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1.
Ecotoxicol Environ Saf ; 266: 115557, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37820476

ABSTRACT

Pesticide stress on plants is receiving increased scrutiny due to its effect on plant secondary metabolism and nutritional quality. Tannic acid (TA) is a natural polyphenolic compound showing excellent antioxidant properties and is involved in alleviating stress. The present study thoroughly investigated the effects and mechanism of exogenous TA on relieving imidacloprid (IMI) stress in tea plants. Our research found that TA(10 mg/L) activated the antioxidant defense system, enhanced the antioxidant ability, reduced the accumulation of ROS and membrane peroxidation, and notably promoted tea plant tolerance to imidacloprid stress. Additionally, TA boosted photosynthetic capacity, strengthened the accumulation of nutrients. regulated detoxification metabolism, and accelerated the digestion and metabolism of imidacloprid in tea plants. Furthermore, TA induced significant changes in 90 important metabolites in tea, targeting 17 metabolic pathways through extensively targeted metabolomics. Specifically, TA activated the flavonoid biosynthetic pathway, resulting in a 1.3- to 3.1-fold increase in the levels of 17 compounds and a 1.5- to 63.8-fold increase in the transcript level of related genes, such as ANR, LAR and CHS in this pathway. As a potential tea health activator, TA alleviates the oxidative damage caused by imidacloprid and improves the yield and quality of tea under pesticide stress.


Subject(s)
Camellia sinensis , Pesticides , Antioxidants/pharmacology , Antioxidants/metabolism , Trees/metabolism , Flavonoids/pharmacology , Flavonoids/metabolism , Biosynthetic Pathways , Oxidative Stress , Camellia sinensis/genetics , Tannins/pharmacology , Tannins/metabolism , Tea , Pesticides/metabolism
2.
Nutrients ; 15(14)2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37513589

ABSTRACT

Chlorogenic acid (CGA), a dietary natural phenolic acid, has been widely reported to regulate glucose and lipid metabolism. However, the protective effects and the underlying mechanisms of CGA on glucagon-induced hepatic glucose production remain largely uncharacterized. Herein, we investigated the efficacy of CGA on hepatic gluconeogenesis both in vivo and in vitro. The elevated levels of endogenous glucose production induced by infusion of glucagon or pyruvate were lowered in mice administered with CGA. Furthermore, chronic CGA treatment ameliorated the accumulation of glucose and ceramide in high-fat diet (HFD)-fed mice. CGA also attenuated HFD-fed-induced inflammation response. The protective effect of CGA on glucose production was further confirmed in primary mouse hepatocytes by inhibiting accumulation of ceramide and expression of p38 MAPK. Moreover, CGA administration in HFD-fed mice preserved the decreased phosphorylation of Akt in the liver, resulting in the inhibition of FoxO1 activation and, ultimately, hepatic gluconeogenesis. However, these protective effects were significantly attenuated by the addition of C2 ceramide. These results suggest that CGA inhibits ceramide accumulation to restrain hepatic glucagon response.


Subject(s)
Chlorogenic Acid , Glucagon , Mice , Animals , Glucagon/metabolism , Chlorogenic Acid/pharmacology , Chlorogenic Acid/metabolism , Liver/metabolism , Glucose/metabolism , Diet, High-Fat/adverse effects , Mice, Inbred C57BL
3.
Front Bioeng Biotechnol ; 11: 1181078, 2023.
Article in English | MEDLINE | ID: mdl-37251561

ABSTRACT

Phosphate solubilizing microorganisms (PSMs) are known as bacteria or fungi that make insoluble phosphorus in soil available to plants. To date, as beneficial microbes, studies on PSMs indicated they have potential applications in agriculture, environmental engineering, bioremediation, and biotechnology. Currently high cost and competition from local microbe are the most important factors hindering PSMs commercialization and application as for instance biofertilizer, soil conditioner or remediation agent, etc. There are several technical strategies can be engaged to approach the solutions of these issues, for instance mass production, advance soil preparation, genetic engineering, etc. On the other hand, further studies are needed to improve the efficiency and effectiveness of PSMs in solubilizing phosphates, promoting plant growth, soil remediation preferably. Hopefully, PSMs are going to be developed into ecofriendly tools for sustainable agriculture, environment protection and management in the future.

4.
Front Microbiol ; 14: 1099103, 2023.
Article in English | MEDLINE | ID: mdl-36937284

ABSTRACT

Finding novel and effective suppression of hepatic glucagon response antidiabetic compounds is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. In this study, four new prenylated indole-terpenoids (1-4), named encindolenes I-L, as well as a known analogue (5), were isolated from the fungus Penicillium sp. HFF16from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the antidiabetic activity assay, compounds 1-5 could inhibit glucagon-induced hepatic glucose output with EC50 values of 67.23, 102.1, 49.46, 25.20, and 35.96 µM, respectively, and decrease the intracellular cAMP contents in primary hepatocytes.

5.
Bioorg Med Chem Lett ; 85: 129239, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36924947

ABSTRACT

A series of 5' monosubstituted chalcone derivatives were synthesized to explore their antitumor activity and mechanism of action in vitro. The structures of 5' monosubstituted chalcone derivatives synthesized by reactions such as Suzuki coupling were confirmed by 1H NMR, 13C NMR and MS, and the target compounds were not reported in the literature. The antitumor activity of the aimed compounds was tested by MTT colorimetric method in vitro. Compound 5c has an IC50 value of 1.97 µM for K562 and a value of 2.23 µM for HepG2. Further investigation of the mechanism of action of compound 5c was found to have effects on K562 cell morphology, proliferation, apoptosis, cell cycle, and wound healing of HepG2 cells. The results showed that compound 5c has research value in antitumor activity and mechanism of action in vitro.


Subject(s)
Antineoplastic Agents , Chalcone , Chalcones , Chalcone/chemistry , Chalcones/chemistry , Structure-Activity Relationship , Cell Proliferation , Antineoplastic Agents/chemistry , Apoptosis , Drug Screening Assays, Antitumor , Cell Line, Tumor , Molecular Structure
6.
BMC Plant Biol ; 22(1): 500, 2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36284279

ABSTRACT

BACKGROUND: Rice is one of the most important cereal crops in the world but is susceptible to cold stress (CS). In this study, we carried out parallel transcriptomic analysis at the reproductive stage on the anthers of two Japonica rice varieties with contrasting CS resistance: cold susceptible Longjing11 (LJ11) and cold resistant Longjing25 (LJ25). RESULTS: According to the obtained results, a total of 16,762 differentially expressed genes (DEGs) were identified under CS, including 7,050 and 14,531 DEGs in LJ25 and LJ11, respectively. Examining gene ontology (GO) enrichment identified 35 up- and 39 down-regulated biological process BP GO terms were significantly enriched in the two varieties, with 'response to heat' and 'response to cold' being the most enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 33 significantly enriched pathways. Only the carbon metabolism and amino acid biosynthesis pathways with down-regulated DEGs were enriched considerably in LJ11, while the plant hormone signal transduction pathway (containing 153 DEGs) was dramatically improved. Eight kinds of plant hormones were detected in the pathway, while auxin, abscisic acid (ABA), salicylic acid (SA), and ethylene (ETH) signaling pathways were found to be the top four pathways with the most DEGs. Furthermore, the protein-protein interaction (PPI) network analysis identified ten hub genes (co-expressed gene number ≥ 30), including six ABA-related genes. Various DEGs (such as OsDREB1A, OsICE1, OsMYB2, OsABF1, OsbZIP23, OsCATC, and so on) revealed distinct expression patterns among rice types when the DEGs between LJ11 and LJ25 were compared, indicating that they are likely responsible for CS resistance of rice in cold region. CONCLUSION: Collectively, our findings provide comprehensive insights into complex molecular mechanisms of CS response and can aid in CS resistant molecular breeding of rice in cold regions.


Subject(s)
Oryza , Abscisic Acid/metabolism , Amino Acids/metabolism , Carbon/metabolism , Cold-Shock Response/genetics , Ethylenes/metabolism , Gene Expression Profiling/methods , Gene Expression Regulation, Plant , Indoleacetic Acids/metabolism , Oryza/metabolism , Plant Growth Regulators/metabolism , Salicylic Acid/metabolism , Transcriptome
7.
Mar Pollut Bull ; 181: 113940, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35853409

ABSTRACT

Microplastics (MPs) are widely present in global oceans, and can pose a threat to marine organisms. This study examined the abundance and characteristics of MPs in seawater, sediment, and organism samples collected from Hangzhou Bay. Abundance of MPs in seawater (n = 26) and sediment (n = 26) were 0.77-9.6 items/m3 and 44-208 items/kg dw, respectively. Size of MPs in sediment (mean 2.5 mm, range 0.21-5.3 mm) was significantly (p < 0.05) larger than that in seawater (1.1 mm, 0.13-4.9 mm). Fiber was consistently the predominant shape of MPs in seawater and sediment. The major polymer composition of MPs was polyethylene (PE; mean 47 %) in seawater, but textile cellulose (60 %) was the main polymer type of MPs in sediment. Average abundance of MPs in marine organisms (n = 388) ranged from 0.064 (zooplankton) to 2.9 (Harpodon nehereus) items/ind, with the mean size of 0.19-1.4 mm. MP abundance in marine organisms was not significantly correlated with their trophic level. Fiber was always the predominant shape of MPs in different marine organisms, contributing mean 67 (fish)-93 % (zooplankton) of total MPs. MPs in crustacean (mean 58 %), shellfish (64 %), and cephalopod (29 %) were dominated by textile cellulose. Whereas, PE (mean 44 %) and polypropylene (43 %) were the major polymer compositions of MPs in fish and zooplankton, respectively. To our knowledge, this is the most comprehensive study investigating the occurrence of MPs in environmental matrixes from Hangzhou Bay, which contributes to the better understanding of environmental behaviors of MPs in estuarine sea environment.


Subject(s)
Microplastics , Water Pollutants, Chemical , Animals , Aquatic Organisms , Bays , Cellulose , Environmental Monitoring , Fishes , Plastics , Seawater , Water Pollutants, Chemical/analysis , Zooplankton
8.
Sci Rep ; 12(1): 6224, 2022 04 13.
Article in English | MEDLINE | ID: mdl-35418703

ABSTRACT

The sensitivity of rice to low-temperature stress (LTS), especially at the reproductive stage, is a primary factor of rice yield fluctuation in cold cultivate region. Here, the changes of reactive oxygen species (ROS), osmotic adjustment substances, and antioxidants in different tissues were analyzed during rice growing under low temperatures (LT) at the reproductive stage. Results showed that LTS increases the levels of proline (Pro), soluble protein (SP), glutathione (GSH), superoxidase (SOD), and ascorbate peroxidase (APX) in LJ25 (LTS-resistant) and LJ11 (LTS-sensitive). The activities of catalase (CAT) and peroxidase (POD) were significantly increased in LJ25 but decreased in LJ11 under LTS, while an opposite trend in ROS and malondialdehyde (MDA) was observed in both varieties. Moreover, most physicochemical properties were higher in flag leaves and panicles compared with those in leaf sheaths. The expression patterns of OsCOIN, OsCATC, OsMAP1, OsPOX1, and OsAPX were the same with phenotypic changes in Pro and the enzymes encoded by them, confirming the accuracy of the physicochemical analysis. Therefore, only CAT and POD increased more in LJ25, suggesting they could be the key factors used for LT-tolerant breeding of rice in cold regions.


Subject(s)
Oryza , Antioxidants/metabolism , Ascorbate Peroxidases/metabolism , Catalase/metabolism , Glutathione/metabolism , Oryza/metabolism , Oxidative Stress , Proline/metabolism , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism , Temperature
9.
J Healthc Eng ; 2021: 6761364, 2021.
Article in English | MEDLINE | ID: mdl-34336164

ABSTRACT

The objective of this study was to explore the diagnosis of severe sepsis complicated with acute kidney injury (AKI) by ultrasonic image information based on the artificial intelligence pulse coupled neural network (PCNN) algorithm. In this study, an algorithm of ultrasonic image information enhancement based on the artificial intelligence PCNN was constructed and compared with the histogram equalization algorithm and linear transformation algorithm. After that, it was applied to the ultrasonic image diagnosis of 20 cases of severe sepsis combined with AKI in hospital. The condition of each patient was diagnosed by ultrasound image performance, change of renal resistance index (RRI), ultrasound score, and receiver operator characteristic curve (ROC) analysis. It was found that the histogram distribution of this algorithm was relatively uniform, and the information of each gray level was obviously retained and enhanced, which had the best effect in this algorithm; there was a marked individual difference in the values of RRI. Overall, the values of RRI showed a slight upward trend after admission to the intensive care unit (ICU). The RRI was taken as the dependent variable, time as the fixed-effect model, and patients as the random effect; the parameter value of time was between 0.012 and 0.015, p=0.000 < 0.05. Besides, there was no huge difference in the ultrasonic score among different time measurements (t = 1.348 and p=0.128 > 0.05). The area under the ROC curve of the RRI for the diagnosis of AKI at the 2nd day, 4th day, and 6th day was 0.758, 0.841, and 0.856, respectively, which was all greater than 0.5 (p < 0.05). In conclusion, the proposed algorithm in this study could significantly enhance the amount of information in ultrasound images. In addition, the change of RRI values measured by ultrasound images based on the artificial intelligence PCNN was associated with AKI.


Subject(s)
Acute Kidney Injury , Sepsis , Acute Kidney Injury/diagnostic imaging , Acute Kidney Injury/therapy , Artificial Intelligence , Humans , Neural Networks, Computer , Prospective Studies , ROC Curve , Sepsis/complications , Sepsis/diagnostic imaging
10.
Front Microbiol ; 12: 710364, 2021.
Article in English | MEDLINE | ID: mdl-34305878

ABSTRACT

Four new indole-terpenoids (1-4) named encindolene A, 18-O-methyl-encindolene A, encindolene B, and encindolene C, as well as three known analogs (5-7), were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of compounds including absolute configurations were elucidated by spectroscopic data and electronic circular dichroism (ECD) analysis. Anti-inflammatory activity evaluation revealed that compounds 1-7 inhibit the production of nitric oxide with IC50 values of 79.4, 49.7, 81.3, 40.2, 86.7, 90.1, and 54.4 µM, respectively, and decrease the levels of tumor necrosis factor-α, interleukin-6 contents in lipopolysaccharide-induced RAW264.7 macrophages.

11.
Genomics ; 113(5): 3083-3091, 2021 09.
Article in English | MEDLINE | ID: mdl-34237377

ABSTRACT

Revealing genomic variation of representative and diverse germplasm is the cornerstone of deploying genomics information into genetic improvement programs of species of agricultural importance. Here we report the re-sequencing of 239 japonica rice elites representing the genetic diversity of japonica germplasm in China, Japan and Korea. A total of 4.8 million SNPs and PAV of 35,634 genes were identified. The elites from Japan and Korea are closely related and relatively less diverse than those from China. A japonica rice pan-genome was constructed, and 35 Mb non-redundant novel sequences were identified, from which 1131 novel genes were predicted. Strong selection signals of genomic regions were detected on most of the chromosomes. The heading date genes Hd1 and Hd3a have been artificially selected during the breeding process. The results from this study lay the foundation for future whole genome sequences-enabled breeding in rice and provide a paradigm for other species.


Subject(s)
Oryza , Alleles , Genetic Variation , Genome, Plant , Oryza/genetics , Plant Breeding , Polymorphism, Single Nucleotide
12.
Am J Transl Res ; 13(6): 6846-6854, 2021.
Article in English | MEDLINE | ID: mdl-34306435

ABSTRACT

OBJECTIVE: This study was designed to demonstrate the predictive value of Pulse indicate Contour Cardiac Output (PiCCO) monitoring technique combined with troponin I (cTnI) detection in septic myocardial dysfunction (SMD) of the elderly. METHODS: One hundred and nineteen elderly patients with SMD treated in our hospital from March 2016 to September 2019 were enrolled and allocated into the joint group (JG; 64 cases) for capacity management of fluid resuscitation under the guidance of PiCCO monitoring technique and cTnI detection, and the control group (CG; 55 cases) for conventional capacity management. Clinical indicators, hemodynamics, improvement of myocardial injury markers and inflammatory factors 6 h and 36 h post intervention, fluid balance 6 h, 12 h and 36 h post intervention, drug consumption (norepinephrine), treatment effect and 28-day hospitalization mortality were compared between the two groups. RESULTS: After resuscitation, the urine volume per hour and the fluid resuscitation volume were higher while the blood lactic acid (BLA) expression was lower in JG as compared to CG. JG presented a remarkably lower central venous pressure (CVP) than CG after resuscitation, with notably higher mean arterial pressure (MAP) and central venous oxygen saturation (ScvO2). In comparison with CG, JG displayed dramatically lower cTnI and N-terminal pro-brain natriuretic peptide (NT-ProBNP) 6 h and 36 h post intervention, as well as evidently reduced interleukin-6 (IL-6), procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP). After 36 h of intervention, the fluid balance was evidently lower in JG than in CG. JG showed statistically less use of norepinephrine, less time of mechanical ventilation and ICU stay, and noticeably lower incidence of multiple organ dysfunction syndrome (MODS), as well as dramatically lower 28-day hospitalization mortality than CG post intervention. CONCLUSIONS: PiCCO monitoring technique combined with cTnI detection is high-performing in fluid resuscitation of elderly patients with SMD, which can meliorate the myocardial function of patients, reduce medication and facilitate disease recovery.

13.
Front Microbiol ; 12: 668938, 2021.
Article in English | MEDLINE | ID: mdl-33841388

ABSTRACT

Two new thio-compounds named aspergerthinol A and B (1 and 2) and two new monoterpenes named aspergerthinacids A and B (3 and 4) were isolated from the fungus Aspergillus sp. CYH26 from the rhizosphere soil of Cynanchum bungei Decne. The structures of compounds were elucidated by spectroscopic data and quantum NMR and ECD calculations. Compounds 1 and 2 represented a new family of sulfur containing natural products with a 3-methyl-4H-cyclopenta[b]thiophen-4-one skeleton. Compounds 1-4 showed inhibitory activities against nitric oxide (NO) with IC50 values of 38.0, 19.8, 46.3, and 56.6 µM, respectively.

14.
New Phytol ; 231(3): 1056-1072, 2021 08.
Article in English | MEDLINE | ID: mdl-33892513

ABSTRACT

The improvement of cold adaptation has contributed to the increased growing area of rice. Standing variation and de novo mutation are distinct natural sources of beneficial alleles in plant adaptation. However, the genetic mechanisms and evolutionary patterns underlying these sources in a single population during crop domestication remain elusive. Here we cloned the CTB2 gene, encoding a UDP-glucose sterol glucosyltransferase, for cold tolerance in rice at the booting stage. A single standing variation (I408V) in the conserved UDPGT domain of CTB2 originated from Chinese Oryza rufipogon and contributed to the cold adaptation of Oryza sativa ssp. japonica. CTB2 is located in a 56.8 kb region, including the previously reported gene CTB4a in which de novo mutation arose c. 3200 yr BP in Yunnan province, China, conferring cold tolerance. Standing variation of CTB2 and de novo mutation of CTB4a underwent stepwise selection to facilitate cold adaptation to expand rice cultivation from high-altitude to high-latitude regions. These results provide an example of stepwise selection on two kinds of variation and describe a new molecular mechanism of cold adaptation in japonica rice.


Subject(s)
Oryza , Alleles , China , Domestication , Genes, Plant , Oryza/genetics , Selection, Genetic
15.
Front Chem ; 9: 792810, 2021.
Article in English | MEDLINE | ID: mdl-35211458

ABSTRACT

Finding novel anti-diabetic compounds with effective suppression activities against hepatic glucagon response is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. As part of our ongoing research, five new indole-terpenoids (1-5), named encindolenes D-H, were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the anti-diabetic activity assay, compounds 1-5 could inhibit the hepatic glucose production with EC50 values of 17.6, 30.1, 21.3, 9.6, and 9.9 µM, respectively, and decrease the cAMP contents in glucagon-induced HepG2 cells.

16.
R Soc Open Sci ; 7(6): 192243, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32742685

ABSTRACT

As one of the abiotic stresses, low temperature severely threatens rice production during its entire growth period, especially during the booting stage. In the present study, transcriptome analysis was performed comparing Longjing (LJ) 25 (chilling-tolerant) and LJ 11 (chilling-sensitive) rice varieties to identify genes associated with chilling tolerance in rice spikelets. A total of 23 845 expressed genes and 13 205 differentially expressed genes (DEGs) were identified, respectively. Gene ontology (GO) enrichment analyses revealed 'response to cold' (containing 180 DEGs) as the only category enriched in both varieties during the entire cold treatment period. Through MapMan analysis, we identified nine and six DEGs related to the Calvin cycle and antioxidant enzymes, respectively, including OsRBCS3, OsRBCS2, OsRBCS4, OsAPX2 and OsCATC, that under chilling stress were markedly downregulated in LJ11 compared with LJ25. Furthermore, we predicted their protein-protein interaction (PPI) network and identified nine hub genes (the threshold of co-expressed gene number ≥ 11) in Cytoscape, including three RuBisCO-related genes with 14 co-expressed genes. Under chilling stress, antioxidant enzyme activities (peroxidase (POD) and catalase (CAT)) were downregulated in LJ11 compared with LJ25. However, the content of malondialdehyde (MDA) was higher in LJ11 compared with LJ25. Collectively, our findings identify low temperature responsive genes that can be effectively used as candidate genes for molecular breeding programmes to increase the chilling tolerance of rice.

17.
RSC Adv ; 10(24): 14337-14346, 2020 Apr 06.
Article in English | MEDLINE | ID: mdl-35498475

ABSTRACT

Anastatins A and B, two flavonoid compounds isolated from desert plant Anastatica hierochuntica, have protective activities for primary rat hepatocytes. Anastatins A and B, and their derivatives, were synthesized by our group previously. In this study, the antioxidant activity and cytotoxicity of these compounds were studied using chemical assessment methods, cell proliferation inhibition experiments, and cell oxidative damage models. The best compound, 38c, was used to study the hepatoprotection activity and mechanism by using a CCl4-induced liver injury model in mice. The results show that most of these flavonoid compounds have good antioxidant activity and low cytotoxicity in vitro. Among them, the most potent compound was 38c, which exhibited a protective effect on CCl4-induced hepatic injury by suppressing the amount of CYP2E1. These findings indicate that anastatin flavonoid derivatives have potential therapeutic utility against oxidative hepatic injury.

18.
R Soc Open Sci ; 7(11): 201081, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33391797

ABSTRACT

Rice is sensitive to low temperatures, specifically at the booting stage. Chilling tolerance of rice is a quantitative trait loci that is governed by multiple genes, and thus, its precise identification through the conventional methods is an arduous task. In this study, we investigated the candidate genes related to chilling tolerance at the booting stage of rice. The F2 population was derived from Longjing25 (chilling-tolerant) and Longjing11 (chilling-sensitive) cross. Two bulked segregant analysis pools were constructed. A 0.82 Mb region containing 98 annotated genes on chromosomes 6 and 9 was recognized as the candidate region associated with chilling tolerance of rice at the booting stage. Transcriptomic analysis of Longjing25 and Longjing11 revealed 50 differentially expressed genes (DEGs) on the candidate intervals. KEGG pathway enrichment analysis of DEGs was performed. Nine pathways were found to be enriched, which contained 10 DEGs. A total of four genes had different expression patterns or levels between Longjing25 and Longjing11. Four out of the 10 DEGs were considered as potential candidate genes for chilling tolerance. This study will assist in the cloning of the candidate genes responsible for chilling tolerance and molecular breeding of rice for the development of chilling-tolerant rice varieties.

19.
Drug Deliv ; 26(1): 328-342, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30905189

ABSTRACT

Efficient cellular delivery of biologically active molecules is one of the key factors that affect the discovery and development of novel drugs. The plasma membrane is the first barrier that prevents direct translocation of chemic entities, and thus obstructs their efficient intracellular delivery. Generally, hydrophilic small molecule drugs are poor permeability that reduce bioavailability and thus limit the clinic application. The cellular uptake of macromolecules and drug carriers is very inefficient without external assistance. Therefore, it is desirable to develop potent delivery systems for achieving effective intracellular delivery of chemic entities. Apart from of the types of delivery strategies, the composition of the cell membrane is critical for delivery efficiency due to the fact that cellular uptake is affected by the interaction between the chemical entity and the plasma membrane. In this review, we aimed to develop a profound understanding of the interactions between delivery systems and components of the plasma membrane. For the purpose, we attempt to present a broad overview of what delivery systems can be used to enhance the intracellular delivery of poorly permeable chemic entities, and how various delivery strategies are applied according to the components of plasma membrane.


Subject(s)
Cell Membrane/metabolism , Drug Delivery Systems , Pharmaceutical Preparations/administration & dosage , Animals , Biological Availability , Biological Transport , Drug Carriers/chemistry , Humans , Hydrophobic and Hydrophilic Interactions , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/metabolism
20.
Future Med Chem ; 10(9): 1055-1066, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29676183

ABSTRACT

AIM: The research of novel and potent antidiabetic agents is urgently needed for the control of the exploding diabetic population. We previously reported the synthesis and antidiabetic activity of natural 8-(6"-umbelliferyl)-apigenin (1), but its antidiabetic targets are not known. Therefore, four series of derivatives were synthesized and evaluated for their antidiabetic activities. Results & methodology: Compounds (5a) and (14a) were identified as new α-glucosidase and α-amylase dual inhibitors. The kinetic analysis of the most potent α-glucosidase inhibitor of each series of compounds revealed that they inhibited α-glucosidase in irreversible modes. In addition, compounds (5a) and (14a) showed potent glucose consumption-promoting activity. CONCLUSION: Compounds (5a) and (14a) could be regarded as promising starting points for the development of antidiabetic candidates.


Subject(s)
Coumarins/chemical synthesis , Coumarins/pharmacology , Flavonoids/chemical synthesis , Flavonoids/pharmacology , Glucose/metabolism , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/pharmacology , Coumarins/chemistry , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Flavonoids/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Hep G2 Cells , Humans , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Kinetics , Structure-Activity Relationship , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , alpha-Glucosidases/metabolism
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