubilization and delivery of water-insoluble antigens in tumor tissues/cells, including water-insoluble antigens into cancer vaccines and delivering such vaccines efficiently to antigen-presenting cells (APCs) remain challenging. To solve these problems, herein, water-insoluble components of tumor tissues/cells are solubilized by 8 m urea and thus whole components of micrometer-sized tumor cells are reasssembled into nanosized nanovaccines. To induce maximized immunization efficacy, various antigens are loaded both inside and on the surface of nanovaccines. By encapsulating both water-insoluble and water-soluble components of tumor tissues/cells into nanovaccines, the nanovaccines are efficiently phagocytosed by APCs and showed better therapeutic efficacy than the nanovaccine loaded with only water-soluble components in melanoma and breast cancer. Anti-PD-1 antibody and metformin can improve the efficacy of nanovaccines. In addition, the nanovaccines can prevent lung cancer (100%) and melanoma (70%) efficiently in mice. T cell analysis and tumor microenvironment analysis indicate that tumor-specific T cells are induced by nanovaccines and both adaptive and innate immune responses against cancer cells are activated by nanovaccines. Overall, this study demonstrates a universal method to make tumor-cell-based nanovaccines for cancer immunotherapy and prevention.

[Antimotion sickness effects of ginsenosides combined with dexamethasone in rats].

OBJECTIVE: To investigate the antimotion sickness effects of ginsenosides combined with dexamethasone in rats. METHODS: Fifty SD rats were randomly divided into 5 groups: normal saline, scopolamine-treated, ginsenosides-treated, dexamethasone-treated and ginsenosides plus dexamethasone-treated groups. There were 10 rats in each group. The rats in each group were fed with corresponding ingredients respectively, and then the rats were exposed to abnormal acceleration for one hour. The motion sickness index, the level of kaolin consumption and the course and time of spontaneous activity were observed. RESULTS: The motion sickness index and the level of kaolin consumption of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group were significantly lower than those in normal saline group. And the course and time of spontaneous activity of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group were significantly higher than those in normal saline group. The level of body weight increment of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group was significantly higher than that in dexamethasone-treated group. CONCLUSION: Ginsenosides combined with dexamethasone can significantly increase tolerance to acceleration of rats, and the drug combination can decrease side effects of methylprednisolone, such as body weight loss.

GPR39 protects against corticosterone-induced neuronal injury in hippocampal cells through the CREB-BDNF signaling pathway.

BACKGROUND: The release of zinc from glutamatergic terminals in the hippocampal CA3 region can activate postsynaptic GPR39 receptors and regulate cognition and depression. However, the role and mechanism of GPR39 in the stress-induced depression is still poorly understood. METHODS: In this study, hippocampal cells (HT-22) were treated with corticosterone (CORT). Then the effects of stress on the activity, mitochondrial function and apoptosis of HT-22 cells were observed. The effects of GPR39 on CORT-induced stress injury were analyzed by both siRNA and agonist (TC-G-1008). RESULTS: Compared with the 500 nM CORT group, the cell viability, apoptosis, mitochondrial membrane potential, and expression levels of BCL-2, CREB and BDNF mRNA were significantly decreased in the GPR39 siRNA+500 nM CORT group, while the expression levels of caspase3, caspase9, AIF and BAX mRNA were significantly increased in the GPR39 siRNA+500 nM CORT group. Compared with the 1 µM CORTgroup, the cell viability, apoptosis, mitochondrial membrane potential, and expression levels of BCL-2, CREB and BDNF were significantly increased in the GPR39 agonist+1 µΜ CORT group, while the expression levels of caspase3, caspase9, AIF and BAX mRNA were significantly decreased in the GPR39 siRNA+500 nM CORT group. Compared with the control group, the mRNA and protein levels of GPR39, CREB and BDNF were significantly increased, and the mRNA and protein levels of CREB and BDNF were significantly decreased after 50 µM zinc sulfate treatment for 6 h. CONCLUSIONS: GPR39 may play a neuroprotective role in CORT-induced cell injury via the improvement of CREB-BDNF expression, by inhibiting pro-apoptotic proteins and by upregulating anti-apoptotic proteins.

A Highly Efficient Tumor-Targeting Nanoprobe with a Novel Cell Membrane Permeability Mechanism.

Efficient tumor targeting has been a great challenge in the clinic for a very long time. The traditional targeting methods based on enhanced permeability and retention (EPR) effects show only an ≈5% targeting rate. To solve this problem, a new graphene-based tumor cell nuclear targeting fluorescent nanoprobe (GTTN), with a new tumor-targeting mechanism, is developed. GTTN is a graphene-like single-crystalline structure amphiphilic fluorescent probe with a periphery that is functionalized by sulfonic and hydroxyl groups. This probe has the characteristic of specific tumor cell targeting, as it can directly cross the cell membrane and specifically target to the tumor cell nucleus by the changed permeability of the tumor cell membranes in the tumor tissue. This new targeting mechanism is named the cell membrane permeability targeting (CMPT) mechanism, which is very different from the EPR effect. These probes can recognize tumor tissue at a very early stage and track the invasion and metastasis of tumor cells at the single cell level. The tumor-targeting rate is improved from less than 5% to more than 50%. This achievement in efficient and accurate tumor cell targeting will speed up the arrival of a new era of tumor diagnosis and treatment.

Is preterm birth associated with asthma among children from birth to 17 years old? -A study based on 2011-2012 US National Survey of Children's Health.

BACKGROUND: Preterm birth can interrupt lung development in utero and is associated with early life factors, which adversely affects the developing respiratory system. Studies on preterm birth and asthma risk are comparatively sparse and the results are not consistent. METHODS: Multivariate analyses were performed on a cross-sectional data from the National Survey of Children's Health (NSCH) collected in 2011 to 2012. The NSCH was a nationally representative telephone survey sponsored by the Maternal and Child Health Bureau and conducted by the National Center for Health Statistics. A cross-sectional analysis using data from the US on 90,721 children was conducted to examine the relationship between preterm birth and asthma risk. RESULTS: A total of 90,721 children under 17 years were included and 12% of the children were reported as preterm birth. The prevalence of diagnosed asthma was 15%, with a male to female ratio of 1.26:1. Children who were born preterm were 1.64 times (95% confidence interval: 1.45-1.84) more likely to develop asthma compared with those who were born term after controlling for confounders. Similarly, children who were low birth weight were 1.43 times (95% confidence interval: 1.25-1.63) more likely for asthma, and the odds ratio increased to 1.77 for those both preborn and low birth weight. Child's gender, race/ethnicity, age, family structure, family income levels, and household smoking were significantly associated with the odds of reported asthma. CONCLUSIONS: Preterm birth was associated with increased risk of asthma among US children, supporting the notion that preterm birth may play a critical role in asthma development.