Publications by authors named "Huimin Guo"

127 Publications

Analysis of blocking antibodies and lymphocyte subsets in patients with recurrent reproductive failure.

Hum Fertil (Camb) 2021 Mar 22:1-6. Epub 2021 Mar 22.

Clinical Laboratory Center, Children's Hospital of Shanxi, Women Health Center of Shanxi, Taiyuan, China.

This study aimed to explore the relationship between recurrent reproductive failure (RRF) and blocking antibody (BA) and lymphocytes, to explore the difference of immune status between recurrent spontaneous abortion (RSA) and recurrent implantation failure (RIF) patients. We undertook a retrospective analysis of BA and lymphocyte subsets detected by flow cytometry in 720 RRF patients (411 RSA and 309 RIF patients) who were treated at Shanxi Maternal and Child Health Hospital from April 2015 to October 2019. The BA negative rate of RRF patients was 81.80%, which was significantly higher than that of normal women (23.46%) ( < 0.05). There was no significant difference in BA negative rates between RSA and RIF patients. Compared with the normal value, the percentage of CD3 T lymphocytes and CD3CD4 T lymphocytes in RRF patients were 71.1% (65.9-76.0) and 36.8% (32.5-41.9) respectively, which were significantly lower than the normal value ( < 0.05). The percentage of B cells in RSA patients [11.0 (8.8-13.9)] was significantly lower than that in RIF patients [11.9 (9.4-14.8)]. The occurrence of RRF is related to the lack of BA and the change of lymphoid subsets. There are some differences in immune status between RSA and RIF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14647273.2021.1903099DOI Listing
March 2021

Transfected DNA is targeted by STING-mediated restriction.

Biochem Biophys Res Commun 2021 Apr 5;549:207-213. Epub 2021 Mar 5.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAM), Department of Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China; Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

DNA transfection is routinely used for delivering expression of gene of interest to target cells. Transfected DNA has been known to activate cellular DNA sensor(s) and innate immune responses, but the effects of such responses on transfected DNA are not fully understood. STING (stimulator of interferon genes) is an important adaptor protein in cellular innate immune response to various DNA and RNA stimuli and upon activation induces significant type I interferon responses. In this work, we characterized the effects of STING on gene expression driven by transfected double-stranded DNA. We observed that gene expression from transfected DNA was repressed in the presence of overexpressed STING, but increased if endogenous STING was knocked down through RNA interference. Endogenous chromosomal genes and chromosome-integrated exogenous genes were not affected by such STING-mediated restriction, which did not depend on DNA circularity or linearity, promoter used, or bacterial sequences in transfected DNA. Mechanistically, STING-mediated repression of transfected DNA correlates with reduced mRNA levels, and partially involves the induction of interferon β production by STING. Collectively, these data indicate that episomal double-stranded DNA is targeted by STING-mediated cell defense.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.02.109DOI Listing
April 2021

Theaflavin-regulated Imd condensates control intestinal homeostasis and aging.

iScience 2021 Mar 6;24(3):102150. Epub 2021 Feb 6.

State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Sciences and Technology, Anhui Agricultural University, Hefei, Anhui 230036, China.

Black tea is the most widely consumed tea drink in the world and has consistently been reported to possess anti-aging benefits. However, whether theaflavins, one type of the characteristic phytochemicals in black tea extracts, are involved in regulating aging and lifespan in consumers remains largely unknown. In this study, we show that theaflavins play a beneficial role in preventing age-onset intestinal leakage and dysbiosis, thus delaying aging in . Mechanistically, theaflavins regulate the condensate assembly of Imd to negatively govern the overactivation of Imd signals in fruit fly intestines. In addition, theaflavins prevent DSS-induced colitis in mice, suggesting theaflavins play a role in modulating intestinal integrity. Overall, our study reveals a molecular mechanism by which theaflavins regulate gut homeostasis likely through controlling Imd coalescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2021.102150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905455PMC
March 2021

Molecular characterization and functional study of a tandem-repeat Galectin-9 from Japanese flounder (Paralichthys olivaceus).

Fish Shellfish Immunol 2021 May 19;112:23-30. Epub 2021 Feb 19.

School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, 266109, China. Electronic address:

Galectin-9 is a β-galactoside-binding lectin which could modulate a variety of biological functions including recognition, aggregation and clearance of pathogen. In this study, one Galectin-9 (named PoGalectin-9) was identified from Japanese flounder Paralichthys olivaceus. PoGalectin-9 belongs to the tandem-repeat type, containing one 127-amino acids CRD domain within N terminal and one 122-amino acids CRD domain within C-terminal. The open reading frame of PoGalectin-9 cDNA was 921 bp encoding 306 amino acids. Sequence similarity comparison confirmed that PoGalectin-9 shared high homology with other Galectin-9. The tissue distribution and expression profiles after bacterial infection were also investigated. PoGalectin-9 was widely distributed in all of the examined tissues of Japanese flounder but was predominantly expressed in the spleen, kidney and intestine. After Edwardsiella tarda challenge, the expression of PoGalectin-9 was up-regulated in spleen and down regulated in kidney. ELISA experiment showed that recombinant PoGalectin-9 (rPoGalectin-9) exhibit binding capacity to lipopolysaccharide (LPS) and peptidoglycan (PGN), which is significantly correlated with the concentration of rPoGalectin-9. Meanwhile, the rPoGalectin-9 protein showed strong agglutinating activities against both Gram-negative bacteria and Gram-positive bacteria. Bacterial binding experiments showed that rPoGalectin-9 could bind all examined bacteria. In conclusion, the present study indicate that PoGalectin-9 might play important roles during the immune responses of Japanese flounder against bacterial pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2021.02.013DOI Listing
May 2021

Characterization of volatile compounds in differently coloured Chenopodium quinoa seeds before and after cooking by headspace-gas chromatography-ion mobility spectrometry.

Food Chem 2021 Jun 18;348:129086. Epub 2021 Jan 18.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Aroma is an important feature of quinoa that influences consumer preferences. Differently coloured quinoa seeds exhibit diverse nutritional characteristics; however, their aromatic profile differences are poorly investigated. The volatile components of 11 quinoa samples were characterized by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 120 peaks were detected, with 61 compounds identified. White quinoa liberated a high concentration of volatiles with grass (n-hexanol) and green ((E)-2-octenal, (E)-2-heptenal, etc.) aromas before and after cooking, respectively. Raw flaxen samples uniquely released a caramel compound (cyclotene) and exhibited several sweet and caramel volatiles (decanal, 5-methyl-furfural, and 2-furfural) after cooking. Additionally, cooked black quinoa exerted more fruity substances (methyl hexanoate and phenylacetaldehyde). Orthogonal partial least square discriminant analysis clearly distinguished the samples before and after cooking and differentiated the seeds into different colours. The results confirm the potential of HS-GC-IMS to evaluate volatiles in quinoa and are meaningful for quinoa consumption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2021.129086DOI Listing
June 2021

Absolute quantitative analysis of endogenous neurotransmitters and amino acids by liquid chromatography-tandem mass spectrometry combined with multidimensional adsorption and collision energy defect.

J Chromatogr A 2021 Feb 5;1638:461867. Epub 2021 Jan 5.

Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, PR China. Electronic address:

Considering that neurotransmitters (NTs) and amino acids (AAs) exert pivotal roles in various neurological diseases, global detection of these endogenous metabolites is of great significance for the treatment of nervous system diseases. Herein, a workflow that could cope with various challenges was proposed to establish an extendable all-in-one injection liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for analyzing these small molecular metabolites with high coverage. To obtain a qualified blank biological matrix for the preparation of standard curves and quality control samples, different absorption solvents, including activated carbon (AC), calcite (Cal) and montmorillonite (Mnt) were systematically evaluated for efficient absorption of endogenous substances with minimum residue. We also firstly proposed a "Collision Energy Defect (CED)" strategy to solve the huge difference of mass signal strength caused by different properties and concentrations of 11 NTs and 17 AAs. The quantitative results were validated by LC-MS/MS. Sensitivity, accuracy, and recovery meeting generally accepted bioanalytic guidelines were observed in a concentration span of at least 100 to 500 times for each analyte. Then the temporal changes of intracerebral and peripheral NTs and AAs in ischemic stroke model and sham operated rats were successfully produced and compared using the described method. All these results suggested that the currently developed assay was powerful enough to simultaneously monitor a large panel of endogenous small molecule metabolites, which was expected to be widely used in the research of various diseases mediated by NTs and AAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2020.461867DOI Listing
February 2021

Comparative analysis of constitutes and metabolites for traditional Chinese medicine using IDA and SWATH data acquisition modes on LC-Q-TOF MS.

J Pharm Anal 2020 Dec 19;10(6):588-596. Epub 2019 Nov 19.

Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, PR China.

Identification of components and metabolites of traditional Chinese medicines (TCMs) employing liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS) techniques with information-dependent acquisition (IDA) approaches is increasingly frequent. A current drawback of IDA-MS is that the complexity of a sample might prevent important compounds from being triggered in IDA settings. Sequential window acquisition of all theoretical fragment-ion spectra (SWATH) is a data-independent acquisition (DIA) method where the instrument deterministically fragments all precursor ions within the predefined range in a systematic and unbiased fashion. Herein, the superiority of SWATH on the detection of TCMs' components was firstly investigated by comparing the detection efficiency of SWATH-MS and IDA-MS data acquisition modes, and was used as a mode TCM. After optimizing the setting parameters of SWATH, rolling collision energy (CE) and variable Q1 isolation windows were found to be more efficient for identification than the fixed CE and fixed Q1 isolation window. More importantly, the qualitative efficiency of SWATH-MS on was found significantly higher than that of IDA-MS data acquisition. In IDA mode, 18 kinds of were detected in . A total of 47 were detected when SWATH-MS was used under rolling CE and flexible Q1 isolation window modes. Besides, 26 metabolites of were identified in rat plasma, and their metabolic pathways could be deduced as decarbonylation, oxidization, reduction, methylation, and glucuronidation according to their fragmental ions acquired in SWATH-MS mode. Thus, SWATH-MS data acquisition could provide more comprehensive information for the component and metabolite identification for TCMs than IDA-MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpha.2019.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775849PMC
December 2020

Predictors of death within 6 months of stroke onset: A model with Barthel index, platelet/lymphocyte ratio and serum albumin.

Nurs Open 2020 Dec 30. Epub 2020 Dec 30.

Nursing Division of the Department of Neurology, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.

Aims: To develop and internally validate a nomogram to predict the risk of death within 6 months of onset of stroke in Chinese. Identifying risk factors with potentially direct effects on the nomogram will improve the quality of risk assessment and help nurses implement preventive measures based on patient-specific risk factors.

Design: A retrospective study.

Methods: We performed a least absolute shrinkage and selection operator (LASSO) regression modelling and multivariate logistic regression analysis to establish a prediction model of death risk in stroke patients within 6 months of onset. LASSO and time-dependent Cox regression models were further used to analyse the 6-month survival of stroke patients. Data were collected from 21 October 2013-6 May 2019.

Results: The independent predictors of the nomogram were Barthel index (odds ratio (OR) = 0.980, 95% confidence interval (CI) = 0.961-0.998, p = .03), platelet/lymphocyte ratio (OR = 1.005, 95% CI = 1.000-1.010, p = .04) and serum albumin (OR = 0.854, 95% CI = 0.774-0.931, p < .01). This model showed good discrimination and consistency, and its discrimination evaluation C-statistic was 0.879 in the training set and 0.891 in the internal validation set. The DCA indicated that the nomogram had a higher overall net benefit over most of the threshold probability range. The time-dependent Cox regression model established the impact of the time effect of the age variable on survival time.

Conclusions: Our results identified three predictors of death within 6 months of stroke in Chinese. These predictors can be used as risk assessment indicators to help caregivers performing clinical nursing work, and in clinical practice, it is suggested that nurses should evaluate the self-care ability of stroke patients in detail. The constructed nomogram can help identify patients at high risk of death within 6 months, so that intervention can be performed as early as possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nop2.754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046075PMC
December 2020

Overexpression of Soybean-Derived Lunasin in Wheat and Assessment of Its Anti-Proliferative Activity in Colorectal Cancer HT-29 Cells.

Int J Mol Sci 2020 Dec 16;21(24). Epub 2020 Dec 16.

Institute of Crop Science, Chinese Academy of Agricultural Sciences, No. 80 South Xueyuan Road, Haidian, Beijing 100081, China.

Lunasin is a soybean-derived peptide that exhibits anticancer bioactivity in different cancer cells and has been identified in different plants. However, recent studies revealed through molecular and chemical analyses that lunasin was absent in wheat and other cereals. In this study, the soybean-derived lunasin was cloned into pCAMBIA3300 and we transferred the expression vector into wheat via an -mediated transformation. The identification of transgenic wheat was detected by polymerase chain reaction, Western blot analysis, and ultra-performance liquid chromatography with tandem mass spectrometry. An enzyme-linked immunosorbent assay showed that lunasin content in transgenic wheat L32-3, L32-6, and L33-1 was 308.63, 436.78, and 349.07 µg/g, respectively, while lunasin was not detected in wild-type wheat. Lunasin enrichment from transgenic wheat displayed an increased anti-proliferative activity compared with peptide enrichment from wild-type wheat in HT-29 cells. Moreover, the results of a real-time quantitative polymerase chain reaction showed a significant elevation in p21, Bax, and caspase-3 expression, while Bcl-2 was significantly downregulated. In conclusion, soybean-derived lunasin was successfully expressed in wheat via -mediated transformation and may exert anti-proliferative activity by regulating the apoptosis pathway in HT-29 cells, which provides an effective approach to compensate for the absence of lunasin in wheat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21249594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767187PMC
December 2020

Protoporphyrin IX and verteporfin potently inhibit SARS-CoV-2 infection and in a mouse model expressing human ACE2.

Sci Bull (Beijing) 2021 May 9;66(9):925-936. Epub 2020 Dec 9.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai 200032, China.

The SARS-CoV-2 infection is spreading rapidly worldwide. Efficacious antiviral therapeutics against SARS-CoV-2 is urgently needed. Here, we discovered that protoporphyrin IX (PpIX) and verteporfin, two Food and Drug Administration (FDA)-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 μmol/L and 0.31 μmol/L, respectively, and their EC50 values of reduction of viral RNA were at nanomolar concentrations. The selectivity indices of PpIX and verteporfin were 952.74 and 368.93, respectively, suggesting a broad margin of safety. Importantly, PpIX and verteporfin prevented SARS-CoV-2 infection in mice adenovirally transduced with human angiotensin-converting enzyme 2 (ACE2). The compounds, sharing a porphyrin ring structure, were shown to bind viral receptor ACE2 and interfere with the interaction between ACE2 and the receptor-binding domain of viral S protein. Our study suggests that PpIX and verteporfin are potent antiviral agents against SARS-CoV-2 infection and sheds new light on developing novel chemoprophylaxis and chemotherapy against SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scib.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724564PMC
May 2021

Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists.

Eur J Med Chem 2021 Feb 19;211:113013. Epub 2020 Nov 19.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 ZhanghengRoad, Pudong, Shanghai, 201203, China. Electronic address:

The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2020.113013DOI Listing
February 2021

Development and validation of a real-time artificial intelligence-assisted system for detecting early gastric cancer: A multicentre retrospective diagnostic study.

EBioMedicine 2020 Dec 27;62:103146. Epub 2020 Nov 27.

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. Electronic address:

Background: We aimed to develop and validate a real-time deep convolutional neural networks (DCNNs) system for detecting early gastric cancer (EGC).

Methods: All 45,240 endoscopic images from 1364 patients were divided into a training dataset (35823 images from 1085 patients) and a validation dataset (9417 images from 279 patients). Another 1514 images from three other hospitals were used as external validation. We compared the diagnostic performance of the DCNN system with endoscopists, and then evaluated the performance of endoscopists with or without referring to the system. Thereafter, we evaluated the diagnostic ability of the DCNN system in video streams. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and Cohen's kappa coefficient were measured to assess the detection performance.

Finding: The DCNN system showed good performance in EGC detection in validation datasets, with accuracy (85.1%-91.2%), sensitivity (85.9%-95.5%), specificity (81.7%-90.3%), and AUC (0.887-0.940). The DCNN system showed better diagnostic performance than endoscopists and improved the performance of endoscopists. The DCNN system was able to process oesophagogastroduodenoscopy (OGD) video streams to detect EGC lesions in real time.

Interpretation: We developed a real-time DCNN system for EGC detection with high accuracy and stability. Multicentre prospective validation is needed to acquire high-level evidence for its clinical application.

Funding: This work was supported by the National Natural Science Foundation of China (grant nos. 81672935 and 81871947), Jiangsu Clinical Medical Center of Digestive System Diseases and Gastrointestinal Cancer (grant no. YXZXB2016002), and Nanjing Science and Technology Development Foundation (grant no. 2017sb332019).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.103146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708824PMC
December 2020

mA Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1.

Front Oncol 2020 29;10:553045. Epub 2020 Sep 29.

Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

N6-methyladenosine (mA) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that mA modification and mA RNA methylation regulators were involved in cancer progression. However, the mA level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of mA regulators using The Cancer Genome Atlas data and found 14 of 19 mA regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of mA regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of mA and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of mA and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.553045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550530PMC
September 2020

Dietary supplementation of Huangshan Maofeng green tea preventing hypertension of older C57BL/6 mice induced by desoxycorticosterone acetate and salt.

J Nutr Biochem 2021 02 17;88:108530. Epub 2020 Oct 17.

State Key Laboratory of Tea Plant Biology and Utilization, School of Tea and Food Sciences and Technology, Anhui Agricultural University, Hefei, China. Electronic address:

Senile hypertension affects the life quality of aged population. Dietary intervention plays a pivotal role in the prevention of hypertension. There are few reports concerning the effects and mechanisms of green tea supplementation preventing age related hypertension. The current study investigated the effect and mechanism of dietary supplement of Huangshan Maofeng green tea (HSMF) on prevention of hypertension induced by deoxycorticosterone acetate (DOCA) and salt in old C57BL/6 mice. Our results showed that HSMF dose-dependently prevented the increase of systolic blood pressure and diastolic blood pressure induced by DOCA plus salt (DS) at 51-week-old mice. And HSMF significantly reduced the agonists' stimulated contraction of mesenteric arteries isolated from the old mice. The expression of vasoconstrictor genes and inflammatory cytokines in aorta were suppressed observably by HSMF supplementation compared with DS group. The protein expression of PKCα in the aorta was dose-dependently decreased by HSMF compared to DS group. The phosphorylation level of MYPT1, CPI-17and MLC was also restrained by HSMF in the aorta. Furthermore, HSMF protected kidney by maintaining integrity of glomeruli and tubules and remarkably decreased the NGAL level in plasma. HSMF also suppressed the kidney inflammation by decreasing inflammatory cytokines expression and the macrophage infiltration. Our results proved that dietary supplement of HSMF remarkably improved the vascular functions and protected kidney injury, and thus prevented hypertension induced by DS in older C57BL/6 mice. Our data indicated that the dietary supplement of HSMF may potentially be used as a food additive for preventing hypertension for aged people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jnutbio.2020.108530DOI Listing
February 2021

Metabolite Profiling and Transcriptome Analysis Revealed the Chemical Contributions of Tea Trichomes to Tea Flavors and Tea Plant Defenses.

J Agric Food Chem 2020 Oct 9;68(41):11389-11401. Epub 2020 Sep 9.

State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China.

Tea trichomes contain special flavor-determining metabolites; however, little is known about how and why tea trichomes produce them. Integrated metabolite and transcriptome profiling on tea trichomes in comparison with that on leaves showed that trichomes contribute to tea plant defense and tea flavor and nutritional quality. These unicellular, nonglandular, and unbranched tea trichomes produce a wide array of tea characteristic metabolites, such as UV-protective flavonoids, insect-toxic caffeine, herbivore-defensive volatiles, and theanine, as evidenced by the expression of whole sets of genes involved in different metabolic pathways. Both dry and fresh trichomes contain several volatiles and flavonols that were not found or at much low levels in trichome-removed leaves, including benzoic acid derivatives, lipid oxidation derivatives, and monoterpene derivatives. Trichomes also specifically expressed many disease signaling genes and various antiherbivore or antiabiotic peptides. Trichomes are one of the domestication traits in tea plants. Tea trichomes contribute to tea plant defenses and tea flavors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c04075DOI Listing
October 2020

Effect of pyriproxyfen exposure on cocooning and gene expression in the silk gland of Bombyx mori (Linnaeus, 1758).

Ecotoxicol Environ Saf 2020 Oct 4;202:110914. Epub 2020 Jul 4.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu, 212018, China; Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang, Jiangsu, 212018, China. Electronic address:

Bombyx mori(Linnaeus, 1758) is an important economical insect, and the sericulture is a flourishing industry in many developing countries. Pyriproxyfen, a juvenile hormone pesticide, is often applied to cultivations widely in the world, and its exposure often resulted in silk yield reduction and non-cocooning. However, the effect of pyriproxyfen exposure on cocooning and gene expression level in the silk gland of B. mori has not been studied yet, and this study focused on the above issues. The result indicated that pyriproxyfen exposure can lead to silk gland injury, reduction of silk yield and cocooning rate. Furthermore, the expression levels of silk protein synthesis related genes were down regulated significantly. The same change trends were shown between PI3K/Akt and CncC/Keap1 pathway, which is the expressions of key genes can be elevated by pyriproxyfen exposure. In addition, the activity of detoxification enzymes (P450, GST and CarE) and the expression levels of detoxification genes were elevated after pyriproxyfen exposure, suggesting that detoxification enzymes may play an important role in detoxification of pyriproxyfen in silk gland. These results provided possible clues to the silk gland injury and gene transcriptional level changes in silkworm after pyriproxyfen exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2020.110914DOI Listing
October 2020

Multiomics Profiling Reveals Protective Function of Lignans against Acetaminophen-Induced Hepatotoxicity.

Drug Metab Dispos 2020 10 27;48(10):1092-1103. Epub 2020 Jul 27.

Key Laboratory of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P.R. China (C.Y., H.G., Y.S., D.K., T.Y., C.L., H.H., Y.D., H.W., K.H., L.X., G.W., Y.L.) and Department of Geriatric Oncology, First Affiliated Hospital of Nanjing Medical University (Jiangsu People's Hospital), Nanjing, P.R. China (Q.D.)

The action principles of traditional Chinese medicines (TCMs) feature multiactive components, multitarget sites, and weak combination with action targets. In the present study, we performed an integrated analysis of metabonomics, proteomics, and lipidomics to establish a scientific research system on the underlying mechanism of TCMs, and lignan extract (SLE) was selected as a model TCM. In metabonomics, several metabolic pathways were found to mediate the liver injury induced by acetaminophen (APAP), and SLE could regulate the disorder of lipid metabolism. The proteomic study further proved that the hepatoprotective effect of SLE was closely related to the regulation of lipid metabolism. Indeed, the results of lipidomics demonstrated that SLE dosing has an obvious callback effect on APAP-induced lipidic profile shift. The contents of 25 diglycerides (DAGs) and 21 triglycerides (TAGs) were enhanced significantly by APAP-induced liver injury, which could further induce liver injury and inflammatory response by upregulating protein kinase C (PKC, PKC, PKC, and PKC). The upregulated lipids and PKCs could be reversed to the normal level by SLE dosing. More importantly, phosphatidic acid phosphatase, fatty acid transport protein 5, and diacylglycerol acyltransferase 2 were proved to be positively associated with the regulation of DAGs and TAGs. SIGNIFICANCE STATEMENT: Integrated multiomics was first used to reveal the mechanism of APAP-induced acute liver failure (ALF) and the hepatoprotective role of SLE. The results showed that the ALF caused by APAP was closely related to lipid regulation and that SLE dosing could exert a hepatoprotective role by reducing intrahepatic diglyceride and triglyceride levels. Our research can not only promote the application of multicomponent technology in the study of the mechanism of traditional Chinese medicines but also provide an effective approach for the prevention and treatment of ALF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/dmd.120.000083DOI Listing
October 2020

Effects of pyriproxyfen exposure on immune signaling pathway and transcription of detoxification enzyme genes in fat body of silkworm, Bombyx mori.

Pestic Biochem Physiol 2020 Sep 2;168:104621. Epub 2020 Jun 2.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212018, China; Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang, Jiangsu 212018, China. Electronic address:

Sericulture is a very important and flourishing industry in developing countries. Bombyx mori is a kind of important and well-studied economic insects in the whole world. In China, applying of pyriproxyfen pesticide often resulted in non-cocooning and silk yield reduction. However, the effects of pyriproxyfen exposure on immune signaling pathway in fat body of silkworm has not been reported yet now. In the present study, we found that the growth and development of silkworm were significantly affected by pyriproxyfen exposure and the fat body tissues were injured after treatment. It was also showed that the expressions of key genes of PI3K/Akt and CncC/Keap1 pathway can be elevated at 24-96 h after pyriproxyfen exposure. Furtherly, the relative expression levels of detoxification enzyme genes and the activities of detoxification enzymes were both increased by pyriproxyfen exposure. These results provided comprehensive view of fat body injury and gene expression changes in silkworm after pyriproxyfen exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pestbp.2020.104621DOI Listing
September 2020

Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists.

Eur J Med Chem 2020 Sep 5;202:112536. Epub 2020 Jul 5.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China. Electronic address:

GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76% inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1, exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2020.112536DOI Listing
September 2020

Antihypertensive effect of quinoa protein under simulated gastrointestinal digestion and peptide characterization.

J Sci Food Agric 2020 Dec 29;100(15):5569-5576. Epub 2020 Jul 29.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

Background: Quinoa protein is a potential source of bioactive peptides. Although some studies have demonstrated its angiotensin converting enzyme (ACE) inhibitory properties, research into its in vivo effect on blood-pressure regulation and peptide characterization remains limited.

Results: Quinoa protein hydrolyzate (QPH) was prepared by simulated gastrointestinal digestion. QPH lowered the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive model rats (SHRs) from 2 h to10 h after oral administration, effectively controlling blood pressure in these SHRs. An in vitro study showed that QPH is capable of inhibiting ACE activity. This was attributed to the activity of a number of low-molecular-weight peptides. With relatively high scores predicted by PeptideRanker, three promising bioactive peptides, FHPFPR, NWFPLPR, and NIFRPF, were further studied and their ACE-inhibition effects were confirmed with IC values of 34.92, 16.77, and 32.40 μM, respectively. A molecular docking study provided insights into the binding of ACE with peptides, and revealed that the presence of specific amino acids in the peptide sequence (Pro, Phe, and Arg at the C-terminal, and Asn at the N-terminal) could contribute to the interaction between ACE and peptides.

Conclusion: These results demonstrated the potential of QPH for the management of hypertension, which indicates that it could be a good candidate for inclusion in functional foods to control high blood pressure. © 2020 Society of Chemical Industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jsfa.10609DOI Listing
December 2020

Pharmacokinetics of T0901317 in mouse serum and tissues using a validated UFLC-IT-TOF/MS method.

J Pharm Biomed Anal 2020 Sep 15;189:113420. Epub 2020 Jun 15.

Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China; Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

T0901317, a liver X receptors (LXRs) agonist with high-affinity, is widely used to explore the functions of LXRs in various diseases such as atherosclerosis and Alzheimer's disease. However, there is currently little information available about the pharmacokinetics (PK) behavior of T0901317. Here we established a novel ultrafast liquid chromatography-high resolution mass spectrometry method to quantify the concentration of T0901317 in serum, liver, and brain. The chromatographic separation was attained on a C18 (2.1 × 100 mm, 1.8 μm) column using acetonitrile and 0.1 % of formic acid in water as mobile phase operated in gradient elution mode. The mass detection was carried out using negative ions m/z 479.9809 and 322.0882 for T0901317 and internal standard, respectively. The proposed method was fully validated according to the FDA guidelines, and it generally provides good results in terms of linearity (r > 0.99), precision (RSD < 18 % and 12 % for LLOQ and other QC levels, respectively), accuracy (between 92.30 % and 108.16 %), and matrix effect (between 86.56 % and 113.81 %). We then for the first time determined and computed the PK parameters of T0901317 in mouse after intraperitoneal administration of a 20 mg/kg dosage. The peak times (T) in serum, liver, and brain were 1.5, 1.5, and 4 h, respectively, while the half-lives (t) were 4.9, 3.3, and 4.5 h, respectively. Taken together, our results provide a significant choice to study the PK property of T0901317, from which the design of the dosing and sampling protocols of LXRs receptor-antagonist experiments employing T0901317 can also benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2020.113420DOI Listing
September 2020

Emerging role of RNA methyltransferase METTL3 in gastrointestinal cancer.

J Hematol Oncol 2020 05 19;13(1):57. Epub 2020 May 19.

Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.

Gastrointestinal cancer, the most common solid tumor, has a poor prognosis. With the development of high-throughput sequencing and detection technology, recent studies have suggested that many chemical modifications of human RNA are involved in the development of human diseases, including cancer. mA, the most abundant modification, was revealed to participate in a series of aspects of cancer progression. Recent evidence has shown that methyltransferase-like 3 (METTL3), the first identified and a critical methyltransferase, catalyzes mA methylation on mRNA or non-coding RNA in mammals, affecting RNA metabolism. Abnormal mA levels caused by METTL3 have been reported to be involved in different aspects of cancer development, including proliferation, apoptosis, and metastasis. In this review, we will shed light on recent findings regarding the biological function of METTL3 in gastrointestinal cancer and discuss future research directions and potential clinical applications of METTL3 for gastrointestinal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13045-020-00895-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238608PMC
May 2020

Efficient Photooxidation of Sulfides with Amidated Alloxazines as Heavy-atom-free Photosensitizers.

ACS Omega 2020 May 28;5(18):10586-10595. Epub 2020 Apr 28.

Institut für Physikalische und Theoretische Chemie, Universität Regensburg, Universitätsstr. 31, Regensburg 93053, Germany.

Photooxidation utilizing visible light, especially with naturally abundant O as the oxygen source, has been well-accepted as a sustainable and efficient procedure in organic synthesis. To ensure the intersystem crossing and triplet quantum yield for efficient photosensitization, we prepared amidated alloxazines (AAs) and investigated their photophysical properties and performance as heavy-atom-free triplet photosensitizers and compared with those of flavin (FL) and riboflavin tetraacetate (RFTA). Because of the difference in the framework structure of AAs and FL and the introduction of carbonyl moiety, the absorption of FL at ∼450 nm is blue-shifted to ∼380 nm and weakened (ε = 8.7 × 10 for FL to ∼6.8 × 10 M cm), but the absorption at ∼340 nm is red-shifted to ∼350 nm and enhanced by ∼50% (from ε = 6.4 × 10 for FL to ∼9.9 × 10 M cm) in AAs. The intersystem crossing rates from the S to T are also enhanced in these AAs derivatives, while the fluorescence quantum yield decreases from ∼30 to ∼7% for FL and AAs, respectively, making the triplet excited state lifetime and the singlet oxygen quantum yield of AAs at least comparable to those of FL and RFTA. We examined the performance of these heave-atom-free chromophores in the photooxidation of sulfides to afford sulfoxides. In accordance with the prolonged triplet excited state lifetime and enhanced triplet quantum yield, 2-5-fold performance enhancements were observed for AAs in the photooxidation of sulfides with respect to FL. We proposed that the key reactive oxygen species of AA-sensitized photooxidation are singlet oxygen and superoxide radical anion based on mechanistic investigations. The research highlights the superior performance of AAs in photocatalysis and would be helpful to rationalize the design of efficient heavy-atom-free organic photocatalysts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.0c01087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227068PMC
May 2020

Novel dipeptidyl peptidase-IV and angiotensin-I-converting enzyme inhibitory peptides released from quinoa protein by in silico proteolysis.

Food Sci Nutr 2020 Mar 27;8(3):1415-1422. Epub 2020 Jan 27.

Institute of Crop Science Chinese Academy of Agricultural Sciences Beijing China.

Quinoa protein has been paid more and more attention because of its nutritional properties and beneficial effects. With the development of bioinformatics, bioactive peptide database and computer-assisted simulation provide an efficient and time-saving method for the theoretical estimation of potential bioactivities of protein. Therefore, the potential of quinoa protein sequences for releasing bioactive peptides was evaluated using the BIOPEP database, which revealed that quinoa protein, especially globulin, is a potential source of peptides with dipeptidyl peptidase-IV (DPP-IV) and angiotensin-I-converting enzyme (ACE) inhibitory activities. Three plant proteases, namely papain, ficin, and stem bromelain, were employed for the in silico proteolysis of quinoa protein. Furthermore, four tripeptides (MAF, NMF, HPF, and MCG) were screened as novel promising bioactive peptides by PeptideRanker. The bioactivities of selected peptides were confirmed using chemical synthesis and in vitro assay. The present work suggests that quinoa protein can serve as a good source of bioactive peptides, and in silico approach can provide theoretical assistance for investigation and production of functional peptides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/fsn3.1423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063354PMC
March 2020

Regulation of E2F Transcription Factor 3 by microRNA-152 Modulates Gastric Cancer Invasion and Metastasis.

Cancer Manag Res 2020 14;12:1187-1197. Epub 2020 Feb 14.

Department of Gastroenterology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing 210008, People's Republic of China.

Background: The transcription factor, E2F transcription factor 3 (E2F3), has been proved to modulate metastasis in multiple human cancers. The present study was aimed to expound the function and specific mechanism of E2F3 in gastric cancer (GC) progression.

Materials And Methods: The expression of E2F3, microRNA-152 (miR-152) and PLK1 (polo-like kinase 1) in GC cell lines was detected by quantitative RT-PCR and Western blot. The roles of E2F3 and miR-152 in GC metastasis were classified using gain-of-function and loss-of-function assays. The miRNAs directly targeting E2F3 were identified by bioinformatics analysis and luciferase reporter experiment. Chromatin immunoprecipitation was carried out to reveal the correlation between E2F3 and PLK1.

Results: E2F3 expression was frequently up-regulated in GC tissues, and its high expression might imply poor prognosis. Downregulation of E2F3 restrained GC migration and invasion in vitro and in vivo. Interestingly, we proved that miR-152 was an upstream regulator of E2F3. Moreover, miR-152 reduced E2F3 expression by directly targeting its 3'-UTR, and then modulated GC metastasis via polo-like kinase 1 (PLK1) mediated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signals.

Conclusion: E2F3 plays a crucial role in GC progression and the newly discovered miR-152/E2F3/PLK1 axis provides a new underlying target for therapy of metastasis in GC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S239752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034297PMC
February 2020

Ginsenoside Rb1 exerts neuroprotective effects through regulation of abundance and GABA receptor expression.

J Ginseng Res 2020 Jan 19;44(1):86-95. Epub 2018 Sep 19.

Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure.

Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora.

Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1.

Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of () increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with (1 × 10 CFU) by gavage 15 d before I/R surgery. Both Rb1 and upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and .

Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating and GABA receptors rather than through direct distribution to the target sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgr.2018.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033341PMC
January 2020

Encapsulation of Flavin Cofactor within a Manganese Porphyrin-Based Metal-Organic Polyhedron for Reductive Dioxygen Activation.

Inorg Chem 2020 Mar 14;59(5):2636-2640. Epub 2020 Feb 14.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. China.

Encapsulation of flavin mononucleotide (FMN) in a porphyrinatomanganese(III)-based cubic cage allowed the fast reduction of manganese(III) porphyrin in the presence of nicotinamide adenine dinucleotide (NADH). This supramolecular system was capable of efficiently activating dioxygen and catalyzing the oxidation of benzyl alcohol. Control experiments suggested that the close proximity between FMN and manganese(III) porphyrins forced by the host-guest interaction might benefit the electron-transfer process from the FMN cofactor to the metal centers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.9b03430DOI Listing
March 2020

Overexpression of the bioactive lunasin peptide in soybean and evaluation of its anti-inflammatory and anti-cancer activities in vitro.

J Biosci Bioeng 2020 Apr 26;129(4):395-404. Epub 2019 Nov 26.

Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, No. 80 South Xueyuan Road, Haidian District, Beijing 100081, People's Republic of China. Electronic address:

Lunasin, a bioactive peptide with a variety of physiological functions, was overexpressed in soybean to generate a transgenic soybean. Polymerase chain reaction (PCR) analysis suggested that lunasin was successfully inserted into the soybean genome, and three transgenic lines, L12, L43, and L45, were selected for further study. Lunasin expression was characterized in the lines by Western blot and ultra-performance liquid chromatography with tandem mass spectrometry. Enzyme-linked immunosorbent assay showed that lunasin content in L12, L43, and L45 lines was 1.47 mg g, 1.32 mg g and 1.98 mg g, respectively; these values were significantly higher than that in wild-type soybean (0.94 mg g). Lunasin enrichments from transgenic soybean (LET) exhibited stronger DPPH, ABTS, and oxygen radical scavenging activity than lunasin enrichments from wild-type soybean (LEW). Further, LET presented superior anti-inflammatory activity on lipopolysaccharide-induced macrophage cells compared to LEW, and it significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines including interleukin-1 and -6. Moreover, LET showed higher anti-proliferation activity on MDA-MB-231 cells than LEW. Immunofluorescence staining showed that LET could internalize into NIH-3T3 cells, and localize in the nucleus. In conclusion, it is feasible and efficient to produce lunasin through a transgenic soybean expression system. Lunasin overexpressing soybean could be consumed as a functional food in the diets of patients with cancer and obesity in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiosc.2019.11.001DOI Listing
April 2020

Insights into the Authentic Active Ingredients and Action Sites of Oral Exogenous Glutathione in the Treatment of Ischemic Brain Injury Based on Pharmacokinetic-Pharmacodynamic Studies.

Drug Metab Dispos 2020 01 8;48(1):52-62. Epub 2019 Nov 8.

Key Laboratory of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University (C.C., B.S., T.Y., H.W., K.H., L.X., G.W., Y.L.), and Department of Geriatric Oncology, First Affiliated Hospital of Nanjing Medical University (Jiangsu People's Hospital (Q.D.), Nanjing, P.R. China

Glutathione (GSH) has been reported to be closely related to various diseases of the central nervous system, yet its authentic active ingredients and action sites remain unclear. In the present study, oral exogenous GSH significantly alleviated ischemic brain injury, but this result was inconsistent with its low bioavailability and blood-brain barrier (BBB) permeability. To ascertain the exposure of GSH-derived ingredients, including GSH, cysteine (CYS), glutamate (Glu), glycine (GLY), CYS-GLY, and -glutamylcysteine (-GC) were systematically studied both in vitro and in vivo. The outcomes demonstrated that oral GSH not only increases the GSH and CYS levels in rat striatum and cortex, but it also can decrease the rise of intracerebral Glu concentration caused by ischemia/reperfusion surgery. Then the influence of GSH on the BBB was investigated via measuring IgG leakage, intracerebral endotoxin, and tight-junction proteins. All indicators showed that GSH dosing can repair the destroyed BBB. Oral GSH greatly enhances the exposure of GSH, CYS, CYS-GLY, and -GC in rat duodenum, jejunum, ileum, and colon. Accumulating evidence reveals a close link between brain injury and gastrointestinal dysfunction. Our findings further suggest that oral GSH significantly improves intestinal inflammatory damage and barrier disruptions. In conclusion, oral GSH can have a direct therapeutic role in brain injury by stabilizing intracerebral levels of GSH, CYS, and Glu. It can also play an indirect therapeutic role by enhancing the intestinal exposure of GSH, CYS, CYS-GLY, and -GC and improving intestinal barrier disruptions. SIGNIFICANCE STATEMENT: The authentic active ingredients and action sites of exogenous glutathione (GSH) in the treatment of ischemic brain injury are unclear. We have shown that oral exogenous GSH not only stabilizes intracerebral levels of GSH, cysteine (CYS), and glutamate (Glu) to act directly on brain injury, but it can also exert an indirect therapeutic role by improving intestinal barrier disruptions. These findings have great significance for revealing the therapeutic effect of GSH on ischemic brain injury and for promoting its further development and clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/dmd.119.089458DOI Listing
January 2020

Effect of extruded adzuki bean flour on the quality and α-glucosidase inhibitory activity of Chinese steamed bread.

Food Sci Nutr 2019 Oct 22;7(10):3244-3252. Epub 2019 Aug 22.

Institute of Crop Sciences Chinese Academy of Agricultural Sciences Beijing China.

In order to improve the commercial and nutritional quality of Chinese steamed bread (CSB), effect of extruded adzuki bean flour (EABF) substitution (10%, 20%, 30%, and 40%) for wheat flour on the quality properties of blended flour and CSB was studied. Results showed that the development time, stability time, and farinograph quality number of blended flours were decreased with EABF addition, although water absorption and softening degree were increased. Pasting properties of them were also degraded with the addition. EABF substitution lowered the lightness and strengthened the hardness of CSB. The sensory evaluation total scores of CSB were both improved with 10% and 20% EABF addition, because slight red color of them was favored by the panelist. Nutritional analysis showed that CSB with 10% and 20% EABF ranked higher protein and essential amino acids content than that of WF-CSB, especially lysine and threonine. Addition of EABF contributed to the superior α-glucosidase inhibitory activity of protein isolated from CSBs. α-Glucosidase inhibition rate of CSB made from EABF (39.88%) was improved nearly five times compared with that of WF. It might be concluded that CSB with addition of 10% and 20% EABF could be used as a nutritional and healthy staple food.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/fsn3.1181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804769PMC
October 2019