Integrated transcriptome and metabolome analysis provide insights into the mechanism of saponin biosynthesis and its role in alleviating cadmium-induced oxidative damage in Ophiopogon japonicum.

Zhe-Maidong, a cultivar of Ophiopogon japonicus is a prominent traditional herbal medicine rich in saponins. This study explored the mechanism of saponin biosynthesis and its role in alleviating Cd-induced oxidative damage in the Zhe-Maidong cultivar using three experimental groups undergoing Cd stress. In the Cd-contaminated soil treatment, total saponins were 1.68 times higher than those in the control. The saponin content in the Cd-2 and Cd-3 treatments was approximately twice as high as that in the Cd-CK treatment. These findings revealed that Cd stress leads to total saponin accumulation. Metabolomic analysis identified the accumulated saponins, primarily several monoterpenoids, diterpenoids, and triterpenoids. The increased saponins exhibited an antioxidant ability to prevent the accumulation of Cd-induced reactive oxygen species (ROS). Subsequent saponin application experiments provided strong evidence that saponin played a crucial role in promoting superoxide dismutase (SOD) activity and reducing ROS accumulation. Transcriptome analysis revealed vital genes for saponin synthesis under Cd stress, including SE, two SSs, and six CYP450s, positively correlated with differentially expressed metabolite (DEM) levels in the saponin metabolic pathway. Additionally, the TF-gene regulatory network demonstrated that bHLH1, bHLH3, mTERF, and AUX/IAA transcript factors are crucial regulators of hub genes involved in saponin synthesis. These findings significantly contribute to our understanding of the regulatory network of saponin synthesis and its role in reducing oxidative damage in O. japonicum when exposed to Cd stress.

A Combination of Magnoflorine and Spinosin Improves the Antidepressant effects on CUMS Mouse Model.

BACKGROUND: Depression is a common neuropsychiatric disease. As a famous traditional Chinese medicine with significant anti-depressive and sleep-promoting effects, Ziziphi Spinosae Semen (ZSS) has attracted the attention of many researchers. Although it is well known that Magnoflorine (MAG) and Spinosin (SPI) were the main active components isolated from ZSS, there is a lack of research on the combined treatment of depression with these two ingredients. METHODS: The shaking bottle method was used to simulate the human environment for detecting the changes in oil-water partition coefficient before and after the drug combination. Cell viability was evaluated by the MTT assay. To establish a mouse model of depression and insomnia by CUMS method, and then to explore the effect of combined administration of MAG and SPI on depression in CUMS model by observing behavior and analyzing pharmacokinetics. RESULTS: The change in LogP values affected the lipid solubility of MAG and increased the water solubility of SPI, allowing them to penetrate more easily through the blood-brain barrier into the brain. Compared with the model group, MAG-SPI with a concentration of 60 µM significantly increased cell survival rate. In both the TST and FST experiments, the mice showed a decrease in immobilization time. Pharmacokinetic results showed that the pharmacokinetic parameters, Cmax and AUC of MAG and SPI, were increased in the case of combination, which resulted in enhancement of their relative bioavailability and improvement of in vivo effects. CONCLUSIONS: The present study demonstrated that a combination of MAG and SPI had a synergistic antidepressant effect in CUMS mouse model.

The metabolic mechanism of flavonoid glycosides and their contribution to the flavor evolution of white tea during prolonged withering.

This study was the first to comprehensively investigate the metabolic mechanism of flavonoid glycosides (FGs) and their contribution to flavor evolution during white tea processing using quantitative descriptive analysis, metabolomics, dose-over-threshold factors and pseudo-first-order kinetics. A total of 223 flavonoids were identified. Total FGs decreased from 7.02 mg/g to 4.35 mg/g during processing, compared to fresh leaves. A total of 86 FGs had a significant impact on the flavor evolution and 9 key flavor FGs were identified. The FG biosynthesis pathway was inhibited during withering, while the degradation pathway was enhanced. This promoted the degradation of 9 key flavor FGs following pseudo-first-order kinetics during withering. The degradation of the FGs contributed to increase the taste acceptance of white tea from -4.18 to 1.32. These results demonstrated that water loss stress during withering induces the degradation of key flavor FGs, contributing to the formation of the unique flavor of white tea.

[Research progress on Rhododendron molle in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

Effects of Exogenous Application of Glycine Betaine Treatment on 'Huangguoggan' Fruit during Postharvest Storage.

Loss of quality in citrus fruit is a common occurrence during postharvest storage due to oxidative stress and energy consumption. In recent years, glycine betaine (GB) has been widely applied to postharvest horticulture fruit. This study aimed to investigate the effect of GB treatment (10 mM and 20 mM) on the quality and antioxidant activity of 'Huangguogan' fruit during postharvest storage at room temperature. Our results indicated that both 10 mM and 20 mM treatments effectively reduced weight and firmness losses and maintained total soluble solid (TSS), titratable acidity (TA), and ascorbic acid contents. Additionally, GB treatment significantly increased the activity of antioxidant enzymes, maintained higher levels of total phenols and total flavonoids, and led to slower accumulation of H2O2. A transcriptome analysis conducted at 28 days after treatment (DAT)identified 391 differentially expressed genes (DEGs) between 20 mM GB (GB-2) and the control (CK) group. These DEGs were enriched in various pathways, particularly related to oxygen oxidoreductase, peroxidase activity, and flavonoid biosynthesis. Overall, the application of GB proved beneficial in enhancing the storability and extending the shelf life of 'Huangguogan' fruit.

Cognitive Activities, Lifestyle Factors, and Risk of Cognitive Impairment, with an Analysis of the Apolipoprotein Epsilon 4 Genotype.

INTRODUCTION: Cognitive stimulating activities and a healthy lifestyle are associated with less cognitive impairment. However, whether the association is varied by Apolipoprotein epsilon 4 (APOE ε4) allele carrier status remains inconclusive. We aimed to investigate whether the association of cognitively stimulating activities and a healthy lifestyle with the risk of cognitive impairment varied by APOE ε4 allele carrier status. METHODS: A case-control study was conducted for adults aged 60 years and above. Six province administrative units (Beijing, Shanghai, Hubei, Sichuan, Guangxi, and Yunnan) were included using stratified multistage cluster sampling. A total of 1,300 individuals were identified with cognitive impairment (cases) at enrollment and were matched 1:2 on sex, age (±2 years), and residential district with controls who were cognitively normal at the time of the evaluation. We used a standardized questionnaire to collect information on cognitive stimulating activities, lifestyle factors, demographics, and comorbidity. Cognitive stimulating activities included reading books or newspapers, playing cards or mahjong, using the Internet, socializing with neighbors, and community activities. Lifestyle factors included smoking, alcohol drinking, daily tea drinking, and regular exercise. We used logistic regression to assess the interaction between cognitive stimulating activities, lifestyle factors, and APOE ε4 allele carrier status (yes/no) on the risk of cognitive impairment. We tested for additive interaction by estimating relative excess risk (RERI) due to interaction and multiplicative interaction employing the p value of the interaction term of each lifestyle factor and APOE ε4 into the model. RESULTS: Four cognitive stimulating activities were associated with less cognitive impairment regardless of APOE ε4 status. Using the Internet (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.30-0.95), daily tea drinking (OR: 0.79; 95% CI: 0.63-0.98), and regular exercise (OR: 0.78; 95% CI: 0.65-0.94) were associated with less cognitive impairment only in noncarriers. Multiplicative and additive interactions were found between community activities and APOE ε4 carrier status (multiplicative p value = 0.03; RERI 0.738, 95% CI: 0.201-1.275). CONCLUSION: The associations between cognitive activities and cognitive impairment were robust regardless of the APOE ε4 carrier status, while the associations between lifestyle factors and cognitive impairment varied by APOE ε4 carrier status.

Flavan-3-ol Galloylation-Related Functional Gene Cluster and the Functional Diversification of SCPL Paralogs in Camellia sp.

The high accumulation of galloylated flavan-3-ols in Camellia sp. is a noteworthy phenomenon. We identified a flavan-3-ol galloylation-related functional gene cluster in tannin-rich plant Camellia sp., which included UGT84A22 and SCPL-AT gene clusters. We investigated the possible correlation between the accumulation of metabolites and the expression of SCPL-ATs and UGT84A22. The results revealed that C. sinensis, C. ptilophylla, and C. oleifera accumulated galloylated cis-flavan-3-ols (EGCG), galloylated trans-flavan-3-ols (GCG), and hydrolyzed tannins, respectively; however, C. nitidissima did not accumulate any galloylated compounds. C. nitidissima exhibited no expression of SCPL-AT or UGT84A22, whereas the other three species of Camellia exhibited various expression patterns. This indicated that the functions of the paralogs of SCPL-AT vary. Enzymatic analysis revealed that SCPL5 was neofunctionalized as a noncatalytic chaperone paralog, a type of chaerone-like protein, associating with flavan-3-ol galloylation; moreover, CsSCPL4 was subfunctionalized in association with the galloylation of cis- and trans-flavan-3-ols. In C. nitidissima, an SCPL4 homolog was noted with mutations in two cysteine residues forming a disulfide bond, which suggested that this homolog was defunctionalized. The findings of this study improve our understanding of the functional diversification of SCPL paralogs in Camellia sp.

Effects of Pollen Sources on Fruit Set and Fruit Characteristics of 'Fengtangli' Plum (Prunus salicina Lindl.) Based on Microscopic and Transcriptomic Analysis.

Adequate yield and fruit quality are required in commercial plum production. The pollen source has been shown to influence fruit set and fruit characteristics. In this study, 'Siyueli', 'Fenghuangli' and 'Yinhongli' were used as pollinizers of 'Fengtangli' plum. Additionally, self-pollination, mixed pollination, and open pollination were performed. We characterized the differences in pollen tube growth, fruit set and fruit quality among pollination combinations. 'Fengtangli' flowers pollinated by 'Fenghuangli' had more pistils with pollen tubes penetrating the ovary and the highest fruit set rate, while the lowest fruit set rate was obtained from self-pollination. In self-pollinated flowers, 33% of pistils had at least one pollen tube reaching the ovary, implying that 'Fengtangli' is partially self-compatible. Pollen sources affected 'Fengtangli' fruit size, weight, pulp thickness, soluble solids, and sugar content. Transcriptome analysis of 'Siyueli'-pollinated and 'Yinhongli'-pollinated fruits revealed 2762 and 1018 differentially expressed genes (DEGs) involved in the response to different pollen sources. DEGs were enriched in plant hormone signal transduction, starch and sucrose metabolism, and MAPK signaling pathways. Our findings provide a reference for the selection of suitable pollinizers for 'Fengtangli' plum and promote future research on the metaxenia effect at the molecular level.

Ultra-HPLC-MS pseudo-targeted metabolomic profiling reveals metabolites and associated metabolic pathway alterations in Asian plum (Prunus salicina) fruits in response to gummosis disease.

Plum (Prunus spp.) is an economically and nutritionally important stone fruit that is grown worldwide. Gummosis disease (GD) is one of the most common limiting factors that adversely affects the yield and quality of stone fruits such as plum. Elucidating plum fruit metabolomics responses is essential to develop sustainable agricultural practices to combat GD in the future. Herein, an ultra-high-performance liquid chromatography coupled to mass-spectrometry (UHPLC-MS) pseudo-targeted metabolomic profiling was first performed to elucidate the overall metabolic alterations in Asian plum (Prunus salicina Lindl.) fruit in response to GD. The most pivotal differential metabolites, including certain amino acids and proanthocyanidins, in GD and control groups were identified by combining multivariate data analysis with strict statistical criteria. Metabolic pathway enrichment analysis showed that GD induced a series of coordinated defence responses and reprogramming of various metabolic pathways, including glucosinolate biosynthesis, 2-oxocarboxylic acid metabolism, valine, leucine and isoleucine degradation, and isoquinoline alkaloid biosynthesis pathways. Using UHPLC-MS-based pseudo-targeted metabolomic profiling, we systematically evaluated overall metabolic modifications in Asian plum fruits in response to GD for the first time. The identified metabolic pathway alterations helped to better understand the internal relationships and related metabolic networks.

Study and Field Trials on Dissolvable Frac Plugs for Slightly Deformed Casing Horizontal Well Volume Fracturing.

In view of the need for slightly deformed casing horizontal well fracturing, a new dissolvable frac plug has been designed using mechanical and material methods. The results of simulation analysis, laboratory research, and field test verification show that: (1) the integral half-split inlaid tooth slip and implicit-shaped single sealing element are adopted. Under the same pressure resistance index, the outer diameter and the total length of the frac plug are small, the inner diameter is big, and the pressure resistance downhole passing performance are better. (2) Using dissolvable magnesium-based powder, hydrogenated butadiene-acrylonitrile rubber, fluororubber polyglycolic acid, and the cellulose fiber and coating process, the solubility of the frac plug is observed to be more reliable. (3) Using the structural modular design, the frac plug has outstanding advantages in terms of on-site installation, preventing early seat sealing, self-separation after release, less dissolvable matter, and so on. (4) The finite element simulation and physical simulation experiments show that 121.36 mm ID casing with the frac plug can tolerate deformation in the range of 15 mm, which meets the needs for the casing usage. The temperature increases from 60 to 98 °C, and the maximum sustainable pressure differential decreases from 7.6 to 11.2 h at 70 MPa without any leakage. The frac plug can be completely dissolved within 300 h, and the final size of the residual solid is less than 0.3 mm. (5) In field trials of eight wells, through the minimum set of change inner diameter of 107 mm, the maximum wellhead fracturing pressure is 83.9 MPa in the formation, with the temperature ranging from 36 to 110 °C, and the plug can be completely self-dissolved in 16 days (the shortest time that has been found). After the fracturing operation with this dissolvable frac plug, the average daily oil production is maintained as high as 10.45 t with 22,000 m3 gas production. A new dissolvable frac plug tool solves the problem of continuous fracturing in slightly casing variable wells, restores the full bore of the wellbore after staged fracturing, and realizes the production of oil and gas wells without drilling plug and the smooth implementation of follow-up measures. It has a wider application range, higher efficiency, safety, and economy. It is of great significance for industrialized staged fracturing of unconventional oil and gas horizontal wells and platform wells.

Targeted Phage Display-based Pulmonary Vaccination in Mice and Non-human Primates.

BACKGROUND: The extensive alveolar capillary network of the lungs is an attractive route for administration of several agents. One key functional attribute is the rapid onset of systemic action due to the absence of first-pass metabolism. METHODS: Here we applied a combinatorial approach for ligand-directed pulmonary delivery as a unique route for systemic targeting in vaccination. FINDINGS: We screened a phage display random peptide library in vivo to select, identify, and validate a ligand (CAKSMGDIVC) that specifically targets and is internalized through its receptor, α3ß1 integrin, on the surface of cells lining the lung airways and alveoli and mediates CAKSMGDIVC-displaying phage binding and systemic delivery without compromising lung homeostasis. As a proof-of-concept, we show that the pulmonary delivery of targeted CAKSMGDIVC-displaying phage particles in mice and non-human primates elicit a systemic and specific humoral response. CONCLUSIONS: This broad methodology blueprint represents a robust and versatile platform tool enabling new ligand-receptor discovery with many potential translational applications. FUNDING: Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center (CA016672), University of New Mexico Comprehensive Cancer Center (CA118100), Rutgers Cancer Institute of New Jersey (CA072720), research awards from the Gillson Longenbaugh Foundation, and National Institutes of Health (NIH) grant no. 1R01CA226537.

Mowing enhances the phytoremediation ability of cadmium-contaminated soil in the post-grafting generations of potential cadmium-hyperaccumulator Solanum photeinocarpum.

The study aimed at accessing the effects of mowing on the growth and cadmium (Cd) accumulation of the first post-grafting generation of potential Cd-hyperaccumulator plant Solanum photeinocarpum through the pot and plot experiments. Four grafting treatments were employed such as ungrafted (UG), self-rooted grafting by the same S. photeinocarpum seedling (SG), self-rooted grafting by two different development stages of S. photeinocarpum seedlings (DG), and grafting on the rootstock of wild potato (PG). The biomass, Cd content, and Cd extraction amount of S. photeinocarpum shoots significantly decreased with the increase of mowing times in the pot and plot experiments. The order of the grafting on the biomass, Cd content, and Cd extraction amountof in the first, second, third mowing shoots were PG > DG > SG > UG. For the Cd extraction amountof total moving shoots, SG, DG, and PG increased by 20.42%, 35.54%, and 52.94%, respectively, in the pot experiment, and increased by 11.56%, 26.28%, and 44.90%, respectively, in the plot experiment, compared with the UG. Therefore, mowing provides an insight into the phytoremediation ability of S. photeinocarpum to Cd.

Effects of intercropping with two Solanum species on the growth and cadmium accumulation of Cyphomandra betacea seedlings.

The contamination of orchard by cadmium (Cd) has recently increased in severity. To decrease the Cd content in fruit tree, a pot-based experiment was conducted to study the effects of intercropping with two Solanum species (Solanum alatum and Solanum diphyllum) on the growth and Cd accumulation of Cyphomandra betacea seedlings. The data revealed that intercropping with two Solanum species significantly increased the biomass, photosynthetic pigment contents, antioxidant enzyme activities, and soluble protein contents of C. betacea seedlings under Cd stress condition. The intercropping significantly decreased the Cd content in C. betacea seedlings. However, the intercropping significantly decreased the S. alatum and S. diphyllum biomasses, while increased the Cd content and accumulation in the roots and shoots of two Solanum species, and the Cd uptake by S. alatum was lower than that of S. diphyllum. Therefore, intercropping with these two Solanum species, especially S. diphyllum, may promote the growth and decrease the Cd content in C. betacea.

Size-Optimized Ultrasmall Porous Silica Nanoparticles Depict Vasculature-Based Differential Targeting in Triple Negative Breast Cancer.

Rapid sequestration and prolonged retention of intravenously injected nanoparticles by the liver and spleen (reticuloendothelial system (RES)) presents a major barrier to effective delivery to the target site and hampers clinical translation of nanomedicine. Inspired by biological macromolecular drugs, synthesis of ultrasmall (diameter ≈12-15 nm) porous silica nanoparticles (UPSNs), capable of prolonged plasma half-life, attenuated RES sequestration, and accelerated hepatobiliary clearance, is reported. The study further investigates the effect of tumor vascularization on uptake and retention of UPSNs in two mouse models of triple negative breast cancer with distinctly different microenvironments. A semimechanistic mathematical model is developed to gain mechanistic insights into the interactions between the UPSNs and the biological entities of interest, specifically the RES. Despite similar systemic pharmacokinetic profiles, UPSNs demonstrate strikingly different tumor responses in the two models. Histopathology confirms the differences in vasculature and stromal status of the two models, and corresponding differences in the microscopic distribution of UPSNs within the tumors. The studies demonstrate the successful application of multidisciplinary and complementary approaches, based on laboratory experimentation and mathematical modeling, to concurrently design optimized nanomaterials, and investigate their complex biological interactions, in order to drive innovation and translation.

Antioxidant enzyme activity and growth responses of Huangguogan citrus cultivar to nitrogen supplementation.

This study examined the physiological effects of different amounts of nitrogen (N) supplementation (0 to 2.72 kg/year) on the citrus cultivar Huangguogan (Citrus reticulata × Citrus sinensis). Root activity, chlorophyll content, and fruit quality were measured, and the activities of the antioxidant enzymes superoxide dismutase (SOD), guaiacol peroxidase (POD), and catalase (CAT), and the contents of malondialdehyde (MDA) and soluble protein in root, leaf, and fruit tissues were examined at different developmental stages. Root activity, chlorophyll content, fruit quality, antioxidant enzyme activity, MDA content, and soluble protein content increased in plants treated with an appropriate amount of N. Both excessive N and N deficiency decreased the content of MDA and the activities of antioxidant enzymes. Application of 1.36-1.81 kg N/year is suggested for citrus fertilization and the lower end of this range is recommended for minimizing environmental impact and production cost.

Cadmium-accumulator straw application alleviates cadmium stress of lettuce (Lactuca sativa) by promoting photosynthetic activity and antioxidative enzyme activities.

The effects of application of straw derived from cadmium (Cd) accumulator plants (Siegesbeckia orientalis, Conyza canadensis, Eclipta prostrata, and Solanum photeinocarpum) on growth and Cd accumulation of lettuce plants grown under Cd exposure were studied. Treatment with straw of the four Cd-accumulator species promoted growth, photosynthesis, and soluble protein contents and enhanced the activities of peroxidase in leaves of lettuce seedlings. The biomass of shoot of lettuce from high to low in turn is the treatment of C. canadensis straw > S. photeinocarpum straw > S. orientalis > E. prostrata > Control. The Cd content in edible parts (shoots) of the lettuce plants was significantly decreased in the presence of straw from the Cd-accumulator species, except the presence of the straw of E. prostrata. And, the greatest reduction in Cd content in shoots was 27.09% in the S. photeinocarpum straw treatment compared with that of the control. Therefore, application of straw of S. orientalis, C. canadensis, and S. photeinocarpum can promote the growth of lettuce seedlings, and decrease their Cd accumulation, when grown in Cd-contaminated soil, which is beneficial for production of lettuce safe for human consumption.

Transcriptomic insights into citrus segment membrane's cell wall components relating to fruit sensory texture.

BACKGROUND: During fresh fruit consumption, sensory texture is one factor that affects the organoleptic qualities. Chemical components of plant cell walls, including pectin, cellulose, hemicellulose and lignin, play central roles in determining the textural qualities. To explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture, we performed mRNA-seq analyses of the segment membranes of two citrus cultivars, Shiranui and Kiyomi, with different organoleptic textures. RESULTS: Segment membranes were sampled at two developmental stages of citrus fruit, the beginning and end of the expansion period. More than 3000 differentially expressed genes were identified. The gene ontology analysis revealed that more categories were significantly enriched in 'Shiranui' than in 'Kiyomi' at both developmental stages. In total, 108 significantly enriched pathways were obtained, with most belonging to metabolism. A detailed transcriptomic analysis revealed potential critical genes involved in the metabolism of cell wall structures, for example, GAUT4 in pectin synthesis, CESA1, 3 and 6, and SUS4 in cellulose synthesis, CSLC5, XXT1 and XXT2 in hemicellulose synthesis, and CSE in lignin synthesis. Low levels, or no expression, of genes involved in cellulose and hemicellulose, such as CESA4, CESA7, CESA8, IRX9 and IRX14, confirmed that secondary cell walls were negligible or absent in citrus segment membranes. A chemical component analysis of the segment membranes from mature fruit revealed that the pectin, cellulose and lignin contents, and the segment membrane's weight (% of segment) were greater in 'Kiyomi'. CONCLUSION: Organoleptic quality of citrus is easily overlooked. It is mainly determined by sensory texture perceived in citrus segment membrane properties. We performed mRNA-seq analyses of citrus segment membranes to explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture. Transcriptomic data showed high repeatability between two independent biological replicates. The expression levels of genes involved in cell wall structure metabolism, including pectin, cellulose, hemicellulose and lignin, were investigated. Meanwhile, chemical component contents of the segment membranes from mature fruit were analyzed. This study provided detailed transcriptional regulatory profiles of different organoleptic citrus qualities and integrated insights into the mechanisms affecting citrus' sensory texture.

Antagonistic effects of selenium on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens.

Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has antagonistic effects on Pb. In our study, brown layer chickens were randomly allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and 350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the 90th day; spleen tissues were subjected to observation of ultrastructure and detection of spleen-related indexes. The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin (mTOR) was downregulated. The results of transmission electron microscopy indicated that Pb induced mitochondrial fragmentation, and triggered autophagy in the spleen of chickens. The Se and Pb co-treatment remarkably alleviated these injuries induced by Pb in the spleen of chickens. In conclusion, Pb can induce the oxidative stress to influence the mitochondrial dynamics balance and lead to autophagy, which triggers the immune dysfunction in the spleen of chickens; the Se exhibits the antagonistic effects on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens.

Ascorbic acid metabolism during sweet cherry (Prunus avium) fruit development.

To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium 'Hongdeng'), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit.

Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mitochondrial pathway.

Bromodomain and Extra-Terminal Domain (BET) inhibitors, such as JQ1 have emerged as novel drug candidates and are being enthusiastically pursued in clinical trials for the treatment of cancer. However, many solid cancers are resistance to BET inhibitors. To explore methods for improving the therapeutic potential of BET inhibitors, we investigated the combinational activity of JQ1 with Oridonin, a bioactive molecules derived from Traditional Chinese Medicine in hepatocellular carcinoma (HCC) cells. Our results showed that Oridonin synergistically enhanced the abilities of JQ1 to inhibit cell viability in HCC cells and, significantly augmented JQ1-triggered apoptosis in HCC cells and in HCC cancer stem-like cells. Moreover, Oridonin dose-dependently inhibited the expression of several anti-apoptotic proteins, such as Bcl-2, Mcl-1, and x-linked inhibitor of apoptosis (xIAP) in HCC cells. Cell fractionation and western blotting analysis showed that the enhancement of apoptosis by Oridonin was associated with cytochrome c release, activation of caspase-9, -3 and cleavage of PARP, indicating the activation of mitochondrial apoptosis pathway. Altogether, our findings demonstrate that Oridonin may be used to effectively enhance the sensitivity of BET inhibitors in HCC therapy via downregulation of the expression of multiple anti-apoptotic proteins.