Publications by authors named "Haiyu Zhao"

57 Publications

Goat : Indel Mutation Detection, Association Analysis With Litter Size and Alternative Splicing Variant Expression.

Front Genet 2021 21;12:648256. Epub 2021 May 21.

School of Life Sciences, Lanzhou University, Lanzhou, China.

A-kinase anchoring protein 12 () plays key roles in male germ cells and female ovarian granulosa cells, whereas its influence on livestock litter size remains unclear. Herein we detected the genetic variants of gene and their effects on litter size as well as alternative splicing variants expression in Shaanbei white cashmere (SBWC) goats, aiming at exploring theoretical basis for goat molecular breeding. We identified two Insertion/deletions (Indels) (7- and 13-bp) within the gene. Statistical analyses demonstrated that the 13-bp indel mutation in the 3' UTR was significantly associated with litter size ( = 1,019), and the carriers with DD genotypes presented lower litter sizes compared with other carriers ( < 0.01). Bioinformatics analysis predicted that this 13-bp deletion sequence could bind to the seed region of miR-181, which has been documented to suppress porcine reproductive and respiratory syndrome virus (PRRSV) infection by targeting PRRSV receptor CD163 and affect the pig litter size. Therefore, luciferase assay for this 13-bp indel binding with miRNA-181 was performed, and the luciferase activity of pcDNA-miR-181-13bp-Deletion-allele vector was significantly lower than that of the pcDNA-miR-181-13bp-Insertion-allele vector ( < 0.05), suggesting the reduced binding capability with miR-181 in DD genotype. Given that alternative spliced variants and their expression considerably account for the Indel genetic effects on phenotypic traits, we therefore detected the expression of the alternative spliced variants in different tissues and identified that exhibited the highest expression levels in testis tissues. Interestingly, the expression levels of homozygote DD carriers were significantly lower than that of individuals with heterozygote ID, in both testis and ovarian tissues ( < 0.05), which is consistent with the effect of the 13-bp deletion on the reduced litter size. Taken together, our results here suggest that this 13-bp indel mutation within goat might be utilized as a novel molecular marker for improving litter size in goat breeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.648256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176285PMC
May 2021

Fertility-Associated Polymorphism within Bovine and Its Significant Correlations with Ovarian and Luteal Traits.

Animals (Basel) 2021 May 28;11(6). Epub 2021 May 28.

School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, China.

There is an urgent need to improve bovine fertility, and molecular marker-assisted selection (MAS) can accelerate this process. Genome-wide association studies suggest that might affect fertility in bovines. As a member of the integrins family, ITGβ5 can bind to the extracellular matrix and mediate various cellular processes. In our study, primers spanning six potential insertion/deletion (indel) polymorphisms within the gene were designed and 696 ovary samples from different individuals, the vast majority not in oestrum were collected for genetic variation detection. A deletion locus, rs522759246, namely P1-D, was found to be polymorphic. The allele D frequency was 0.152 and the polymorphism information content (PIC) value was 0.224, indicating a low-degree PIC. This locus did not follow the Hardy-Weinberg equilibrium ( = 1.200E-23). Importantly, associations between P1-D and ovarian morphological traits were established. Polymorphisms of this locus had significant correlations with ovarian width ( = 0.015). The corpus luteum is also linked to fertility and P1-D was significantly correlated with corpus luteum diameter ( = 0.005). In conclusion, an indel mutation within the bovine gene was identified, which was significantly associated with several ovarian and luteal traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani11061579DOI Listing
May 2021

Huanglian Jiedu Decoction in the Treatment of the Traditional Chinese Medicine Syndrome "Shanghuo"-An Intervention Study.

Front Pharmacol 2021 30;12:616318. Epub 2021 Apr 30.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

"Shanghuo" ("excessive internal heat") is caused by exuberant endogenous fire, which does not have a comprehensive and systematic traditional Chinese medicine theory. In previous study, we had evaluated the therapeutic effect of Huanglian Jiedu Decoction (HLJDD) (granule) on patients with "Shanghuo", however, the specific mechanism was not clear, which need further exploration. To explain its intervention mechanism, we select 57 patients with oral diseases caused by "Shanghuo" and 20 health volunteers to divide into oral disease group, HLJDD intervention group and healthy control group. Firstly, biochemical indicators before and after HLJDD intervention are detected, such as inflammatory factors, oxidative stress factors and energy metabolism factors. The results exhibit that HLJDD significantly decreases indicators succinic acid ( < 0.001); tumor necrosis factor-alpha, adenosine triphosphate, citric acid ( < 0.01); interleukin-8 (IL-8), 4-hydroxynonenal, pyruvic acid, lactate dehydrogenase ( < 0.05). The levels of glucocorticoid, adrenocorticotropic hormone ( < 0.01); lactic acid, IL-4, IL-10 ( < 0.05) significantly increase after HLJDD intervention. In addition, we adopt multi-omics analysis approach to investigate the potential biomarkers. Nontargeted metabolomics demonstrate that the levels of 7 differential metabolites approach that in the healthy control group after HLJDD intervention, which are correlated with histidine metabolism, beta-alanine metabolism and sphingolipid metabolism through metabolic pathway analysis. Targeted lipidomics results and receiver operating characteristic curve analysis show that 13 differential lipids are identified in the three groups mainly focuse on lysophosphatidylcholines, lysophosphatidylethanolamines. Finally, the network associations of those differential biomarkers reveal the regulation of adenosine triphosphate and tricarboxylic acid cycle play essential role in the therapeutic effect mechanism of HLJDD in "Shanghuo". The study has laid the foundation for further revealing the mechanism and finding clinical biomarkers related to "Shanghuo".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.616318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120301PMC
April 2021

A multi-herb-combined remedy to overcome hyper-inflammatory response by reprogramming transcription factor profile and shaping monocyte subsets.

Pharmacol Res 2021 Apr 17;169:105617. Epub 2021 Apr 17.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China. Electronic address:

Traditional Chinese multi-herb-combined prescriptions usually show better performance than a single agent since a group of effective compounds interfere multiple disease-relevant targets simultaneously. Huang-Lian-Jie-Du decoction is a remedy made of four herbs that are widely used to treat oral ulcers, gingivitis, and periodontitis. However, the active ingredients and underlying mechanisms are not clear. To address these questions, we prepared a water extract solution of Huang-Lian-Jie-Du decoction (HLJDD), called it as WEH (Water Extract Solution of HLJDD), and used it to treat LPS-induced systemic inflammation in mice. We observed that WEH attenuated inflammatory responses including reducing production of cytokines, chemokines and interferons (IFNs), further attenuating emergency myelopoiesis, and preventing mice septic lethality. Upon LPS stimulation, mice pretreated with WEH increased circulating Ly6C patrolling and splenic Ly6C inflammatory monocytes. The acute myelopoiesis related transcriptional factor profile was rearranged by WEH. Mechanistically we confirmed that WEH interrupted LPS/TLR4/CD14 signaling-mediated downstream signaling pathways through its nine principal ingredients, which blocked LPS stimulated divergent signaling cascades, such as activation of NF-κB, p38 MAPK, and ERK1/2. We conclude that the old remedy blunts LPS-induced "danger" signal recognition and transduction process at multiple sites. To translate our findings into clinical applications, we refined the crude extract into a pure multicomponent drug by directly mixing these nine chemical entities, which completely reproduced the effect of protecting mice from lethal septic shock. Finally, we reduced a large number of compounds within a multi-herb water extract to seven-chemical combination that exhibited superior therapeutic efficacy compared with WEH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105617DOI Listing
April 2021

Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer's disease progression based on the "brain-gut" axis through multiple integrated omics.

Alzheimers Res Ther 2021 02 12;13(1):44. Epub 2021 Feb 12.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

Background: In recent years, excellent results have suggested an association between the "brain-gut" axis and Alzheimer's disease (AD) progression, yet the role of the "brain-gut" axis in AD pathogenesis still remains obscure. Herein, we provided a potential link between the central and peripheral neuroinflammatory disorders in AD progression.

Methods: The Morris water maze (MWM) test, immunohistochemistry, ELISA, ProcartaPlex Multiplex immunoassay, multiple LC-MS/MS methods, and the V3-V4 regions of 16S rRNA genes were applied to explore potential biomarkers.

Results: In Tg-APP/PS1 mice, gut dysbiosis and lipid metabolism were highly associated with AD-like neuroinflammation. The combination of inflammatory factors (IL-6 and INF-γ), phosphatidylcholines (PCs) and SCFA-producing bacteria were expected to be early diagnostic biomarkers for AD. Huanglian Jiedu decoction (HLJDD) suppressed gut dysbiosis and the associated Aβ accumulation, harnessed neuroinflammation and reversed cognitive impairment.

Conclusion: Together, our findings highlighted the roles of neuroinflammation induced by gut dysbiosis and lipid metabolism disorder in AD progression. This integrated metabolomics approach showed its potential to understand the complex mechanisms of HLJDD in the treatment of AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-021-00779-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881564PMC
February 2021

The impact of malnutrition on atrial fibrillation recurrence post ablation.

Nutr Metab Cardiovasc Dis 2021 03 10;31(3):834-840. Epub 2020 Dec 10.

Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address:

Background And Aims: Both malnutrition and atrial fibrillation (AF) are the major health problems in modern society. Only a few studies focused on the relationship between malnutrition and recurrence of atrial arrhythmias post AF ablation (AF recurrence), which used body mass index (BMI) as nutrition assessment tool. However, BMI can't credibly reflect body composition and has limitation in patients with water-sodium retention. In this study, we used controlling nutritional status score (CONUT score) and geriatric nutritional risk index (GNRI) to identify the malnutrition patients and explored the effect of malnutrition on AF recurrence.

Methods And Results: This retrospective study included 246 patients who underwent AF ablation. During a median 11-month follow-up, 77 patients (31.3%) experienced AF recurrence. The recurrence group had higher CONUT score (2.3 ± 1.5 vs. 0.9 ± 1.0, P < 0.001) and lower GNRI (99.9 ± 7.6 vs. 103.9 ± 5.6, P < 0.001). After balancing the traditional risk factors, both CONUT score (OR: 2.614, 95%CI: 1.831-3.731, P < 0.001) and GNRI (OR: 0.884, 95%CI: 0.828-0.944, P < 0.001) were the independent predictors for AF recurrence. Pre-ablation CONUT score ≥1 and GNRI≥95.66 are indicative of AF recurrence. Adding CONUT score or GNRI to the base prediction model for AF recurrence significantly improved the discrimination and calibration. However, adding BMI to the base prediction model did not improve the model performance.

Conclusions: CONUT score and GNRI are ideal tools to evaluate the nutrition status of AF patients. Undernourished patients are more likely to suffer from AF recurrence. Improving nutrition status may be a potential target for reducing the postoperative recurrence rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2020.12.003DOI Listing
March 2021

Regulation of ddb2 expression in blind cavefish and zebrafish reveals plasticity in the control of sunlight-induced DNA damage repair.

PLoS Genet 2021 02 5;17(2):e1009356. Epub 2021 Feb 5.

Institute of Biological and Chemical Systems, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.

We have gained considerable insight into the mechanisms which recognize and repair DNA damage, but how they adapt to extreme environmental challenges remains poorly understood. Cavefish have proven to be fascinating models for exploring the evolution of DNA repair in the complete absence of UV-induced DNA damage and light. We have previously revealed that the Somalian cavefish Phreatichthys andruzzii, lacks photoreactivation repair via the loss of light, UV and ROS-induced photolyase gene transcription mediated by D-box enhancer elements. Here, we explore whether other systems repairing UV-induced DNA damage have been similarly affected in this cavefish model. By performing a comparative study using P. andruzzii and the surface-dwelling zebrafish, we provide evidence for a conservation of sunlight-regulated Nucleotide Excision Repair (NER). Specifically, the expression of the ddb2 gene which encodes a key NER recognition factor is robustly induced following exposure to light, UV and oxidative stress in both species. As in the case of the photolyase genes, D-boxes in the ddb2 promoter are sufficient to induce transcription in zebrafish. Interestingly, despite the loss of D-box-regulated photolyase gene expression in P. andruzzii, the D-box is required for ddb2 induction by visible light and oxidative stress in cavefish. However, in the cavefish ddb2 gene this D-box-mediated induction requires cooperation with an adjacent, highly conserved E2F element. Furthermore, while in zebrafish UV-induced ddb2 expression results from transcriptional activation accompanied by stabilization of the ddb2 mRNA, in P. andruzzii UV induces ddb2 expression exclusively via an increase in mRNA stability. Thus, we reveal plasticity in the transcriptional and post transcriptional mechanisms regulating the repair of sunlight-induced DNA damage under long-term environmental challenges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891740PMC
February 2021

Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in for ameliorating heart failure.

PeerJ 2020 30;8:e10107. Epub 2020 Oct 30.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.

(VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components-main HF putative targets-main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.10107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605218PMC
October 2020

[Success rate of one-stop procedure for atrial fibrillation ablation and its impact on cardiac function: a propensity-matched study].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Oct;40(10):1415-1421

Department of Cardiovascular Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Objective: To investigate the effect of the combination of atrial fibrillation (AF) ablation and left atrial appendage closure (LAAC) on cardiac function and the success rate of AF ablation.

Methods: We retrospectively analyzed the data of 56 patients with AF undergoing a one-stop procedure for AF ablation and LAAC in our hospital between May, 2015 and May, 2019. Propensity score matching (PSM) at the ratio of 1:1 was used to select 56 control patients undergoing AF ablation at high risk of stroke, for matching with the hybrid procedure group. The perioperative complications, thromboembolic events, recurrence of atrial arrhythmia and cardiac function were compared between the groups.

Results: The two groups of patients were comparable for age, gender, BMI, duration and type of AF, concomitant diseases, CHA2DS2-VASc and HAS-BLED scores ( > 0.05). The incidence of complications did not differ significantly between the hybrid procedure group and AF ablation group (17.9% 12.5%, =0.430). Compared with the control patients with AF ablation alone, the patients undergoing the hybrid procedure had a lowered incidence of thromboembolic events, but the difference was not statistically significant (1.8% 3.6%, =1.000). The hybrid procedure did not improve the success rate of AF ablation (OR: 1.338, 95%: 0.451-3.973, = 0.600) but significantly improved the cardiac function parameters including NT-pro BNP (945.3±1401.6 pg/mL 1520.7±2089.1 pg/mL, =0.010), LVEF[(60.8±7.0)% (58.6±7.8)%, =0.044], and left atrial diameter (43.9±7.5 mm 45.6±6.3 mm, =0.076); but the improvement of cardiac function was more obvious in the control patients undergoing AF ablation alone ( < 0.039).

Conclusions: The combination of AF ablation and LAAC is safe but does not improve the success rate of AF ablation. The one-stop procedure can improve cardiac function of the patients, but AF ablation alone can achieve better improvement of cardiac function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12122/j.issn.1673-4254.2020.10.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606248PMC
October 2020

Hellebrigenin anti-pancreatic cancer effects based on apoptosis and autophage.

PeerJ 2020 8;8:e9011. Epub 2020 May 8.

Institute of Chinese Materia Medica, China Academy of Chinese Medicine Sciences, Beijing, China.

Hellebrigenin is a natural product found in the toad skin secretions and plants of Urginea, including Hellebores and Kalanchoe genera. It has been shown to be active against Leishmania chagasi promastigotes and Trypanosoma cruzi trypomastigotes and also reported to play an anti-tumor effect on several cancer cell lines in vitro, including pancreatic cancer. This study is aimed to investigate the effects of Hellebrigenin on pancreatic carcinoma cells, SW1990 and BxPC-3 in vitro and its molecular mechanism involved in antitumor activities. Our results showed that Hellebrigenin effectively inhibited the proliferation of SW1990 and BxPC-3 cells in dose- and time-dependent manner. Flow cytometry results showed that Hellebrigenin induced the G0/G1 arrest in both of SW1990 and BxPC-3 cells and promoted cell early apoptosis and autophagy according to morphological observation. Immunofluorescence staining results further confirmed that cell apoptosis and autophagy also increased upon the Hellebrigenin treatment. Moreover, higher dose of Hellebrigenin further increased the cell apoptosis rate while decrease the mitochondrial membrane potential 24 h after treatment. The autophagy rate increased 48 h after treatment with significant difference ( < 0.05). Western blot analysis showed that the expression of caspase 3, 7, cleaved caspase 7, Atg 12, LC3 proteins were increased in SW1990 cell after treatment with Hellebrigenin. In addition, increasing expression of caspase 3, 7, 9, PARP, cleaved caspase 3, 7, 9, PARP, the sub basic protein of the PI3K family, Beclin-1, LC 3, Atg 3, 5, 12, 16 L were also observed after BxPC-3 cells treated with Hellebrigenin. In summary, this study reported for the first time that Hellebrigenin effectively induced autophagy and apoptosis especially the early apoptosis in SW1990 and BxPC-3 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.9011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213012PMC
May 2020

Marsdenia tenacissima extract promotes gefitinib accumulation in tumor tissues of lung cancer xenograft mice via inhibiting ABCG2 activity.

J Ethnopharmacol 2020 Jun 20;255:112770. Epub 2020 Mar 20.

Department of Integration of Chinese and Western Medicine, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, China. Electronic address:

Ethnopharmacological Relevance: Marsdenia tenacissima extract (MTE) is the water-soluble part of a traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn, and is commercially available in China for treating cancers. MTE has been revealed to be effective in improving gefitinib efficacy in treating non-small cell lung cancer (NSCLC). However, the mechanisms remain to be defined.

Aim Of The Study: To determine the effects of MTE on gefitinib metabolism and accumulation in vivo, and to explore the underlying mechanisms.

Materials And Methods: MTE or vehicle were intraperitoneally administrated to the H1975 xenograft model, followed by intragastric administration of gefitinib 12 h later. Mice plasma, tumors and liver tissues were harvested for further analysis. Hoechst 33342, a specific substrate of ATP Binding Cassette Subfamily G Member 2 (ABCG2), was used to determine the effects of MTE on activities of ABCG2 in tumor cells.

Results: A higher concentration of plasma gefitinib was detected in MTE-treated mice at 24 h after delivery of gefitinib, however, it became insignificant in another 24 h. By contrast, gefitinib levels were continuously higher in MTE-pretreated mice tumor tissues at 12-48 h post gefitinib administration. MTE suppressed plasma levels of gefitinib metabolites (M523595, M608236 and M537194) in the first 24 h after gefitinib delivery, and inhibited activities of liver CYP2D6 and CYP3A4 at early stage (within 6 h) after gefitinib treatment. Strikingly, the activities of ABCG2, the primary drug transporter for gefitinib, were significantly inhibited by MTE in H1975 lung cancer cells. Further, it was identified that tenacissoside H, but not tenacissoside I, may contribute to the ABCG2-suppressive effects of MTE.

Conclusions: MTE pretreatment temporarily elevated plasma concentrations of gefitinib via inhibiting CYP450 enzymes. Most importantly, MTE promoted gefitinib accumulation in tumor tissues in a long-lasting manner via decreasing activities of ABCG2, a drug transporter responsible for gefitinib efflux.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.112770DOI Listing
June 2020

Metabolomics study of different parts of licorice from different geographical origins and their anti-inflammatory activities.

J Sep Sci 2020 Apr 26;43(8):1593-1602. Epub 2020 Feb 26.

School of Pharmacy, Lanzhou University, Lanzhou, P. R. China.

Glycyrrhiza uralensis Fisch., known as licorice, is one of the most famous traditional Chinese medicines. In this study, we perform a metabolome analysis using liquid chromatography-tandem mass spectrometry to assign bioactive components in different parts of licorice from different geographical origins in Gansu province of China. Sixteen potential biomarkers of taproots from different geographical origins were annotated, such as glycycoumarin, gancaonin Z, licoricone, and dihydroxy kanzonol H mainly exist in the sample of Jiuquan; neoliquiritin, 6'-acetylliquiritin, licochalcone B, isolicoflavonol, glycyrol, and methylated uralenin mainly exist in Glycyrrhiza uralensis from Lanzhou; gancaonin L, uralenin, and glycybridin I mainly exist in licorice from Wuwei for the first time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jssc.201901013DOI Listing
April 2020

Arenobufagin Inhibits the Phosphatidylinositol 3-kinase/Protein Kinase B/Mammalian Target of Rapamycin Pathway and Induces Apoptosis and Autophagy in Pancreatic Cancer Cells.

Pancreas 2020 02;49(2):261-272

From the Quality Standards, Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.

Objective: The aim of the study was to investigate the effects of arenobufagin on pancreatic carcinoma in vitro and in vivo and its molecular mechanism.

Methods: The proliferation of pancreatic cancer cells was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Transmission electron microscopy was used to observe the formation of autophagic vacuoles after arenobufagin treatment. Hoechst 33258 and monodansylcadaverine fluorescence staining were performed to evaluate cell apoptosis and autophagy. Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and JC-1 staining assays were used to evaluate apoptosis-related changes. Reverse-transcription polymerase chain reaction and western blotting were carried out to examine the expression of apoptosis- and autophagy-related markers after arenobufagin treatment. A tumor xenograft nude mouse model was established to evaluate arenobufagin efficacy in vivo.

Results: Arenobufagin effectively inhibited the proliferation of SW1990 and BxPC3 cells and induced cell arrest, apoptosis, and autophagy. Arenobufagin upregulated the expression of apoptotic- and autophagy-related proteins while downregulated the expression of phosphatidylinositol 3-kinase family proteins. Furthermore, arenobufagin also exerted inhibitory effects on tumor growth in xenograft nude mice.

Conclusions: Arenobufagin inhibits tumor growth in vivo and in vitro. The mechanism underlying arenobufagin action may involve induction of autophagy and apoptosis through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001471DOI Listing
February 2020

Effects of Huang-Lian-Jie-Du Decoction on Oxidative Stress and AMPK-SIRT1 Pathway in Alzheimer's Disease Rat.

Evid Based Complement Alternat Med 2020 2;2020:6212907. Epub 2020 Jan 2.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Huang-Lian-Jie-Du Decoction (HLJDD), traditional Chinese medicine (TCM), is proven to have ameliorative effects on learning and memory deficits of Alzheimer's disease (AD). The current study aims to reveal the underlying mechanism of HLJDD in the treatment of AD by simultaneous determination on the regulation of HLJDD on oxidative stress, neurotransmitters, and AMPK-SIRT1 pathway in AD. AD model rat was successfully established by injection of D-galactose and A-ibotenic acid. Morris Water Maze (MWM) test was used to evaluate the success of AD modelling. On this basis, an advanced technique with UPLC-QqQ MS/MS was built up and applied to determine the levels of 8 neurotransmitters in rat plasma. Significant alternation in methionine, glutamine, and tryptophan was observed in AD rats' plasma after the administration of HLJDD, relative to the model group. Meanwhile, HLJDD could upregulate the levels of SOD, GSH-Px, AMPK, and SIRT1 and downregulate the content of MDA in the peripheral system of the AD rats. The underlying therapeutic mechanism of HLJDD for the treatment of AD was associated with alleviating oxidation stress, inflammation, neurotransmitters, and energy metabolism. These data provide solid foundation for the potential use of HLJDD to treat AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/6212907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959142PMC
January 2020

DNA methylation pattern of the goat gene and its effects on milk performance.

Arch Anim Breed 2019 20;62(1):59-68. Epub 2019 Feb 20.

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.

Paired-like homeodomain transcription factor 1 () is a pivotal gene in the hypothalamic-pituitary-adrenal axis, which is a well-known pathway affecting lactation performance. The aim of this study was to analyze the DNA methylation profile of the gene and its relevance to milk performance in Xinong Saanen dairy goats; thus, potential epigenetic markers of lactation performance were identified. A total of 267 goat blood samples were divided into "low" and "high" groups according to two milk traits: the average milk yield (AMY) and the average milk density (AMD). One CpG island in the 3 -flanking region of the gene was identified as being related to milk performance. Fisher's exact test demonstrated that the methylation rates of the overall CpG island and the 3rd and 12th CpG-dinucleotide loci in the blood were significantly associated with the AMY, and the overall methylation rate of the high AMY group was relative hypomethylation compared with the low AMY group. The overall methylation rates of this CpG island in mammary gland tissue from dry and lactation periods again exhibited a significant difference: the lactation period showed relative hypomethylation compared with the dry period. Bioinformatic transcription factor binding site prediction identified some lactation performance related transcription factors in this CpG island, such as CTCF, STAT, SMAD, CDEF, SP1, and KLFS. Briefly, overall methylation changes of the CpG island in the gene are relevant to lactation performance, which will be valuable for future studies and epigenetic marker-assisted selection (eMAS) in the breeding of goats with respect to lactation performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5194/aab-62-59-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852879PMC
February 2019

The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics.

Metabolomics 2019 11 25;15(12):153. Epub 2019 Nov 25.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Introduction: Formononetin (MBHS) and its glycosylated derivative ononin (MBHG), as the major isoflavones, have exhibited the anti-inflammatory impacts on the lipopolysaccharide (LPS)-induced inflammation. Although various researches have focused on interpreting the pharmaceutical activities of MBHG and MBHS, the molecular mechanisms in zebrafish models are still unclear.

Objective: The purpose of the present work is to investigate the molecular mechanisms of the anti-inflammatory effects of MGHG and MBHS based on lipidomics and targeted transcriptomics.

Methods: UHPLC-MS was applied for the lipid analyses and RT-PCR was adopted for the mRNA analyses, and the results of different groups were compared for exploring the significantly changed lipids and mRNAs.

Results: The results of lipidomics revealed that phosphatidylcholines (PCs) were drastically down-regulated in the MBHG or MBHS treated LPS-induced inflammatory zebrafish models. Besides, MBHS can also decrease the levels of triacylglycerols (TAGs). For the targeted transcriptomics analyses, 4 cytokines (TNF-α, IL-1β, IL-6 and IFN-γ) and 3 mRNA (JNK1, ERK1 and p38a) involved in the MAPK pathway were down-regulated and IL-10 was up-regulated under the treatment of MBHG or MBHS.

Conclusion: Combining the results of lipidomics and targeted transcriptomics, we indicated that MBHG and MBHS exerted potent anti-inflammatory effects on the LPS-induced zebrafish models through the MyD88 or TRIF MAPK/ERK and MAPK/JNK pathways and the glycerophospholipid, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerolipid metabolisms. Our results provided new insights into the anti-inflammatory mechanisms of MBHG or MBHS and supplied an effective method to interpret the pharmacological mechanisms of drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11306-019-1614-2DOI Listing
November 2019

The Disturbance of Hepatic and Serous Lipids in Aristolochic Acid Ι Induced Rats for Hepatotoxicity Using Lipidomics Approach.

Molecules 2019 Oct 17;24(20). Epub 2019 Oct 17.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Aristolochic acid I (AAI) was regarded as the major toxic component of aristolochic acid (AA). In addition to aristolochic acid nephropathy (AAN), liver cancers induced by AAI has aroused increasing attention recently. In this paper, the discovery of diagnostic biomarkers for AAI-induced liver injury has been studied, especially for the lipid markers. From the histopathological characteristics, the injury was observed clearly in the liver apart from the kidney after 30 mg/kg of AAΙ treatment for one week, while the lesion alleviated after AAΙ discontinuance. The serum biochemical indexes were manifested to the normal tendency after AAΙ discontinuance for two weeks. According to the evaluation of pathology slices and serum biochemical indexes, they indicated that the hepatotoxicity induced by AAΙ was reversible to some extent. A total of 44 lipid markers were identified in the liver, as well as 59 in the serum. Twenty-six common lipid markers were observed in both serum and liver. Furthermore, nine out of 26 lipids exhibited the excellent diagnostic ability to differentiate the control group from the AAΙ group and AAΙ discontinuance group with high sensitivity and specificity. The changed lipid markers might serve as characteristics to explain the mechanisms of pathogenesis and progression in hepatotoxicity induced by AAΙ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24203745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832582PMC
October 2019

Anti-inflammatory and Regulatory Effects of Huanglian Jiedu Decoction on Lipid Homeostasis and the TLR4/MyD88 Signaling Pathway in LPS-Induced Zebrafish.

Front Physiol 2019 26;10:1241. Epub 2019 Sep 26.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Huanglian Jiedu decoction (HLJDD) has been used in the clinical treatment of inflammatory conditions. To clarify the mechanism of its comprehensive anti-inflammatory activities, the correlation between lipid homeostasis and the TLR4/MyD88 signaling pathway in zebrafish was established in the present study. In the lipopolysaccharide (LPS)-induced inflammation in zebrafish model, RT-PCR assays of five inflammatory cytokines and six targeted proteins were measured. Lipidomics analysis was conducted to identify potential lipid markers. HLJDD displayed strong efficacies, with a 61% anti-inflammatory rate at a concentration of 50 μg/mL. The activation of TLR4/MyD88 played an essential role in the inflammatory process. All protein indexes in the HLJDD group exhibited a tendency to reverse back to normal levels. Moreover, 79 potential pathological lipid biomarkers were identified. Compared with the model group, 61 therapeutic lipid biomarkers were detected in HLJDD group. Most perturbations of lipids were ameliorated by HLJDD, mainly through the glycerophospholipid metabolic pathway. In the visual network study, the corresponding lipoproteins such as PLA, SGMS, and SMDP were observed as important intermediates between lipid homeostasis and the TLR4/MyD88 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.01241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775191PMC
September 2019

Multiple cytotoxic effects of gamabufotalin against human glioblastoma cell line U-87.

Chem Biol Interact 2019 Dec 11;314:108849. Epub 2019 Oct 11.

Department of Applied Biochemistry, Tokyo University of Pharmacy & Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

To provide novel insight into approaches designed to combat glioblastoma, the molecular details of the cytotoxicity of gamabufotalin, were investigated in the human glioblastoma cell line U-87. A dose-dependent cytotoxicity was observed in the cells, whereas no detectable toxicity was confirmed in mouse primary astrocytes. LDH leakage was only observed in the cells treated with a relatively high concentration (>80 ng/ml). Downregulation of the expression levels of Aurora B, cdc25A, cdc25C, cdc2, Cyclin B1 and survivin, and upregulation of the expression level of p21 were observed in treated cells and occurred in parallel with G/M phase arrest. Treatment with gamabufotalin also downregulated the expression level of uPA, CA9, and upregulated the expression level of TIMP3, all of which are closely associated with invasion/metastasis. Autophagy induction was observed in the treated cells and the addition of wortmannin, a potent autophagy inhibitor, significantly rescued U-87 cells. These results indicate that gamabufotalin exhibits cytotoxicity against cancerous glial cells with high potency and selectivity through multiple cytotoxic signaling pathways. The activation of p38 MAPK pathway along with the upregulation of VEGF/VEGFR2 was observed in the treated cells, both of which are likely to be compensatory changes in response to gamabufotalin treatment. Intriguingly, a specific inhibitor of p38 MAPK enhanced the cytotoxicity of the drug, suggesting an important prosurvival role for p38 MAPK. We thus suggest that developing a new combination regimen of gamabufotalin plus a p38 MAPK inhibitor and/or inhibitors for VEGF/VEGFR could improve the efficacy of the drug, and may provide more therapeutic benefits to patients with glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2019.108849DOI Listing
December 2019

Pharmacokinetics of the Yougui pill in experimental autoimmune encephalomyelitis model rats and its pharmacological activity in vitro.

Drug Des Devel Ther 2019 16;13:2357-2370. Epub 2019 Jul 16.

School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, China.

Purpose: To determine the pharmacokinetic properties and pharmacological activity of the Yougui pill (YGP), which is a well-known Chinese medicine formula.

Methods: An ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry via electrospray ionization interface (UPLC-ESI-MS/MS) method was developed and validated for the simultaneous determination of several components in rat plasma. The method was then successfully applied to the pharmacokinetics of six bioactive components in experimental autoimmune encephalomyelitis (EAE) model rats after oral administration of YGP. The expression of cAMP response element binding protein (CREB) and growth-associated protein-43 (GAP-43) in SH-SY5Y cells treated with these six components, YGP extract, and YGP-containing serum were investigated to determine the pharmacodyamic material basis of YGP. Six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside, which were rapidly absorbed after administration in EAE model rats.

Results: The main pharmacokinetic parameters of six bioactive components were determined, and the constituents increased CREB and GAP-43 expressions in serum-deprived SH-SY5Y cells. The YGP-containing serum, six bioactive components, and YGP extract significantly increased the expression of both CREB and GAP-43 (<0.01), and there was no difference between the three groups.

Conclusion: The songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside were confirmed as the major bioactive components in YGP. The acquired data will be helpful for understanding the pharmacological and effective constituents of YGP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S203874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643060PMC
February 2020

The protection of indolealkylamines from LPS-induced inflammation in zebrafish.

J Ethnopharmacol 2019 Oct 26;243:112122. Epub 2019 Jul 26.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. Electronic address:

Ethnopharmacological Relevance: Toad skin came from Bufo bufo gargarizans Cantor and Bufo melanostictus Schneider. As the traditional Chinese medicine, it had the effect of clearing away heat and detoxification. In traditional applications, toad skin was often used for the treatment of cancer and inflammation. Total indolealkylamines (IAAs) from this medicine were proved the main compounds exert anti-inflammatory activity in our previous research.

Aim Of The Study: In the present study, we aimed to investigate the potential mechanism of anti-inflammatory activity of IAAs on LPS induced zebrafish.

Materials And Methods: LPS induced zebrafish was applicated as an in vivo inflammation model to clarify the structure-activity relationship of 4 major IAAs (N-methyl serotonin, bufotenine, dehydrobufotenine and bufothionine) from toad skin. Quantitative RT-PCR was applied to detect key cytokines and members of the MyD88-dependent signaling pathway. In addition, the targeted lipidomics was conducted to find out the potential biomarkers in the inflammatory zebrafish. Network pharmacology was used to unveil the main enzymes closely related to the target lipids.

Results: Our results showed that the anti-inflammatory activity of free IAAs (N-methyl serotonin, bufotenine and dehydrobufotenine) was more potent than that of combined IAAs (bufothionine). RT-PCR demonstrated that 4 IAAs exerted antiendotoxin inflammatory effect via suppressing the TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs signaling pathway. A total of 33 possible inflammatory biomarkers, including 14 SM, 6 Cer, 11 PC and 2 GlcCer, triggered by LPS were screened out. The levels of most of candidates could be regulated toward a normal level by IAAs, especially in N-methyl serotonin and dehydrobufotenine groups. Enzymes especially LBP, PLA, CERK, SMPD and SGMS were found closely associated with the regulation of most lipid markers.

Conclusions: Overall, the mechanism underlying the anti-inflammatory activity of IAAs probably attributed to their capability to suppress NF-κB and MAPKs inflammatory pathway. Meanwhile, IAAs could also interfere the metabolism of SM, Cer and PC probably by regulating LBP, PLA, CERK, SMPD and SGMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2019.112122DOI Listing
October 2019

Optimization of Ultrasonic-Assisted Extraction and Purification of Rhein from Pod Pulp.

Molecules 2019 May 26;24(10). Epub 2019 May 26.

Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4/1, A-8010 Graz, Austria.

Rhein is used as an active ingredient in laxatives in medicinal herbal products and is a chemical marker for quality control purposes. Thus, a simple and effective method for the optimized extraction of a high amount of rhein from the fruit pulp of was investigated using ultrasonic-assisted extraction (UAE). The response surface methodology was applied to find the most suitable parameters for optimizing the extraction process and to study the factors' relationships with each other. The best conditions for ultrasonic extraction were the application of 1:40 g/mL solid-to-liquid ratio and 10% EtOH-HO as a solvent at 75 °C for 40 min. This method was compared to a conventional decoction in two variations. In these experiments, it was confirmed that the UAE was more favorable than the decoction methods. The resulting crude extract was further purified by liquid-liquid extraction with a basic pH adjustment, followed by recrystallization. High-purity rhein was obtained by using chromatographic techniques and nuclear magnetic resonance spectroscopy. Therefore, this study suggests that UAE is an efficient alternative method for the extraction of rhein from pod pulp. The resulting optimized conditions can be applied as a useful tool for the large-scale industrial production of a rhein-rich plant extract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24102013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572533PMC
May 2019

Aqueous extract of Salvia miltiorrhiza Bunge-Radix Puerariae herb pair ameliorates diabetic vascular injury by inhibiting oxidative stress in streptozotocin-induced diabetic rats.

Food Chem Toxicol 2019 Jul 29;129:97-107. Epub 2019 Apr 29.

Medical College, Qingdao University, Qingdao, 266071, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China; Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi, 563003, China. Electronic address:

Vascular diabetic complications are the leading cause of mortality and morbidity for diabetes. The present study was designed to investigate the protective effect of herb pair Salvia miltiorrhiza Bunge-Radix Puerariae (DG) on diabetic vascular injury induced by streptozotocin. The protective effect of DG was determined by oral administration of DG (50 and 200 mg/kg) in rats and on high glucose (HG)-induced endothelial injury. DG showed no effect on body weight, fasting blood glucose (FBG) but decreased the serum levels of insulin, nitric oxide (NO), hydrogen peroxide (HO), malondialdehyde (MDA), soluble intercellular cell adhesion molecule-1 (s-ICAM-1) and vascular cell adhesion molecule-1 (s-VCAM-1), and increased superoxide dismutase (SOD) and catalase (CAT) levels. The pathological alterations of aorta was improved by DG. Furthermore, the increased expression of ICAM-1,VCAM-1, NOX2, and NOX4 in aorta were inhibited by DG. HG-induced endothelial ROS formation, ICAM-1,VCAM-1, NOX4 expression and monocyte-endothelial adhesion were dramatically suppressed by DG as well. In addition, both GKT137831, a NOX4 inhibitor, and PDTC, a NF-κB inhibitor, could significantly inhibited HG-induced ICAM-1, VCAM-1 expression and monocyte-endothelial adhesion. These results suggested that DG improved diabetic vascular injury possibly by reducing oxidative stress, which provides scientific evidence for the application of DG for diabetic vascular therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2019.04.018DOI Listing
July 2019

DIY Automated Feeding and Motion Recording System for the Analysis of Fish Behavior.

SLAS Technol 2019 08 23;24(4):394-398. Epub 2019 Apr 23.

2 Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen, Germany.

Fish species such as medaka or zebrafish are widely used as animal models to study physiology, disease development, and treatment efficacy. They are also used to study the rapidly growing field of behavior research, such as social interactions, anxiety, and the influence of environmental factors. Here we describe an automated experimental setup allowing the recording of general locomotor activity in combination with a food-on-demand system. It can simply be built with some basic electronic knowledge. Our setup enables the recording of locomotor and feeding activity of several fish for long-term studies, excluding disturbing external influences. A description of the automated recording system is given, as well as examples of recordings to illustrate its applicability for the study of fish behavior. The construction manual and operation instructions can be downloaded for free.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2472630319841412DOI Listing
August 2019

Simultaneous high-performance liquid chromatography with tandem mass spectrometry quantification of six bioactive components in rat plasma after oral administration of Yougui pill.

J Sep Sci 2019 May 28;42(10):1867-1877. Epub 2019 Mar 28.

School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing, P. R. China.

Yougui pills are a classic Chinese medicine that shows significant effects on nerve regeneration and neuroprotection in modern pharmacological studies. With a complex formula, Yougui pills have faced significant challenges in the fields of bioanalysis and pharmacokinetics in animals and human studies. In the present study, a specific and accurate high-performance liquid chromatography with tandem mass spectrometry method was developed and validated for the quantitative determination of the six bioactive components in rat plasma after oral administration of Yougui pills. Chromatographic separation was performed on a C18 column with a gradient elution system. Samples were analysed using positive ion mode with multiple reaction monitoring mode. The assay showed good linearity for all six bioactive components in the dynamic range of 0.50 to 50 ng/mL with acceptable intra- and inter-batch accuracy and precision. The lower limits of quantification were 0.50 ng/mL for all six bioactive components. The method was successfully applied to rat pharmacokinetics after oral administration of Yougui pills. All six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside, while some other target compounds were not detected, such as rhmannioside A, loganin, and cornuside I. After oral administration of Yougui pills at a dose of 2500 mg/kg, all six bioactive components were rapidly absorbed, resulting in t values less than 1 h and relative lower C values. The t values for songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside were calculated to be 2.62 ± 0.67, 2.11 ± 0.45, 1.94 ± 0.35, 1.88 ± 0.31, 2.07 ± 0.44, and 1.59 ± 0.30 h, which indicated that Yougui pills should be taken in multiple oral doses over a relatively short period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jssc.201800772DOI Listing
May 2019

Effects of genetic variations within goat gene on growth traits and mRNA expression.

Anim Biotechnol 2020 Apr 17;31(2):107-114. Epub 2019 Jan 17.

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

Paired-like homeodomain 2 (), a key gene in hypothalamic-pituitary-adrena axis, influences animal growth and development. The objective of this study was to identify the association of the functional genetic variations within goat gene with growth traits and mRNA expression levels. According to the reported single nucleotide polymorphisms (SNPs) information in Guanzhong dairy goat (GZDG), we identified genotypes of the known SNPs in Hainan black goat (HNBG). Association analysis uncovered that the SNPs of AC_000163: g.18117T > C, g.18161C > G and g.18353T > C loci were significantly associated with several growth traits (e.g., body height and body length) in HNBG and GZDG breeds. According to the quantitative real-time PCR assay, and ribosomal protein L19 () were the most stable expressed housekeeping genes in heart and skeletal muscle, respectively; meanwhile, glyceraldehyde-3-phosphate dehydrogenase () was the most stable expressed housekeeping gene in the other tissues. Based on the best housekeeping gene of varied tissues, we found the different genotypes of above loci were significantly associated with mRNA expression in heart, muscle and small intestine. Briefly, the genetic variants of goat associating with mRNA expression affected growth traits significantly, which would benefit for goat breeding in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10495398.2018.1551229DOI Listing
April 2020

Corrigendum to "Effect of on the Diuretic Function of : An Ascites Mouse Model".

Evid Based Complement Alternat Med 2018 16;2018:5171687. Epub 2018 Dec 16.

College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.

[This corrects the article DOI: 10.1155/2016/7620817.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/5171687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311286PMC
December 2018

Comparative Analysis of Hydrophilic Ingredients in Toad Skin and Toad Venom Using the UHPLC-HR-MS/MS and UPLC-QqQ-MS/MS Methods Together with the Anti-Inflammatory Evaluation of Indolealkylamines.

Molecules 2018 Dec 27;24(1). Epub 2018 Dec 27.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Toad skin and toad venom, as two kinds of Chinese medicine, are prepared from Cantor and Schneider. However, they display distinct properties in traditional application, and the hydrophilic ingredients are the possible distinguishing chemicals between them. In this work, 36 and 22 hydrophilic components were characterized from toad skin and venom, respectively, by UHPLC-HR-MS/MS, including amino acids, nucleosides, polypeptides, and indolealkylamines (IAAs). Among them, 15 compounds were unambiguously confirmed by comparison with standards. The CID-MS/MS fragmentation behaviors of seven indolealkylamine references were investigated to ascertain three types of structures. Subsequently, 11 high abundance contents of hydrophilic ingredients were determined from 11 batches of toad skin and 4 batches of toad venom by UPLC-QqQ-MS/MS. The quantitative results showed that the content of main IAAs in toad venom was much higher than in skin. In addition, the -methyl serotonin (free IAA), bufothionine (combined IAA), and total IAAs sample were selected for anti-inflammatory evaluation in lipopolysaccharide (LPS) stimulated zebrafish embryo models. The obvious anti-inflammatory activities of IAAs were observed, especially for the free IAAs. This study illustrated IAAs were the main distinct hydrophilic components that probably lead to the difference between toad skin and toad venom in traditional applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24010086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337282PMC
December 2018

Integrated Proteomics and Lipidomics Investigation of the Mechanism Underlying the Neuroprotective Effect of -benzylhexadecanamide.

Molecules 2018 Nov 9;23(11). Epub 2018 Nov 9.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Macamides are very important secondary metabolites produced by Walp, which possess multiple bioactivities, especially in the neuronal system. In a previous study, we observed that macamides exhibited excellent effects in the recovery of injured nerves after 1-methyl-4-phenylpyridinium (MPP⁺)-induced dopaminergic neuronal damage in zebrafish. However, the mechanism underlying this effect remains unclear. In the present study, we observed that -benzylhexadecanamide (XA), which is a typical constituent of macamides, improved the survival rate of neurons in vitro. We determined the concentration of neurotransmitters in MN9D cells and used it in conjunction with an integrated proteomics and lipidomics approach to investigate the mechanism underlying the neuroprotective effects of XA in an MPP⁺-induced neurodegeneration cell model using QqQ MS, Q-TOF MS, and Orbitrap MS. The statistical analysis of the results led to the identification of differentially-expressed biomarkers, including 11 proteins and 22 lipids, which may be responsible for the neuron-related activities of XA. All these potential biomarkers were closely related to the pathogenesis of neurodegenerative diseases, and their levels approached those in the normal group after treatment with XA. Furthermore, seven lipids, including five phosphatidylcholines, one lysophosphatidylcholine, and one phosphatidylethanolamine, were verified by a relative quantitative approach. Moreover, four proteins (Scarb2, Csnk2a2, Vti1b, and Bnip2) were validated by ELISA. The neurotransmitters taurine and norepinephrine, and the cholinergic constituents, correlated closely with the neuroprotective effects of XA. Finally, the protein⁻lipid interaction network was analyzed. Based on our results, the regulation of sphingolipid metabolism and mitochondrial function were determined to be the main mechanisms underlying the neuroprotective effect of XA. The present study should help us to better understand the multiple effects of macamides and their use in neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules23112929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278518PMC
November 2018

Modulation of DNA Repair Systems in Blind Cavefish during Evolution in Constant Darkness.

Curr Biol 2018 10 11;28(20):3229-3243.e4. Epub 2018 Oct 11.

Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany. Electronic address:

How the environment shapes the function and evolution of DNA repair systems is poorly understood. In a comparative study using zebrafish and the Somalian blind cavefish, Phreatichthys andruzzii, we reveal that during evolution for millions of years in continuous darkness, photoreactivation DNA repair function has been lost in P. andruzzii. We demonstrate that this loss results in part from loss-of-function mutations in pivotal DNA-repair genes. Specifically, C-terminal truncations in P. andruzzii DASH and 6-4 photolyase render these proteins predominantly cytoplasmic, with consequent loss in their functionality. In addition, we reveal a general absence of light-, UV-, and ROS-induced expression of P. andruzzii DNA-repair genes. This results from a loss of function of the D-box enhancer element, which coordinates and enhances DNA repair in response to sunlight. Our results point to P. andruzzii being the only species described, apart from placental mammals, that lacks the highly evolutionary conserved photoreactivation function. We predict that in the DNA repair systems of P. andruzzii, we may be witnessing the first stages in a process that previously occurred in the ancestors of placental mammals during the Mesozoic era.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2018.08.039DOI Listing
October 2018