Publications by authors named "Yuanyuan Gao"

124 Publications

PEGylated Graphene Oxide Carried OH-CATH30 to Accelerate the Healing of Infected Skin Wounds.

Int J Nanomedicine 2021 13;16:4769-4780. Epub 2021 Jul 13.

School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China.

Background: The treatment of ()-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing.

Purpose: The aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by

Methods: PGO-OH30 nanoparticles were prepared by π-π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated.

Results: Characterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (<0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of in wounds compared with the control group (<0.05). In particular, on day 7, the number of was 100 times lower in the PGO-OH30 group than in the control group.

Conclusion: The PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.
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http://dx.doi.org/10.2147/IJN.S304702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286112PMC
July 2021

Haloarchaea, excellent candidates for removing pollutants from hypersaline wastewater.

Trends Biotechnol 2021 Jul 17. Epub 2021 Jul 17.

Chinese Academy of Sciences Key Laboratory of Urban Pollutant Conversion, Department of Environmental Science and Engineering, University of Science and Technology of China, Hefei 230026, China. Electronic address:

Hypersaline wastewater is difficult to treat due to the inhibition of salt stress on microbes' viability and metabolic capabilities. Haloarchaea, native microorganisms that thrive in hypersaline habitats, overcome this key obstacle naturally. This review provides a comprehensive overview of the metabolic versatility of Haloarchaea in hypersaline wastewater treatment, including carbon, nitrogen, phosphorus, sulfur, and heavy metal metabolism. It also analyzes factors affecting pollutant removal and addresses metabolic mechanisms. Additionally, haloarchaea microbial characteristics and strategies to cope with salt stress are highlighted. Finally, the biotechnological potential of biomolecules produced from haloarchaea is investigated. To get better insight into the potential of haloarchaea, a deeper investigation of basic metabolism and more in-depth studies of their genomics and applications in actual wastewater are also necessary.
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http://dx.doi.org/10.1016/j.tibtech.2021.06.006DOI Listing
July 2021

MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke.

Anim Cells Syst (Seoul) 2021 23;25(2):93-101. Epub 2021 Apr 23.

Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China.

Monocarboxylate transporter 2 (MCT2) is the predominant monocarboxylate transporter expressed by neurons. MCT2 plays an important role in brain energy metabolism. Stroke survivors are at high risk of cognitive impairment. We reported previously that stroke-induced cognitive impairment was related to impaired energy metabolism. In the present study, we report that cognitive function was impaired after stroke in rats. We found that MCT2 expression, but not that of MCT1 or MCT4, was markedly decreased in the rat hippocampus at 7 and 28 days after transient middle cerebral artery occlusion (tMCAO). Moreover, MCT2 overexpression promoted recovery of cognitive function after stroke. The molecular mechanism underlying these effects may be related to an increase in adenosine monophosphate-activated protein kinase-mediated mitochondrial biogenesis induced by overexpression of MCT2. Our findings suggest that MCT2 activation ameliorates cognitive impairment after stroke.
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http://dx.doi.org/10.1080/19768354.2021.1915379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118516PMC
April 2021

Deconvolution-based partial volume correction of PET images with parallel level set regularization.

Phys Med Biol 2021 Jul 9;66(14). Epub 2021 Jul 9.

Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States of America.

The partial volume effect (PVE), caused by the limited spatial resolution of positron emission tomography (PET), degrades images both qualitatively and quantitatively. Anatomical information provided by magnetic resonance (MR) images has the potential to play an important role in partial volume correction (PVC) methods. Post-reconstruction MR-guided PVC methods typically use segmented MR tissue maps, and further, assume that PET activity distribution is uniform in each region, imposing considerable constraints through anatomical guidance. In this work, we present a post-reconstruction PVC method based on deconvolution with parallel level set (PLS) regularization. We frame the problem as an iterative deconvolution task with PLS regularization that incorporates anatomical information without requiring MR segmentation or assuming uniformity of PET distributions within regions. An efficient algorithm for non-smooth optimization of the objective function (invoking split Bregman framework) is developed so that the proposed method can be feasibly applied to 3D images and produces sharper images compared to PLS method with smooth optimization. The proposed method was evaluated together with several other PVC methods using both realistic simulation experiments based on the BrainWeb phantom as well ashuman data. Our proposed method showed enhanced quantitative performance when realistic MR guidance was provided. Further, the proposed method is able to reduce image noise while preserving structure details onhuman data, and shows the potential to better differentiate amyloid positive and amyloid negative scans. Overall, our results demonstrate promise to provide superior performance in clinical imaging scenarios.
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http://dx.doi.org/10.1088/1361-6560/ac0d8fDOI Listing
July 2021

Functional characterization of the transcription factors AhR and ARNT in Nilaparvata lugens.

Pestic Biochem Physiol 2021 Jul 14;176:104875. Epub 2021 May 14.

Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address:

In the present study, the aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) of Nilaparvata lugens were cloned and identified. The NlAhR and NlARNT expression levels significantly increased after imidacloprid, etofenprox and isoprocarb treatments. Knockdowns of NlAhR and NlARNT increased the susceptibility of N. lugens to imidacloprid, etofenprox and isoprocarb, and the detoxification enzyme activities were also significantly decreased. In addition, NlCYP301A1, NlGSTt1 and NlCarE7 were significantly down-regulated after injections of dsNlAhR and dsNlARNT, with the NlCarE7 expression decreasing by greater than 80%. Moreover, after knocking down NlCarE7, the susceptibility of N. lugens to etofenprox and isoprocarb significantly increased. Both NlAhR and NlARNT bound the NlCarE7 promoter and significantly enhanced the transcriptional activity. Our research revealed the functional roles of transcription factors NlAhR and NlARNT in the detoxification metabolism of N. lugens. The results provide a theoretical basis for the pest management and comprehensive control of N. lugens and increase our knowledge of insect toxicology.
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http://dx.doi.org/10.1016/j.pestbp.2021.104875DOI Listing
July 2021

Occurrence of Chordoid Glioma With Sodium Ion Metabolism Disorder 5 Years After Meningioma Surgery and Whole-Exome Sequencing: A Case Report and Literature Review.

Front Genet 2021 10;12:617575. Epub 2021 May 10.

Department of VIP Unit, China-Japan Union Hospital of Jilin University, Changchun, China.

Chordoid glioma (CG), a rare slow-growing brain tumor, mainly occurs in the region of the third ventricle. Although its degree of malignancy is relatively low, its clinical prognosis is poor due to obscure clinical manifestations and the particular growing position. Currently, gross total resection is the best available method for treatment of CG. However, the tumor is located in the deep structure of the brain and close to neurovascular structure so it is difficult to remove completely. This study reported a case of CG of the third ventricle 5 years after surgery of right frontal parietal fibrous meningioma, accompanied with peri and post-operative sodium ion metabolism disorder. Whole-exome sequencing (WES) revealed 25 gene mutations shared by meningioma and CG. In addition, the CG marker gene mutation also existed in this patient. We reviewed the latest literature on this rare brain tumor, summarized its clinical manifestations, imaging and pathological characteristics, and discussed the mechanism related to its occurrence and the reasons for sodium ion disorder.
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http://dx.doi.org/10.3389/fgene.2021.617575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143433PMC
May 2021

Degraded Porphyra haitanensis sulfated polysaccharide relieves ovalbumin-induced food allergic response by restoring the balance of T helper cell differentiation.

Food Funct 2021 May 30;12(10):4707-4719. Epub 2021 Apr 30.

Allergy Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

We previously described that Porphyra haitanensis sulfated polysaccharide (PHSP) maintains the balance of pro-inflammation and immunosuppression. However, it is unclear whether degraded PHSP (DPHSP) still shows the immunomodulatory activity. Here, we degraded PHSP by four different methods alone or combined in pairs, and the results showed that the molecular weight and viscosity of DPHSP were significantly decreased, while the main chemical bonds and functional structure were consistent with those of PHSP. We then investigated the immunomodulatory function of DPHSP in vitro and in vivo. Actually, DPHSP enhances the inhibitory effects on mast cell activation and improves the suppression activity of PHSP on the food anaphylactic response. In an ovalbumin-induced food allergy mouse model, the production of allergic mediators and cytokines (interleukin-4 and 13, and interferon-γ) was inhibited by DPHSP. Meanwhile, DPHSP had a stronger ability to up-regulate the differentiation of regulatory T (Treg) cells and its related cytokines. These results suggested that DPHSP showed a better anti-food allergic ability than PHSP by regulating T helper cell balance and promoting Treg cell differentiation, which indicates that DPHSP is a novel potential nutrient component against food allergy.
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http://dx.doi.org/10.1039/d1fo00335fDOI Listing
May 2021

Encapsulation of Hydrophobic and Low-Soluble Polyphenols into Nanoliposomes by pH-Driven Method: Naringenin and Naringin as Model Compounds.

Foods 2021 Apr 28;10(5). Epub 2021 Apr 28.

Key Laboratory of Tropical Crop Products Processing of Ministry of Agriculture and Rural Affairs, Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524001, China.

Naringenin and naringin are a class of hydrophobic polyphenol compounds and both have several biological activities containing antioxidant, anti-inflammatory and anti-tumor properties. Nevertheless, they have low water solubility and bioavailability, which limits their biological activity. In this study, an easy pH-driven method was applied to load naringenin or naringin into nanoliposomes based on the gradual reduction in their water solubility after the pH changed to acidity. Thus, the naringenin or naringin can be embedded into the hydrophobic region within nanoliposomes from the aqueous phase. A series of naringenin/naringin-loaded nanoliposomes with different pH values, lecithin contents and feeding naringenin/naringin concentrations were prepared by microfluidization and a pH-driven method. The naringin-loaded nanoliposome contained some free naringin due to its higher water solubility at lower pH values and had a relatively low encapsulation efficiency. However, the naringenin-loaded nanoliposomes were predominantly nanometric (44.95-104.4 nm), negatively charged (-14.1 to -19.3 mV) and exhibited relatively high encapsulation efficiency (EE = 95.34% for 0.75 mg/mL naringenin within 1% lecithin). Additionally, the naringenin-loaded nanoliposomes still maintained good stability during 31 days of storage at 4 °C. This study may help to develop novel food-grade colloidal delivery systems and apply them to introducing naringenin or other lipophilic polyphenols into foods, supplements or drugs.
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http://dx.doi.org/10.3390/foods10050963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146953PMC
April 2021

Preparation and characterization of selenium-rich polysaccharide from Phellinus igniarius and its effects on wound healing.

Carbohydr Polym 2021 Jul 24;264:117982. Epub 2021 Mar 24.

Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biopharmaceuticals, School of Life Science and Technology, Weifang Medical University, Weifang, 261053, China. Electronic address:

The modified of polysaccharides show various bio-activities. In our work, Phellinus igniarius Selenium-enriched mycelias polysaccharides (PSeP) were prepared from Phellinus igniarius, and its antioxidant and anti-inflammatory effects on injured mice were evaluated. The selenium content and physical properties of polysaccharides were characterized by GC, HPGPC, and FT-IR analysis. The results showed that PSeP could reduce reactive oxygen species (ROS) levels, myeloperoxidase (MPO) activity as well as malondialdehyde (MDA) content. Meanwhile, it increased the enzyme activities of glutathione peroxidase (GSH-Px) and catalase (CAT). Finally, it showed obvious wound healing effects in vivo. Moreover, PSeP could clear the ROS without obvious cytotoxicity. PSeP could further improve its ability to clear ROS level to promote skin wound healing in mice three days in advance.
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http://dx.doi.org/10.1016/j.carbpol.2021.117982DOI Listing
July 2021

Gentamicin Combined With Hypoionic Shock Rapidly Eradicates Aquaculture Bacteria and .

Front Microbiol 2021 6;12:641846. Epub 2021 Apr 6.

Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.

Bacterial pathogens are a major cause of infectious diseases in aquatic animals. The abuse of antibiotics in the aquatic industry has led to the proliferation of antibiotic resistance. It is therefore essential to develop more effective and safer strategies to increase the efficacy and extend the life span of the antibiotics used in aquaculture. In this study, we show that six aquaculture bacterial pathogens (i.e., , , , , , and ) in the stationary phase can be rapidly killed after immersion in gentamicin- or neomycin-containing, ion-free solutions for a few minutes. Such hypoionic shock treatment enhances the bacterial uptake of gentamicin in an ATP-dependent manner. Importantly, we demonstrate, as a proof of concept, that gentamicin under hypoionic shock conditions can effectively kill in a skin infection model of zebrafish (), completely curing the infected fish. Given that pathogenic bacteria generally adhere to the skin surface and gills of aquatic animals, our strategy is of potential significance for bacterial infection control, especially for small-scale economic fish farming and ornamental fish farming. Further, the combined treatment can be completed within 5 min with a relatively small volume of solution, thus minimizing the amount of residual antibiotics in both animals and the environment.
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http://dx.doi.org/10.3389/fmicb.2021.641846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055967PMC
April 2021

Decreasing the Surgical Errors by Neurostimulation of Primary Motor Cortex and the Associated Brain Activation via Neuroimaging.

Front Neurosci 2021 22;15:651192. Epub 2021 Mar 22.

Center for Modeling, Simulation and Imaging in Medicine, Rensselaer Polytechnic Institute, Troy, NY, United States.

Acquisition of fine motor skills is a time-consuming process as it is based on learning via frequent repetitions. Transcranial electrical stimulation (tES) is a promising means of enhancing simple motor skill development via neuromodulatory mechanisms. Here, we report that non-invasive neurostimulation facilitates the learning of complex fine bimanual motor skills associated with a surgical task. During the training of 12 medical students on the Fundamentals of Laparoscopic Surgery (FLS) pattern cutting task over a period of 12 days, we observed that transcranial direct current stimulation (tDCS) decreased error level and the variability in performance, compared to the Sham group. Furthermore, by concurrently monitoring the cortical activations of the subjects via functional near-infrared spectroscopy (fNIRS), our study showed that the cortical activation patterns were significantly different between the tDCS and Sham group, with the activation of primary motor cortex (M1) and prefrontal cortex (PFC) contralateral to the anodal electrode significantly decreased while supplemental motor area (SMA) increased by tDCS. The lowered performance errors were retained after 1-month post-training. This work supports the use of tDCS to enhance performance accuracy in fine bimanual motor tasks.
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http://dx.doi.org/10.3389/fnins.2021.651192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019915PMC
March 2021

Differential Effects of Serum Lipoprotein-Associated Phospholipase A2 on Periventricular and Deep Subcortical White Matter Hyperintensity in Brain.

Front Neurol 2021 8;12:605372. Epub 2021 Mar 8.

Department of Neurology, The Affiliated Jiangning Hospital With Nanjing Medical University, Nanjing, China.

Serum level of lipoprotein-associated phospholipase A2 (Lp-PLA2) was associated with white matter hyperintensity (WMH). There were differences in the anatomical structure and pathophysiological mechanism between periventricular WMH (PVWMH) and deep subcortical WMH (DSWMH). In this study, we aimed to investigate the effects of serum Lp-PLA2 on the PVWMH and DSWMH. In total, 711 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this cross-sectional study, who had received physical examinations in the Department of Neurology, the Affiliated Jiangning Hospital of Nanjing Medical University due to dizziness and headaches between January 2016 and July 2019. Enzyme linked immunosorbent assay (ELISA) was utilized to determine the serum Lp-PLA2. Fazekas scale was used to measure the severity of PVWMH (grade 0-3) and DSWMH (grade 0-3) on MRI scans. Ordinal regression analysis was carried out to investigate the relationship between serum Lp-PLA2 and PVWMH or DSWMH. Finally, 567 cases were included in this study. The average level of serum Lp-PLA2 was 213.35±59.34 ng/ml. There were statistical differences in the age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Lp-PLA2 grade, creatinine, Hcy, and H-CRP ( < 0.05) in PVWMH groups. Ordinal regression analysis indicated that there was a lower risk of PVWMH in the patients with normal and moderately elevated serum Lp-PLA2 compared with those with significantly elevated serum Lp-PLA2 after adjusting age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Cr, Hcy, and H-CRP. In addition, PVWMH was correlated to advanced age, hypertension, diabetes mellitus, and lacunar infarction. After adjusting for confounding factors, DSWMH was correlated to advanced age and lacunar infarction. There was no correlation between serum Lp-PLA2 and DSWMH. Serum Lp-PLA2 was closely associated with the pathogenesis of PVWMH rather than DSWMH. There might be different pathological mechanisms between PVWMH and DSWMH.
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http://dx.doi.org/10.3389/fneur.2021.605372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982574PMC
March 2021

Functional brain connectivity related to surgical skill dexterity in physical and virtual simulation environments.

Neurophotonics 2021 Jan 3;8(1):015008. Epub 2021 Mar 3.

Rensselaer Polytechnic Institute, Center for Modeling, Simulation, and Imaging in Medicine, Troy, New York, United States.

Surgical simulators, both virtual and physical, are increasingly used as training tools for teaching and assessing surgical technical skills. However, the metrics used for assessment in these simulation environments are often subjective and inconsistent. We propose functional activation metrics, derived from brain imaging measurements, to objectively assess the correspondence between brain activation with surgical motor skills for subjects with varying degrees of surgical skill. Cortical activation based on changes in the oxygenated hemoglobin (HbO) of 36 subjects was measured using functional near-infrared spectroscopy at the prefrontal cortex (PFC), primary motor cortex, and supplementary motor area (SMA) due to their association with motor skill learning. Inter-regional functional connectivity metrics, namely, wavelet coherence (WCO) and wavelet phase coherence were derived from HbO changes to correlate brain activity to surgical motor skill levels objectively. One-way multivariate analysis of variance found a statistically significant difference in the inter-regional WCO metrics for physical simulator based on Wilk's Λ for expert versus novice, , . Partial eta squared effect size for the inter-regional WCO metrics was found to be highest between the central prefrontal cortex (CPFC) and SMA, CPFC-SMA ( ). Two-tailed Mann-Whitney U tests with a 95% confidence interval showed baseline equivalence and a statistically significant ( ) difference in the CPFC-SMA WPCO metrics for the physical simulator training group ( ) versus the untrained control group ( ) following training for 10 consecutive days in addition to the pretest and posttest days. We show that brain functional connectivity WCO metric corresponds to surgical motor skills in the laparoscopic physical simulators. Functional connectivity between the CPFC and the SMA is lower for subjects that exhibit expert surgical motor skills than untrained subjects in laparoscopic physical simulators.
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http://dx.doi.org/10.1117/1.NPh.8.1.015008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927423PMC
January 2021

Tracing steroidogenesis in prostate biopsy samples to unveil prostate tissue androgen metabolism characteristics and potential clinical application.

J Steroid Biochem Mol Biol 2021 Jun 4;210:105859. Epub 2021 Mar 4.

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. Electronic address:

Androgens are essential for prostate cancer development. However, steroidogenesis has mainly been investigated in a limited number of prostate cancer cell lines, leading to varied conclusions and elusive clinical significance. Here, we established an ex vivo research platform with fresh biopsy samples transiently cultured with tritium- labelled androgens to trace steroidogenesis in prostate tissues and investigate its potential clinical application. DHEA was confirmed as the major precursor for androgen synthesis in the prostate. Significant amounts of oxidized DHEA and 5α-androstanedione were generated from DHEA in prostate biopsy samples. Prostatic steroidogenesis was independent of other clinical factors. Furthermore, prostatic steroidogenesis was suppressed after androgen deprivation therapy but increased upon treatment resistance, indicating that prostatic steroidogenesis was affected by clinical treatments. Overall, we provide an accessible research platform to characterize steroidogenesis in prostate tissue and indicate the correlation between prostatic steroidogenesis and disease progression.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105859DOI Listing
June 2021

Pediatric anti-N-methyl-d-aspartate receptor encephalitis in southern China: Analysis of 111 cases.

J Neuroimmunol 2021 03 15;352:577479. Epub 2021 Jan 15.

Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9# Jin Sui Road, 510623 Guangzhou, Guangdong Province, PR China. Electronic address:

Objective: To study the clinical features of children diagnosed with anti-NMDAR encephalitis in southern China.

Methods: Clinical data of children diagnosed with anti-NMDAR encephalitis from October 2014 to June 2020 from one national regional medical center were analyzed. Neurological disability was assessed by modified Rankin Scale (mRS) throughout the course of disease.

Results: 111 children (M/F = 49/62; mean onset age = 6.8 y) with anti-NMDAR encephalitis were involved. Prodromal events occurred in 34.2% of patients with infectious events being the most common. Seizure was the most common initial symptom, though movement disorder served as the most common event throughout the course of disease. 9.9% of patients had overlapped with other neuronal autoantibodies. Electroencephalogram showed abnormalities with slow wave (100.0%), epileptic discharge (31.5%) and delta brush (8.1%) respectively. 41.4% of patients had abnormal brain MRI, with focal lesions being the most common. None patients had tumor. 80.9% of patients had good response to first line therapy (steroid plus immunoglobulin), while 14 patients accepted second-line therapy (Rituximab) and all had a good response. Boys were significantly more likely to need more course of steroid. 13.8% of patients relapsed. 2 male patients died. mRS score was significantly improved after treatment. 51.4% of patients had a full recovery and 81.7% had mRS score ≤ 2. The median mRS score of boys after treatment was higher than that of girls. Non-infectious prodromal event, past medical history, perivascular lesions in brain MRI, hospital stay, initial mRS score higher than 3, and RTX treatment were independent risk factors associated with poor prognosis, defined as mRS score > 2.

Conclusion: Of pediatric anti-NMDAR encephalitis in southern China: median onset age around 7 years; girls more common; boys might have poor outcome than girls; seizure or movement disorder respectively being most common onset or course symptom; a few overlapped with other neuronal autoantibodies; rare combined with tumor; most had a good response to immunotherapy and a good prognosis; relapse rate relatively high; fatality rate relatively low; some risk factors associated with poor prognosis.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577479DOI Listing
March 2021

SZB120 Exhibits Immunomodulatory Effects by Targeting eIF2α to Suppress Th17 Cell Differentiation.

J Immunol 2021 03 22;206(5):953-962. Epub 2021 Jan 22.

Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis, Shanghai Institute of Immunology, Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

IL-17-secreting Th17 cells play an important role in the pathogenesis of various inflammatory and autoimmune diseases. IL-17-targeted biologics and small molecules are becoming promising treatments for these diseases. In this study, we report that SZB120, a derivative of the natural compound 3-acetyl-β-boswellic acid, inhibits murine Th17 cell differentiation by interacting with the α-subunit of eukaryotic initiation factor 2 (eIF2α). We showed that SZB120 directly interacts with eIF2α and contributes to serine 51 phosphorylation of eIF2α. The suppressive effect of SZB120 on Th17 cell differentiation was reversed by GSK2606414, an inhibitor of eIF2α phosphokinase. Phosphorylation of eIF2α induced by SZB120 decreased the protein expression of IκBζ, which is important for Th17 cell differentiation. Notably, interaction with eIF2α by SZB120 also impaired glucose uptake and glycolysis in T cells. In vivo, SZB120 treatment of C57BL/6 mice significantly attenuated IL-17/Th17-mediated autoimmune disease. Our study indicates that SZB120 is a promising drug candidate for IL-17/Th17-mediated inflammatory diseases.
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http://dx.doi.org/10.4049/jimmunol.2000036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887737PMC
March 2021

The effects of NONRATT008453.2 on autophagy in genital tubercle fibroblasts of rats with hypospadias induced by dibutyl phthalate.

Birth Defects Res 2021 Mar 15;113(5):399-408. Epub 2021 Jan 15.

Section of Pediatric Urology, Children's Hospital of Soochow University, Suzhou, P. R. China.

Background: Hypospadias is a common birth defect that might be caused by inadequate fusion of the urethral folds in the process of male external genital development. We intended to discover the crucial long noncoding RNAs (lncRNAs) regulating autophagy from the gene expression profile of the genital tubercle (GT) of dibutyl phthalate (DBP) induced hypospadiac rats.

Methods: Whole transcriptome resequencing was used to determine the expression of the total RNA in GTs and cultured fibroblasts obtained from GTs of DBP-induced hypospadiac male rat fetuses. Autophagosomes and autolysosomes were examined under a transmission electron microscope after overexpression of lncRNA NONRATT008453.2 in the fibroblasts by adenovirus transfection. Finally, the protein expression levels of Atg5, Beclin-1, Atg7, and the LC3A/B-II:LC3A/B-I ratio were detected in the fibroblasts by western blotting.

Results: NONRATT008453.2 suppressed autophagy by promoting the expression of Atg7, but inhibited the expressions of Atg5, Beclin-1, and the LC3A/B-II:LC3A/B-I ratio in the GT fibroblasts.

Conclusions: NONRATT008453.2 may have an influence on autophagy in the fibroblasts of the GT in DBP-induced hypospadiac rats.
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http://dx.doi.org/10.1002/bdr2.1863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986160PMC
March 2021

Differential proteomics reveals main determinants for the improved pectinase activity in UV-mutagenized Aspergillus niger strain.

Biotechnol Lett 2021 Apr 15;43(4):909-918. Epub 2021 Jan 15.

Engineering Research Center of Industrial Microbiology of Ministry of Education, College of Life Sciences, Fujian Normal University, No.8, Shangsan Road, Cangshan District, Fuzhou, 350108, Fujian, China.

Objectives: To reveal the potential mechanism and key determinants that contributed to the improved pectinase activity in Aspergillus niger mutant EIMU2, which was previously obtained by UV-mutagenesis from the wild-type A. niger EIM-6.

Results: Proteomic analysis for Aspergillus niger EIMU2 by two-dimensional electrophoresis demonstrated that mutant EIMU2 harbored a multiple enzyme system for the degradation of pectin, mainly constituting by main-chain-cleaving enzymes polygalacturonase, pectate lyase, pectinesterase, and some accessory enzymes rhamnogalacturonan lyase and arabinofuranosidase. Further quantitatively differential proteomic analysis revealed that the quantities of four proteins, pectinesterase, rhamnogalacturonan lyase A, DNA-directed RNA polymerase A, and a hypothetical protein in strain EIMU2 were much higher than those in EIM-6. PCR amplification, sequencing and alignment analysis of genes for the two main members of pectin-degrading enzymes, pectate lyase and polygalacturonase showed that their sequences were completely consistent in A. niger EIM-6 and mutant EIMU2.

Conclusions: The result demonstrated that the improved pectinase activity by UV-mutagenesis in A. niger EIMU2 was probably contributed to the up-regulated expression of rhamnogalacturonan lyase, or pectinesterase, which resulted in the optimization of synergy amongst different components of pectin-degrading enzymes.
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http://dx.doi.org/10.1007/s10529-020-03075-wDOI Listing
April 2021

Association of neuroimaging markers of cerebral small vessel disease with short-term outcomes in patients with minor cerebrovascular events.

BMC Neurol 2021 Jan 13;21(1):21. Epub 2021 Jan 13.

Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, 211100, Jiangsu, China.

Background: Increasing evidences have showed that neuroimaging markers of SVD can predict the short-term outcome of acute ischemic stroke (AIS). It is unclear that whether neuroimaging markers of SVD are also associated with short-term outcomes of minor cerebrovascular events. In the present study, we investigate neuroimaging markers of SVD in order to explore their roles in prediction of short-term outcome in patients with minor cerebrovascular events.

Methods: Consecutive first-ever stroke patients (n = 546) from the Affiliated Jiangning Hospital of Nanjing Medical University were enrolled. A total of 388 patients were enrolled according to minor cerebrovascular events definition (National Institutes of Health Stroke Scale Score ≤ 3) and exclusion criteria. MRI scans were performed within 7 days of stroke onset, and then neuroimaging markers of SVD including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS), SVD burden scores were assessed. We completed baseline characteristics and evaluated the relationships of short-term outcomes to SVD neuroimaging markers and SVD scores. The 90-day modified Rankin Scale (mRS) was thought as primary outcome and was dichotomized as good functional outcome (mRS 0-1) and poor outcome (mRS 2-6). Secondary outcomes were stroke progression and stroke recurrence.

Results: Higher age, National Institutes of Health Stroke Scale (NIHSS) upon admission, lipoprotein-associated phospholipase A2 (LP-PLA2) and lacunes, Fazekas score were correlated with poor functional outcome (P < 0.05), But after adjusting for confounding variables, among the neuroimaging markers of cerebral small vessel disease, only Fazekas score (OR, 1.343; 95% confidence interval, 1.020-1.770; P = 0.036) was found to be associated with poor outcome at 90 days. Higher Fazekas and SVD scores were not associated with stroke progression or stroke recurrence.

Conclusion: WMH can predict the poor functional outcome of minor cerebrovascular events. Adding other neuroimaging markers of SVD and total SVD burden score, however, does not improve the prediction, which indicated WMH can as neuroimaging markers for guiding the treatment of minor cerebrovascular events.
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http://dx.doi.org/10.1186/s12883-021-02043-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805057PMC
January 2021

DFT Quest of the Active Species of the Gallium-Mediated Coupling of Methylidenemalonates and Acetylenes.

Inorg Chem 2021 Jan 3;60(2):995-1006. Epub 2021 Jan 3.

State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. China.

In this study, three different Ga-containing systems based on GaCl, GaCl, or ionic [Ga(L)][GaCl] (L = methylidenemalonate) complex were screened to elucidate the mechanism, regioselectivity, chemoselectivity, and role of Ga mediator in the reaction between two types of acetylenes (phenylacetylene and but-1-yn-1-ylbenzene) and methylidenemalonates, i.e., the 1,2-zwitterionic precursors that are similar to intermediates derived from donor-acceptor cyclopropanes (DACs). Our DFT calculation results clearly show that the ionic gallium complex [Ga(L)][GaCl] represents the key mediator in the title reaction. After the formation of such a complex, the first reaction step is the nucleophilic addition of phenylacetylene or but-1-yn-1-ylbenzene to [Ga(L)][GaCl], generating an unstable vinyl cation intermediate. In the phenylacetylene system, this vinyl cation intermediate accepts a chlorine atom from [GaCl] to give -configuration intermediate. Then, the above process occurs to other two ligands of the Ga(III) complex to furnish a final product. On the other hand, in the but-1-yn-1-ylbenzene system, the vinyl cation intermediate prefers to undergo Friedel-Crafts (F-C) alkylation to generate a five-membered ring intermediate. This process is repeated on the other two methylidenemalonate ligands, giving rise to a final cyclization product. The distortion/interaction analysis shows that in the nucleophilic addition step the distortion energy of the Ga complex part is the main factor that influences the activation energy. Furthermore, the global reactivity index (GRI) analysis indicates that the Ga-complex model has the highest electrophilicity index ω, thus leading to the lowest energy barrier among three Ga-based models. In addition, DFT results reveal that the regioselectivity (-configuration preference) and chemoselectivity (chloration or F-C alkylation) are mainly controlled by the steric effect rather than the electronic effect. The main findings of the present work provide a new way to analyze and rationalize various Ga-mediated reactions, which might also be extrapolated to organic transformations undergoing in the presence of aluminum and indium complexes.
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http://dx.doi.org/10.1021/acs.inorgchem.0c03113DOI Listing
January 2021

Efficacy of Omaha system-based nursing management on nutritional status in patients undergoing peritoneal dialysis: A randomized controlled trial protocol.

Medicine (Baltimore) 2020 Dec;99(51):e23572

Department of Critical Care Medicine, Wuhan No.1 Hospital, Hubei, China.

Abstract: The chronic kidney disease (CKD) patients may have a variety of complications during receiving peritoneal dialysis (PD). The malnutrition in CKD patients is related to their lower life quality, higher hospitalization rates, and higher risk of cardiovascular disease, as well as the increased morbidity and mortality. Hence, it is very important to monitor and then manage the nutritional status of CKD patients. Thus, we perform this randomized controlled study protocol to introduce a continuing nursing program based on Omaha system (OS) for the patients with CKD receiving PD treatment.The randomized trial will be implemented from November 2020 to May 2021 and was granted through the Research Ethics Committee of Wuhan No.1 Hospital (2020003281). Two hundred patients meet inclusion criteria and exclusion criteria are included.Patients who meet the following criteria will be selected: voluntary participation, aged 20 to 60; undergoing the regular PD treatment for at least 3 months. Patients will be excluded if the patients are in unstable status, or experience the intermittent PD or some other kinds of dialysis mode, have severe cachexia, infection, or malnutrition, or if they have mental disorders. In control group, patients are given routine treatment, containing general guidance associated with PD and the outpatient telephone calls from the clinical nurses during follow-up. In study group, the patients are given the continuous nursing treatment scheme based on OS. The clinical results are the biochemical parameters after intervention, anthropometry, as well as the subjective global assessment.Table 1 reveals the clinical endpoints between the 2 groups.This protocol can guide nurses to develop a nursing program based on evidence for patients with CKD receiving PD.

Trial Registration: This study protocol was registered in Research Registry (researchregistry6202).
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http://dx.doi.org/10.1097/MD.0000000000023572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748208PMC
December 2020

Nitrogen removal mechanism of marine anammox bacteria treating nitrogen-laden saline wastewater in response to ultraviolet (UV) irradiation: High UV tolerance and microbial community shift.

Bioresour Technol 2021 Jan 28;320(Pt A):124325. Epub 2020 Oct 28.

Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-environmental Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Salt stress can be naturally overcome by marine anammox bacteria (MAB), while their low growth rate and sensitivity to operational conditions are still challenges for the application of anammox. To enhance the enrichment of MAB and decipher the effects of ultraviolet (UV) irradiation on MAB, UV was introduced in the nitrogen removal of MAB treating nitrogen-laden saline wastewater for the first time. The results indicated that MAB were resistant to a fairly high UV-C dose, 12000 mJ/cm. Their relative abundance was enhanced by 1.2 folds under 12000 mJ/cm UV-C. However, the relative abundance of Actinobacteria, Acidobacteria, Chloroflexi and Marinicella were greatly dropped with enhanced UV-C dose. The tolerance mechanism was diversified, e.g. excessive extracellular polymeric substances, special structure of MAB and interspecific competition/cooperation. Although further study was still needed, the findings shed a light on MAB enrichment and exploited great potentials of MAB in nitrogen-laden saline wastewater treatment.
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http://dx.doi.org/10.1016/j.biortech.2020.124325DOI Listing
January 2021

Recent advances in synthetic biology of cyanobacteria for improved chemicals production.

Bioengineered 2020 12;11(1):1208-1220

Department of Aging and Geriatric Research, Institute on Aging, University of Florida , Gainesville, FL, USA.

Cyanobacteria are Gram-negative photoautotrophic prokaryotes and have shown great importance to the Earth's ecology. Based on their capability in oxygenic photosynthesis and genetic merits, they can be engineered as microbial chassis for direct conversion of carbon dioxide to value-added biofuels and chemicals. In the last decades, attempts have given to the application of synthetic biology tools and approaches in the development of cyanobacterial cell factories. Despite the successful proof-of-principle studies, large-scale application is still a technical challenge due to low yields of bioproducts. Therefore, recent efforts are underway to characterize and develop genetic regulatory parts and strategies for the synthetic biology applications in cyanobacteria. In this review, we present the recent advancements and application in cyanobacterial synthetic biology toolboxes. We also discuss the limitations and future perspectives for using such novel tools in cyanobacterial biotechnology.
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http://dx.doi.org/10.1080/21655979.2020.1837458DOI Listing
December 2020

Recent advances: peptides and self-assembled peptide-nanosystems for antimicrobial therapy and diagnosis.

Biomater Sci 2020 Sep 28;8(18):4975-4996. Epub 2020 Jul 28.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, China.

Bacterial infections, especially the refractory treatment of drug-resistant bacteria, are one of the greatest threats to human health. During the past decades, biomedical nanomaterials have been developed in an increasing number of fields, which significantly contribute to our public healthcare systems. Peptide-based drugs, such as antimicrobial peptides, cyclopeptides, and glycopeptides, play important roles in the treatment of drug-resistant bacterial infections, due to their unique lower resistance antibacterial mechanism. Among them, biomimetic nanostructures fabricated by self-assembled peptide nanomaterials have received considerable development in surface protection, tissue engineering, bactericides, etc. Besides, bacterial diagnostic reagents based on self-assembled peptide materials also provide strong support for early detection and infection imaging of bacterial infections. In this review, we have systematically discussed peptide-based self-assembled nanomaterials, including their sequences, subunits, secondary structures, assembled nanostructures, and biomedical applications for antibacterial therapy and diagnosis. We have reviewed and discussed the structure-function relationship, molecular design strategy, and structure effect of antimicrobial peptides. The sequence design of self-assembled peptides and the application of self-assembled peptide nanomaterials in the diagnosis and treatment of bacterial infections are emphasized. Also, we analyzed and summarized the design and development of smart materials, reviewed the innovative "in vivo self-assembly" nanotechnology, and proposed the future design and prospect of smart self-assembly nanomaterials based on peptides in the biological antibacterial field.
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http://dx.doi.org/10.1039/d0bm00789gDOI Listing
September 2020

The Effects of Transcranial Electrical Stimulation on Human Motor Functions: A Comprehensive Review of Functional Neuroimaging Studies.

Front Neurosci 2020 24;14:744. Epub 2020 Jul 24.

Center for Modeling, Simulation and Imaging in Medicine, Rensselaer Polytechnic Institute, Troy, NY, United States.

Transcranial electrical stimulation (tES) is a promising tool to enhance human motor skills. However, the underlying physiological mechanisms are not fully understood. On the other hand, neuroimaging modalities provide powerful tools to map some of the neurophysiological biomarkers associated with tES. Here, a comprehensive review was undertaken to summarize the neuroimaging evidence of how tES affects human motor skills. A literature search has been done on the PubMed database, and 46 relative articles were selected. After reviewing these articles, we conclude that neuroimaging techniques are feasible to be coupled with tES and offer valuable information of cortical excitability, connectivity, and oscillations regarding the effects of tES on human motor behavior. The biomarkers derived from neuroimaging could also indicate the motor performance under tES conditions. This approach could advance the understanding of tES effects on motor skill and shed light on a new generation of adaptive stimulation models.
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http://dx.doi.org/10.3389/fnins.2020.00744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393222PMC
July 2020

Functional Brain Imaging Reliably Predicts Bimanual Motor Skill Performance in a Standardized Surgical Task.

IEEE Trans Biomed Eng 2021 07 18;68(7):2058-2066. Epub 2021 Jun 18.

Currently, there is a dearth of objective metrics for assessing bi-manual motor skills, which are critical for high-stakes professions such as surgery. Recently, functional near-infrared spectroscopy (fNIRS) has been shown to be effective at classifying motor task types, which can be potentially used for assessing motor performance level. In this work, we use fNIRS data for predicting the performance scores in a standardized bi-manual motor task used in surgical certification and propose a deep-learning framework 'Brain-NET' to extract features from the fNIRS data. Our results demonstrate that the Brain-NET is able to predict bi-manual surgical motor skills based on neuroimaging data accurately ( R=0.73). Furthermore, the classification ability of the Brain-NET model is demonstrated based on receiver operating characteristic (ROC) curves and area under the curve (AUC) values of 0.91. Hence, these results establish that fNIRS associated with deep learning analysis is a promising method for a bedside, quick and cost-effective assessment of bi-manual skill levels.
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http://dx.doi.org/10.1109/TBME.2020.3014299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265734PMC
July 2021

Systemic lupus erythematosus with hypothyroidism as the initial clinical manifestation: A case report.

Exp Ther Med 2020 Aug 25;20(2):996-1002. Epub 2020 May 25.

Department of VIP Unit, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and hypothyroidism is an organ-specific autoimmune disease. The two diseases may occur successively or simultaneously. The majority of previous studies observed that thyroid disease was more frequent in patients with SLE than in the general population, particularly those who had a higher incidence of anti-thyroid antibodies. However, there are no reported cases of SLE with hypothyroidism as the initial clinical manifestation, to the best of our knowledge. The present study reported on a case of SLE with this unusual initial clinical manifestation and reviewed the literature to estimate the prevalence of clinical hypothyroidism in patients with SLE (range, 3.0-21.4%). The case of the present study had no obvious facial erythema, photosensitivity or recurrent oral ulcers, and only had hypothyroidism as the initial clinical symptom, but the laboratory examination supported the diagnosis of SLE. The present study suggested that in the clinical diagnosis, attention should be paid to screening for connective tissue diseases when diagnosing hypothyroidism, and the importance of thyroid dysfunction should also be recognized in the treatment of SLE.
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http://dx.doi.org/10.3892/etm.2020.8788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388410PMC
August 2020

A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune inflammation via modulating antigen presentation.

Sci Adv 2020 May 20;6(21):eaaz2059. Epub 2020 May 20.

Department of Immunology and Microbiology, Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.

Many annotated long noncoding RNAs (lncRNAs) harbor predicted short open reading frames (sORFs), but the coding capacities of these sORFs and the functions of the resulting micropeptides remain elusive. Here, we report that human lncRNA MIR155HG encodes a 17-amino acid micropeptide, which we termed miPEP155 (P155). MIR155HG is highly expressed by inflamed antigen-presenting cells, leading to the discovery that P155 interacts with the adenosine 5'-triphosphate binding domain of heat shock cognate protein 70 (HSC70), a chaperone required for antigen trafficking and presentation in dendritic cells (DCs). P155 modulates major histocompatibility complex class II-mediated antigen presentation and T cell priming by disrupting the HSC70-HSP90 machinery. Exogenously injected P155 improves two classical mouse models of DC-driven auto inflammation. Collectively, we demonstrate the endogenous existence of a micropeptide encoded by a transcript annotated as "non-protein coding" and characterize a micropeptide as a regulator of antigen presentation and a suppressor of inflammatory diseases.
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http://dx.doi.org/10.1126/sciadv.aaz2059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314557PMC
May 2020

Perturbation of Specific Signaling Pathways Is Involved in Initiation of Mouse Liver Fibrosis.

Hepatology 2021 Apr 19;73(4):1551-1569. Epub 2021 Mar 19.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Background And Aims: To identify the regulatory role of protein phosphatase 2A (PP2A) in the development of liver disease, we generated a mouse model with hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit).

Approach And Results: Homozygote (HO) mice and matched wild-type littermates were investigated at 3, 6, 9, 12, 15, and 18 months of age. Pathological examination showed that PP2A Aα deficiency in hepatocytes resulted in progressive liver fibrosis phenotype from 9 months of age. No hepatocyte death was observed in HO mice. However, perturbation of pathways including epidermal growth factor receptor 1 (EGFR1), amino acid metabolism, and translation factors as well as leptin and adiponectin led to pronounced hepatic fibrosis. In vitro studies demonstrated the involvement of specific B subunit complexes in the regulation of EGFR1 signaling pathway and cross talk between defected hepatocytes and stimulation of interstitial hyperplasia. It is noteworthy that HO mice failed to develop hepatocellular carcinoma for as long as 22 months of age. We further demonstrate that PP2A Aβ-containing holoenzymes played a critical role in preventing hepatocyte apoptosis and antagonizing tumorigenesis through specific pathways on Aα loss. Furthermore, PP2A Aα and Aβ were functionally distinct, and the Aβ isoform failed to substitute for Aα in the development of inflammation and liver fibrosis.

Conclusions: These observations identify pathways that contribute to the pathogenesis of liver fibrosis and provide putative therapeutic targets for its treatment.
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http://dx.doi.org/10.1002/hep.31457DOI Listing
April 2021

Veratramine suppresses human HepG2 liver cancer cell growth in vitro and in vivo by inducing autophagic cell death.

Oncol Rep 2020 Aug 25;44(2):477-486. Epub 2020 May 25.

Department of Oncology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.

Liver cancer is the second leading cause of cancer‑related deaths. Traditional therapeutic strategies, such as chemotherapy, targeted therapy and interventional therapy, are inefficient and are accompanied by severe side effects for patients with advanced liver cancer. Therefore, it is crucial to develop a safer more effective drug to treat liver cancer. Veratramine, a known natural steroidal alkaloid derived from plants of the lily family, exerts anticancer activity in vitro. However, the underlying mechanism and whether it has an antitumor effect in vivo remain unknown. In the present study, the data revealed that veratramine significantly inhibited HepG2 cell proliferation, migration and invasion in vitro. Moreover, it was revealed that veratramine induced autophagy‑mediated apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway, which partly explained the underlying mechanism behind its antitumor activity. Notably, the results of in vivo experiments also revealed that veratramine treatment (2 mg/kg, 3 times a week for 4 weeks) significantly inhibited subcutaneous tumor growth of liver cancer cells, with a low systemic toxicity. Collectively, the results of the present study indicated that veratramine efficiently suppressed liver cancer HepG2 cell growth in vitro and in vivo by blocking the PI3K/Akt/mTOR signaling pathway to induce autophagic cell death. Veratramine could be a potential therapeutic agent for the treatment of liver cancer.
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http://dx.doi.org/10.3892/or.2020.7622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336414PMC
August 2020
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