Publications by authors named "Zhiqiang Lu"

129 Publications

Hepatic miR-378 modulates serum cholesterol levels by regulating hepatic bile acid synthesis.

Theranostics 2021 25;11(9):4363-4380. Epub 2021 Feb 25.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

An improved understanding of thyroid hormone (TH) action on cholesterol metabolism will facilitate the identification of novel therapeutic targets for hypercholesterolemia. TH-regulated microRNAs (miRNAs) have been implicated in TH-controlled biological processes; however, whether and how TH-regulated miRNAs mediate the cholesterol-lowering effect of TH remains unclear. Our aim was to identify TH-regulated microRNAs that have cholesterol-lowering effects and explore the underlying mechanism. Microarray and RNA-seq were performed to identify TH-regulated microRNAs and the genes regulated by mmu-miR-378-3p (miR-378) in the liver of mice, respectively. Recombinant adenoviruses encoding miR-378, , and shRNA for , antagomiR-378, liver-specific miR-378 transgenic mice, and miR-378 knockout mice were employed to investigate the roles of hepatic miR-378 and MAFG in cholesterol and bile acid homeostasis. The levels of bile salt species were determined by using UFLC-Triple-time of flight/MS. Here, we show that hepatic miR-378 is positively regulated by TH. Transient overexpression of miR-378 in the liver of mice reduces serum cholesterol levels, accompanied with an increase in the expression of key enzymes in primary bile acid synthetic pathways and corresponding increases in biliary and fecal bile acid levels. Consistently, liver-specific miR-378 transgenic mice with moderate overexpression of hepatic miR-378 display decreased serum cholesterol levels and resistance to diet-induced hypercholesterolemia, while mice lacking miR-378 exhibit defects in bile acid and cholesterol homeostasis. Mechanistically, hepatic miR-378 regulates the expression of key enzymes in both classic and alternative bile acid synthetic pathways through MAFG, a transcriptional repressor, thereby modulating bile acid and cholesterol metabolism. TH-responsive hepatic miR-378 is capable of modulating serum cholesterol levels by regulating both the classic and alternative BA synthetic pathways. Our study not only identifies a previously undescribed role of hepatic miR-378 but also provides new cholesterol-lowering approaches.
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http://dx.doi.org/10.7150/thno.53624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977473PMC
February 2021

A novel cholesterol-free mayonnaise made from Pickering emulsion stabilized by apple pomace particles.

Food Chem 2021 Mar 3;353:129418. Epub 2021 Mar 3.

College of Food Science, Southwest University, Chongqing 400715, PR China; Chongqing Engineering Research Centre for Sweet Potato, Chongqing 400715, PR China. Electronic address:

Yolk-based mayonnaise is widely used to enhance the flavor of daily food. In view of health concerns on dietary cholesterol, novel mayonnaises (NMs) were made from Pickering emulsions stabilized by apple pomace particles using micro-jet (MJ-NM), ultrasonic (US-NM), and high-speed-shear homogenizer (HSS-NM), respectively. NMs and commercial mayonnaise (CM) were comparatively investigated in appearance, droplet size, rheological, tribological, and stability properties. NMs presented almost identical appearances to CM except for color. The droplets' size in NMs were larger than CM. Both NMs and CM demonstrated shear-thinning behavior and solid-like properties. Among mayonnaises, MJ-NM was demonstrated the most rapid thixotropy recovery with its storage modulus recovered within 51 s. Although both NMs and CM were of mixed tribology nature, NMs presented lower oral lubricity. Upon 210-day storage, both NMs and CM exhibited excellent stabilities without any oil-water separation occurred. Overall, the Pickering emulsions are promising and health alternatives for traditional mayonnaise.
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http://dx.doi.org/10.1016/j.foodchem.2021.129418DOI Listing
March 2021

Pea Aphid Rearing, Bacterial Infection and Hemocyte Phagocytosis Assay.

Bio Protoc 2020 Dec 20;10(24):e3862. Epub 2020 Dec 20.

Department of Entomology, College of Plant Protection, Northwest A & F University, Yangling, Shaanxi, China.

Insects rely on the simple but effective innate immune system to combat infection. Cellular and humoral responses are interconnected and synergistic in insects' innate immune system. Phagocytosis is one major cellular response. It is difficult to collect clean hemolymph from the small insect like pea aphid. Here, we provide a practicable method for small insects hemocyte phagocytosis assay by taking pea aphid as an example. Furthermore, we provide the protocols for pea aphid rearing and bacterial infection, which offer referential method for related research.
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http://dx.doi.org/10.21769/BioProtoc.3862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842581PMC
December 2020

Whole-Genome Diversification Analysis of the Hornbeam Species Reveals Speciation and Adaptation Among Closely Related Species.

Front Plant Sci 2021 10;12:581704. Epub 2021 Feb 10.

State Key Laboratory of Grassland Agro-Ecosystem, Institute of Innovation Ecology and School of Life Sciences, Lanzhou University, Lanzhou, China.

Speciation is the key evolutionary process for generating biological diversity and has a central place in evolutionary and ecological research. How species diverge and adapt to different habitats is one of the most exciting areas in speciation studies. Here, we sequenced 55 individuals from three closely related species in the genus : , , and to understand the strength and direction of gene flow and selection during the speciation process. We found low genetic diversity in , which reflects its extremely small effective population size. The speciation analysis between and revealed that both species diverged ∼1.2 Mya with bidirectional gene flow. A total of 291 highly diverged genes, 223 copy number variants genes, and 269 positive selected genes were recovered from the two species. Genes associated with the diverged and positively selected regions were mainly involved in thermoregulation, plant development, and response to stress, which included adaptations to their habitats. We also found a great population decline and a low genetic divergence of , which suggests that this species is extremely vulnerable. We believe that the current diversification and adaption study and the important genomic resource sequenced herein will facilitate the speciation studies and serve as an important methodological reference for future research.
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http://dx.doi.org/10.3389/fpls.2021.581704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902934PMC
February 2021

The Corylus mandshurica genome provides insights into the evolution of Betulaceae genomes and hazelnut breeding.

Hortic Res 2021 Mar 1;8(1):54. Epub 2021 Mar 1.

State Key Laboratory of Grassland Agro-Ecosystem, Institute of Innovation Ecology & School of Life Sciences, Lanzhou University, Lanzhou, China.

Hazelnut is popular for its flavor, and it has also been suggested that hazelnut is beneficial to cardiovascular health because it is rich in oleic acid. Here, we report the first high-quality chromosome-scale genome for the hazelnut species Corylus mandshurica (2n = 22), which has a high concentration of oleic acid in its nuts. The assembled genome is 367.67 Mb in length, and the contig N50 is 14.85 Mb. All contigs were assembled into 11 chromosomes, and 28,409 protein-coding genes were annotated. We reconstructed the evolutionary trajectories of the genomes of Betulaceae species and revealed that the 11 chromosomes of the hazelnut genus were derived from the most ancestral karyotype in Betula pendula, which has 14 protochromosomes, by inferring homology among five Betulaceae genomes. We identified 96 candidate genes involved in oleic acid biosynthesis, and 10 showed rapid evolution or positive selection. These findings will help us to understand the mechanisms of lipid synthesis and storage in hazelnuts. Several gene families related to salicylic acid metabolism and stress responses experienced rapid expansion in this hazelnut species, which may have increased its stress tolerance. The reference genome presented here constitutes a valuable resource for molecular breeding and genetic improvement of the important agronomic properties of hazelnut.
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http://dx.doi.org/10.1038/s41438-021-00495-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917096PMC
March 2021

Species delimitation and hybridisation history of a hazel species complex.

Ann Bot 2021 Feb 10. Epub 2021 Feb 10.

State Key Laboratory of Grassland Agro-Ecosystem, Institute of Innovation Ecology & School of Life Sciences, Lanzhou University, Lanzhou, Gansu, China.

Background And Aims: Hybridisation increases species adaptation and biodiversity but also obscures species boundaries. In this study, species delimitation and hybridisation history were examined within one Chinese hazel species complex (Corylus chinensis-Corylus fargesii). Two species including four varieties have already been described for this complex, with overlapping distributions.

Methods: A total of 322 trees from 44 populations of these four varieties across their ranges were sampled for morphological and molecular analyses. Climatic datasets based on 108 geographical locations were used to evaluate their niche differentiations. Flowering phenology was also observed for two co-occurring species or varieties.

Key Results: Four statistically different phenotypic clusters were revealed, but these clusters were highly inconsistent with the traditional taxonomic groups. All the clusters showed statistically distinct niches, with complete or partial geographic isolation. Only two clusters displayed a distributional overlap, but they had distinct flowering phenologies at the site where they co-occurred. Population-level evidence based on the genotypes of 10 simple sequence repeat (SSR) loci supported four phenotypic clusters. In addition, one cluster was shown to have an admixed genetic composition derived from the other three clusters through repeated historical hybridisations.

Conclusions: Based on our new evidence, it is better to treat the four clusters identified here as four independent species. One of them was shown to have an admixed genetic composition derived from the other threes through repeated historical hybridisations. This study highlights the importance of applying integrative and statistical methods to infer species delimitations and hybridisation history. Such a protocol should be adopted widely for future taxonomic studies.
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http://dx.doi.org/10.1093/aob/mcab015DOI Listing
February 2021

Scavenger receptor B1 mediates phagocytosis and the antimicrobial peptide pathway in the endoparasitic wasp Micropilits mediator.

Dev Comp Immunol 2021 Jun 4;119:104039. Epub 2021 Feb 4.

Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, China; State Key Laboratory of Crop Stress Biology for Arid Areas, Northwest A&F University, Yangling, Shaanxi, China. Electronic address:

Scavenger receptors (SRs) are a family of pattern recognition receptors (PRRs) in the immune system. They are required for phagocytosis and act as co-receptors of Toll-like receptors to regulate immune signaling pathways in the fight against pathogens. Little is known about the function of SRs in insects. Here, we reported on a member of the SR family from the parasitic wasp Micropilits mediator (designated MmSR-B1) that is responsive to bacterial infection. The recombinant extracellular CD36 domain of MmSR-B1 produced in Escherichia coli cells is capable of binding to peptidoglycans and bacterial cells, causing agglutination of bacteria. Furthermore, we demonstrated that double-stranded RNA-mediated knockdown of MmSR-B1 impedes hemocyte phagocytosis and downregulates the expression of antimicrobial peptide (AMP) genes defensins and hymenoptaecins. Knockdown of MmSR-B1 led to increased death of the wasps when challenged by bacteria. Our study suggests that MmSR-B1 mediates phagocytosis and the production of AMPs in M. mediator wasps.
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http://dx.doi.org/10.1016/j.dci.2021.104039DOI Listing
June 2021

Hybrid speciation via inheritance of alternate alleles of parental isolating genes.

Mol Plant 2021 02 18;14(2):208-222. Epub 2020 Nov 18.

Key Laboratory for Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences & State Key Lab of Hydraulics & Mountain River Engineering, Sichuan University, Chengdu 610065, China; State Key Laboratory of Grassland Agro-Ecosystem, Innovation Institute of Ecology and Life Sciences, Lanzhou University, Lanzhou 730000, China. Electronic address:

It is increasingly realized that homoploid hybrid speciation (HHS), which involves no change in chromosome number, is an important mechanism of speciation. HHS will likely increase in frequency as ecological and geographical barriers between species are continuing to be disrupted by human activities. HHS requires the establishment of reproductive isolation between a hybrid and its parents, but the underlying genes and genetic mechanisms remain largely unknown. In this study, we reveal by integrated approaches that reproductive isolation originates in one homoploid hybrid plant species through the inheritance of alternate alleles at genes that determine parental premating isolation. The parent species of this hybrid species are reproductively isolated by differences in flowering time and survivorship on soils containing high concentrations of iron. We found that the hybrid species inherits alleles of parental isolating major genes related to flowering time from one parent and alleles of major genes related to iron tolerance from the other parent. In this way, it became reproductively isolated from one parent by the difference in flowering time and from the other by habitat adaptation (iron tolerance). These findings and further modeling results suggest that HHS may occur relatively easily via the inheritance of alternate parental premating isolating genes and barriers.
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http://dx.doi.org/10.1016/j.molp.2020.11.008DOI Listing
February 2021

(Rhamnaceae), a new evergreen species from southwest Guangxi.

PhytoKeys 2020 4;159:115-126. Epub 2020 Sep 4.

CAS Key Laboratory of Tropical Forest Ecology, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla 666303, Yunnan, China Chinese Academy of Sciences Mengla China.

, a new evergreen species from southwest Guangxi, is described and illustrated in this study. This species is similar to by the size and ratio of length to width of dried fruit and seeds, by which it differs from and . However, it differs from by rarely mucronate seed apices, larger ratio of length to width of leaves, leaf apices acuminate to long acuminate, shorter leaf petioles, and longer fruiting pedicels. Principal component analysis based on phenotypic traits further recognised three separated groups. and were clustered into one group; the other two groups represented and two Guangxi populations, respectively. Furthermore, phylogenetic analysis of nuclear ITS sequence variations highly supported that the two Guangxi populations represented an independent evolutionary lineage and were closest to . Four fixed nucleotide sites were found and were different from . However, besides the differentiated traits in seeds and fruit, densely pilose young branches also separated them from . In addition, during our field investigations, none of the three closely related species were found at locations where this new species was distributed. Therefore, this new species, based on the two Guangxi populations, is named . The key to four closely related species is also presented.
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http://dx.doi.org/10.3897/phytokeys.159.53177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486312PMC
September 2020

Hemolymph protease-5 links the melanization and Toll immune pathways in the tobacco hornworm, .

Proc Natl Acad Sci U S A 2020 09 8;117(38):23581-23587. Epub 2020 Sep 8.

Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078;

Proteolytic activation of phenoloxidase (PO) and the cytokine Spätzle during immune responses of insects is mediated by a network of hemolymph serine proteases (HPs) and noncatalytic serine protease homologs (SPHs) and inhibited by serpins. However, integration and conservation of the system and its control mechanisms are not fully understood. Here we present biochemical evidence that PO-catalyzed melanin formation, Spätzle-triggered Toll activation, and induced synthesis of antimicrobial peptides are stimulated via hemolymph (serine) protease 5 (HP5) in Previous studies have demonstrated a protease cascade pathway in which HP14 activates proHP21; HP21 activates proPAP2 and proPAP3, which then activate proPO in the presence of a complex of SPH1 and SPH2. We found that both HP21 and PAP3 activate proHP5 by cleavage at ESDR*IIGG. HP5 then cleaves proHP6 at a unique site of LDLH*ILGG. HP6, an ortholog of Persephone, activates both proHP8 and proPAP1. HP8 activates proSpätzle-1, whereas PAP1 cleaves and activates proPO. HP5 is inhibited by serpin-4, serpin-1A, and serpin-1J to regulate its activity. In summary, we have elucidated the physiological roles of HP5, a CLIPB with unique cleavage specificity (cutting after His) that coordinates immune responses in the caterpillar.
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http://dx.doi.org/10.1073/pnas.2004761117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519321PMC
September 2020

Genomic basis of homoploid hybrid speciation within chestnut trees.

Nat Commun 2020 07 6;11(1):3375. Epub 2020 Jul 6.

CAS Key Laboratory of Tropical Forest Ecology, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, 666303, Yunnan, China.

Hybridization can drive speciation. We examine the hypothesis that Castanea henryi var. omeiensis is an evolutionary lineage that originated from hybridization between two near-sympatric diploid taxa, C. henryi var. henryi and C. mollissima. We produce a high-quality genome assembly for mollissima and characterize evolutionary relationships among related chestnut taxa. Our results show that C. henryi var. omeiensis has a mosaic genome but has accumulated divergence in all 12 chromosomes. We observe positive correlation between admixture proportions and recombination rates across the genome. Candidate barrier genomic regions, which isolate var. henryi and mollissima, are re-assorted in the hybrid lineage. We further find that the putative barrier segments concentrate in genomic regions with less recombination, suggesting that interaction between natural selection and recombination shapes the evolution of hybrid genomes during hybrid speciation. This study highlights that reassortment of parental barriers is an important mechanism in generating biodiversity.
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http://dx.doi.org/10.1038/s41467-020-17111-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338469PMC
July 2020

JNK pathway plays a key role in the immune system of the pea aphid and is regulated by microRNA-184.

PLoS Pathog 2020 06 25;16(6):e1008627. Epub 2020 Jun 25.

Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, China.

Different from holometabolous insects, the hemipteran species such as pea aphid Acyrthosiphon pisum exhibit reduced immune responses with the absence of the genes coding for antimicrobial peptide (AMP), immune deficiency (IMD), peptidoglycan recognition proteins (PGRPs), and other immune-related molecules. Prior studies have proved that phenoloxidase (PO)-mediated melanization, hemocyte-mediated phagocytosis, and reactive oxygen species (ROS) participate in pea aphid defense against bacterial infection. Also, the conserved signaling, Jun N-terminal kinase (JNK) pathway, has been suggested to be involved in pea aphid immune defense. However, the precise role of the JNK signaling, its interplay with other immune responses and its regulation in pea aphid are largely unknown. In this study, using in vitro biochemical assays and in vivo bioassays, we demonstrated that the JNK pathway regulated hemolymph PO activity, hydrogen peroxide concentration and hemocyte phagocytosis in bacteria infected pea aphids, suggesting that the JNK pathway plays a central role in regulating immune responses in pea aphid. We further revealed the JNK pathway is regulated by microRNA-184 in response to bacterial infection. It is possible that in common the JNK pathway plays a key role in immune system of hemipteran insects and microRNA-184 regulates the JNK pathway in animals.
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http://dx.doi.org/10.1371/journal.ppat.1008627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343183PMC
June 2020

Micronized apple pomace as a novel emulsifier for food O/W Pickering emulsion.

Food Chem 2020 Nov 13;330:127325. Epub 2020 Jun 13.

College of Food Science, Southwest University, Chongqing 400715, People's Republic of China; Chongqing Engineering Research Centre for Sweet Potato, Chongqing 400715, People's Republic of China. Electronic address:

In order to develop natural, food-grade particles as emulsifiers, wet-milled has been conducted to obtain apple pomace particles in varying sizes. Structural characteristics, physicochemical properties and Pickering emulsifying potential of the particle in different sizes were investigated. Particle size of apple pomace was gradually reduced from 12.9 μm to 550 nm during 8 h milling. With the decrease of particles size, the morphology became less angular. Meanwhile, some insoluble dietary fibers transformed into soluble ones, and the wettability tended to be hydrophilic, therefore, the water and oil holding capacities and free-radical-scavenging capacities increased. The properties of Pickering emulsions stabilized by wet-milled apple pomace particles in different sizes were then investigated. The decrease of particle size resulted in the size reduction of emulsion droplets, and gave rise to enhance gel-like properties and antioxidative activities of emulsions. The results demonstrated promising prospect of wet-milled apple pomace particles as emulsifiers in food industry.
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http://dx.doi.org/10.1016/j.foodchem.2020.127325DOI Listing
November 2020

Coexistence of Sarcoidosis and Sjögren's syndrome with hypercalcemia and renal involvement: A case report and literature review.

Endocr Metab Immune Disord Drug Targets 2020 Jun 19. Epub 2020 Jun 19.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai. China.

Background: Sarcoidosis and Sjögren's syndrome (SS) are chronic multi-system inflammatory diseases of unknown origin that most commonly attack the salivary glands. Both of the diseases have vague and nonspecific symptoms, causing difficulties for the clinicians to distinguish between the two diseases. Most diagnostic criteria of SS exclude sarcoidosis. However, a coexistence of both diseases should be noted. Here, we reported a case of coexisting sarcoidosis and Sjögren's syndrome, complicated with severe hypercalcemia and renal failure, in addition to a literature review.

Case Report: A 71-year-old man visited our hospital complaining of daily progressive oral dryness, thirst and blurred vision with a feeling of dry eyes for one-year duration. His physical examination showed enlargement of both sides of cervical and supraclavicular lymph nodes. Lung auscultation showed decreased breath sounds with bibasilar inspiratory crackles. However, initial laboratory results revealed severe hypercalcemia with moderate hypercalciuria and renal failure. The final diagnosis was coexisting SS and sarcoidosis according to clinical, radiological and laboratory data. The patient received oral prednisone therapy for 18 months. After a follow-up of years, the serum calcium concentration, renal function, and chest CT scan remained normal after prednisone treatment stopped for more than 18 months.

Conclusion: In the literature, calcium metabolic disorder and renal involvement have not been reported among patients with Sarcoidosis and Sjögren's syndrome, suggesting that calcium metabolic disorder may be underestimated. Serum and urine calcium concentration should be measured in addition to routine laboratory test.
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http://dx.doi.org/10.2174/1871530320666200619133654DOI Listing
June 2020

Obesity-induced excess of 17-hydroxyprogesterone promotes hyperglycemia through activation of glucocorticoid receptor.

J Clin Invest 2020 07;130(7):3791-3804

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Endocrinology and Metabolism, and.

Type 2 diabetes mellitus (T2DM) has become an expanding global public health problem. Although the glucocorticoid receptor (GR) is an important regulator of glucose metabolism, the relationship between circulating glucocorticoids (GCs) and the features of T2DM remains controversial. Here, we show that 17-hydroxyprogesterone (17-OHP), an intermediate steroid in the biosynthetic pathway that converts cholesterol to cortisol, binds to and stimulates the transcriptional activity of GR. Hepatic 17-OHP concentrations are increased in diabetic mice and patients due to aberrantly increased expression of Cyp17A1. Systemic administration of 17-OHP or overexpression of Cyp17A1 in the livers of lean mice promoted the pathogenesis of hyperglycemia and insulin resistance, whereas knockdown of Cyp17A1 abrogated metabolic disorders in obese mice. Therefore, our results identify a Cyp17A1/17-OHP/GR-dependent pathway in the liver that mediates obesity-induced hyperglycemia, suggesting that selectively targeting hepatic Cyp17A1 may provide a therapeutic avenue for treating T2DM.
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http://dx.doi.org/10.1172/JCI134485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324200PMC
July 2020

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to , , and Species.

Antibiotics (Basel) 2020 May 14;9(5). Epub 2020 May 14.

Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, SC 29208, USA.

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species.

Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection.

Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis.

Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.
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http://dx.doi.org/10.3390/antibiotics9050254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277875PMC
May 2020

Extracellular Vesicle Delivery of TRAIL Eradicates Resistant Tumor Growth in Combination with CDK Inhibition by Dinaciclib.

Cancers (Basel) 2020 May 4;12(5). Epub 2020 May 4.

Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 51006, China.

Tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) is a promising anti-cancer agent that rapidly induces apoptosis in cancer cells. Unfortunately, the clinical application of recombinant TRAIL (rTRAIL) has been hampered by its common cancer resistance. Naturally TRAIL is delivered as a membrane-bound form by extracellular vesicles (EV-T) and is highly efficient for apoptosis induction. SCH727965 (dinaciclib), a potent cyclin-dependent kinase (CDK) inhibitor, was shown to synergize with other drugs to get better efficacy. However, it has never been investigated if dinaciclib coordinates with EV-T to enhance therapeutic results. This study explores the potential of combination therapy with EV-T and dinaciclib for cancer treatment. EV-T was successfully derived from human TRAIL transduced cells and shown to partially overcome resistance of A549 cells. Dinaciclib was shown to drastically enhance EV-T killing effects on cancer lines that express good levels of death receptor (DR) 5, which are associated with suppression of CDK1, CDK9 and anti-apoptotic proteins. Combination therapy with low doses of EV-T and dinaciclib induced strikingly enhanced apoptosis and led to complete regression in A549 tumors without any adverse side effects observed in a subcutaneous xenograft model. Tumor infiltration of mass NK cells and macrophages was also observed. These observations thus indicate that the combination of EV-T with dinaciclib is a potential novel therapy for highly effective and safe cancer treatment.
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http://dx.doi.org/10.3390/cancers12051157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281120PMC
May 2020

Reactive oxygen species and antimicrobial peptides are sequentially produced in silkworm midgut in response to bacterial infection.

Dev Comp Immunol 2020 09 25;110:103720. Epub 2020 Apr 25.

Department of Entomology, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, China; State Key Laboratory of Crop Stress Biology for Arid Areas, Northwest A&F University, Yangling, Shaanxi, China. Electronic address:

The silkworm, Bombyx mori, is utilized as a research model in many aspects of biological studies, including genetics, development and immunology. Previous biochemical and genomic studies have elucidated the silkworm immunity in response to infections elicited by bacteria, fungi, microsporidia, and viruses. The intestine serves as the front line in the battle between insects and ingested harmful microorganisms. In this study, we performed RNA sequencing (RNA-seq) of the larval silkworm midgut after oral infection with the Gram-positive bacterium Bacillus bombysepticus and the Gram-negative bacterium Yersinia pseudotuberculosis. This enables us to get a comprehensive understanding of the midgut responses to bacterial infection. We found that B. bombysepticus induced much stronger immune responses than Y. pseudotuberculosis did. Bacterial infection resulted in more energy consumption including carbohydrates and fatty acids. The midgut immune system was characterized by the generation of reactive oxygen species and antimicrobial peptides. The former played a critical role in eliminating invading bacteria during early stage, while the latter executed during late stage. Our results provide an integrated insight into the midgut systematic responses to bacterial infection.
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http://dx.doi.org/10.1016/j.dci.2020.103720DOI Listing
September 2020

, a new species from southeast Yunnan, China.

Authors:
Zhiqiang Lu

PhytoKeys 2020 10;145:47-56. Epub 2020 Apr 10.

CAS Key Laboratory of Tropical Forest Ecology, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla 666303, Yunnan, China Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences Mengla China.

Z. Qiang Lu, a new hornbeam species from southeast Yunnan of China, is described and illustrated in this study. It possesses extremely large bracts and is closely related to Hu and Maxim., based on the characters of large bract size and bracts without lobes at the base of inner margins. Furthermore, morphological comparison suggested it was distinctly different from by a series of characters from leaf, infructescence, bract and nutlet and from by its leaf length to width ratio (1.4-2.0 vs. 2.0-2.4), lateral veins significantly impressed adaxially, number of lateral veins on each side of midvein (9-14 vs. 14-17), bract length (3.9-4.8 vs. 2.5-3.2 cm) and bract length to width ratio (2.3-3.1 vs. 1.5-2.1). Therefore, this hornbeam, based on only one population from southeast Yunnan, is here erected as a new species, named as .
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http://dx.doi.org/10.3897/phytokeys.145.49488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165198PMC
April 2020

A RhoGAP venom protein from Microplitis mediator suppresses the cellular response of its host Helicoverpa armigera.

Dev Comp Immunol 2020 07 12;108:103675. Epub 2020 Mar 12.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China; Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 311300, China. Electronic address:

Female parasitoid wasps normally inject virulence factors together with eggs into their host to counter host immunity defenses. A newly identified RhoGAP protein in the venom of Microplitis mediator compromises the cellular immunity of its host, Helicoverpa armigera. RhoGAP1 proteins entered H. armigera hemocytes, and the host cellular cytoskeleton was disrupted. Depletion of MmGAP1 by injection of dsRNA or antibody increased the wasp egg encapsulation rate. An immunoprecipitation assay of overexpressed MmGAP1 protein in a Helicoverpa cell line showed that MmGAP1 interacts with many cellular cytoskeleton associated proteins as well as Rho GTPases. A yeast two-hybrid and a pull-down assay demonstrated that MmGAP1 interacts with H. armigera RhoA and Cdc42. These results show that the RhoGAP protein in M. mediator can destroy the H. armigera hemocyte cellular cytoskeleton, restrain host cellular immune defense, and increase the probability of successful parasitism.
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http://dx.doi.org/10.1016/j.dci.2020.103675DOI Listing
July 2020

The Association between eGFR and the Aldosterone-to-Renin Ratio and Its Effect on Screening for Primary Aldosteronism.

Int J Endocrinol 2020 7;2020:2639813. Epub 2020 Feb 7.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Objectives: Long-term exposure to excessive aldosterone secretion from the adrenal gland may cause renal damage in patients with primary aldosteronism (PA). The aldosterone-to-renin ratio (ARR) may be significantly affected by renal function, especially in patients with renal damage related to long-term PA. The objective of this study was to investigate the association between the estimated glomerular filtration rate (eGFR) and ARR as well as its effect on screening for PA.

Methods: This study was performed in Zhongshan Hospital, Fudan University, China. 803 patients with hypertension were consecutively recruited from 2012 to 2015. All participants underwent routine biochemical measurements, including plasma renin activity (PRA) and plasma aldosterone concentration (PAC). In all patients with a PAC higher than 10 ng/dl, a saline perfusion test was conducted, and a CT scan or adrenal venous sampling was also performed if needed. Receiver operating characteristic (ROC) analysis was conducted in all eGFR < 90 and eGFR ≥ 90 groups separately to determine the optimal cut-off values of ARR.

Results: The optimal cut-off point for PA was an ARR of 40 ng/dl per ng/ml.h in the whole population, 52 ng/dl per ng/ml.h in subjects with an eGFR higher than 90 ml/min/1.73 m, and 18 ng/dl per ng/ml.h in subjects with an eGFR lower than 90 ml/min/1.73 m. Patients with an eGFR higher than 90 ml/min/1.73 m had significantly lower PRA and higher ARR levels than patients with an eGFR lower than 90 ml/min/1.73 m ( < 0.05).

Conclusions: Unsuppressed renin and lower ARR levels were associated with decreased eGFR in patients with primary aldosteronism. Diagnostic criteria of ARR by stratified eGFR may be an optimal strategy for the screening of primary aldosteronism.
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http://dx.doi.org/10.1155/2020/2639813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029269PMC
February 2020

Isosteviol sodium protects heart embryonic H9c2 cells against oxidative stress by activating Akt/GSK-3β signaling pathway.

Pharmazie 2020 01;75(1):36-40

Oxidative stress plays a crucial role in pathogenesis of various cardiovascular diseases. Recent studies reported that isosteviol sodium (STVNa) harbor cardioprotective properties. Here, we explore the potential cardioprotective effect of STVNa on H₂ O₂ -induced oxidative stress on heart embryonic H9c2 cardiomyocytes and the underlying mechanism. We have found that STVNa pretreatment improved cell viability, nuclear morphology and prevented LDH release induced by oxidative stress. STVNa pretreatment also reduced production of reactive oxygen species, preserved mitochondrial function, restored biological antioxidant defense systems and prevented cell death. Western blotting analysis revealed that STVNa regulated the mitochondrial related pro- and anti-apoptotic protein (Bax and Bcl-2 respectively) levels, increased phosphorylation of Akt (ser473) and GSK-3β (ser9) and promoted binding between HK-II and mitochondria under the normal or oxidative stress conditions. LY294002, a PI3K inhibitor, abolished cytoprotective effects of STVNa by inhibiting activation of Akt and GSK-3β. Based on these findings, we conclude that STVNa protects H9c2 cells against oxidative stress by activating Akt/GSK-3β signaling pathway, which, in turn, leads to recruitment of HK-II to mitochondria and regulating Bcl2/Bax levels.
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http://dx.doi.org/10.1691/ph.2020.9851DOI Listing
January 2020

Comparison between ultrasound-guided percutaneous radiofrequency and microwave ablation in benign thyroid nodules.

J Cancer Res Ther 2019 ;15(7):1535-1540

Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Objective: The purpose of this study was to compare the efficacy and safety of radiofrequency ablation (RFA) and microwave ablation (MWA) for the treatment of benign thyroid nodules (BTNs).

Methods: Patients with BTNs were treated in our hospital, including 72 patients treated with RFA and 100 patients treated with MWA from June 2016 to March 2019. The volume reduction rates (VRRs), thyroid function, clinical status, and complications were compared at each postoperative duration to evaluate the efficacy and safety of the two modalities.

Results: The mean VRRs of the RFA group vs. the MWA group at 1, 3, 6, and 12 months were 22.7±13.4% vs. 24.0±16.1% (P = 0.681), 56.1±19.5% vs. 54.8±22.8% (P = 0.788), 77.9±21.0% vs. 68.7±19.1% (P = 0.038), and 85.4±18.9% vs. 75.8±19.4% (P = 0.029), respectively. There was no significant difference in the VRRs between the two treatments at 1 and 3 months and the RFA group achieved higher VRRs than MWA group at 6 and 12 months. Moreover, the symptom and cosmetic scores decreased significantly in both groups and all patients succeeded in preserving thyroid function. Of the total patients, 2.8% in the RFA group and 4% in the MWA group experienced voice changes after undergoing thyroid ablation, and one patient in the RFA group had intraoperative hemorrhage of about 10 mL.

Conclusions: RFA and MWA are both effective and safe techniques for treating BTNs. Higher VRRs were observed at the 6- and 12-month follow-ups in the RFA group.
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http://dx.doi.org/10.4103/jcrt.JCRT_322_19DOI Listing
June 2020

Multiple chronic conditions and associated health care expenses in US adults with cancer: a 2010-2015 Medical Expenditure Panel Survey study.

BMC Health Serv Res 2019 Dec 19;19(1):981. Epub 2019 Dec 19.

Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, 307 N. Broad St., Clinton, SC, 29325, USA.

Background: Cancer increases the risk of developing one or more chronic conditions, yet little research describes the associations between health care costs, utilization patterns, and chronic conditions in adults with cancer. The objective of this study was to examine the treated prevalence of chronic conditions and the association between chronic conditions and health care expenses in US adults with cancer.

Methods: This retrospective observational study used US Medical Expenditure Panel Survey (MEPS) Household Component (2010-2015) data sampling adults diagnosed with cancer and one or more of 18 select chronic conditions. The measures used were treated prevalence of chronic conditions, and total and chronic condition-specific health expenses (per-person, per-year). Generalized linear models assessed chronic condition-specific expenses in adults with cancer vs. without cancer and the association of chronic conditions on total health expenses in adults with cancer, respectively, by controlling for demographic and health characteristics. Accounting for the complex survey design in MEPS, all data analyses and statistical procedures applied longitudinal weights for national estimates.

Results: Among 3657 eligible adults with cancer, 83.9% (n = 3040; representing 16 million US individuals per-year) had at least one chronic condition, and 29.7% reported four or more conditions. Among those with cancer, hypertension (59.7%), hyperlipidemia (53.6%), arthritis (25.6%), diabetes (22.2%), and coronary artery disease (18.2%) were the five most prevalent chronic conditions. Chronic conditions accounted for 30% of total health expenses. Total health expenses were $6388 higher for those with chronic conditions vs. those without (p < 0.001). Health expenses associated with chronic conditions increased by 34% in adults with cancer vs. those without cancer after adjustment.

Conclusions: In US adults with cancer, the treated prevalence of common chronic conditions was high and health expenses associated with chronic conditions were higher than those without cancer. A holistic treatment plan is needed to improve cost outcomes.
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http://dx.doi.org/10.1186/s12913-019-4827-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924021PMC
December 2019

A compartmental approach to isosteviol's disposition in Sprague-Dawley rats.

Naunyn Schmiedebergs Arch Pharmacol 2020 06 9;393(6):1003-1011. Epub 2019 Dec 9.

Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.

Isosteviol has been reported to reverse hypertrophy and related inflammatory responses in in vitro models representative of cardiac muscle cells. The disposition of isosteviol is, however, characterized by secondary peaks and long plasma residence time despite reports of a relatively short half-life in liver fractions. The present study describes a compartmental approach to modelling the secondary peaks characteristic of isosteviol's concentration-time data in Sprague-Dawley rats. Oral (4 mg/kg) and intravenous (4 mg/kg) doses of isosteviol were administered to male and female Sprague-Dawley rats. Plasma samples collected between 0 and 72 h, and total bile secreted in 24 h, were analysed for isosteviol content with LC-MS/MS techniques. The disposition of isosteviol was, thereafter, described with a structural model that accounted for the sampling, liver and biliary secretion compartments, with a gap-time characterizing the accumulation and subsequent emptying of isosteviol for re-absorption. The half-life of isosteviol following oral dosing was about 103% greater in female rats than in the male, and the model-derived area under the concentration-time curve (AUC) in 72 h was about 756% greater in female animals than in males. Following the administration of intravenous doses of isosteviol, half-life and AUC in 24 h were about 332% and 595%, respectively, higher in female rats than in males. Isosteviol equivalent secreted into bile over 24 h accounted for about 94% of orally administered dose in male rats, and about 59% of oral dose in females. These findings show a differential systemic removal of isosteviol in Sprague-Dawley rats, likely explainable by gender-related differences in the glucuronidation-capacity of isosteviol.
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http://dx.doi.org/10.1007/s00210-019-01757-5DOI Listing
June 2020

Efficient green light-excited switches based on dithienylethenes with BF-doped π-conjugated systems.

Chem Commun (Camb) 2019 Nov 23;55(89):13430-13433. Epub 2019 Oct 23.

College of Chemistry and Chemical Engineering, and Henan Key Laboratory of Function-Oriented Porous Materials, Luoyang Normal University, Luoyang, 471934, China.

A series of dithienylethenes 1a-1d with BF-doped π-conjugation have been successfully developed. Upon alternating irradiation with green light and red/NIR light, they show efficient photochromism and fluorescence switching behaviors in toluene and PMMA film. Moreover, the fluorescence of 1a can be switched effectively in living cells.
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http://dx.doi.org/10.1039/c9cc06838dDOI Listing
November 2019

(Rhamnaceae), a new species from Hainan Island, China.

PhytoKeys 2019 26;132:19-29. Epub 2019 Sep 26.

CAS Key Laboratory of Tropical Forest Ecology, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla 666303, Yunnan, China Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences Mengla China.

Z. Qiang Lu & Y. Shuai Sun, a new evergreen woody species from Hainan Island, is described and illustrated. The specimens of this new species have previously been identified and placed under (H. Lév.) Rehder, with which it shares evergreen leaves, erect and climbing habits and axillary flowering branches with bracteole leaves. However, the specimens from three distinct Hainan populations significantly differ from those of from other regions with smaller length to width ratios of leaves, fruit and seeds, smaller sizes of fruit and seeds and mucronate seed apices. Principal Component Analysis of the closely related taxa, based on multiple morphological characters, further recognised two separated groups. One of them comprises and , the other merely includes all individuals from these distinct Hainan populations. Therefore, , based on these distinct Hainan populations, is here erected as a new species, distinctly different from its published relatives.
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http://dx.doi.org/10.3897/phytokeys.132.36776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776559PMC
September 2019

Blue-/NIR Light-Excited Fluorescence Switch Based on a Carbazole-Dithienylethene-BFbdk Triad.

J Org Chem 2019 Nov 20;84(21):13364-13373. Epub 2019 Sep 20.

The development of novel solid-state fluorescence switches, particularly triggered by visible light, is of increasing interest for the potential application in optical data storage and super-resolution fluorescence microscopies. In this study, two carbazole-dithienylethene-BFbdk triads and , suspending carbazole and BFbdk moieties on both sides of dithienylethene unit, have been developed. They exhibit blue-/NIR light-controlled photochromism with solvent-dependent characteristics. Moreover, reveals blue-/NIR light-induced reversible fluorescent switching behaviors in toluene, chloroform, poly(methyl methacrylate) (PMMA) film, and powder state, while its analogue in the powder state exhibits no fluorescence due to a strong intermolecular π-π stacking interaction, and the fluorescent switching performance is observed only in toluene and PMMA film. The density functional theory calculations further validate the differences in their optical properties in the solution and powder states.
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http://dx.doi.org/10.1021/acs.joc.9b01508DOI Listing
November 2019

The spatial-temporal working pattern of cold ultrasound treatment in improving the sensory, nutritional and safe quality of unpasteurized raw tomato juice.

Ultrason Sonochem 2019 Sep 3;56:240-253. Epub 2019 Apr 3.

College of Food Science, Southwest University, Chongqing 400715, People's Republic of China; Chongqing Engineering Research Center of Regional Foods, Chongqing 400715, People's Republic of China. Electronic address:

In considering the adverse nutritional and flavor consequences of thermal pasteurization on fruit juices, freshly squeezed and unpasteurized fruit juices, commonly called raw juices, are of increasing demand as they are served in bars, restaurants and at home. Apparently, due to lack of controlled processing regime as did in a juice factory, the raw juice often undergoes a rapid phase separation and is at the risk of microbial unsafety. To this end, an attempt of cold ultrasound treatment (CUT, 87.52 W/cm, 10 °C) was implemented to a raw tomato juice up to 30 min. Appreciatively, the physical stability, nutritional value and microbial safety substantially improved. On a CUT time scale, cloud stability and total phenolic content continuously increased; the total plate count was adversely altered; the rheological parameters (viscosity, thixotropy and shear-thinning tendency) and total carotenoids obtained shared a parabolic changing pattern but peaked at 15 min and 10 min, respectively. Finally, the ascorbic acid sharply increased at an earlier stage (5 min), and then remained stable throughout the whole process. Notably, the occurrences of these improvements are of spatial-temporal nature and resulted from different cavitation induced stress fields. At the initial stage, CUT chiefly worked via the mechanical field with the particles in pulp phase, making them smaller and releasing the soluble materials into serum phase. When the particles larger than approximately of 160 μm were completely disintegrated, the CUT entered its second stage and mainly functioned in the serum phase via both mechanical and chemical fields. As a result, the serum pectin and carotenoids were depolymerized and degraded, respectively. The present results are valuable in uncovering the mechanism and kinetics underlying the ultrasound treatment of fruit juices and the present CUT is highly recommended due to its high maneuverability and excellent performance.
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http://dx.doi.org/10.1016/j.ultsonch.2019.04.013DOI Listing
September 2019

In vitro metabolic stability and biotransformation of isosteviol in human and rat liver fractions.

Drug Metab Pharmacokinet 2019 Jun 28;34(3):194-200. Epub 2019 Feb 28.

Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China. Electronic address:

Isosteviol is a lead compound whose cardioprotective property has been partly explained by its regulation of ion channels and interference with signalling pathways in the metabolism of some fatty acids. This study determined the metabolic stability of isosteviol in human liver microsomes and H9c2 cell line, and the identity of its metabolites in human and rat liver fractions. Isosteviol was largely unmetabolized in H9c2 cells and in NADPH-only supplemented human liver fractions, suggesting a very limited contribution of phase I biotransformation to its hepatic clearance. The in vitro half-life of isosteviol in UDPGA-only supplemented medium was observed to be 24.9 min with an estimated intrinsic clearance of 0.349 mL/min/kg in man. Analysis by LC-MS/MS and Q-tof showed that isosteviol is mainly metabolised to its acyl-β-D-glucuronide in humans and rats. Mono-hydroxy-isosteviol and dihydroisosteviol were also identified. Rat liver fraction, however, generated dihydroxy-isosteviol in addition to two mono-hydroxy derivatives. Further studies confirmed that dihydroisosteviol is subsequently biotransformed to its acyl-β-D-glucuronide in man and rat. These findings suggest that future studies of the efficacy and toxicity of isosteviol might have to consider xenobiotics that alter the glucuronidation pathways significantly in man.
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http://dx.doi.org/10.1016/j.dmpk.2019.02.005DOI Listing
June 2019