OsGA3ox genes regulate rice fertility and plant height by synthesizing diverse active GA.

Gibberellin (GA) is an important hormone, which is involved in regulating various growth and development. GA biosynthesis pathway and synthetase have been basically clarified. Gibberellin 3ß hydroxylase (GA3ox) is the key enzyme for the synthesis of various active GA. There are two GA3ox genes (OsGA3ox1 and OsGA3ox2) in rice, and their physiological functions have been preliminarily studied. However, it is not clear how they work together to synthesize active GA to regulate rice development. In this study, the knockout mutants ga3ox1 and ga3ox2 were obtained by CRISPR/Cas9 technology. The pollen fertility of ga3ox1 decreased significantly, while the plant height of ga3ox2 decreased significantly. It shows that OsGA3ox1 is necessary for normal pollen development, while OsGA3ox2 is necessary for stem and leaf elongation. Tissue expression analysis showed that OsGA3ox1 was mainly expressed in unopened flowers, while OsGA3ox2 was mainly expressed in unexpanded leaves. The GA in different tissues of wild type (WT), and two ga3ox mutants were detected. It was found that pollen fertility is most closely related to the content of GA7, and plant height is most closely related to the content of GA1. It was found that OsGA3ox1 catalyzes GA9 to GA7 in flowers, which is closely related to pollen fertility; OsGA3ox2 catalyzes the GA20 to GA1 in unexpanded leaves, thereby regulating plant height; OsGA3ox1 catalyzes the GA19 to GA20 in roots, regulating the generation of GA3. OsGA3ox1 and OsGA3ox2 respond to developmental and environmental signals, and cooperate to synthesize endogenous GA in different tissues to regulate rice development. This study provides a reference for clarifying its role in GA biosynthesis pathway and further understanding the function of OsGA3ox.

Food Sources of Selenium and Its Relationship with Chronic Diseases.

Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.

Antidepressant functions of Jie Yu Chu Fan capsule in promoting hippocampal nerve cell neurogenesis in a mouse model of chronic unpredictable mild stress.

BACKGROUND: Depression is a major public health challenge that imposes a great societal burden. Depression has been attributed to the decreased level of neurotransmitters and brain-derived neurotrophic factor (BDNF) levels. Chinese herbal medicine Jie Yu Chu Fan (JYCF) capsule has been shown to be effective in the management of depression. However, the mechanism has yet to be determined. This study aimed to explore the activity of JYCF against depression by establishing a mouse model of chronic unpredictable mild stress (CUMS) with fluoxetine as the positive control drug. METHODS: The open field test, sucrose preference test, forced swim test, and tail suspension test were carried out to observe the behavioral changes of animals. The levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine, as well as their respective metabolic products 5-hydroxyindoleacetic acid, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid in the mouse hippocampi were quantified by high-performance liquid chromatography (HPLC). Cell proliferation and apoptosis, and early and mature nerve cells in the hippocampi were observed by immunofluorescence. Reverse transcription polymerase chain reaction was used to identify BDNF expression in the hippocampi. RESULTS: After 5 weeks of unpredictable stimulation, a CUMS mouse model was successfully obtained, as indicated by sharply decreased sucrose preference and locomotor activity, as well as an increased immobility time in the forced swim test. Our results demonstrated that treatment with JYCF (1 and 5 g/kg) and fluoxetine (20 mg/kg) dramatically reversed the behavioral abnormalities in CUMS mice. At 1 g/kg, JYCF significantly increased NE, DA, and HVA levels in the hippocampi of CUMS mice. JYCF up-regulated the mRNA expression of BDNF and promoted cell proliferation in hippocampi of CUMS mice. CONCLUSIONS: Our study demonstrated that JYCF exhibits antidepressant activity comparable to that of fluoxetine in CUMS mice. Moreover, the antidepressant-like activity of JYCF was shown to be mediated by enhancing hippocampal nerve cell neurogenesis through increasing the levels of monoamine neurotransmitters and BDNF expression.

Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial.

BACKGROUND AND PURPOSE: Tianzhi granule (TZ) is usually used for patients with vascular dementia (VaD) in China. The aim was to assess the effect of TZ by a randomized clinical trial (RCT). METHODS: A 24-week RCT was conducted in 16 centres. Participants were grouped into TZ, donepezil or placebo. The co-primary outcomes were the Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) and Clinician's Interview-based Impression of Change-plus caregiver information (CIBIC-plus). RESULTS: A total of 543 patients with mild to moderate VaD were enrolled, of whom 242 took TZ granules, 241 took donepezil, and 60 took placebo. The least-squares mean changes from baseline and 95% CI were 6.20 (5.31, 7.09) (TZ group), 6.53 (5.63, 7.42) (donepezil group) and 3.47 (1.76, 5.19) (placebo group), both TZ and donepezil showed small but significantly improvement compared with placebo group. The percent of improvement on the global impression which was measured by CIBIC-plus was 73.71% in TZ and 58.18% in placebo, there was significant different between TZ and placebo group (P = 0.004). No significant differences were observed between TZ and donepezil. No significant differences of adverse events were found. CONCLUSIONS: TZ and donepezil could bring symptomatic benefit for mild to moderate VaD. Trial registration The protocol had retrospectively registered at clinical trial.gov, Unique identifier: NCT02453932, date of registration: May 27, 2015; https://www.clinicaltrials.gov/ct2/show/NCT02453932?term=NCT02453932&rank=1.

Isolation and Characterization of Three New Monoterpene Synthases from Artemisia annua.

Artemisia annua, an annual herb used in traditional Chinese medicine, produces a wealth of monoterpenes and sesquiterpenes, including the well-known sesquiterpene lactone artemisinin, an active ingredient in the treatment for malaria. Here we report three new monoterpene synthases of A. annua. From a glandular trichome cDNA library, monoterpene synthases of AaTPS2, AaTPS5, and AaTPS6, were isolated and characterized. The recombinant proteins of AaTPS5 and AaTPS6 produced multiple products with camphene and 1,8-cineole as major products, respectively, and AaTPS2 produced a single product, ß-myrcene. Although both Mg(2+) and Mn(2+) were able to support their catalytic activities, altered product spectrum was observed in the presence of Mn(2+) for AaTPS2 and AaTPS5. Analysis of extracts of aerial tissues and root of A. annua with gas chromatography-mass spectrometry detected more than 20 monoterpenes, of which the three enzymes constituted more than 1/3 of the total. Mechanical wounding induced the expression of all three monoterpene synthase genes, and transcript levels of AaTPS5 and AaTPS6 were also elevated after treatments with phytohormones of methyl jasmonate, salicylic acid, and gibberellin, suggesting a role of these monoterpene synthases in plant-environment interactions. The three new monoterpene synthases reported here further our understanding of molecular basis of monoterpene biosynthesis and regulation in plant.

[Impacts of eye acupuncture on neurological deficit and Barthel index in patients of infarction hemiplegia].

OBJECTIVE: To observe the impacts of eye acupuncture on neurological deficit and Barthel index in the patients of infarction hemiplegia and explore its function mechanism. METHODS: Ninety-six patients of infarction hemiplegia were randomized into an observation group and a control group, 48 cases in each one. In the control group, the routine western medicines such as thrombolysis and antiplatelet aggregation were used. In the observation group, on the basis of the treatment as the control group, eye acupuncture was added at Shangjiao and Xiajiao areas bilaterally, once a day, 5 times a week. Separately, before treatment and after 2 weeks' treatment the score changes of the modified Edinburgh Scandinavia stroke scale (MESSS) and the activity of daily life scale (ADL, Barthel index, BI) were observed and the efficacy was compared between the two groups. The plasma endothelin was determined and compared before and after treatment in the two groups. RESULTS: After treatment, the effective rate was 93.8% (45/48) in the observation group and was 79.2% (38/48) in the control group. The effective rate in the observation group was higher apparently than that in the control group (P<0.05). The scores of neurological deficit were (13.29±1.45) and (18.24±1.33) in the observation group and control group respectively after treatment, which all lower apparently than (28.44±1.45) and (28.14±1.89) before treatment (both P<0.05). Additionally, the difference was significant between the two groups after treatment (P<0.05). The scores of Barthel index were (82.33±1.56) and (63.34±2.14) in the observation group and control group respectively, which all higher apparently than (38.53±1.54) and (38.14±2.56) before treatment (both P<0.05), and the difference was significant between the two groups after treatment (P<0.05). The levels of plasma endothelin were (54.55±11.48)ng/L and (62.44±9.88)ng/L in the observation group and the control group after treatment respectively, which were all lower apparently than (78.24±9.25)ng/L and (78.14±10.78)ng/L before treatment (both P<0.05). Additionally, the difference was significant between the two groups after treatment (P<0.05). CONCLUSIONS: Eye acupuncture effectively improves the neurological deficit and Brathel index in the patients of infarction hemiplegia and comprehensively improves the efficacy. The effect mechanism is possibly relevant with reducing plasma endothelin.

The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine--Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model.

Jie Yu Chu Fan capsule (JYCF) is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS) mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC). The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg) and fluoxetine (20 mg/kg) significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg) significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively) and 5-HT in hippocampus (P < 0.05). In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE.

Emodin prevents hypoxic-ischemic neuronal injury: Involvement of the activin A pathway.

Emodin, an extract of dried rhizomes and the root of the Rhizoma Polygoni Cuspidati, can protect neurons from hypoxic-ischemic brain damage. This study aimed to verify the underlying mechanism. After PC12 cells had differentiated into neuron-like cells under the induction of mouse nerve growth factor, cells were subjected to oxygen-glucose deprivation and treated with emodin. Results showed that the viability of neuron-like cells cultured under an ischemia-hypoxia environment decreased, while the expression of activin A and caspase-3 in cells increased. Emodin raised the survival rate of oxygen-glucose deprived neuron-like cells, increased activin A expression, and decreased caspase-3 expression. Experimental findings indicate that emodin can inhibit neuronal apoptosis and alleviate the injury of nerve cells after oxygen-glucose deprivation through the activin A pathway.

Hyperthermia induces the ER stress pathway.

BACKGROUND: The ER chaperone GRP78/BiP is a homolog of the Hsp70 family of heat shock proteins, yet GRP78/BiP is not induced by heat shock but instead by ER stress. However, previous studies had not considered more physiologically relevant temperature elevation associated with febrile hyperthermia. In this report we examine the response of GRP78/BiP and other components of the ER stress pathway in cells exposed to 40°C. METHODOLOGY: AD293 cells were exposed to 43°C heat shock to confirm inhibition of the ER stress response genes. Five mammalian cell types, including AD293 cells, were then exposed to 40°C hyperthermia for various time periods and induction of the ER stress pathway was assessed. PRINCIPAL FINDINGS: The inhibition of the ER stress pathway by heat shock (43°C) was confirmed. In contrast cells subjected to more mild temperature elevation (40°C) showed either a partial or full ER stress pathway induction as determined by downstream targets of the three arms of the ER stress pathway as well as a heat shock response. Cells deficient for Perk or Gcn2 exhibit great sensitivity to ER stress induction by hyperthermia. CONCLUSIONS: The ER stress pathway is induced partially or fully as a consequence of hyperthermia in parallel with induction of Hsp70. These findings suggest that the ER and cytoplasm of cells contain parallel pathways to coordinately regulate adaptation to febrile hyperthermia associated with disease or infection.

[History of the use of immunoglobulin].

In 1890, the German scholar Von Behring found animal serum antitoxin. In 1940, Cenci advocated to use recovery-stage patients' serum instead of animal serum for its anaphylactic reaction. In 1973, Tiselius separated immunoglobulin from serum with electrophoresis techniques. In 1940, immunoglobulin's preparation process was published by Cohn and his colleagues. After the Second World War, immunoglobulin was used by civilians for prevention and treatment of infectious diseases. Bruton found the lack of γ-globulins in primary immunodeficiency patients in 1952, and immunoglobulin was used to treat this disease. From then on, immunoglobulin began to be used for immunodeficiency disease. In 1981, Imbach achieved success in idiopathic thrombocytopenic purpura with immunoglobulin. Immunoglobulin came into use for autoimmune disease subsequent to that.