Publications by authors named "Yitao Wang"

313 Publications

Protects against Diabetes-Associated Endothelial Dysfunction: Comparison between Ethanolic Extract and Total Saponin.

Oxid Med Cell Longev 2021 4;2021:4722797. Epub 2021 Sep 4.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.

Previous studies revealed a cardioprotective potential of to relieve acute myocardial infarction and focal cerebral ischemia-reperfusion. However, whether protects endothelial function in diabetes and the underlying mechanisms remain to be explored. contains several chemical components including saponins, which are commonly believed as the major bioactive ingredients. The present study was aimed to examine and compare the vaso-protective effects of the ethanolic extract of (PNE) and total saponin (PNS). Both aortas and carotid arteries were isolated from male C57BL/6J mice for treatment with risk factors (high glucose or tunicamycin) with and without the presence of PNS and PNE. Diabetic model was established by feeding the mice with a high-fat diet (45% kcal% fat) for 12 weeks, while PNS and PNE were administrated by oral gavage at 20 mg/kg/day for another 4 weeks. exposure to high glucose impaired acetylcholine-induced endothelium-dependent relaxations in mouse aortas, decreased phosphorylation of AMPK and eNOS, and induced endoplasmic reticulum (ER) stress and oxidative stress. These effects were reversed by cotreatment of PNS and PNE with PNS being more potent. Furthermore, the vaso-protective effects were abolished by Compound C (AMPK inhibitor). Chronic treatment with PNS and PNE improved endothelium-dependent relaxations and alleviated ER stress and oxidative stress in aortas from high-fat diet-induced obese mice. PNE was more effective to improve glucose sensitivity and normalize blood pressure in diabetic mice. The present results showed that PNS and PNE reduced ER stress and oxidative stress and, subsequently, improved endothelial function in diabetes through AMPK activation. This study provides new inspiration on the therapeutic potential of extract against vascular diseases associated with metabolic disorders.
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http://dx.doi.org/10.1155/2021/4722797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437594PMC
September 2021

Lentinan-Based Oral Nanoparticle Loaded Budesonide With Macrophage-Targeting Ability for Treatment of Ulcerative Colitis.

Front Bioeng Biotechnol 2021 27;9:702173. Epub 2021 Aug 27.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Ulcerative colitis (UC) is a global, chronic, and refractory disease. Corticosteroids are first-line drugs for the treatment of UC but also cause adverse side effects. Budesonide (BUD), a corticosteroid with relatively low side effects, has been approved by the Food and Drug Administration for use as enteric capsules (Entocort EC) for the treatment of inflammatory bowel disease (IBD). However, this formulation lacks specific targeting ability to UC lesions. Herein, we describe the development of an advanced macrophage-targeted oral lentinan (LNT)-based nanoparticles (NPs) loaded BUD for treatment of UC. Briefly, LNT was used as a food source and natural carrier to load BUD by a simple solvent evaporation method to form LNT/BUD-NPs. LNT showed good loading capacity with high encapsulation and loading efficiencies to BUD of approximately 92.19 and 9.58%, respectively. Evaluation of the gastric stability of LNT/BUD-NPs indicated that LNT could effectively protect BUD from gastric acid and digestive enzymes. The release behavior and transmission electron microscopy image of LNT/BUD-NPs in the intestinal content of mice confirmed that intestinal flora can promote BUD release from LNT. Moreover, evaluation of cellular uptake showed that LNT/BUD-NPs could specifically target macrophages and enhance their uptake rate the Dectin-1 receptor. In biodistribution studies, LNT/BUD-NPs were able to efficiently accumulate in the inflamed colon of mice. As expected, LNT/BUD-NPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, LNT/BUD-NPs have the advantages of good gastric stability, release mediated by mouse intestinal content, macrophage-targeting, and anti-UC effects. These advantages indicate LNT-based NPs are a promising oral drug delivery system for UC therapy.
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http://dx.doi.org/10.3389/fbioe.2021.702173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429481PMC
August 2021

The key issues and development strategy of Chinese Classical Formulas pharmaceutical preparations.

Chin Med 2021 Aug 4;16(1):70. Epub 2021 Aug 4.

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

It is well-known that Prof. Tu Youyou won the Nobel Prize in Physiology or Medicine in 2015 due to the research on artemisinin treating malaria, and this can be regarded as the milestone of modernization of Traditional medicine. This first Nobel Prize in Traditional Chinese medicine (TCM) has aroused profound impetus in the investigation of TCM and attracted global attention to the ancient books of TCM. Three new medicines for the treatment of COVID-19 derived from Chinese Classical Formula (, CCF) have been approved in 2021 due to their effectiveness for the treatment of COVID-19. This article introduced the research background of CCF pharmaceutical preparation (CCFPP), explained the ideas for the modernization of CCF and analyzed related issues involved in the development process of CCFPP, including the origin of medicinal materials, processing methods, dosages and the preparation process of CCF Material Reference. The strategy for industrialization was proposed in terms of the evaluation of the pharmaceutical properties, industrialization considerations, and clinical positioning of CCFPP. The key contents and requirements for the development CCFPP were also summarized according to the recently published registration guidance by the Center for Drug Evaluation in China. In addition, the safety issues of CCFPP were described, including the discussion on the non-clinical safety evaluation and analyzation on the international registration of Traditional herbal medicines. This article is aimed to provide references for enterprises, researchers, and relevant personnel of government departments that are engaged in the development of CCF to speed up the developing process of CCFPP.
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http://dx.doi.org/10.1186/s13020-021-00483-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334328PMC
August 2021

Notoginsenoside R1 intervenes degradation and redistribution of tight junctions to ameliorate blood-brain barrier permeability by Caveolin-1/MMP2/9 pathway after acute ischemic stroke.

Phytomedicine 2021 Sep 25;90:153660. Epub 2021 Jul 25.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China. Electronic address:

Background: The leakage of blood-brain barrier (BBB) is main pathophysiological change in acute stage of ischemic stroke, which not only deteriorates neurological function, but also increases the risk of hemorrhagic transformation after thrombolysis.

Purpose/study Design: This article investigates the efficacy of Notoginsenoside R1, an active ingredient of Panax notoginseng, on BBB permeability and explores related mechanisms after acute ischemic stroke.

Methods: In vivo, male Sprague-Dawley rats (260-280 g) were selected and randomly divided into 6 groups: sham group, model group, low, middle and high doses of Notoginsenoside R1 groups and positive drug Dl-3-n-Butylphthalide group. Except for sham group, rats were performed with permanent middle cerebral artery occlusion model in each group. Twelve hours later, rats were evaluated for Bederson neurological function, and BBB integrity by Evans blue leak imaging; Triphenyltetrazolium chloride staining was used to detect the volume of cerebral infarction. Frozen sections of rats' brain tissue were prepared for detection of MMPs activity in situ zymography. Peripheral tissue of cerebral infarction was collected and tested the expression of MMP2, 9 and tight junction proteins (zo1, claudin5, occludin) by western blot. In vitro, transwell endothelial barrier model was established by bEnd.3 cells. Oxygen glucose deprivation (OGD) was chosen to simulate the hypoxic environment. Suitable OGD stimulation time as well as Notoginsenoside R1 and Dl-3-n-Butylphthalide optimal dose concentrations were determined through transwell leakage and CCK8 assay. Furthermore, endothelial subcellular component proteins were extracted. The change of zo1, claudin5, occludin and caveolin1 was detected by western blot.

Results: Notoginsenoside R1 treatment significantly reduced BBB leakage and cerebral infarction volume, weakened neurological deficits in post-stroke rats. Moreover, it inhibited the activity of MMPs in infarcted cortex and striatum, down-regulated MMP2, 9 and up-regulated zo1 and claudin5 expressions in penumbra. In vitro, Notoginsenoside R1 treatment decreased OGD-induced endothelial barrier permeability, restored expressions of zo1, claudin5 on cellular membrane and cytoplasm, as well as mediated membrane redistribution of occludin and caveolin1 from actin cytoskeletal fraction.

Conclusions: Notoginsenoside R1 treatment attenuates BBB permeability, cerebral infarction volume and neurological impairments in rats with acute cerebral ischemia. The mechanisms might be related to intervening degradation and redistribution of zo1, caludin5 and occludin by caveolin1/ MMP2/9 pathway. More effects and mechanisms of Notoginsenoside R1 on rehabilitation of stroke are worthy to be explored in the future.
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http://dx.doi.org/10.1016/j.phymed.2021.153660DOI Listing
September 2021

B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2.

Oncogene 2021 Sep 27;40(37):5613-5625. Epub 2021 Jul 27.

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.

B-Myb is an important transcription factor that plays a critical role in gene expression regulation and tumorigenesis. However, its functional implication in colorectal cancer remains elusive. In this study, we found that B-Myb was significantly upregulated at both mRNA and protein levels in colorectal cancer samples compared to non-tumor counterparts. B-Myb overexpression accelerated cell proliferation, cell cycle progression and cell motility in colorectal cancer cells, and promoted tumor growth in orthotopic nude mouse models in vivo. In contrast, B-Myb depletion inhibited these malignant phenotypes. Mechanistic investigations revealed that E2F2 was a novel transcriptional target of B-Myb and is essential to B-Myb-induced malignant phenotypes. Notably, B-Myb and E2F2 exhibited positive expression correlation, and interacted with each other in colorectal cancer cells. In addition to their autoregulatory mechanisms, B-Myb and E2F2 can also directly transactivate each other, thus constituting consolidated reciprocal feed-forward transactivation loops. Moreover, both B-Myb and E2F2 are required for the activation of ERK and AKT signaling pathways in colorectal cancer cells. Taken together, our data clarified a critical role for B-Myb in colorectal cancer and unraveled an exquisite mutual collaboration and reciprocal cross regulation between B-Myb and E2F2 that contribute to the malignant progression of human colorectal cancer.
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http://dx.doi.org/10.1038/s41388-021-01961-9DOI Listing
September 2021

Quality Evaluation of Randomized Controlled Trials of Species: A Systematic Review.

Evid Based Complement Alternat Med 2021 1;2021:9989546. Epub 2021 Jul 1.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, China.

Background: is a worldwide used medicinal plant for its various medicinal functions, and the number of randomized controlled trials (RCTs) of is increasing in recent years. This study aims to evaluate the reporting quality and risk of bias of the current RCT reports of different species.

Methods: Six databases including Embase, PubMed, Web of Science, the Cochrane Library, ClinicalTrial.gov, and China National Knowledge Infrastructure were searched to identify RCTs that used as a single intervention and were published in English or Chinese from inception to December 2020. The Consolidated Standards of Reporting Trials (CONSORT) 2010 statement was used as the checklist for assessment, and a scoring system was applied to the evaluation of RCTs. Score 0 represents no reporting or inadequate reporting, and score 1 represents adequate reporting. The risk of bias of the included studies was also assessed using the Cochrane Risk of Bias tool.

Results: A total of 39 RCTs were included in this study, including 23 RCTs of (. ), 8 RCTs of (. ), and 8 RCTs of (. ). None of the included studies met all the CONSORT statement criteria, and the reporting quality of RCTs of the three species was all generally poor. Based on the risk of bias assessment, the majority of included studies were judged to have an unclear risk of bias in most domains due to inadequate reporting.

Conclusions: There is inadequate reporting among the included RCTs of different species, and RCTs of with higher reporting quality and better methodological quality are needed.
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http://dx.doi.org/10.1155/2021/9989546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266448PMC
July 2021

Coptisine Attenuates Diabetes-Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress.

Molecules 2021 Jul 11;26(14). Epub 2021 Jul 11.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.

Coptisine is the major bioactive protoberberine alkaloid found in Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.
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http://dx.doi.org/10.3390/molecules26144210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303502PMC
July 2021

Multifaceted role of phyto-derived polyphenols in nanodrug delivery systems.

Adv Drug Deliv Rev 2021 09 16;176:113870. Epub 2021 Jul 16.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address:

As naturally occurring bioactive products, several lines of evidence have shown the potential of polyphenols in the medical intervention of various diseases, including tumors, inflammatory diseases, and cardiovascular diseases. Notably, owing to the particular molecular structure, polyphenols can combine with proteins, metal ions, polymers, and nucleic acids providing better strategies for polyphenol-delivery strategies. This contributes to the inherent advantages of polyphenols as important functional components for other drug delivery strategies, e.g., protecting nanodrugs from oxidation as a protective layer, improving the physicochemical properties of carbohydrate polymer carriers, or being used to synthesize innovative functional delivery vehicles. Polyphenols have emerged as a multifaceted player in novel drug delivery systems, both as therapeutic agents delivered to intervene in disease progression and as essential components of drug carriers. Although an increasing number of studies have focused on polyphenol-based nanodrug delivery including epigallocatechin-3-gallate, curcumin, resveratrol, tannic acid, and polyphenol-related innovative preparations, these molecules are not without inherent shortcomings. The active biochemical characteristics of polyphenols constitute a prerequisite to their high-frequency use in drug delivery systems and likewise to provoke new challenges for the design and development of novel polyphenol drug delivery systems of improved efficacies. In this review, we focus on both the targeted delivery of polyphenols and the application of polyphenols as components of drug delivery carriers, and comprehensively elaborate on the application of polyphenols in new types of drug delivery systems. According to the different roles played by polyphenols in innovative drug delivery strategies, potential limitations and risks are discussed in detail including the influences on the physical and chemical properties of nanodrug delivery systems, and their influence on normal physiological functions inside the organism.
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http://dx.doi.org/10.1016/j.addr.2021.113870DOI Listing
September 2021

The Extracts of and from Oriental Medicinal Foods Regulate Inflammatory and Autophagic Pathways against Neural Injury after Ischemic Stroke.

Oxid Med Cell Longev 2021 26;2021:9663208. Epub 2021 Jun 26.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.

The study indicates inflammation and autophagy are closely related to neural apoptosis in the pathology of ischemic stroke. In the study, we investigate the effects and mechanisms of the extracts of and (AC) from oriental medicinal foods on inflammatory and autophagic pathways in rat permanent middle cerebral artery occlusion model. Three doses of AC extract were, respectively, administered for 7 days. It suggests that AC extract treatment ameliorated scores of motor and sensory functions and ratio of glucose utilization in thalamic lesions in a dose-dependent manner. Expression of Iba1 was decreased and CD206 was increased by immunofluorescence staining, western blotting results showed expressions of TLR4, phosphorylated-IKK and IB, nuclear P65, NLRP3, ASC, and Caspase-1 were downregulated, and Beclin 1 and LC3 II were upregulated. Low concentrations of TNF-, IL-1, and IL-6 were presented by ELISA assay. Additionally, caspase 8 and cleaved caspase-3 expressions and the number of TUNEL positive cells in ipsilateral hemisphere were decreased, while the ratio of Bcl-2/Bax was increased. Simultaneously, in LPS-induced BV2 cells, it showed nuclear P65 translocation and secretion of proinflammatory cytokines were suppressed by AC extract-contained cerebrospinal fluid, and its intervened effects were similar to TLR4 siRNA treatment. Our study demonstrates that AC extract treatment attenuates inflammatory response and elevates autophagy against neural apoptosis, which contributes to the improvement of neurological function poststroke. Therefore, AC extract may be a novel neuroprotective agent by regulation of inflammatory and autophagic pathways for ischemic stroke treatment.
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http://dx.doi.org/10.1155/2021/9663208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257381PMC
June 2021

A new strategy for quality evaluation and control of Chinese patent medicine based on chiral isomer ratio analysis: With Yuanhuzhitong tablet as an example.

Biomed Chromatogr 2021 Jul 3:e5211. Epub 2021 Jul 3.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Chiral compounds commonly exist in traditional Chinese medicine (TCM), but little research on the quality control of TCM has been conducted. In this study, a new strategy is proposed, taking Yuanhuzhitong tablet [YHZT, consisting of Radix Angelicae Dahuricae and Rhizoma Corydalis (Yan Hu Suo, YHS)] for example, which is based on chiral isomer ratio analysis to monitor the production process of Chinese patent medicine companies. In the process of content determination for tetrahydropalmatine (THP) in YHZT from different companies, noticeable differences were observed in their chromatographic behaviors. It is known that THP has two enantiomers, naturally coexisting in YHS as a racemic mixture, so we prepared THP twice and subsequently performed chiral separation analysis using supercritical fluid chromatography. As a result, the peak area ratios of two enantiomers from different companies varied remarkably, demonstrating that some companies did not probably manufacture YHZT products in accordance with the prescription proportion, used inferior or extracted YSH crude materials in the production process, and added raw chemical medicine in the production to reach the standard and lower the costs. In conclusion, the peak area ratio of chiral isomers could be taken as a key quality index.
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http://dx.doi.org/10.1002/bmc.5211DOI Listing
July 2021

Correction to: Immunomodulatory effects of a new whole ingredients extract from Astragalus: a combined evaluation on chemistry and pharmacology.

Chin Med 2021 May 6;16(1):38. Epub 2021 May 6.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, China.

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http://dx.doi.org/10.1186/s13020-021-00440-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101214PMC
May 2021

Excessive Intake of Longan Arillus Alters gut Homeostasis and Aggravates Colitis in Mice.

Front Pharmacol 2021 26;12:640417. Epub 2021 Mar 26.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.

Longan is the fruit of Lour. and the longan arillus has long been used in traditional Chinese medicine possessing various health benefits. However, the excessive intake of longan is found in daily life to cause "" syndrome. "" has been linked to increased disease susceptibility. The present study thus aimed to investigate the toxicological outcomes after excessive longan treatment. Longan extract at a normal dosage of 4 g/kg and two excess dosages of 8 and 16 g/kg was orally administered to normal C57BL/6J mice for two weeks or to C57BL/6J mice with DSS-induced colitis. Mouse gut microbiome were analyzed by 16S rRNA sequencing. Short chain fatty acid (SCFA) contents in colonic contents were measured by GC-MS. Colon tissue was used for histopathological observation after H and E staining, detection of protein expression by western blot, analysis of gene expression by qPCR, and detection of apoptotic cells by TUNEL assay. ELISA was used for biochemical analysis in serum. In normal mice, repeated longan intake at excess doses, but not the normal dose, increased infiltration of inflammatory cells, elevated serum levels of TNF-α and IL-6 and reduced production of SCFAs. In DSS-induced colitic mice, longan intake at 4 g/kg did not promote colitis in mice, while excessive longan (8 or 16 g/kg) aggravated colitis in mice, showing increased inflammation, more serious histological abnormalities, increased gut permeability, and increased epithelia injury when compared to DSS alone. Excessive longan induced a significant reduction of microbial diversity in colitic mice, accompanied with aggravated alterations of DSS-associated bacteria including the increase of Proteobacteria phylum and genera of , , and , and the decrease of . The changed microbial compositions were accompanied with decreased SCFAs when longan was supplemented with DSS. The aggravated colon injury by excessive intake of longan in colitic mice was tightly correlated with the altered microbial communities and decreased SCFAs production. Excessive longan intake disturbs gut homeostasis and aggravates colitis via promoting inflammation and altering gut microbe compositions and associated metabolism in mice. Our findings warrant rational longan arillus consumption as a dietary supplement or herbal medicine.
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http://dx.doi.org/10.3389/fphar.2021.640417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033040PMC
March 2021

Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-[Formula: see text]B and MAPK Signaling Pathways.

Am J Chin Med 2021 7;49(4):925-939. Epub 2021 Apr 7.

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao 999078, P. R. China.

saponins (PNS) are the main active ingredients of (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.
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http://dx.doi.org/10.1142/S0192415X21500440DOI Listing
April 2021

Mechanical and Viscoelastic Properties of Wrinkled Graphene Reinforced Polymer Nanocomposites - Effect of Interlayer Sliding within Graphene Sheets.

Carbon N Y 2021 Jun 22;177:128-137. Epub 2021 Feb 22.

Department of Mechanical Engineering, Clemson University, Clemson, SC 29634, USA.

Multilayer graphene sheets (MLGSs) are promising nano-reinforcements that can effectively enhance the properties of polymer matrices. Despite many studies on MLGSs-reinforced polymer nanocomposites, the effect of wrinkles formed in MLGSs on the reinforcement effect and the viscoelastic properties of polymer nanocomposites has remained unknown. In this study, building upon previously developed coarse-grained models of MLGSs and poly(methyl methacrylate) coupled with molecular dynamics simulations, we have systematically investigated nanocomposites with different numbers of graphene layers and various wrinkle configurations. We find that with decreasing degree of waviness and increasing numbers of layers, the elastic modulus of the nanocomposites increases. Interestingly, we observe a sudden stress drop during shear deformation of certain wrinkled MLGSs-reinforced nanocomposites. We further conduct small amplitude oscillatory shear simulations on these nanocomposites and find that the nanocomposites with these specific wrinkle configurations also show peculiarly large loss tangents, indicating an increasing capability of energy dissipation. These behaviors are attributed to the activation of the interlayer sliding among these wrinkled MLGSs, as their interlayer shear strengths are indeed lower than flat MLGSs measured by steered molecular dynamics technique. Our study demonstrates that the viscoelastic properties and deformation mechanisms of polymer nanocomposites can be tuned through MLGS wrinkle engineering.
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http://dx.doi.org/10.1016/j.carbon.2021.02.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990119PMC
June 2021

The dietary supplement Rhodiola crenulata extract alleviates dextran sulfate sodium-induced colitis in mice through anti-inflammation, mediating gut barrier integrity and reshaping the gut microbiome.

Food Funct 2021 Apr 17;12(7):3142-3158. Epub 2021 Mar 17.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.

Rhodiola species are edible medicinal plants, which have been traditionally used in both Asia and Europe as an adaptogen, a tonic, an anti-depressant and anti-inflammatory supplement. However, whether it presents a therapeutic effect on colitis or not remains unknown. The aim of this study is to investigate the protective effect of a Rhodiola crenulata extract (RCE) on mice with DSS-induced colitis. RCE significantly alleviated the pathological abnormalities in colitic mice, including the correspondingly increased colon length, ameliorated colonic injury and reduced pro-inflammatory factors. The protective effect was similar to that of the positive control, 5-aminosalicylic acid. The DSS-induced epithelial apoptosis and maintained intestinal barrier function were attenuated by RCE through the upregulation of the level of tight junction proteins such as ZO-1 and occludin. Notably, RCE prevented gut dysbiosis in colitic mice by restoring the microbial richness and diversity, and decreasing the abundance of Proteobacteria phylum and opportunistic pathogenic Parasutterella and Staphylococcus, as well as increasing the abundance of beneficial microbes in Lactobacillus and Bifidobacterium, which were closely correlated with its protective effect against colitis. Meanwhile, chemical characterization of RCE was performed by UPLC-HR-MS to explain its material basis. A total of 63 compounds were identified, while the content of two bioactive ingredients (salidroside, 1.81%; rosavin, 0.034%) was determined.
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http://dx.doi.org/10.1039/d0fo03061aDOI Listing
April 2021

Integrating Transcriptomics and Metabolomics to Characterize Metabolic Regulation to Elevated CO in Chlamydomonas Reinhardtii.

Mar Biotechnol (NY) 2021 Apr 10;23(2):255-275. Epub 2021 Mar 10.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, 106 Nanjing Road, Qingdao, 266071, China.

With atmospheric CO increasing, a large amount of CO is absorbed by oceans and lakes, which changes the carbonate system and affects the survival of aquatic plants, especially microalgae. The main aim of our study was to explore the responses of Chlamydomonas reinhardtii (Chlorophyceae) to elevated CO by combined transcriptome and metabolome analysis under three different scenarios: control (CK, 400 ppm), short-term elevated CO (ST, 1000 ppm), and long-term elevated CO (LT, 1000 ppm). The transcriptomic data showed moderate changes between ST and CK. However, metabolic analysis indicated that fatty acids (FAs) and partial amino acids (AAs) were increased under ST. There was a global downregulation of genes involved in photosynthesis, glycolysis, lipid metabolism, and nitrogen metabolism but increase in the TCA cycle and β-oxidation under LT. Integrated transcriptome and metabolome analyses demonstrated that the nutritional constituents (FAs, AAs) under LT were poor compared with CK, and most genes and metabolites involved in C and N metabolism were significantly downregulated. However, the growth and photosynthesis of cells under LT increased significantly. Thus, C. reinhardtii could form a specific adaptive evolution to elevated CO, affecting future biogeochemical cycles.
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http://dx.doi.org/10.1007/s10126-021-10021-yDOI Listing
April 2021

Anticancer Effects of Ginsenoside Rh2: A Systematic Review.

Curr Mol Pharmacol 2021 Mar 8. Epub 2021 Mar 8.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao. China.

Background: As one of the effective pharmacological constituents of Ginseng Radix et Rhizoma, ginsenoside Rh2 (Rh2) exerts a remarkable anticancer effect on various cancer cell lines in vitro and strongly inhibits tumor growth in vivo without severe toxicity.

Objective: This article reviewed existing evidence supporting the anticancer effects of Rh2 to classify and conclude previous and current knowledge on the mechanisms and therapeutic effects of Rh2, as well as to promote the clinical application of this natural product.

Conclusion: This article reviewed the anticancer efficacies and mechanisms of Rh2, including the induction of cell cycle arrest and programmed cell death, repression of metastasis, alleviation of drug resistance, and regulation of the immune system. Finally, this paper discussed the research and application prospects of Rh2.
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http://dx.doi.org/10.2174/1874467214666210309115105DOI Listing
March 2021

LncRNA DLEU2 promotes cervical cancer cell proliferation by regulating cell cycle and NOTCH pathway.

Exp Cell Res 2021 05 4;402(1):112551. Epub 2021 Mar 4.

Basic Medical College, Chongqing Medical University, Chongqing, China. Electronic address:

Long noncoding RNAs (lncRNAs) are known to play a crucial role in the onset and progression of cervical cancer (CC). Here, the results of RNA microarray and RNA-sequencing dataset analysis showed that lncRNA DLEU2 was significantly upregulated in CC tissues. Clinicopathologic analysis indicated that lncRNA DLEU2 was closely related to tumor topography. Functional experiments and bioinformatics analysis revealed that lncRNA DLEU2 promoted CC cell proliferation and accelerated the cell cycle. Mechanistically, lncRNA DLEU2 promoted the progression of the cell cycle and inhibited the activity of the Notch signaling pathway by inhibiting p53 expression. Additionally, lncRNA DLEU2 probably interacted with ZFP36 Ring Finger Protein (ZFP36) to inhibit the expression of p53. In conclusion, this study revealed the function of lncRNA DLEU2 in CC tumorigenesis, suggesting new therapeutic targets in CC.
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http://dx.doi.org/10.1016/j.yexcr.2021.112551DOI Listing
May 2021

The complete chloroplast genome of the brown alga sp. ye-B (Laminariaceae: Phaeophyceae) from Sakhalin, Russia.

Mitochondrial DNA B Resour 2021 Feb 19;6(2):648-649. Epub 2021 Feb 19.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, PR China.

The complete chloroplast genome sequence of sp. ye-B was determined using Illumina sequencing data. The chloroplast genome of sp. ye-B is 130,587 bp in length, containing 139 protein-coding genes (PCGs), 3 ribosomal RNAs (rRNAs), and 28 transfer RNAs (tRNAs) genes. The phylogenetic reconstruction based on the chloroplast genomes of 11 brown algae resolves sp. ye-B in a fully supported clade with . The determination of the chloroplast genome of sp. ye-B will benefit future algal genetics, evolution, and systematic studies in the Laminariaceae.
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http://dx.doi.org/10.1080/23802359.2021.1878964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899685PMC
February 2021

Specific NLRP3 inflammasome inhibitors: promising therapeutic agents for inflammatory diseases.

Drug Discov Today 2021 06 23;26(6):1394-1408. Epub 2021 Feb 23.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address:

Innate immunity serves as a first line of defence against danger signals, invading pathogens and microbes. The inflammasomes, as pattern recognition receptors, sense these danger signals to initiate pro-inflammatory cascades. The nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome is the most well characterised inflammasome, and its aberrant activation is implicated in many inflammatory diseases. In the past decade, targeting the NLRP3 inflammasome has become an emerging strategy for inflammatory diseases. To avoid off-target immunosuppressive effects, specific NLRP3 inhibitors have been developed and show promising therapeutic effects. This review discusses the therapeutic effects and clinical perspectives of specific NLRP3 inhibitors, as well as recent progress in the development of these inhibitors for the treatment of inflammatory diseases.
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http://dx.doi.org/10.1016/j.drudis.2021.02.018DOI Listing
June 2021

Research progress on quality assurance of genuine Chinese medicinal in Sichuan.

Chin Med 2021 Feb 8;16(1):19. Epub 2021 Feb 8.

Sichuan Institute for Translational Chinese Medicine, Sichuan Academy of Chinese Medical Sciences, Chengdu, China.

The genuine Chinese medicinal (GCM), also known as Dao-di Herbs, is a synonym for high quality Chinese medicinal materials, which has been established in thousands of years of clinical practice and is a comprehensive standard for evaluating the quality of Chinese medicinal materials. The newest data from the Fourth National Survey of Chinese Medicinal Resources showed that Sichuan Province has 7290 types of Chinese medicine and 86 GCM, both ranking highly in China. The characteristics like diverse species, wide distribution, higher yield, and good quality are considered as advantages of geo-herbals grown in Sichuan. Resources guarantee and high-quality development of those medicine materials make a difference in local Chinese medicine quality promotion and Chinese medicine industry and technology development to serve the public's needs, assist targeted poverty alleviation, and strengthen ecological protection. This review aims to outline significant progress in the recent ten years regarding regionalization, germplasm resources, and quality evaluation around the quality assurance of GCM in Sichuan, China.
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http://dx.doi.org/10.1186/s13020-021-00428-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871544PMC
February 2021

The oxylipin messenger 1-octen-3-ol induced rapid responses in kelp Macrocystis pyrifera.

Physiol Plant 2021 Jul 4;172(3):1641-1652. Epub 2021 Mar 4.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China.

Oxylipins are important oxygenated derivatives of fatty acids that regulate a variety of plant physiological and pathological processes in response to specific external challenges. A large body of evidence has indicated that algae can also produce a surprisingly diverse array of volatile oxylipins, yet little is known about the roles of volatile oxylipins as defense signals in macroalgae. In this study, the kelp Macrocystis pyrifera was treated by the oxylipin messenger 1-octen-3-ol and then a genome-wide gene expression profile and fatty acid spectrum analysis were performed. We found that M. pyrifera responded rapidly to the exposure of the oxylipin messenger 1-octen-3-ol. It regulated the expression levels of genes mainly involved in signal transduction, lipid metabolism, oxidation prevention, cell wall synthesis, photosynthesis, and development. Moreover, 1-octen-3-ol treatments decreased several types of total fatty acid contents and increased free fatty acid contents, especially for the C18 and C20 fatty acids. In addition, it decreased the content of indole-3-acetic acid, abscisic acid, and zeatin and increased the gibberellic acid content. Our findings demonstrated that 1-octen-3-ol is an available inducer for M. pyrifera, which is capable of rapidly upregulating kelp's defense response.
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http://dx.doi.org/10.1111/ppl.13358DOI Listing
July 2021

Association of hospital pharmacy-related knowledge and skills with occupational stress of clinical pharmacists in tertiary hospitals of China.

J Am Pharm Assoc (2003) 2021 May-Jun;61(3):266-275. Epub 2021 Jan 31.

Objective: Occupational stress of health care providers may lower the quality of care. Person-environment fit theory and practical evidence have indicated that various types of knowledge and skills of health care providers are differentially associated with occupational stress. Clinical pharmacists are an indispensable part of medical teams. Clinical pharmacists in China are generally under high occupational stress, but what kind of knowledge and skills can relieve their occupational stress remains unclear. This study aimed to assess the association between the specific knowledge and skills of clinical pharmacists and their occupational stress in China. This study aimed to assess the association between the specific knowledge and skills of clinical pharmacists and their occupational stress in China.

Methods: A field questionnaire survey using a stratified sampling was conducted to gather data on occupational stress, knowledge and skills related to hospital pharmacy, and other factors of occupational stress using the Brief Job Stress Questionnaire and a self-developed instrument. Ordinary least squares regression was used to evaluate the association of the participants' knowledge, skills, and other factors with their occupational stress.

Results: A total of 625 clinical pharmacists from 311 tertiary hospitals in China (response rate = 84%) participated. Knowledge of or skills related to pharmaceutical care service provision (P = 0.02), the use of computers and the Internet in pharmacy practice (P = 0.02), interpersonal communication (P = 0.10), or pharmacoepidemiology (P = 0.08) was associated with reduced occupational stress of the participants. Participants who had credentials of nation-level specialized (P = 0.09) and general training (P = 0.04) for clinical pharmacist had lower degrees of occupational stress than those without these credentials. The participants' clinical professions, routine tasks, technical titles, and type of hospital they work in were also associated with their occupational stress.

Conclusion: Enhancing several aspects of knowledge or skills among clinical pharmacists in tertiary hospitals in China may help reduce their occupational stress. Efforts are needed to improve the education and training system of clinical pharmacists in China.
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http://dx.doi.org/10.1016/j.japh.2021.01.011DOI Listing
August 2021

Integrative analysis of chloroplast DNA methylation in a marine alga-Saccharina japonica.

Plant Mol Biol 2021 Apr 2;105(6):611-623. Epub 2021 Feb 2.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, 266071, China.

Key Message: We applied an integrative approach using multiple methods to verify cytosine methylation in the chloroplast DNA of the multicellular brown alga Saccharina japonica. Cytosine DNA methylation is a heritable process which plays important roles in regulating development throughout the life cycle of an organism. Although methylation of nuclear DNA has been studied extensively, little is known about the state and role of DNA methylation in chloroplast genomes, especially in marine algae. Here, we have applied an integrated approach encompassing whole-genome bisulfite sequencing, methylated DNA immunoprecipitation, gene co-expression networks and photophysiological analyses to provide evidence for the role of chloroplast DNA methylation in a marine alga, the multicellular brown alga Saccharina japonica. Although the overall methylation level was relatively low in the chloroplast genome of S. japonica, gametophytes exhibited higher methylation levels than sporophytes. Gene-specific bisulfite-cloning sequencing provided additional evidence for the methylation of key photosynthetic genes. Many of them were highly expressed in sporophytes whereas genes involved in transcription, translation and biosynthesis were strongly expressed in gametophytes. Nucleus-encoded photosynthesis genes were co-expressed with their chloroplast-encoded counterparts potentially contributing to the higher photosynthetic performance in sporophytes compared to gametophytes where these co-expression networks were less pronounced. A nucleus-encoded DNA methyltransferase of the DNMT2 family is assumed to be responsible for the methylation of the chloroplast genome because it is predicted to possess a plastid transit peptide.
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http://dx.doi.org/10.1007/s11103-020-01113-9DOI Listing
April 2021

HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas.

Genes (Basel) 2021 01 19;12(1). Epub 2021 Jan 19.

Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.

We previously demonstrated that proline-rich protein 11 (PRR11) and spindle and kinetochore associated 2 (SKA2) constituted a head-to-head gene pair driven by a prototypical bidirectional promoter. This gene pair synergistically promoted the development of non-small cell lung cancer. However, the signaling pathways leading to the ectopic expression of this gene pair remains obscure. In the present study, we first analyzed the lung squamous cell carcinoma (LSCC) relevant RNA sequencing data from The Cancer Genome Atlas (TCGA) database using the correlation analysis of gene expression and gene set enrichment analysis (GSEA), which revealed that the PRR11-SKA2 correlated gene list highly resembled the Hedgehog (Hh) pathway activation-related gene set. Subsequently, GLI1/2 inhibitor GANT-61 or GLI1/2-siRNA inhibited the Hh pathway of LSCC cells, concomitantly decreasing the expression levels of PRR11 and SKA2. Furthermore, the mRNA expression profile of LSCC cells treated with GANT-61 was detected using RNA sequencing, displaying 397 differentially expressed genes (203 upregulated genes and 194 downregulated genes). Out of them, one gene set, including BIRC5, NCAPG, CCNB2, and BUB1, was involved in cell division and interacted with both PRR11 and SKA2. These genes were verified as the downregulated genes via RT-PCR and their high expression significantly correlated with the shorter overall survival of LSCC patients. Taken together, our results indicate that GLI1/2 mediates the expression of the PRR11-SKA2-centric gene set that serves as an unfavorable prognostic indicator for LSCC patients, potentializing new combinatorial diagnostic and therapeutic strategies in LSCC.
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http://dx.doi.org/10.3390/genes12010120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833434PMC
January 2021

The complete chloroplast genome of .

Mitochondrial DNA B Resour 2020 Oct 5;5(3):3481-3482. Epub 2020 Oct 5.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China.

is a brown algal (class Phaeophyceae) belonging to the family Laminariaceae. We reported the assembly and the annotation of the complete chloroplast genome of . The circled cpDNA of is 130,619 bp in length with a large and a small single-copy region (LSC and SSC), separated by two copies of inverted repeats (IRa and IRb). The genome contains 139 protein-coding genes (PCGs), 3 kinds of ribosomal RNAs (rRNAs), and 29 transfer RNAs (tRNAs) genes that are typical of cpDNA. A phylogenetic analysis strongly supported the close phylogenetic affinity of and . The complete cpDNA of will provide valuable molecular data for further analysis of evolutionary and conservation genetic resources.
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http://dx.doi.org/10.1080/23802359.2020.1825999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782001PMC
October 2020

Acclimation and adaptation to elevated pCO increase arsenic resilience in marine diatoms.

ISME J 2021 06 15;15(6):1599-1613. Epub 2021 Jan 15.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China.

Arsenic pollution is a widespread threat to marine life, but the ongoing rise pCO levels is predicted to decrease bio-toxicity of arsenic. However, the effects of arsenic toxicity on marine primary producers under elevated pCO are not well characterized. Here, we studied the effects of arsenic toxicity in three globally distributed diatom species (Phaeodactylum tricornutum, Thalassiosira pseudonana, and Chaetoceros mulleri) after short-term acclimation (ST, 30 days), medium-term exposure (MT, 750 days), and long-term (LT, 1460 days) selection under ambient (400 µatm) and elevated (1000 and 2000 µatm) pCO. We found that elevated pCO alleviated arsenic toxicity even after short acclimation times but the magnitude of the response decreased after mid and long-term adaptation. When fed with these elevated pCO selected diatoms, the scallop Patinopecten yessoensis had significantly lower arsenic content (3.26-52.83%). Transcriptomic and biochemical analysis indicated that the diatoms rapidly developed arsenic detoxification strategies, which included upregulation of transporters associated with shuttling harmful compounds out of the cell to reduce arsenic accumulation, and upregulation of proteins involved in synthesizing glutathione (GSH) to chelate intracellular arsenic to reduce arsenic toxicity. Thus, our results will expand our knowledge to fully understand the ecological risk of trace metal pollution under increasing human activity induced ocean acidification.
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http://dx.doi.org/10.1038/s41396-020-00873-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163839PMC
June 2021

Highly convenient and highly specific-and-sensitive PCR using Se-atom modified dNTPs.

Chem Commun (Camb) 2021 Jan;57(1):57-60

Key Laboratory of Bio-Resource and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, P. R. China.

Primer design and condition optimization for PCR are tedious and labour-intensive. To conveniently achieve high selectivity, sensitivity and robustness, herein, we first report a new strategy with Se-dNTPs to enhance PCR specificity (over 240-fold) and sensitivity (up to single-digit), effectively eliminating non-specific products and simplifing PCR design and optimization.
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http://dx.doi.org/10.1039/d0cc06172gDOI Listing
January 2021

Influence of ocean acidification on thermal reaction norms of carbon metabolism in the marine diatom Phaeodactylum tricornutum.

Mar Environ Res 2021 Feb 3;164:105233. Epub 2020 Dec 3.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China; Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

Under the present CO condition, the efficiency of biological pump mediating carbon sequestration is predicted to decline in the future because respiration tends to be more sensitive to rising temperature than is photosynthesis. However, it remains unknown whether the impacts of global warming on metabolic rates of phytoplankton can be modulated by elevated CO induced ocean acidification. Here we show that in the model diatom species Phaeodactylum tricornutum, E (activation energy) of photosynthesis (~0.5 eV) was significantly lower than that of respiration (1.8 eV), while CO concentration had no effect on the E value. E (deactivation energy) of respiration was increased to 2.5 eV, that was equivalent to E of photosynthesis in high CO-grown cells and 28.4% higher than that in low CO-grown ones. The respiration to photosynthesis ratio (R/P) was consistently higher in high CO condition, which increased with temperature at the beginning and subsequently decreased in both CO conditions. The ratio of R/P in high CO to R/P in low CO gradually increased with temperature above the optimal temperature. Our results imply that ocean acidification will aggravate the negative impacts or offset the alleviating effects of warming on the R/P ratio depending on the temperature range in Phaeodactylum tricornutum.
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http://dx.doi.org/10.1016/j.marenvres.2020.105233DOI Listing
February 2021

Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites.

Pharmacol Res 2021 02 4;164:105358. Epub 2020 Dec 4.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Inflammatory bowel diseases (IBD) are kind of recurrent inflammatory issues that occur in the gastrointestinal tract, and currently clinical treatment is still unideal due to the complex pathogenesis of IBD. Basically, gut barrier dysfunction is triggered by gut microbiota dysbiosis that is closely associated with the development of IBD, we thus investigated the therapeutic capacity of berberine (BBR) to improve the dysregulated gut microbiota, against IBD in rats, using a combinational strategy of targeted metabolomics and 16 s rDNA amplicon sequencing technology. Expectedly, our data revealed that BBR administration could greatly improve the pathological phenotype, gut barrier disruption, and the colon inflammation in rats with dextran sulfate sodium (DSS)-induced colitis. In addition, 16S rDNA-based microbiota analysis demonstrated that BBR could alleviate gut dysbiosis in rats. Furthermore, our targeted metabolomics analysis illustrated that the levels of microbial tryptophan catabolites in the gastrointestinal tract were significantly changed during the development of the colitis in rats, and BBR treatment can significantly restore such changes of the tryptophan catabolites accordingly. At last, our in vitro mechanism exploration was implemented with a Caco-2 cell monolayer model, which verified that the modulation of the dysregulated gut microbiota to change microbial metabolites coordinated the improvement effect of BBR on gut barrier disruption in the colitis, and we also confirmed that the activation of AhR induced by microbial metabolites is indispensable to the improvement of gut barrier disruption by BBR. Collectively, BBR has the capacity to treat DSS-induced colitis in rats through the regulation of gut microbiota associated tryptophan metabolite to activate AhR, which can greatly improve the disrupted gut barrier function. Importantly, our finding elucidated a novel mechanism of BBR to improve gut barrier function, which holds the expected capacity to promote the BBR derived drug discovery and development against the colitis in clinic setting.
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http://dx.doi.org/10.1016/j.phrs.2020.105358DOI Listing
February 2021
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