Publications by authors named "Juan Wan"

46 Publications

Research progress of epigallocatechin-3-gallate (EGCG) on anti-pathogenic microbes and immune regulation activities.

Food Funct 2021 Sep 22. Epub 2021 Sep 22.

National Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China.

At the end of 2019, the COVID-19 virus spread worldwide, infecting millions of people. Infectious diseases induced by pathogenic microorganisms such as the influenza virus, hepatitis virus, and are also a major threat to public health. The high mortality caused by infectious pathogenic microorganisms is due to their strong virulence, which leads to the excessive counterattack by the host immune system and severe inflammatory damage of the immune system. This paper reviews the efficacy, mechanism and related immune regulation of epigallocatechin-3-gallate (EGCG) as an anti-pathogenic microorganism drug. EGCG mainly shows both direct and indirect anti-infection effects. EGCG directly inhibits early infection by interfering with the adsorption on host cells, inhibiting virus replication and reducing bacterial biofilm formation and toxin release; EGCG indirectly inhibits infection by regulating immune inflammation and antioxidation. At the same time, we reviewed the bioavailability and safety of EGCG . At present, the bioavailability of EGCG can be improved to some extent using nanostructured drug delivery systems and molecular modification technology in combination with other drugs. This study provides a theoretical basis for the development of EGCG as an adjuvant drug for anti-pathogenic microorganisms.
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http://dx.doi.org/10.1039/d1fo01352aDOI Listing
September 2021

Anti-damage effect of theaflavin-3'-gallate from black tea on UVB-irradiated HaCaT cells by photoprotection and maintaining cell homeostasis.

J Photochem Photobiol B 2021 Sep 11;224:112304. Epub 2021 Sep 11.

National Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha 410128, China; Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China. Electronic address:

Keratinocytes are rich in lipids and are the main sensitive cells to ultraviolet (UV) rays. Theaflavins are the core functional components of black tea and are known as the "soft gold" in tea. In this study, ultraviolet-B (UVB) irradiation caused apoptosis and necrosis of human epidermal keratinocytes (HaCaT). EGCG and the four theaflavins had anti-UVB damage activity, among which theaflavin-3'-gallate (TF3'G) had the best activity. The results of biophysical and molecular biology experiments showed that TF3'G has anti-damage effects on UVB-irradiated HaCaT cells through the dual effects of photoprotection and maintenance of cell homeostasis. That is, TF3'G preincubation could absorb UV rays, reduce the accumulation of aging-related heterochromatin (SAHF) formation, increase mitochondrial membrane potential, downregulate NF-κB inflammation pathways, inhibit the formation of cytotoxic aggregates, and protect biological macromolecules Structure, etc. The accumulation of conjugated π bonds and the balance benzoquinone are the core functional structure of TF3'G with high efficiency and low toxicity. The study indicates that TF3'G has the potential to inhibit the photoaging and intrinsic aging of skin cells.
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http://dx.doi.org/10.1016/j.jphotobiol.2021.112304DOI Listing
September 2021

Melanoma-Differentiation-Associated gene 5 protects against nonalcoholic steatohepatitis in mice.

Hepatology 2021 Sep 5. Epub 2021 Sep 5.

Gannan Institute of Translational Medicine, Ganzhou, China.

Background And Aims: Nonalcoholic steatohepatitis (NASH) is a complicated disease characterized by hepatocyte steatosis, inflammation infiltration, and liver fibrosis. Accumulating evidence suggests that the innate immunity plays a key role in NASH progression. Here, we aimed to reveal the role of melanoma-differentiation-associated gene 5 (MDA5, also known as Ifih1), a conventional innate immune regulator upon viral infection, in the progression of NASH and investigate its underlying mechanism.

Approach And Results: We first examined the expression of MDA5 and found that MDA5 was markedly downregulated in the livers with NASH in human individuals and mice models. MDA5 overexpression significantly inhibited the free fatty acid (FFA) induced lipid accumulation and inflammation in hepatocyte in vitro, while MDA5 knockdown promotes hepatocyte lipotoxicity. Using hepatocyte-specific Mda5 gene knockout and transgenic mice, we found that diet induced hepatic steatosis, inflammation and liver fibrosis were markedly exacerbated by Mda5 deficiency but suppressed by Mda5 overexpression. Mechanistically, we found that the activation of ASK1-MAPK pathway was significantly inhibited by MDA5 but enhanced by MDA5 deletion. We further validated that MDA5 directly interacted with ASK1 and suppressed its N-terminal dimerization. Importantly, blockage of ASK1 with adenovirus expressing dominant negative ASK1 (dnASK1) obviously reversed the lipid accumulation and ASK1 pathway activation when Mda5 knockout.

Conclusions: These data indicate that MDA5 is an essential suppressor in NASH, the findings support MDA5 as a novel regulator of ASK1 and a promising therapeutic target for NASH.
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http://dx.doi.org/10.1002/hep.32139DOI Listing
September 2021

Pathogenicity and Metabolites of Endoparasitic Nematophagous Fungus YMF1.01759 against Nematodes.

Microorganisms 2021 Aug 14;9(8). Epub 2021 Aug 14.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming 650091, China.

Plant parasitic nematodes cause severe damage to crops. Endoparasitic nematophagous fungi (ENF) are a type of important biocontrol fungi, which can cause disease or kill nematodes by producing various spores. As a major ENF, displays certain potential for controlling plant-parasitic nematodes. In this study, the pathogenicity and secondary metabolites of the endoparasitic fungus YMF1.01759 were investigated. The strain YMF1.01759 had high infection efficiency against nematodes. The process of infecting nematodes by the strain was observed under an electron microscope. Here, 13 metabolites including one new compound 4()-butoxy-3-(butoxymethyl)-2-hydroxycyclopent-2-en-1-one () were isolated and identified from the fermentation products of YMF1.01759 cultured in a SDAY solid medium. Furthermore, a bioassay showed that 5-hydroxymethylfuran-2-carboxylic acid () is toxic to the root knot nematode and affects the hatching of its egg. Thereby, the nematicidal mortality attained 81.50% at 100 μg/mL for 48 h. Furthermore, egg hatching was inhibited at the tested concentrations, compared with water control eggs. This is the first report on the secondary metabolites of the ENF . The results indicated that could infect nematodes by spores and produce active metabolites to kill nematodes. The biological control potential of against nematodes was expounded further.
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http://dx.doi.org/10.3390/microorganisms9081735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401723PMC
August 2021

SIMPLE is an endosomal regulator that protects against non-alcoholic fatty liver disease by targeting the lysosomal degradation of EGFR.

Hepatology 2021 Jul 28. Epub 2021 Jul 28.

Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has become a tremendous burden for public health, however, there is no drug for NAFLD therapy at present. Impaired endo-lysosome-mediated protein degradation is observed in a variety of metabolic disorders, such as atherosclerosis, type 2 diabetes mellitus and NAFLD. Small integral membrane protein of lysosome/late endosome (SIMPLE) is a regulator of endosome-to-lysosome trafficking and cell signaling. But the role that SIMPLE plays in NAFLD progression remains unknown. Here we investigated SIMPLE function in NAFLD development and sophisticated mechanism therein.

Approach & Results: This study found in vitro knockdown of SIMPLE significantly aggravated lipid accumulation, inflammation in hepatocytes treated with metabolic stimulation. Consistently, in vivo experiments showed that liver-specific Simple-knockout (Simple-HKO) mice exhibited more severe high-fat diet (HFD)-, high-fat-high-cholesterol diet (HFHC)-, and methionine-choline-deficient diet (MCD)- induced steatosis, glucose intolerance, inflammation, and fibrosis than those fed with normal-chow diet. Meanwhile, RNA-sequencing demonstrated the up-regulated signaling pathways and signature genes involved in lipid metabolism, inflammation and fibrosis in Simple-HKO mice compared to control mice under metabolic stress. Mechanically, we found SIMPLE directly interact with epidermal growth factor receptor (EGFR). SIMPLE deficiency results in dysregulated degradation of EGFR, subsequently hyperactivated EGFR phosphorylation, exaggerating NAFLD development. Moreover, we further demonstrated that using EGFR inhibitor or silencing EGFR expression could ameliorate lipid accumulation induced by the knockdown of SIMPLE.

Conclusions: SIMPLE ameliorated NASH by prompting EGFR degradation and can also be a potential therapeutic candidate for NASH.
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http://dx.doi.org/10.1002/hep.32075DOI Listing
July 2021

Gastrodin Improves Nonalcoholic Fatty Liver Disease Through Activation of the Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway.

Hepatology 2021 Jul 23. Epub 2021 Jul 23.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Background And Aims: NASH is currently one of the most common causes of liver transplantation and hepatocellular carcinoma. Thus far, there is still no effective pharmacological therapy for this disease. Recently, Gastrodin has demonstrated hepatoprotective effects in a variety of liver diseases. The aim of this study is to investigate the function of Gastrodin in NASH.

Approach And Results: In our study, Gastrodin showed potent therapeutic effects on NASH both in vivo and in vitro. In high-fat diet or high-fat and high-cholesterol diet-fed mice, the liver weight, hepatic and serum triglyceride and cholesterol contents, and serum alanine aminotransferase and aspartate aminotransferase activity levels were markedly reduced by Gastrodin treatment as compared with the corresponding vehicle groups. Notably, Gastrodin showed minimal effects on the function and histological characteristics of other major organs in mice. We further examined the effects of Gastrodin on lipid accumulation in primary mouse hepatocytes and human hepatocyte cell line and observed that Gastrodin showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. Furthermore, RNA-sequencing analysis systemically indicated that Gastrodin suppressed the pathway and key regulators related to lipid accumulation, inflammation, and fibrosis in the pathogenesis of NASH. Mechanistically, we found that Gastrodin protected against NASH by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway, which was supported by the result that the AMPK inhibitor Compound C or AMPK knockdown blocked the Gastrodin-mediated hepatoprotective effect.

Conclusions: Gastrodin attenuates steatohepatitis by activating the AMPK pathway and represents a therapeutic for the treatment of NASH.
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http://dx.doi.org/10.1002/hep.32068DOI Listing
July 2021

A single-domain small protein Med-ORF10 regulates the production of antitumour agent medermycin in Streptomyces.

Microb Biotechnol 2021 Sep 17;14(5):1918-1930. Epub 2021 Jun 17.

Helmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China.

Med-ORF10, a single-domain protein with unknown function encoded by a gene located in a gene cluster responsible for the biosynthesis of a novel antitumour antibiotic medermycin, shares high homology to a group of small proteins widely distributed in many aromatic polyketide antibiotic pathways. This group of proteins contain a nuclear transport factor-2 (NTF-2) domain and appear to undergo an evolutionary divergence in their functions. Gene knockout and interspecies complementation suggested that Med-ORF10 plays a regulatory role in medermycin biosynthetic pathway. Overexpression of med-ORF10 in its wild-type strain led to significant increase of medermycin production. It was also shown by qRT-PCR and Western blot that Med-ORF10 controls the expression of genes encoding tailoring enzymes involved in medermycin biosynthesis. Transcriptome analysis and qRT-PCR revealed that Med-ORF10 has pleiotropic effects on more targets. However, there is no similar conserved domain available in Med-ORF10 compared to those of mechanistically known regulatory proteins; meanwhile, no direct interaction between Med-ORF10 and its target promoter DNA was detected via gel shift assay. All these studies suggest that Med-ORF10 regulates medermycin biosynthesis probably via an indirect mode.
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http://dx.doi.org/10.1111/1751-7915.13834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449675PMC
September 2021

Tripartite-motif protein 21 knockdown extenuates LPS-triggered neurotoxicity by inhibiting microglial M1 polarization via suppressing NF-κB-mediated NLRP3 inflammasome activation.

Arch Biochem Biophys 2021 07 13;706:108918. Epub 2021 May 13.

Department of Neurosurgery, The First Affiliated Hospital Of University Of South China, Hunan Province, China.

Tripartite motif-containing 21 (TRIM21) has been confirmed to mediate the production of inflammatory mediators via NF-κB signaling. However, the function of TRIM21 in microglia-mediated neuroinflammation remains unclear. This study aimed to explore the effect of TRIM21 on LPS-activated BV2 microglia and its underlying mechanism. BV2 cells exposed to lipopolysaccharide (LPS) were used to simulated neuroinflammation in vitro. Loss-of-function and gain-of-function of TRIM21 in BV2 cells were used to assess the effect of TRIM21 on LPS-induced neuroinflammation. BV2 microglia and HT22 cells co-culture system were used to investigate whether TRIM21 regulated neuronal inflammation-mediated neuronal death. TRIM21 knockdown triggered the polarization of BV2 cells from M1 to M2 phenotype. Knockdown of TRIM21 reduced the secretion of TNF-α, IL-6, and IL-1β, while increased the content of IL-4 in LPS-treated cells. Knockdown of TRIM21 inhibited the expression of p65 and the binding activity of NF-κB-DNA. Additionally, TRIM21 siRNA eliminated the increase in NLRP3 and cleaved caspase-1 proteins expression and caspase-1 activity induced by LPS. TRIM21 knockdown could resist cytotoxicity induced by activated microglia, including increasing the viability of co-cultured HT22 cells and reducing the emancipation of LDH. Moreover, the increased apoptosis and caspase-3 activity of HT22 neurons induced by activated BV2 cells were blocked by TRIM21 siRNA. Blocking of NF-κB abolished the effect of TRIM21 in promoting the expression of M1 phenotype marker genes. Similarly, the blockade of NF-κB pathway eliminated the promotion of TRIM21 on neurotoxicity induced by neuroinflammation. TRIM21 knockdown suppressed the M1 phenotype polarization of microglia and neuroinflammation-mediated neuronal damage via NF-κB/NLRP3 inflammasome pathway, which suggested that TRIM21 might be a potential therapeutic target for the therapy of central nervous system diseases.
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http://dx.doi.org/10.1016/j.abb.2021.108918DOI Listing
July 2021

Ketogenic diet and growth in Chinese infants with refractory epilepsy.

Asia Pac J Clin Nutr 2021 ;30(1):113-121

Department of Nutrition, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders. Email:

Background And Objectives: This study evaluated the impact of 12 months of ketogenic dietary treatment (KDT) on growth in Chinese infants with refractory epilepsy.

Methods And Study Design: The KDT group included patients who were divided into groups A (age 6-12 months), B (12-24 months) and C (24-36 months). The normal group included infants aged approximately 6-12 months, 12-24 months and 24-36 months who were classified into groups A1, B1 and C1, respectively. Data on height, weight, aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), zinc, iron, calcium, magnesium, and haemoglobin (Hb) were extracted from the medical records. Then, we compared the impacts of 12 months of KDT on growth.

Results: Forty-one patients were included in the KDT group, and 90 infants were included in the normal group. The overall prevalence of underweight (WAZ <-2 SD), stunting (HAZ <-2 SD), wasting (BAZ <-2 SD), and overweight/obesity (BAZ ≥2 SD) were relatively lower in the A and B groups. The prevalence of anaemia in group A was significantly higher than that in group A1. No significant differences were observed in the KDT groups with regard to HDL, LDL, AST, ALT, iron, calcium, magnesium, or zinc. A greater than 50% reduction in weekly seizure frequency was evident in 100% of group A, 78.6% of group B and 77.8% of group C.

Conclusions: The results revealed that patients less than 2 years old who received KDT maintained appropriate growth at the 12-month follow-up.
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http://dx.doi.org/10.6133/apjcn.202103_30(1).0014DOI Listing
January 2021

Research progress on the potential delaying skin aging effect and mechanism of tea for oral and external use.

Food Funct 2021 Apr 5;12(7):2814-2828. Epub 2021 Mar 5.

National Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Changsha 410128, China.

Skin aging is characterized by the gradual loss of elasticity, the formation of wrinkles and various color spots, the degradation of extracellular matrix proteins, and the structural changes of the dermis. With the increasingly prominent problems of environmental pollution, social pressure, ozone layer thinning and food safety, skin problems have become more and more complex. The skin can reflect the overall health of the body. Skincare products for external use alone cannot fundamentally solve skin problems; it needs to improve the overall health of the body. Based on the literature review in recent 20 years, this paper systematically reviewed the potential delaying effect of tea and its active ingredients on skin aging by oral and external use. Tea is the second-largest health drink after water. It is rich in tea polyphenols, l-theanine, tea pigments, caffeine, tea saponins, tea polysaccharides and other secondary metabolites. Tea and its active substances have whitening, nourishing, anti-wrinkle, removing spots and other skincare effects. Its mechanism of action is ultraviolet absorption, antioxidant, anti-inflammatory, inhibition of extracellular matrix aging, inhibiting the accumulation of melanin and toxic oxidation products, balancing intestinal and skin microorganisms, and improving mood and sleep, among other effects. At present, tea elements skincare products are deeply loved by consumers. This paper provides a scientific theoretical basis for tea-assisted beauty and the high-end application of tea in skincare products.
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http://dx.doi.org/10.1039/d0fo02921aDOI Listing
April 2021

Magnetotactic Bacteria Accumulate a Large Pool of Iron Distinct from Their Magnetite Crystals.

Appl Environ Microbiol 2020 10 28;86(22). Epub 2020 Oct 28.

Department of Plant and Microbial Biology, University of California, Berkeley, California, USA

Magnetotactic bacteria (MTB) are ubiquitous aquatic microorganisms that form intracellular nanoparticles of magnetite (FeO) or greigite (FeS) in a genetically controlled manner. Magnetite and greigite synthesis requires MTB to transport a large amount of iron from the environment. Most intracellular iron was proposed to be contained within the crystals. However, recent mass spectrometry studies suggest that MTB may contain a large amount of iron that is not precipitated in crystals. Here, we attempted to resolve these discrepancies by performing chemical and magnetic assays to quantify the different iron pools in the magnetite-forming strain AMB-1, as well as in mutant strains showing defects in crystal precipitation, cultivated at various iron concentrations. All results show that magnetite represents at most 30% of the total intracellular iron under our experimental conditions and even less in the mutant strains. We further examined the iron speciation and subcellular localization in AMB-1 using the fluorescent indicator FIP-1, which was designed for the detection of labile Fe(II). Staining with this probe suggests that unmineralized reduced iron is found in the cytoplasm and associated with magnetosomes. Our results demonstrate that, under our experimental conditions, AMB-1 is able to accumulate a large pool of iron distinct from magnetite. Finally, we discuss the biochemical and geochemical implications of these results. Magnetotactic bacteria (MTB) produce iron-based intracellular magnetic crystals. They represent a model system for studying iron homeostasis and biomineralization in microorganisms. MTB sequester a large amount of iron in their crystals and have thus been proposed to significantly impact the iron biogeochemical cycle. Several studies proposed that MTB could also accumulate iron in a reservoir distinct from their crystals. Here, we present a chemical and magnetic methodology for quantifying the iron pools in the magnetotactic strain AMB-1. Results showed that most iron is not contained in crystals. We then adapted protocols for the fluorescent Fe(II) detection in bacteria and showed that iron could be detected outside crystals using fluorescence assays. This work suggests a more complex picture for iron homeostasis in MTB than previously thought. Because iron speciation controls its fate in the environment, our results also provide important insights into the geochemical impact of MTB.
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http://dx.doi.org/10.1128/AEM.01278-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642088PMC
October 2020

Micropulse Cyclophotocoagulation: A Multicenter Study of Efficacy, Safety, and Factors Associated With Increased Risk of Complications.

J Glaucoma 2020 12;29(12):1126-1131

Glaucoma Center of San Francisco.

PRéCIS:: Micropulse cyclophotocoagulation (MPCP) lowered intraocular pressure (IOP) in the short-term but nearly half required additional intervention. Mydriasis was the most common complication (11%); 15% lost ≥3 Snellen lines of acuity; 11% had persistent complications at last follow-up.

Purpose: The purpose of this study was to evaluate the efficacy and complications of MPCP in a large series of patients with all stages of glaucoma.

Design: Multicenter, retrospective chart review of patients from 3 clinical sites.

Participants: One hundred sixty-seven eyes of 143 patients.

Methods: MPCP was performed with 2000 mW energy, 31.3% duty cycle and 2 to 4 180-degree applications of 80 seconds duration each per treatment. The procedure was considered a failure if any of the following occurred: additional IOP lowering intervention, <20% IOP reduction from baseline at the last follow-up (with or without medication), or severe complications.

Results: Mean age was 71 years, 53% were female, and 53% were Asian. 60% of eyes had POAG, 63% were pseudophakic, 38% had prior glaucoma surgery, and 51% had Snellen visual acuity (VA) of 20/40 or better. Mean follow-up time was 11.9±7.8 months. Mean IOP was 21.9±8.4 mm Hg before intervention, and 17.4±7.2 mm Hg at last follow-up (P<0.0001). There was no change in mean logMAR VA (P=0.0565) but 15% lost ≥3 Snellen lines of VA. The success rate was 36.5% (61/167 eyes) at last follow-up. The probability of survival by Kaplan-Meier analysis was 82%, 71%, and 57% at 3, 6, and 12 months after the procedure, respectively. The reasons for failure were additional intervention in 47%, inadequate IOP reduction in 14%, and severe complication in 1.8%. In a multivariable Cox proportional hazard model, female sex was associated with a 56% decrease in failure rate compared with males (P<0.0001), while a unit increase in baseline IOP corresponded with a 5.7% increase in failure rate (P<0.0001). If repeat MPCP was allowed then success rate increased to 58%. There were no complications in 73% (122/167) but 11% (18/167) had persistent complications at the last follow-up and half of these 18 eyes had decrease in VA of 1 to 6 Snellen lines. Asian race (odds ratio 13.5, P=0.0131) and phakic status (odds ratio 3.1, P=0.0386) were associated with higher odds of developing mydriasis, which was the most common complication.

Conclusions: MPCP lowered IOP in the short-term but nearly half required additional IOP lowering intervention. Potential complications should be discussed in detail especially when the procedure is being considered for those with good VA and early stage disease.
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http://dx.doi.org/10.1097/IJG.0000000000001644DOI Listing
December 2020

Electroacupuncture intervention of visceral hypersensitivity is involved in PAR-2-activation and CGRP-release in the spinal cord.

Sci Rep 2020 07 7;10(1):11188. Epub 2020 Jul 7.

College of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan Street, Hongshan District, Wuhan, 430070, Hubei Province, People's Republic of China.

Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases. However, the mechanism by which EA treats ileitis-induced VH is not clearly known. To assess the effects of EA on ileitis-induced VH and confirm whether EA attenuates VH through spinal PAR-2 activation and CGRP release, goats received an injection of 2,4,6-trinitro-benzenesulfonic-acid (TNBS) solution into the ileal wall. TNBS-injected goats were allocated into VH, Sham acupuncture (Sham-A) and EA groups, while goats treated with saline instead of TNBS solution were used as the control. Goats in EA group received EA at bilateral Hou-San-Li acupoints for 0.5 h at 7 days and thereafter repeated every 3 days for 6 times. Goats in the Sham-A group were inserted with needles for 0.5 h at the aforementioned acupoints without any hand manipulation and electric stimulation. Visceromotor responses to colorectal distension, an indicator of VH, were recorded by electromyography. The terminal ileum and thoracic spinal cord (T) were sampled for evaluating ileitis at days 7 and 22, and distribution and expression-levels of PAR-2, CGRP and c-Fos on day 22. TNBS-treated-goats exhibited apparent transmural-ileitis on day 7, microscopically low-grade ileitis on day 22 and VH at days 7-22. Goats of Sham-A, VH or EA group showed higher (P < 0.01) VH at days 7-22 than the Control-goats. EA-treated goats exhibited lower (P < 0.01) VH as compared with Sham-A or VH group. Immunoreactive-cells and expression-levels of spinal PAR-2, CGRP and c-Fos in the EA group were greater (P < 0.01) than those in the Control group, but less (P < 0.01) than those in Sham-A and VH groups on day 22. Downregulation of spinal PAR-2 and CGRP levels by EA attenuates the ileitis and resultant VH.
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http://dx.doi.org/10.1038/s41598-020-67702-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341736PMC
July 2020

Endoscopic Surgery versus Minimal Puncture Drainage Surgery for Treatment of Supratentorial Intracerebral Hemorrhage.

Turk Neurosurg 2020 ;30(4):565-572

First Affiliated Hospital of University of South China, Department of Neurosurgery, Hunan Province, China.

Aim: To compare neuroendoscopy versus minimal puncture drainage for surgical treatment of supratentorial hypertensive intracerebral hemorrhage.

Material And Methods: A total of 108 cases involving supratentorial intracerebral hemorrhage were retrospectively analyzed. In 30 cases, endoscopic surgery was performed, while 78 cases involved puncture surgery. We compared hematoma clearance rate, postoperative rebleeding rate, incidence of postoperative complications, operation duration, and Glasgow coma score seven days after surgery. Clinical data such as early postoperative rehabilitation time, Glasgow outcome score three months after surgery, and intensive care unit (ICU) stay were also compared between the two groups.

Results: The results showed that endoscopic surgery was associated with a superior clinical therapeutic effect in hematoma clearance rates, GCS scores on postoperative day 7, the average ICU stay, early postoperative rehabilitation time and intracranial infection outcomes than minimal puncture drainage surgery for the treatment of supratentorial intracerebral hemorrhage (p < 0.05). Three months after surgery, the favorable prognosis rate in the endoscopic treatment group was significantly higher than that in the craniotomy group [83.3% (28/34) vs. 61.5% (31/51), respectively; ? < sup > 2 < /sup > =4.698, p=0.030]. In contrast, no significant differences in rebleeding, pulmonary infection, tracheotomy, secondary epilepsy, gastrointestinal hemorrhage, death in late postoperative period, or in baseline parameters were observed between the two groups (p > 0.05).

Conclusion: Endoscopic surgery potentially represents a beneficial surgical procedure for treatment of supratentorial spontaneous intracerebral hemorrhage.
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http://dx.doi.org/10.5137/1019-5149.JTN.27977-19.2DOI Listing
November 2020

Effect of enhanced recovery after surgery program on patient-reported outcomes and function recovery in patients undergoing liver resection for hepatocellular carcinoma.

Medicine (Baltimore) 2020 May;99(20):e20062

Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.

The aim of this study was to investigate the effect of enhanced recovery after surgery (ERAS) on perioperative outcomes, with an emphasis on patient-reported outcomes (PROs) and functional recovery.We compared the clinical outcomes in a cohort of 275 patients undergoing liver resection before and after the implementation of ERAS. The PROs were preoperatively and postoperatively compared until 14 days after surgery using the MD Anderson Symptom Inventory.The patients in the ERAS group experienced fewer symptoms and a shorter functional recovery time than the patients in the non-ERAS group. The group × time interactions were different between the groups for pain (F = 4.70, P = .001) and walking (F = 2.75, P = .03). On the 3rd, 4, and 5th days after surgery, the ERAS group experienced less pain and more walking than the non-ERAS group. The ERAS group experienced less fatigue (0.407 [95% confidence interval, CI: -0.795, -0.020], P = .035), less sleep interference (0.615 [95% CI: -1.215, -0.014], P = .045), a lower rate of reduced appetite (0.281 [95% CI: -0.442, -0.120], P = .001), and less abdominal distension (0.262 [95% CI: -0.504, -0.020], P = .034) than the non-ERAS group. Those in the ERAS group had a significantly shorter median time from surgery to mild fatigue (5.41 vs 6.87 days, P = .003), mild pain (4.45 vs 6.09 days, P = .001), mild interference when walking (3.85 vs 5.54 days, P < .001), and mild interference when sleeping (5.49 vs 7.43 days, P < .001). ERAS patients were more likely than non-ERAS patients to achieve a functional recovery (5.70 vs 6.79 days, P < .001) status in a shorter time period. The ERAS pathway, operation time, and the minimally invasive approach were independent predictors of functional recovery time.In hepatocellular carcinoma liver resection patients, the primary mechanism of ERAS is to reduce the postoperative interference burden and promote rapid functional recovery.
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http://dx.doi.org/10.1097/MD.0000000000020062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254517PMC
May 2020

MiR-370 accelerated cerebral ischemia reperfusion injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway.

Kaohsiung J Med Sci 2020 Sep 20;36(9):741-749. Epub 2020 Apr 20.

Department of Anesthesiology, Affiliated Nanhua Hospital, University of South China, Hengyang City, Hunan Province, China.

Cerebral ischemia reperfusion (CIR) is one of the highly lethal diseases in the world. MicroRNA-370 (miR-370) exerts multiple functions in different diseases. However, further research is needed to investigate the potential role of miR-370 in CIR injury. The in vivo middle cerebral artery occlusion (MCAO) rat model and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) SH-SY5Y cell model were successfully established to mimic CIR injury. The infarct sizes of brain tissues from rats were evaluated. The relationship between miR-370 and silencing information regulatory protein 6 (SIRT6) was confirmed by luciferase activity assay. The cell viability and apoptosis were determined by CCK-8 assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining. In this study, miR-370 was upregulated in brain tissues of MCAO rats and knockdown of miR-370 decreased cerebral infarction volume of MCAO rats and it alleviated CIR injury in vivo. The in vitro experiments indicated that knockdown of miR-370 promoted cell viability and alleviated OGD/R-induced SH-SY5Y cell apoptosis. Additionally, the TargetScan predicted that SIRT6 was a target of miR-370 and confirmed by luciferase activity assay. Moreover, miR-370 inhibited SIRT6 expression and regulated Nrf2/ARE signal pathway, whereas overexpression of SIRT6 partly reversed the effect of miR-370 on OGD/R-induced SH-SY5Y cell injury. Thus, we could conclude that miR-370 accelerated CIR injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway, which might provide novel therapeutic targets for CIR injury treatment.
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http://dx.doi.org/10.1002/kjm2.12219DOI Listing
September 2020

Synaptotagmin 1 Is Involved in Neuropathic Pain and Electroacupuncture-Mediated Analgesic Effect.

Int J Mol Sci 2020 Jan 31;21(3). Epub 2020 Jan 31.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

Numerous studies have verified that electroacupuncture (EA) can relieve neuropathic pain through a variety of mechanisms. Synaptotagmin 1 (Syt-1), a synaptic vesicle protein for regulating exocytosis of neurotransmitters, was found to be affected by EA stimulation. However, the roles of Syt-1 in neuropathic pain and EA-induced analgesic effect remain unclear. Here, the effect of Syt-1 on nociception was assessed through an antibody blockade, siRNA silencing, and lentivirus-mediated overexpression of spinal Syt-1 in rats with spared nerve injury (SNI). EA was used for stimulating bilateral "Sanjinjiao" and "Zusanli" acupoints of the SNI rats to evaluate its effect on nociceptive thresholds and spinal Syt-1 expression. The mechanically and thermally nociceptive behaviors were assessed with paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different temperatures, respectively, at day 0, 7, 8, 14, and 20. Syt-1 mRNA and protein levels were determined with qRT-PCR and Western blot, respectively, and its distribution was observed with the immunohistochemistry method. The results demonstrated Syt-1 antibody blockade and siRNA silencing increased ipsilateral PWTs and PWLs of SNI rats, while Syt-1 overexpression decreased ipsilateral PWTs and PWLs of rats. EA significantly attenuated nociceptive behaviors and down-regulated spinal Syt-1 protein levels (especially in laminae I-II), which were reversed by Syt-1 overexpression. Our findings firstly indicate that Syt-1 is involved in the development of neuropathic pain and that EA attenuates neuropathic pain, probably through suppressing Syt-1 protein expression in the spinal cord.
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http://dx.doi.org/10.3390/ijms21030968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037106PMC
January 2020

Study on the mechanical properties of flax fiber-reinforced silty clay contaminated by zinc-ion solution.

Environ Technol 2021 Mar 27;42(7):1071-1083. Epub 2019 Aug 27.

School of Civil Engineering and Architecture, Hubei University of Technology, Wuhan, People's Republic of China.

Mechanical properties of fiber-reinforced soil after soaking in heavy metal ion solution have great influences on safety and stability of the reinforcement, herein the mechanical properties of optimum moisture content of different concentrations of zinc ions contaminated soil were studied through shear test, compression test and triaxial test. The compressive modulus, compression coefficient and porosity ratio of different concentrations of the zinc-ion contaminated soil under different pressure were studied, and the variation characteristics of internal friction angle and cohesion were also investigated, thereafter, the causes of the change of cohesion and internal friction angle were analyzed from the microscopic perspective. The results show that the shear strength of contaminated reinforced soil increases with the increase of confining pressure at the same zinc ions concentration. And at the same confining pressure, with the increase of zinc ions concentration, the shear strength of contaminated reinforced soil first increases and then decreases. With the increase of zinc ions concentration, the internal friction angle and compression coefficient increase, the cohesion and the modulus of compression decrease. With the increase of normal stress, the compression coefficient decreases firstly and then increases, and the compression modulus increases and then decreases. With the concentration of zinc ions increases at lower normal stress, the amount of shrinkage increases and the compression coefficient decreases. While at higher normal stress, the compressive modulus decreases and the compression coefficient increases.
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http://dx.doi.org/10.1080/09593330.2019.1652697DOI Listing
March 2021

Electro-Acupuncture Affects the Activity of the Hypothalamic-Pituitary-Ovary Axis in Female Rats.

Front Physiol 2019 24;10:466. Epub 2019 Apr 24.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Hypothalamic-pituitary-ovary (HPO) axis is a dominant system controlling ovulation during puberty. Electro-acupuncture (EA) has been widely used to cure the reproductive diseases associated with endocrinological disorders. However, whether EA treatment affects HPO axis activity of physiological animals and induces alterations on the hormones in the HPO axis was also unclear. Here, we performed the EA stimuli on bilateral acupoints of Sanyinjiao (SP6) and Zusanli (ST36) on female virgin rats every 3 days and for a total of 5 times. The results showed that GnRH levels in hypothalamus were greatly upregulated in EA-treated rats than untreated animals at day 7 and 13. The serum levels for FSH and LH were severely reduced after EA treatment compared with EA-untreated animals at day 1, while they were greatly increased at day 7 and 13. The serum concentrations of 17β-estradiol were lower in EA-treated rats versus untreated animals at day 7, while they were higher in EA-treated rats than other groups at day 13. However, the progesterone concentrations were lower in EA-treated rats than Control and Sham-EA rats both at day 7 and 13. More importantly, we found that the prostaglandin E level in serum was reduced in EA-treated rats versus untreated rats at day 1, while they were upregulated at day 7 and 13. Conversely, the norepinephrine level in serum was increased at day 1, while they were decreased greatly in EA-treated rats versus untreated rats at day 7 and 13. The current results demonstrated that EA could modulate homeostasis of HPO axis in physiologic rats, which would be useful to clarify the mechanisms of EA application on pathological and physiological animals or human.
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http://dx.doi.org/10.3389/fphys.2019.00466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491808PMC
April 2019

Turnip Mosaic Virus Components Are Released into the Extracellular Space by Vesicles in Infected Leaves.

Plant Physiol 2019 07 24;180(3):1375-1388. Epub 2019 Apr 24.

Department of Biology, McGill University, Montréal, Québec, H3A 1B1, Canada

Turnip mosaic virus (TuMV) reorganizes the endomembrane system of the infected cell to generate endoplasmic-reticulum-derived motile vesicles containing viral replication complexes. The membrane-associated viral protein 6K plays a key role in the formation of these vesicles. Using confocal microscopy, we observed that this viral protein, a marker for viral replication complexes, localized in the extracellular space of infected leaves. Previously, we showed that viral RNA is associated with multivesicular bodies (MVBs). Here, using transmission electron microscopy, we observed the proliferation of MVBs during infection and their fusion with the plasma membrane that resulted in the release of their intraluminal vesicles in the extracellular space. Immunogold labeling with a monoclonal antibody that recognizes double-stranded RNA indicated that the released vesicles contained viral RNA. Focused ion beam-extreme high-resolution scanning electron microscopy was used to generate a three-dimensional image that showed extracellular vesicles in the cell wall. The presence of TuMV proteins in the extracellular space was confirmed by proteomic analysis of purified extracellular vesicles from and Arabidopsis (). Host proteins involved in biotic defense and in interorganelle vesicular exchange were also detected. The association of extracellular vesicles with viral proteins and RNA emphasizes the implication of the plant extracellular space in viral infection.
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http://dx.doi.org/10.1104/pp.19.00381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752911PMC
July 2019

Thymosin Beta 4 Is Involved in the Development of Electroacupuncture Tolerance.

Front Cell Neurosci 2019 26;13:75. Epub 2019 Mar 26.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Electroacupuncture (EA) tolerance, a negative therapeutic effect, is a gradual decline in antinociception because of its repeated or prolonged use. This study aims to explore the role of thymosin beta 4 (Tβ4), having neuro-protection properties, in EA tolerance (EAT). Rats were treated with EA once daily for eight consecutive days to establish EAT, effect of Tβ4 on the development of EAT was determined through microinjection of Tβ4 antibody and siRNA into the cerebroventricle. The mRNA and protein expression profiles of Tβ4, opioid peptides (enkephalin, dynorphin and endorphin), and anti-opioid peptides (cholecystokinin octapeptide, CCK-8 and orphanin FQ, OFQ), and mu opioid receptor (MOR) and CCK B receptor (CCKBR) in the brain areas (hypothalamus, thalamus, cortex, midbrain and medulla) were characterized after Tβ4 siRNA was administered. Tβ4 levels were increased at day 1, 4, and 8 and negatively correlated with the changes of tail flick latency in all areas. Tβ4 antibody and siRNA postponed EAT. Tβ4 siRNA caused decreased Tβ4 levels in all areas, which resulted in increased enkephalin, dynorphin, endorphin and MOR levels in most measured areas during repeated EA, but unchanged OFQ, CCK-8, and CCKBR levels in most measured areas. Tβ4 levels were negatively correlated with enkephalin, dynorphin, endorphin, or MOR levels in all areas except medulla, while positively correlated with OFQ and CCK-8 levels in some areas. These results confirmed Tβ4 facilitates EAT probably through negatively changing endogenous opioid peptides and their receptors and positively influencing anti-opioid peptides in the central nervous system.
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http://dx.doi.org/10.3389/fncel.2019.00075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444270PMC
March 2019

The Expressing Patterns of Opioid Peptides, Anti-opioid Peptides and Their Receptors in the Central Nervous System Are Involved in Electroacupuncture Tolerance in Goats.

Front Neurosci 2018 13;12:902. Epub 2018 Dec 13.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

To investigate dynamic processes of enkephalin (ENK), cholecystokinin octapeptide (CCK-8), orphanin FQ (OFQ) and their receptors (μ opioid receptor, MOR; CCK B type receptor, CCKBR and opioid receptor-like 1 receptor, OPRL1) in the central nerve system (CNS) during electroacupuncture (EA) tolerance, EA of Sixty Hz was used to stimulate goats for 6 h. Pain threshold was measured using potassium iontophoresis. The expression levels of ENK, CCK-8, and OFQ and their receptors were determined with ELISA and qPCR, respectively. The results showed that the change rates of pain threshold in EA-treated goats decreased from 89.9 ± 11.7% at 0.5 h to -11.4 ± 8.9% at 6 h. EA induced the decreased ENK and increased CCK-8 and OFQ in the most measured nuclei. EA caused decreased preproenkephalin mRNAs in ACB, CAU, PVH, and PAG at 4 h, and decreased or unchanged MOR mRNAs at 2-6 h, but increased CCK mRNAs in CAU, PVT, PVH, PAG, and SCD at 4-12 h. Increased prepronociceptin mRNAs and fluctuated CCKBR and OPLR1 mRNAs were found in the most measured nuclei. ENK levels were positively correlated ( < 0.01) with the change rates of pain thresholds in the measured nuclei or areas while CCK-8 levels (or OFQ levels) were negatively correlated ( < 0.01) with the pain thresholds in CAU (or CAU and ACB). These results suggest that the development and recovery of EA tolerance may be associated with the specific expression patterns of opioid peptides, anti-opioid peptides and their receptors in the analgesia-related nuclei or areas.
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http://dx.doi.org/10.3389/fnins.2018.00902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300483PMC
December 2018

Molecular cloning and characterization of a methyl parathion hydrolase from an organophosphorus-degrading bacterium, Serratia marcescens MEW06.

FEMS Microbiol Lett 2018 12;365(24)

State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, School of Life Sciences, Hubei University, Wuhan, 430062, PR China.

An organophosphorus-degrading bacterium MEW06, which exhibited excellent biodegradation capabilities towards 50 mg/L of methyl parathion (MP), paraoxon and dimethoate, was isolated from Sand Lake (Wuhan, China) and identified as Serratia marcescens subsp. marcescens based on physiological-biochemical characteristics and a 16S rDNA sequence-based phylogenetic tree. MEW06 genome contains a 31.09-kDa methyl parathion hydrolase (MPH) (MPHGM004539) that was 54.9% similar to Pseudomonas sp. WBC-3's MPH. RT-qPCR revealed that mphGM004539 gene expression was significant up-regulated when co-cultured with MP. mphGM004539 without signal peptide (mphGM004539Δsp) was successful cloned and expressed in Escherichia coli BL21 (DE3). Optimized specific enzyme activity of MPHGM004539ΔSP was 5.26 U/mg under 35°C and pH 11.0 conditions when MP as the substrate. Additionally, Co2+, Cd2+and Fe2+ increased the enzyme activity level. MP could be degraded by MPHGM004539ΔSP into p-nitrophenol probably by hydrolyzing the P-O ester bond. Virulence of MP towards Drosophila melanogaster W1118 was reduced by MEW06 or MPHGM004539ΔSP biodegradation. This is the first cloning and characterization of MPH from the organophosphorus-degrading bacterium S. marcescens. MEW06 and its MPH have potential roles in the bioremediation of organophosphorus pesticide-contaminated eco-systems.
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http://dx.doi.org/10.1093/femsle/fny279DOI Listing
December 2018

Organelle Formation in Bacteria and Archaea.

Annu Rev Cell Dev Biol 2018 10 16;34:217-238. Epub 2018 Aug 16.

Department of Plant and Microbial Biology, University of California, Berkeley, California 94720, USA; email:

Uncovering the mechanisms that underlie the biogenesis and maintenance of eukaryotic organelles is a vibrant and essential area of biological research. In comparison, little attention has been paid to the process of compartmentalization in bacteria and archaea. This lack of attention is in part due to the common misconception that organelles are a unique evolutionary invention of the "complex" eukaryotic cell and are absent from the "primitive" bacterial and archaeal cells. Comparisons across the tree of life are further complicated by the nebulous criteria used to designate subcellular structures as organelles. Here, with the aid of a unified definition of a membrane-bounded organelle, we present some of the recent findings in the study of lipid-bounded organelles in bacteria and archaea.
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http://dx.doi.org/10.1146/annurev-cellbio-100616-060908DOI Listing
October 2018

The effect of temporal concept on the automatic activation of spatial representation: From axis to plane.

Conscious Cogn 2018 10 6;65:95-108. Epub 2018 Aug 6.

School of Psychology, South China Normal University, Guangzhou 510631, China.

Temporal concepts could be represented horizontally(X-axis) or vertically (Y-axis). However, whether the spatial representation of time exists in the whole plane remains unclear. In this study, we investigated whether processing temporal concepts would automatically activate spatial representations in a whole plane without any guidance or cue. Participants first indicated whether a word was past-related or future-related, then, they identified a target in different visual fields. In Experiment 1, the results demonstrated that past time mapped onto the left and top in a plane or axis, while future time mapped onto the right and bottom, with the horizontal effect being stronger than the vertical effect. In Experiment 2, an index of eye movement showed a similar data pattern. Thinking about temporal concepts activates spatial schema automatically without guidance or cue, and the time-space metaphor is represented not only as an axis but also as a whole plane. The results were discussed in terms of the possible cultural differences that made the Chinese participants tend to be more flexible in spatial representation of time because of their comprehensive thinking.
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http://dx.doi.org/10.1016/j.concog.2018.06.020DOI Listing
October 2018

Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Plant Virus Replication.

Front Plant Sci 2018 30;9:57. Epub 2018 Jan 30.

State Key Laboratory of Agro-Biotechnology and Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China.

Positive-sense (+) RNA viruses represent the most abundant group of viruses and are dependent on the host cell machinery to replicate. One remarkable feature that occurs after (+) RNA virus entry into cells is the remodeling of host endomembranes, leading to the formation of viral replication factories. Recently, rapid progress in three-dimensional (3D) imaging technologies, such as electron tomography (ET) and focused ion beam-scanning electron microscopy (FIB-SEM), has enabled researchers to visualize the novel membrane structures induced by viruses at high resolution. These 3D imaging technologies provide new mechanistic insights into the viral infection cycle. In this review, we summarize the latest reports on the cellular remodeling that occurs during plant virus infection; in particular, we focus on studies that provide 3D architectural information on viral replication factories. We also outline the mechanisms underlying the formation of these membranous structures and discuss possible future research directions.
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http://dx.doi.org/10.3389/fpls.2018.00057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797596PMC
January 2018

Lysyl oxidase inhibition via β-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro.

Mol Med Rep 2018 Apr 26;17(4):5029-5036. Epub 2018 Jan 26.

Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.

Lysyl oxidase (LOX) is an enzyme that oxidizes lysine residues in collagens and elastin. It stabilizes or remodels the extracellular matrix and basement membrane of blood vessels. Current oncology studies have revealed that LOX is upregulated in invasive cancer cells and bolstered cell movement, and LOX was observed to promote the angiogenesis and migration of endothelial cells. In the present study, angiogenesis and migration were examined in human umbilical vein endothelial cells (HUVECs). Following cell treatment with 0.1-0.4 mM β-aminoproprionitrile (BAPN), a specific inhibitor of LOX, angiogenesis was analyzed with a fibrin gel in vitro angiogenesis assay kit and migration was examined via a Boyden Chamber assay. Angiogenesis-associated gene expression was investigated with a microarray assay and confirmed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results showed that HUVEC angiogenesis substantially increased in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and phorbol 12-myristate 13-acetate (PMA). In addition, LOX inhibition blocked the angiogenesis stimulated by VEGF bFGF and PMA, and the inhibition of LOX reduced the migration of HUVECs. Furthermore, the microarray and RT-qPCR revealed that BAPN downregulated myeloid progenitor inhibitory factor 1, and western blot analysis demonstrated that BAPN decreased the phosphorylation of MAPK and Akt, suggesting that the specific inhibitor of LOX, BAPN, may serve as an alternative strategy for preventing angiogenesis.
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http://dx.doi.org/10.3892/mmr.2018.8508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865964PMC
April 2018

Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System.

Front Neurosci 2017 20;11:644. Epub 2017 Nov 20.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Electroacupuncture (EA) has been used for treating visceral hypersensitivity (VH). However, the underlying molecular mechanism remains unclear. This study was aim to testify the effect of EA on ileitis-provoked VH, and to confirm whether EA attenuates VH through Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway in the periaqueductal gray (PAG)-the rostral ventromedial medulla (RVM)-the spinal cord dorsal horn (SCDH) axis. Goats were anesthetized and laparotomized for injecting 2,4,6-trinitro-benzene-sulfonic acid (TNBS)-ethanol solution (30mg TNBS dissolved in 40% ethanol) into the ileal wall to induce VH. EA was treated for 30min from day 7, then every 3 days for six times. VH was assessed by visceromotor response (VMR) and pain behavior response to 20, 40, 60, 80, and 100 mmHg colorectal distension pressures at day 7, 10, 13, 16, 19, and 22. The spinal cord in the eleventh thoracic vertebra and the brain were collected at day 22. The protein and mRNA levels of IL-6, JAK2, and STAT3 in the SCDH were detected with western blot and qPCR, respectively. The distribution of these substances was observed with immunohistochemistry in the ventrolateral PAG (vlPAG), RVM (mainly the nucleus raphe magnus, NRM), SCDH, the nucleus tractus solitaries (NTS) and the dorsal motor nucleus of vagi (DMV). Goats administered with TNBS-ethanol solution showed diarrhea, enhanced VMR and pain behavior response, and increased IL-6, phosphorylated JAK2 and STAT3 (pJAK2 and pSTAT3) in the vlPAG, NRM, NTS and DMV, and their protein and mRNA levels in the SCDH. EA relieved diarrhea, VMR and pain behavior response, decreased IL-6, pJAK2 and pSTAT3 levels in the vlPAG, NRM, SCDH, NTS, and DMV except for pSTAT3 in the DMV, but did not affect mRNA level of these three substances in the SCDH. EA attenuates VH probably through inhibiting JAK2/STAT3 signaling pathway in the PAG-RVM-SCDH axis.
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http://dx.doi.org/10.3389/fnins.2017.00644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701938PMC
November 2017

Lysyl oxidase is involved in synovial hyperplasia and angiogenesis in rats with collagen‑induced arthritis.

Mol Med Rep 2017 Nov 7;16(5):6736-6742. Epub 2017 Sep 7.

Department of Pathogenic Biology and Immunology, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.

Lysyl oxidase (LOX) serves an important role in remodeling the extracellular matrix and angiogenesis in various types of cancer; however, whether LOX is involved in the pathogenesis of rheumatoid arthritis remains unknown. In order to investigate this in the present study, β‑aminopropionitrile, an inhibitor of LOX, was injected intraperitoneally into rats with type II collagen‑induced arthritis (CIA). Subsequently, synovial hyperplasia was examined by hematoxyl in and eosin staining, and the microvascular density (MVD) and expression levels of LOX, matrix metalloproteinase (MMP)‑2 and MMP‑9 in the synovial membrane and fluid were determined by immunohistochemistry and ELISA, respectively. The enzyme activity of LOX was evaluated by the Amplex Red Hydrogen Peroxide method. The results demonstrated an increased amount of rough synovial membranes, higher MVD in these membranes and more synovial cell layers in CIA rats compared with in the control rats. In addition, higher enzymatic activity of LOX and higher expression levels of MMP‑2 and MMP‑9 were revealed in CIA rats compared with in the control rats. Notably, β‑aminopropionitrile inhibited paw swelling and the decreased the arthritis index, the MVD in the synovial membranes and the expression levels of MMP‑2 and MMP‑9. Furthermore, the expression level of LOX in the synovial membranes was positively associated with the MVD and the expression levels of MMP‑2 and MMP‑9, suggesting that LOX promotes synovial hyperplasia and angiogenesis and that LOX may be a potential therapeutic target for rheumatoid arthritis.
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http://dx.doi.org/10.3892/mmr.2017.7436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865828PMC
November 2017

Neural substrates of embodied natural beauty and social endowed beauty: An fMRI study.

Sci Rep 2017 08 2;7(1):7125. Epub 2017 Aug 2.

Guangdong Key Laboratory of Mental Health and Cognitive Science, Center for Studies of Psychological Application, School of Psychology, South China Normal University, Guangzhou, P. R. China.

What are the neural mechanisms underlying beauty based on objective parameters and beauty based on subjective social construction? This study scanned participants with fMRI while they performed aesthetic judgments on concrete pictographs and abstract oracle bone scripts. Behavioral results showed both pictographs and oracle bone scripts were judged to be more beautiful when they referred to beautiful objects and positive social meanings, respectively. Imaging results revealed regions associated with perceptual, cognitive, emotional and reward processing were commonly activated both in beautiful judgments of pictographs and oracle bone scripts. Moreover, stronger activations of orbitofrontal cortex (OFC) and motor-related areas were found in beautiful judgments of pictographs, whereas beautiful judgments of oracle bone scripts were associated with putamen activity, implying stronger aesthetic experience and embodied approaching for beauty were elicited by the pictographs. In contrast, only visual processing areas were activated in the judgments of ugly pictographs and negative oracle bone scripts. Results provide evidence that the sense of beauty is triggered by two processes: one based on the objective parameters of stimuli (embodied natural beauty) and the other based on the subjective social construction (social endowed beauty).
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http://dx.doi.org/10.1038/s41598-017-07608-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541072PMC
August 2017
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