Publications by authors named "Shuang Sun"

98 Publications

Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats.

Front Neurosci 2021 27;15:645849. Epub 2021 Apr 27.

Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, China.

Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson's disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which become pathologically exaggerated throughout cortico-basal ganglia circuits after dopamine depletion. Furthermore, assessment of different spike-LFP coupling parameters revealed that the putative pyramidal neurons were particularly prone to being phase-locked to ongoing cortical oscillations at 12-35 Hz during reaching. Conversely, putative interneurons were neither hypoactive nor synchronized to ongoing cortical oscillations. These data collectively demonstrate a neuron type-selective alteration in the M1 in hemiparkinsonian rats. These alterations hamper the ability of the M1 to contribute to motor conduction and are likely some of the main contributors to motor impairments in PD.
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http://dx.doi.org/10.3389/fnins.2021.645849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111217PMC
April 2021

Effects of intrastriatal injection of the dopamine receptor agonist SKF38393 and quinpirole on locomotor behavior in hemiparkinsonism rats.

Behav Brain Res 2021 May 1;411:113339. Epub 2021 May 1.

Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, People's Republic of China. Electronic address:

Dopamine (DA) in the striatum is essential to influence motor behavior and may lead to movement impairment in Parkinson's disease (PD). The present study examined the different functions of the DA D1 receptor (D1R) and DA D2 receptor (D2R) by intrastriatal injection of the D1R agonist SKF38393 and the D2R agonist quinpirole in 6-hydroxydopamine (6-OHDA)-lesioned and control rats. All rats separately underwent dose-response behavior testing for SKF38393 (0, 0.5, 1.0, and 1.5 μg/site) or quinpirole (0, 1.0, 2.0, and 3.0 μg/site) to determine the effects of the optimal modulating threshold dose. Two behavior assessment indices, the time of latency to fall and the number of steps on a rotating treadmill, were used as reliable readouts of motor stimulation variables for quantifying the motor effects of the drugs. The findings indicate that at threshold doses, SKF38393 (1.0 μg/site) and quinpirole (1.0 μg/site) produce a dose-dependent increase in locomotor activity compared to vehicle injection. The ameliorated behavioral responses to either SKF38393 or quinpirole in lesioned rats were greater than those in unlesioned control rats. Moreover, the dose-dependent increase in locomotor capacity for quinpirole was greater than that for SKF38393 in lesioned rats. These results can clarify several key issues related to DA receptors directly and may provide a basis for exploring the potential of future selective dopamine therapies for PD in humans.
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http://dx.doi.org/10.1016/j.bbr.2021.113339DOI Listing
May 2021

Systemic conbercept pharmacokinetics and VEGF pharmacodynamics following intravitreal injections of conbercept in patients with retinopathy of prematurity.

Br J Ophthalmol 2021 Apr 9. Epub 2021 Apr 9.

Department of Ophthalmology, Peking University People's Hospital, Eye diseases and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Clinical Centre of Optometry, College of Optometry, Peking University Health science center, Beijing, China

Background: Data on serum vascular endothelial growth factor (VEGF) and drug levels in patients with retinopathy of prematurity (ROP) following intravitreal injections of conbercept (IVC) are lacking.

Methods: Multicentre, prospective, non-randomised study of patients with aggressive posterior retinopathy of prematurity (APROP) or type 1 ROP who had not received other treatment. All infants received therapy in both eyes plus intravitreal IVC 0.25 mg/0.025 mL in one eye and had at least 6 months of follow-up. Blood samples were collected before and 1 week and 4 weeks after IVC. The main outcome measures were serum conbercept and VEGF concentrations.

Results: Forty infants with APROP or type 1 ROP were enrolled. The mean serum VEGF at baseline and 1 week and 4 weeks after a total of 0.25 mg of IVC was 953.35±311.90 pg/mL, 303.46±181.89 pg/mL and 883.12±303.89 pg/mL, respectively. Serum VEGF 1 week after IVC was significantly lower (p0.05) than baseline, and at 4 weeks after IVC, it was significantly higher (p0.05) than at 1 week. There was no significant difference (p0.05) between baseline and 4 weeks. Serum conbercept was below the limit of quantitation (BLOQ) at baseline and 4 weeks and was 19.81±7.60 ng/mL at 1 week.

Conclusion: Serum VEGF 1 week after IVC was significantly lower than baseline but returned to baseline at 4 weeks. Serum conbercept increased at 1 week and was BLOQ at 4 weeks.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319131DOI Listing
April 2021

Risk of cardiac-related mortality in stage IIIA-N2 non-small cell lung cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

Thorac Cancer 2021 05 16;12(9):1358-1365. Epub 2021 Mar 16.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: In this study, we aimed to investigate the association between postoperative radiotherapy (PORT) and cardiac-related mortality in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: The United States (US) population based on the SEER database was searched for cardiac-related mortality among patients with stage IIIA-N2 NSCLC. Cardiac-related mortality was compared between the PORT and Non-PORT groups. Accounting for mortality from other causes, Fine and Gray's test compared cumulative incidences of cardiac-related mortality between both groups. Univariate and multivariate analysis were performed using the competing risk model.

Results: From 1988 to 2016, 7290 patients met the inclusion criteria: 3386 patients were treated with PORT and 3904 patients with Non-PORT. The five-year overall incidence of cardiac-related mortality was 3.01% in the PORT group and 3.26% in the Non-PORT group. Older age, male sex, squamous cell lung cancer, earlier year of diagnosis and earlier T stage were independent adverse factors for cardiac-related mortality. However, PORT use was not associated with an increase in the hazard for cardiac-related mortality (subdistribution hazard ratio [SHR] = 0.99, 95% confidence interval [CI]: 0.78-1.24, p = 0.91). When evaluating cardiac-related mortality in each time period, the overall incidence of cardiac-related mortality was decreased over time. There were no statistically significant differences based on PORT use in all time periods.

Conclusions: With a median follow-up of 25 months, no significant differences were found in cardiac-related mortality between the PORT and Non-PORT groups in stage IIIA-N2 NSCLC patients.
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http://dx.doi.org/10.1111/1759-7714.13908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088942PMC
May 2021

Mechanisms of radiation-induced endothelium damage: Emerging models and technologies.

Radiother Oncol 2021 05 11;158:21-32. Epub 2021 Feb 11.

Department of Mechanical Engineering, Temple University, Philadelphia, USA; Department of Bioengineering, Temple University, Philadelphia, USA; Department of Radiation Oncology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA. Electronic address:

Radiation-induced endothelial/vascular injury is a major complicating factor in radiotherapy and a leading cause of morbidity and mortality in nuclear or radiological catastrophes. Exposure of tissue to ionizing radiation (IR) leads to the release of oxygen radicals and proteases that result in loss of endothelial barrier function and leukocyte dysfunction leading to tissue injury and organ damage. Microvascular endothelial cells are particularly sensitive to IR and radiation-induced alterations in endothelial cell function are thought to be a critical factor in organ damage through endothelial cell activation, enhanced leukocyte-endothelial cell interactions, increased barrier permeability and initiation of apoptotic pathways. These radiation-induced inflammatory responses are important in early and late radiation pathologies in various organs. A better understanding of mechanisms of radiation-induced endothelium dysfunction is therefore vital, as radiobiological response of endothelium is of major importance for medical management and therapeutic development for radiation injuries. In this review, we summarize the current knowledge of cellular and molecular mechanisms of radiation-induced endothelium damage and their impact on early and late radiation injury. Furthermore, we review established and emerging in vivo and in vitro models that have been developed to study the mechanisms of radiation-induced endothelium damage and to design, develop and rapidly screen therapeutics for treatment of radiation-induced vascular damage. Currently there are no specific therapeutics available to protect against radiation-induced loss of endothelial barrier function, leukocyte dysfunction and resulting organ damage. Developing therapeutics to prevent endothelium dysfunction and normal tissue damage during radiotherapy can serve as the urgently needed medical countermeasures.
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http://dx.doi.org/10.1016/j.radonc.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119342PMC
May 2021

The crosstalk of HDAC3, microRNA-18a and ADRB3 in the progression of heart failure.

Cell Biosci 2021 Feb 6;11(1):31. Epub 2021 Feb 6.

Department of Clinical Pharmacy, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161099, P.R. China.

Background: Heart failure (HF) is a clinical syndrome characterized by left ventricular dysfunction or elevated intracardiac pressures. Research supports that microRNAs (miRs) participate in HF by regulating  targeted genes. Hence, the current study set out to study the role of HDAC3-medaited miR-18a in HF by targeting ADRB3.

Methods: Firstly, HF mouse models were established by ligation of the left coronary artery at the lower edge of the left atrial appendage, and HF cell models were generated in the cardiomyocytes, followed by ectopic expression and silencing experiments. Numerous parameters including left ventricular posterior wall dimension (LVPWD), interventricular septal dimension (IVSD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LEVDP), heart rate (HR), left ventricular pressure rise rate (+ dp/dt) and left ventricular pressure drop rate (-dp/dt) were measured in the mice. In addition, apoptosis in the mice was detected by means of TUNEL staining, while RT-qPCR and Western blot analysis were performed to detect miR-18a, HDAC3, ADRB3, cMyb, MMP-9, Collagen 1 and TGF-β1 expression patterns. Dual luciferase reporter assay validated the targeting relationship between ADRB3 and miR-18a. Cardiomyocyte apoptosis was determined by means of flow cytometry.

Results: HDAC3 and ADRB3 were up-regulated and miR-18a was down-regulated in HF mice and cardiomyocytes. In addition, HDAC3 could reduce the miR-18a expression, and ADRB3 was negatively-targeted by miR-18a. After down-regulation of HDAC3 or ADRB3 or over-expression of miR-18a, IVSD, LVEDD, LVESD and LEVDP were found to be decreased but LVPWD, LVEF, LVFS, LVSP, + dp/dt, and -dp/dt were all increased in the HF mice, whereas fibrosis, hypertrophy and apoptosis of HF cardiomyocytes were declined.

Conclusion: Collectively, our findings indicate that HDAC3 silencing confers protection against HF by inhibiting miR-18a-targeted ADRB3.
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http://dx.doi.org/10.1186/s13578-020-00523-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866688PMC
February 2021

Clinical effect of vestibular rehabilitation on benign paroxysmal positional vertigo: A protocol for systematic review.

Medicine (Baltimore) 2021 Jan;100(3):e23906

Department of Geriatric Neurology, Heilongjiang Provincial Hospital, Harbin, China.

Background: This study will evaluate the clinical effect of vestibular rehabilitation (VR) on benign paroxysmal positional vertigo (BPPV).

Methods: In this study, we will identify relevant trials on the topic published in MEDLINE, EBASE, Web of Science, Cochrane Library, Scopus, CINAHL, CBM, and CNKI from inception to the present. We will also search conference proceedings, thesis/dissertation, ongoing trials in clinical trial registry, and reference lists of included studies. Two researchers will independently carry out record selection, data extraction, and study quality assessment, respectively. Any disagreement will be arbitrated and solved with the help of a third researcher. If necessary, we will conduct random-effects meta-analysis to pool the effect estimates of included trials determined to be acceptable heterogeneity.

Results: We will summarize the latest evidence to assess the effect of VR for the treatment of patients with BPPV.

Conclusion: The findings of this study will help determine whether or not VR is effective in treating BPPV.

Osf Registration: osf.io/k83y5.
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http://dx.doi.org/10.1097/MD.0000000000023906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837862PMC
January 2021

Development of multivalent nanobodies blocking SARS-CoV-2 infection by targeting RBD of spike protein.

J Nanobiotechnology 2021 Jan 29;19(1):33. Epub 2021 Jan 29.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.

Background: The outbreak and pandemic of coronavirus SARS-CoV-2 caused significant threaten to global public health and economic consequences. It is extremely urgent that global people must take actions to develop safe and effective preventions and therapeutics. Nanobodies, which are derived from single‑chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking SARS-CoV-2 spike interaction with ACE2 protein were developed.

Results: Totally, four specific nanobodies against spike protein and its RBD domain were screened from a naïve VHH library. Among them, Nb91-hFc and Nb3-hFc demonstrated antiviral activity by neutralizing spike pseudotyped viruses in vitro. Subsequently, multivalent nanobodies were constructed to improve the neutralizing capacity. As a result, heterodimer nanobody Nb91-Nb3-hFc exhibited the strongest RBD-binding affinity and neutralizing ability against SARS-CoV-2 pseudoviruses with an IC value at approximately 1.54 nM.

Conclusions: The present study indicated that naïve VHH library could be used as a potential resource for rapid acquisition and exploitation of antiviral nanobodies. Heterodimer nanobody Nb91-Nb3-hFc may serve as a potential therapeutic agent for the treatment of COVID-19.
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http://dx.doi.org/10.1186/s12951-021-00768-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844813PMC
January 2021

[Brief analysis on pivot effect of Tianshu (ST 25)].

Zhongguo Zhen Jiu 2020 Dec;40(12):1319-21

College of Acupuncture-Moxibustion and Orthopedics, Hubei University of CM, Wuhan 430061, China.

The pivot effect of Tianshu (ST 25) was analyzed, which was explored from 5 aspects, named the ascending and descending of spleen and stomach , the smooth flowing of liver and gallbladder, the transmission of intestine, the passage regulation of three (triple energizer) and conducting from . Tianshu (ST 25) governs and is in charge of its ascending, descending, exiting and entering. In order to understand the effect and application of such acupoint, the theoretic source should be interpreted at first. Hence, the exploration on the pivot effect of Tianshu (ST 25) in terms of the ascending, descending, exiting and entering of activity may provide the guidance to the clinical treatment.
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http://dx.doi.org/10.13703/j.0255-2930.20191018-k0004DOI Listing
December 2020

Postoperative radiotherapy for pathological stage IIIA-N2 non-small cell lung cancer with positive surgical margins.

Thorac Cancer 2021 01 27;12(2):227-234. Epub 2020 Nov 27.

Department of Radiation Oncology.

Background: The aim of this study was to evaluate the efficacy of postoperative radiotherapy (PORT) in stage pIIIA-N2 non-small cell lung cancer (NSCLC) patients with positive surgical margins.

Methods: Between January 2003 and December 2015, patients who had undergone lobectomy or pneumonectomy plus mediastinal lymph node dissection or systematic sampling in our single institution were retrospectively reviewed. Those with pIIIA-N2 NSCLC and positive surgical margins were enrolled into the study. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used to analyze differences between the groups. Univariate and multivariate analyses using Cox proportional hazards regression models were performed to evaluate potential prognostic factors for OS. Statistically significant difference was set as P < 0.05.

Results: Of all the 1547 patients with pIIIA-N2 NSCLC reviewed, 113 patients had positive surgical margins, including 76 patients with R1 resection and 37 with R2 resection. The median overall survival (OS) was 28.3 months in the PORT group and 22.6 months in the non-PORT group (P = 0.568). Subset analysis showed that for patients with R1 resection, the median OS was 52.4 months in the PORT group which was nonsignificantly longer than that of 22.6 months in the non-PORT group (P = 0.127), whereas PORT combined with chemotherapy could significantly improve OS, with a median OS of 52.4 months versus 17.2 months (P = 0.027). For patients with R2 resection, PORT made no significant difference in OS (17.6 vs. 63.8 months, P = 0.529).

Conclusions: For pIIIA-N2 NSCLC patients with positive surgical margins, PORT did not improve OS, but OS was improved in those patients who underwent R1 resection combined with chemotherapy.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Significant findings of the study: Postoperative radiotherapy (PORT) has been recommended to treat patients with positive surgical margins. However, the existing evidence is controversial and high-level evidence is lacking.

What This Study Adds: What this study adds: The PORT group had markedly, but not statistically significant, longer median OS compared with the non-PORT group in patients with R1 resection. OS was significantly longer in the patients with R1 resection receiving adjuvant CRT than the surgery alone group.
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http://dx.doi.org/10.1111/1759-7714.13749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812075PMC
January 2021

Opening the Soul Window Manually: Limbal Tissue Scaffolds with Electrospun Polycaprolactone/Gelatin Nanocomposites.

Macromol Biosci 2021 02 18;21(2):e2000300. Epub 2020 Nov 18.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

Restricted by the difficulty in fabricating scaffolds suitable for cell proliferation, the use of ex vivo expanded limbal stem cell (LSC) for LSC transplantation, an effective treatment method for patients with limb stem cell deficiency (LSCD), is hard to be widely used in clinical practice. To tackle these challenges, a novel electrospun polycaprolactone (PCL)/gelatin nanocomposite is proposed to make 3D scaffolds for limbal niche cells (LNC) proliferation in vitro, which is a milestone in the treatment of diseases such as LSCD. PCL and gelatin in different weight ratios are dissolved in a mixed solvent, and then electrospinning and cross-linking are performed to prepare a scaffold for cell proliferation. The characterizations of the nanocomposites indicate that the gelatin content has a significant effect on its micro-morphology, thermal properties, crystallinity, degradation temperature, hydrophilicity, and mechanical properties. P8G2-C (PCL: gelatin = 80: 20, cross-linked), with smooth fibers and homogeneous pores, has better hydrophilicity, mechanical properties, and flexibility, so it can support LNC as cell proliferation assays revealed. This detailed investigation presented here demonstrates the feasibility of using PCL/gelatin nanocomposites electrospun fiber membranes as a limbus tissue engineering scaffold, which undoubtedly provide a new perspective for the development of tissue engineering field.
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http://dx.doi.org/10.1002/mabi.202000300DOI Listing
February 2021

Virulence factors impair epithelial junctions during bacterial infection.

J Clin Lab Anal 2021 Feb 17;35(2):e23627. Epub 2020 Oct 17.

Institute of Biomedical Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, China.

Epithelial cells are typically connected through different types of cell junctions that are localized from the apical membrane to the basal surface. In this way, epithelium cells form the first barrier against pathogenic microorganisms and prevent their entry into internal organs and the circulatory system. Recent studies demonstrate that bacterial pathogens disrupt epithelial cell junctions through targeting junctional proteins by secreted virulence factors. In this review, we discuss the diverse strategies used by common bacterial pathogens, including Pseudomonas aeruginosa, Helicobacter pylori, and enteropathogenic Escherichia coli, to disrupt epithelial cell junctions during infection. We also discuss the potential of targeting the pathogenic mechanisms in the treatment of pathogen-associated diseases.
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http://dx.doi.org/10.1002/jcla.23627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891540PMC
February 2021

Identification and characterization of putative ovarian lincRNAs in dairy goats treated for repeated estrous synchronization.

Anim Reprod Sci 2020 Oct 17;221:106537. Epub 2020 Jul 17.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

The goal of this study was to identify and characterize effects of repeated estrous synchronization (ES) treatments on the regulation of ovarian intergenic long non-coding RNAs (lincRNAs) in dairy goats. Six does were randomly assigned to a group administered three ES treatment regimens separated by 2 weeks or to a group administered only one ES treatment regimen (control) at the same time as the third ES treatment in the does administered the three hormonal regimens for ES. The paired-end RNA Sequencing procedures were used to evaluate lincRNAs of ovarian tissues. A total of 134 lincRNAs were differentially abundant between the two treatment groups. Several target genes were annotated and were related to hormone activity, cellular response to hormone stimulus, response to hormone, female pregnancy, as well as regulation of hormone secretion. These genes were noticeably enriched in MAPK, Hippo, estrogen signaling pathways, oocyte meiosis, progesterone-mediated oocyte maturation, ovarian steroidogenesis as well as GnRH signaling pathways. According to the enriched GO terms and KEGG pathways of regulated genes, 13 differentially abundant lincRNAs could be promising candidates for regulating reproductive functions of female goats. Current results indicate that repeated treatments with gonadotropins affected hormone sensitivity, estrogen synthesis, and ovarian function. The results also indicated that when there was imposing of the three hormonal treatment regimens for ES, there were several lincRNAs that could contribute to dysregulation of several genes that are important for reproduction in dairy goats. Findings provide novel insights for further investigation of lncRNAs biological functions in goats.
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http://dx.doi.org/10.1016/j.anireprosci.2020.106537DOI Listing
October 2020

The interaction between sodium alginate and myofibrillar proteins: The rheological and emulsifying properties of their mixture.

Int J Biol Macromol 2020 Oct 6;161:1545-1551. Epub 2020 Aug 6.

School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, China. Electronic address:

The interaction between sodium alginate (SA) and turbot myofibrillar proteins (TMP) and the effects of SA concentration (0.1%-0.5%) on the rheological and emulsifying properties of the mixture at neutral pH were investigated. TMP and SA formed complexes through electrostatic repulsion and hydrophobic interaction. The FT-IR analysis indicated that hydrogen bonding was also related to the interaction. With the addition of SA, the electrostatic repulsion between molecules enhanced, which prevented protein aggregation and improved the stability of dispersions. The TMP/SA mixture showed non-Newtonian shear-thinning behavior. The viscosity gradually increased with the increasing SA concentration. TMP and SA formed an interconnected gel-like network structure with a predominant elastic behavior. The strength of network increased due to the strong repulsion between the two biopolymers. Both EAI and ESI of TMP significantly increased after SA addition. The addition of SA reduced droplet size of emulsions. The emulsions also showed pseudoplastic behavior. Addition of SA increased stability of emulsions by increasing viscosity of continuous phase. Complexation with SA effectively improved the rheological and emulsifying properties of fish myofibrillar proteins. These results contributed to the efficient utilization of marine fish proteins as functional ingredients in food products.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.025DOI Listing
October 2020

Injury of photoreceptors and retinal pigment epithelium in macular area of a preterm infant: A case analysis.

Medicine (Baltimore) 2020 Jul;99(29):e21096

Department of Ophthalmology, Henan Children's Hospital, Children's Hospital Affiliated of Zhengzhou University, Zhengzhou, China.

Rational: Injury of photoreceptors and retinal pigment epithelium (RPE) in macular area of premature infants is very rare.

Patient Concerns: A preterm infant delivered under general anesthesia. The infant was born at 28 weeks' and 4 days' gestation, with a birth weight of 1.15 kg and a treatment of oxygen inhalation after birth. According to the related protocol formulated by the Ophthalmology Branch of the Chinese Medical Association in 2014, the infant was regularly checked in our hospital.

Diagnosis: Optical coherence tomography (OCT) examination showed injuries of the photoreceptors and RPE in macular area.

Interventions: The fundus screening at 40 weeks' and 4 days' gestation (corrected gestational age) showed retinopathy of prematurity in bilateral eyes, with round yellow-white lesions at the macular area of right eye and sub-temporal macular area. OCT examination showed interrupted signals in the external limiting membrane (ELM), inner segment of the photoreceptors (IS)/outer segment of the photoreceptors (OS) layer, interdigitation zone (IZ), and RPE of the central fovea of macula of the right eye, with the area of defect of approximately 184 μm. Enhanced signal reflection was found under the defect area. Interrupted signals were also found in the IS/OS layer of the central fovea of macula of the left eye, with the area of defect of approximately 222 μm. Fundus fluorescence angiography (FFA) examination showed transmitted fluorescence at the macular area of the right eye and sub-temporal macular area of the left eye, suggesting retinopathy of prematurity in bilateral eyes.

Outcomes: Several factors, such as photic damage, eye injuries, hyperpyrexia, and underlying diseases, could cause macular retinal injuries. However, the baby had not received any radiation from high energy intense light sources, and had no history of hyperpyrexia or trauma. Fundamental screening was performed 1 year and 4 months of age and no obvious change was found in the round yellow-white lesions of the eyes compared with that in earlier stages. We have contacted with the patient for the follow-up OCT and FFA examinations a month later to check the possible structural changes of the macular area.

Lessons: The retina of a preterm infant is underdeveloped, we speculated that the bilateral retinal injuries in this baby could be caused by various factors.
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http://dx.doi.org/10.1097/MD.0000000000021096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373569PMC
July 2020

Phase separation as a therapeutic target in tight junction-associated human diseases.

Authors:
Shuang Sun Jun Zhou

Acta Pharmacol Sin 2020 Oct 21;41(10):1310-1313. Epub 2020 Jul 21.

Institute of Biomedical Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, 250014, China.

Tight junctions (TJs) play an important role in the maintenance of epithelial and endothelial barriers. Zonula occludens (ZO) proteins are scaffolding molecules essential for the formation of TJ complexes, and abnormalities in ZO proteins have been implicated in various TJ-associated human diseases such as tumor invasion and metastasis, and barrier dysfunction. Recent studies reveal that liquid-liquid phase separation of ZO proteins drives the polymerization of TJ proteins into a continuous belt, which then recruits various proteins to form the TJ complex to regulate selective paracellular permeability and signal transduction. Herein, we describe recent advances on how ZO phase separation contributes to TJ formation and discuss the potential of phase separation as a target for the treatment of TJ-associated diseases.
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http://dx.doi.org/10.1038/s41401-020-0470-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608859PMC
October 2020

Overexpression of the Tuberous sclerosis complex 2 (TSC2) gene inhibits goat myoblasts proliferation and differentiation in understanding the underlying mechanism of muscle development.

Gene 2020 Oct 9;757:144943. Epub 2020 Jul 9.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

The growth of animal skeletal muscle is mainly determined by the synthesis processes of total proteins in skeletal muscle cells, which has a significant impact on the postnatal growth of young animals. An increasing number of studies are focusing on the functions of Tuberous sclerosis complex 2 (TSC2) during the process of cell protein synthesis and growth. However, it is still unclear the effect of whether and how TSC2 on goat myoblasts proliferation and differentiation. Here, we found that TSC2 gene has opposite expression patterns in proliferation and differentiation of myoblasts. An expression vector containing goat TSC2 cDNA sequences linked with pcDNA3.1 plasmid was constructed. Myoblasts proliferation activity was significantly inhibited and cell cycle transition slowed down after the transfection of pcDNA3.1-TSC2 plasmid into goat primary myoblasts by EdU staining, CCK-8 and flow cytometry. Mechanically, we further confirmed that the overexpression TSC2 was able to down-regulate the mRNA and protein expression of mechanistic target of rapamycin (mTOR), p70 ribosomal S6 kinase 1 (p70S6K) and some cell cycle related genes. In addition, the expression of myogenic genes and myotube formation were attenuated. Collectively, all our results of the experiment demonstrate that TSC2 could regulate myoblasts cells proliferation and differentiation via the activation of the mTOR/p70S6K signaling pathway.
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http://dx.doi.org/10.1016/j.gene.2020.144943DOI Listing
October 2020

Physicochemical and emulsifying properties of mussel water-soluble proteins as affected by lecithin concentration.

Int J Biol Macromol 2020 Nov 26;163:180-189. Epub 2020 Jun 26.

School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, China. Electronic address:

The effects of lecithin addition at different concentrations (0-2.0%) on the physicochemical and emulsifying properties of mussel water-soluble proteins (MWP) were investigated. In solution system, low lecithin concentration (0.5%-1.0%) induced the aggregation and increased turbidity of composite particles. Lecithin addition caused changes in secondary structure and induced partial unfolding of MWP. Hydrophobic interactions between MWP and lecithin may contribute to the exposure of chromophores and hydrophobic groups of MWP. The interfacial tension decreased with lecithin addition. However, at a high lecithin concentration (1.5%-2.0%), the degree of aggregation and state of unfolding alleviated due to competitive adsorption. In emulsion system, with the low concentration of lecithin addition (0.5%-1.0%), droplet size and surface charge of emulsion decreased. The emulsion activity index, emulsion stability index, percentage of adsorbed protein increased. Both creaming stability and viscoelastic properties improved. At an intermediate lecithin concentration (1.0%), the emulsion showed the highest physical stability, while further addition of lecithin caused a slight deterioration in emulsifying properties. Overall, these results indicated the possibility that the lecithin-MWP mixed emulsifiers can be used to obtain emulsions with desirable properties.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.225DOI Listing
November 2020

Identification of a Strong Quorum Sensing- and Thermo-Regulated Promoter for the Biosynthesis of a New Metabolite Pesticide Phenazine-1-carboxamide in strain PA1201.

ACS Synth Biol 2020 07 5;9(7):1802-1812. Epub 2020 Jul 5.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Phenazine-1-carboxamide (PCN) produced by multifarious strains represents a promising candidate as a new metabolite pesticide due to its broad-spectrum antifungal activity and capacity to induce systemic resistance in plants. The rice rhizosphere strain PA1201 contains two reiterated gene clusters, and , for phenazine-1-carboxylic acid (PCA) biosynthesis; PCA is further converted into PCN by this strain using a functional -encoding glutamine aminotransferase. However, PCN levels in PA1201 constitute approximately one-fifth of PCA levels and the optimal temperature for PCN synthesis is 28 °C. In this study, the open reading frame (ORF) and promoter region were investigated and reannotated. promoter P was found to be a weak promoter, and PhzH levels were not sufficient to convert all of the native PCA into PCN. Following RNA Seq and promoter- fusion analyses, a strong quorum sensing (QS)- and thermo-regulated promoter P was identified and characterized. The activity of P is approximately 1% of P in PA1201. After three rounds of promoter editing and swapping by P, a new PCN-overproducing strain UP46 was generated. The optimal fermentation temperature for PCN biosynthesis in UP46 was increased from 28 to 37 °C and the PCN fermentation titer increased 179.5-fold, reaching 14.1 g/L, the highest ever reported.
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http://dx.doi.org/10.1021/acssynbio.0c00161DOI Listing
July 2020

Evaluation of the Immunomodulatory and Anti-Inflammatory Activities of Honey Bee Larva Powder.

J Med Food 2020 Jul 26;23(7):772-782. Epub 2020 May 26.

Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Honey bee larva powder (HLP) has traditionally been used as a daily supplement and tonic for health promotion with an uncertain scientific basis. In this study, B16-F10 tumor-bearing mice were established to evaluate the immunomodulatory activity of HLP. The proliferation and apoptosis assays were performed to evaluate the anti-inflammatory activity of honey bee larva extract (HLE) in RAW 264.7 macrophage. The experimental results demonstrated that the oral administration of freeze-dried HLP (4 and 6 g/kg) significantly enhanced the spleen index, the percentage of CD4cells, and the ratio of CD4 and CD8 T lymphocytes (CD4/CD8) in the peripheral blood compared with those in the tumor control mice. The studies demonstrated the potent immunomodulatory activities of HLE through the induction of RAW 264.7 macrophage proliferation and the mitigation of doxorubicin (DOX)-induced toxicity. HLE also exhibits anti-inflammatory activity by decreasing the production of nitric oxide (NO) and the cytokine level of interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage. The present study provides important scientific evidence for the immunomodulatory and anti-inflammatory activities of HLP and HLE.
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http://dx.doi.org/10.1089/jmf.2019.4554DOI Listing
July 2020

Pre- and Postoperative Health Status of Patients with Nonfunctioning and Secretory Pituitary Adenomas and an Analysis of Related Factors.

Int J Endocrinol 2020 20;2020:4056591. Epub 2020 Apr 20.

Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Purpose: To identify the characteristics of the physical and mental health status of patients with pituitary adenomas, explore the postoperative reversibility of impaired health status, and assess the impact of clinical characteristics, hormone levels, anxiety, depression, and disease stigma on health status.

Methods: We prospectively enrolled 147 and 138 patients with nonfunctioning and secretory pituitary adenomas, respectively. Health status was evaluated in 8 domains using the 36-item Short-Form Health Survey before and 3 months after transsphenoidal surgery. The Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the Stigma Scale for Chronic Illness were used to assess the psychological status.

Results: Compared with the healthy population reference values, general physical and mental health, social functioning, and role limitations due to physical and psychological health problems were all found to be significantly impaired in the adenoma patients. Health status was worse in patients with adrenocorticotropic hormone- (ACTH-) secreting and growth hormone- (GH-) secreting adenomas than in patients with nonfunctioning adenomas. Among the patients, 11.6% had anxiety and 30.9% had depression. Higher scores for anxiety, depression, and disease stigma; older age; higher body mass index; and tumor recurrence were independent risk factors for health status impairment in at least one domain. Physical function impairment and role limitations caused by physical health problems became worse after surgery, whereas the mental component of health status remained the same.

Conclusion: Health status was impaired in patients with pituitary adenomas, especially secretory adenomas. Physical function and role limitations were worse 3 months after surgery than before surgery. Mental problems, old age, obesity, and tumor recurrence reduced health status.
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http://dx.doi.org/10.1155/2020/4056591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189308PMC
April 2020

Efficient Technique for Simultaneous Lead Recovery and PbO₂/Ti Electrode Preparation for Electrocatalytic Degradation of Basic Red.

J Nanosci Nanotechnol 2020 09;20(9):5874-5884

Daqing Oilfield Powerlift Pump Industry Co., Ltd., Heilongjiang, Daqing 163311, China.

In order to achieve the effective removal of Pb from low-concentration wastewater as well as the lead recovery for direct reuse simultaneously, a simple electrodeposition method was used in this study. In this process, synthetic lead wastewater with low concentration of 4, 8, 12 and 16 mg/L was treated, more than 67% lead was recovered from wastewater and a PbO₂/Ti electrode was fabricated in a simple reaction tank. The test results of characterizations confirmed that PbO₂ nanoeletrocatalyst was successfully deposited on a Ti substrate. Electrochemical activity tests indicated that PbO₂/Ti electrode had advantages of high oxygen evolution potential (1.90 V) and low electron transfer resistance. Furthermore, the results of electrocatalytic degradation experiments demonstrated that prepared PbO₂/Ti electrode had the superb decolorization and mineralization ability on Basic Red. After 120 min of electrolysis, the Basic Red removal efficiency and TOC removal efficiency could reach to 89.38% and 68.82%, respectively, which was 5.2 and 7.1 times higher than the Ti substrate alone. Besides, the calculated mineralization current efficiency for PbO₂/Ti electrode increased from 5.18% to 36.74% after PbO₂ depositing, and thus an economical benefit was obtained by more than 5 times energy saving. The influences of the applied current density, initial dye concentration, electrolyte concentration and solution pH on the oxidation efficiency were also investigated and optimized. The prepared PbO₂/Ti electrode also showed a great stability with high dye removal efficiency (above 85%) after 10 times repeated experiments. These results suggest that it is a promising technological process to remove and recover lead from low-concentration wastewater efficiently and reuse them as electrocatalyst for other organic wastewater treatments.
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http://dx.doi.org/10.1166/jnn.2020.18553DOI Listing
September 2020

Hyaluronic acid-coated nanostructured lipid carriers for loading multiple traditional Chinese medicine components for liver cancer treatment.

Pak J Pharm Sci 2020 Jan;33(1):109-119

College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China.

This study aimed to develop hyaluronic acid (HA)-coated nanostructured lipid carriers (NLC) loaded simultaneously with oleanolic acid (OA), ursolic acid (UA) and Ginsenoside Rg3 (Rg3), prepared by electrostatic attraction for delivering OA, UA and Rg3 (OUR), termed HA-OUR-NLC, to tumors over expressing cluster determinant 44(CD44). The dialysis method was used to assess the in vitro release of OUR. Parameters such as pharmacokinetics, biodistribution, fluorescence in vivo endo-microscopy (FIVE), optical in vivo imaging (OIVI) data, and in vivo antitumor effects were evaluated. The results showed a total drug loading rate of 8.76±0.95% for the optimized HA-OUR-NLC; total encapsulation efficiency was 45.67±1.14%; particle size was 165.15±3.84%; polydispersity index was 0.227±0.01; zeta potential was -22.87±0.97 mV. Drug release followed the Higuchi kinetics. Pharmacokinetics and tissue distribution, as well as antitumor effects were evaluated in nude mice in vivo. HA-OUR-NLC were better tolerated, with increased antitumor activity compared with 5-Fu. In in vivo optical imaging, we use 1,1'-dioctadecyl-3,3,3',3'-tetramethy(DiR) as a fluorescent dye to label the NLC. The DiR-OUR-NLC group showed bright systemic signals, while the tumor site was weak. The present findings indicated that HA-OUR-NLC accumulated in the tumor site, prolonging OUR duration in the circulation and enhancing tumoral concentrations. Therefore, NLC prepared by electrostatic attraction constitute a good system for delivering OUR to tumors.
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January 2020

Spatio-temporal characteristics of agro-climatic indices and extreme weather events during the growing season for summer maize (Zea mays L.) in Huanghuaihai region, China.

Int J Biometeorol 2020 May 10;64(5):827-839. Epub 2020 Feb 10.

Institute of Crop Science, Chinese Academy of Agricultural Sciences/Key Laboratory of Crop Physiology and Ecology, Ministry of Agriculture, Beijing, 100081, China.

The stability of maize production is essential to global food security. Climate factors, such as temperature, precipitation, and solar radiation, directly affect the development of maize plants and hence the final grain yield. In this study, we investigated the spatial distributions and temporal trends of agro-climatic indices and severe weather indicators during the actual growing season for summer maize in Huanghuaihai region of China. The results showed that during the growing season, accumulated effective thermal time had significantly increased. From R3 to R6, accumulated effective thermal time, effective precipitation, and photosynthesis active radiation all showed an increasing trend, with the rate of 20.3 °C day, 1.1 mm, and 7.3 MJ m per decade, respectively. From VE to R3, most of the study years showed a > 50% ratio of high-temperature days to subtotal days and > 7 consecutive days without available precipitation. During most of the study years, there were at least 0.5 thunderstorm events from V6 to VT stage in the locations of study; days with strong winds accounted for more than half the subtotal days during the V6-VT stage. And potential risk of lodging may be reduced by the decrease in days with strong wind. The results of this study could be used in optimizing agricultural management in summer maize production in order to take advantage of beneficial climatic elements while combating adverse climatic elements.
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http://dx.doi.org/10.1007/s00484-020-01872-6DOI Listing
May 2020

Correction to: LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells.

Cell Mol Immunol 2020 Mar;17(3):302-304

Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41423-019-0351-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052133PMC
March 2020

Progesterone attenuates Aβ-induced neuronal toxicity by activating the Ras signalling pathway through progesterone receptor membrane component 1.

Life Sci 2020 Jul 27;253:117360. Epub 2020 Jan 27.

Hebei Medical University, Shijiazhuang 050017, Hebei Province, China; Department of Pharmacy, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang 050082, Hebei Province, China. Electronic address:

Aims: Progesterone receptor membrane component 1 (PGRMC1) has been reported to mediate the neuroprotective effect of progesterone, but the exact mechanism has not been elucidated. Therefore, the purpose of this study was to investigate the signalling pathway downstream of PGRMC1 in progesterone-induced neuroprotection. Recognition of the mechanism of progesterone opens novel perspectives for the treatment of diseases of the nervous system.

Main Methods: The PGRMC1 protein level was knocked down in rat primary cortical neurons, and Aβ was used to establish an Alzheimer's disease cell model. The neuroprotective effect of progesterone was assessed by Hoechst 33258 staining and a cell counting kit-8 (CCK-8) assay. Then, proteomic and bioinformatic methods were used to analyse the proteins altered in response to PGRMC1 silencing to identify target proteins and signalling pathways involved in PGRMC1-mediated progesterone-induced neuroprotection. These findings were further verified by using signalling pathway inhibitors and western blotting.

Key Findings: The neuroprotective effect of progesterone was significantly attenuated with PGRMC1 silencing. The expression of many proteins in the Ras signalling pathway was significantly changed in response to PGRMC1 silencing. FTI-277 inhibited progesterone-induced neuroprotection. Progesterone increased the expression of total Ras and Grb2.

Significance: These findings provide new perspectives for understanding the mechanism of and role of PGRMC1 in progesterone-induced neuroprotection. The Ras signalling pathway is the signalling pathway downstream of PGRMC1 in the mediation of progesterone-induced neuroprotection.
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http://dx.doi.org/10.1016/j.lfs.2020.117360DOI Listing
July 2020

Neutrophil-endothelial interactions of murine cells is not a good predictor of their interactions in human cells.

FASEB J 2020 02 23;34(2):2691-2702. Epub 2019 Dec 23.

Department of Mechanical Engineering, College of Engineering, Temple University, Philadelphia, PA, USA.

All drugs recently developed in rodent models to treat inflammatory disease have failed in clinical trials. We therefore used our novel biomimetic microfluidic assay (bMFA) to determine whether the response of murine cells to inflammatory activation or anti-inflammatory treatment is predictive of the response in human cells. Under physiologically relevant flow conditions, permeability and transendothelial electrical resistance (TEER) of human or mouse lung microvascular endothelial cells (HLMVEC or MLMVEC), and neutrophil-endothelial cell interaction was measured. The differential impact of a protein kinase C-delta TAT peptide inhibitor (PKCδ-i) was also quantified. Permeability of HLMVEC and MLMVEC was similar under control conditions but tumor necrosis factor α (TNF-α) and PKCδ-i had a significantly higher impact on permeability of HLMVEC. TEER across HLMVEC was significantly higher than MLMVEC, but PKCδ-i returned TEER to background levels only in human cells. The kinetics of N-formylmethionyl-leucyl-phenylalanine (fMLP)-mediated neutrophil migration was significantly different between the two species and PKCδ-i was significantly more effective in attenuating human neutrophil migration. However, human and mouse neutrophil adhesion patterns to microvascular endothelium were not significantly different. Surprisingly, while intercellular adhesion molecule 1 (ICAM-1) was significantly upregulated on activated HLMVEC, it was not significantly upregulated on activated MLMVEC. Responses to activation and anti-inflammatory treatment in mice may not always be predictive of their response in humans.
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http://dx.doi.org/10.1096/fj.201900048RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018548PMC
February 2020

Protein kinase C-delta inhibition is organ-protective, enhances pathogen clearance, and improves survival in sepsis.

FASEB J 2020 02 23;34(2):2497-2510. Epub 2019 Dec 23.

Center for Inflammation, Clinical and Translational Lung Research, Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.

Sepsis is a leading cause of morbidity and mortality in intensive care units. Previously, we identified Protein Kinase C-delta (PKCδ) as an important regulator of the inflammatory response in sepsis. An important issue in development of anti-inflammatory therapeutics is the risk of immunosuppression and inability to effectively clear pathogens. In this study, we investigated whether PKCδ inhibition prevented organ dysfunction and improved survival without compromising pathogen clearance. Sprague Dawley rats underwent sham surgery or cecal ligation and puncture (CLP) to induce sepsis. Post-surgery, PBS or a PKCδ inhibitor (200µg/kg) was administered intra-tracheally (IT). At 24 hours post-CLP, there was evidence of lung and kidney dysfunction. PKCδ inhibition decreased leukocyte influx in these organs, decreased endothelial permeability, improved gas exchange, and reduced blood urea nitrogen/creatinine ratios indicating organ protection. PKCδ inhibition significantly decreased bacterial levels in the peritoneal cavity, spleen and blood but did not exhibit direct bactericidal properties. Peritoneal chemokine levels, neutrophil numbers, or macrophage phenotypes were not altered by PKCδ inhibition. Peritoneal macrophages isolated from PKCδ inhibitor-treated septic rats demonstrated increased bacterial phagocytosis. Importantly, PKCδ inhibition increased survival. Thus, PKCδ inhibition improved survival and improved survival was associated with increased phagocytic activity, enhanced pathogen clearance, and decreased organ injury.
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http://dx.doi.org/10.1096/fj.201900897RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568544PMC
February 2020

Overexpression of Increases Phenazine-1-Carboxylic Acid Biosynthesis via Small RNA in the Rhizobacterium Strain PA1201.

Mol Plant Microbe Interact 2020 Mar 7;33(3):488-498. Epub 2020 Jan 7.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Phenazine-1-carboxylic acid (PCA) is the primary active component in the newly registered, commercial biopesticide Shenqinmycin and is produced during fermentation by the engineered rhizobacterium strain PA1201. Both and gene clusters contribute to PCA biosynthesis. In this study, we evaluated the role of OxyR in the regulation of PCA biosynthesis in PA1201. We first showed a functional link between expression and PCA biosynthesis. Deletion of and overexpression of both increase PCA biosynthesis. The molecular mechanisms underlying OxyR regulation of PCA production were investigated using several approaches. OxyR acts divergently in and . Overexpression of activated the expression of and -dependent PCA production. However, overexpression of had little effect on -dependent PCA biosynthesis, while deletion of promoted -dependent PCA production and exerted a negative effect on expression. Further, OxyR directly bound to the promoter region. In addition, the regulation of PCA biosynthesis by OxyR was associated with quorum sensing (QS) systems. Overexpression of OxyR positively regulated QS system. Finally, transcriptomic analysis and subsequent genetic analysis revealed the small RNA plays a key role in OxyR-dependent PCA accumulation. Specifically, OxyR directly binds to the promoter region to positively regulate expression wherein PhrS regulates the PCA positive regulator MvfR in order to control PCA biosynthesis.
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http://dx.doi.org/10.1094/MPMI-09-19-0264-RDOI Listing
March 2020

LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells.

Cell Mol Immunol 2020 03 7;17(3):272-282. Epub 2019 Nov 7.

Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.

We recently demonstrated that leukocyte Ig-like receptor 4 (LILRB4) expressed by monocytic acute myeloid leukemia (AML) cells mediates T-cell inhibition and leukemia cell infiltration via its intracellular domain. The cytoplasmic domain of LILRB4 contains three immunoreceptor tyrosine-based inhibitory motifs (ITIMs); the tyrosines at positions 360, 412, and 442 are phosphorylation sites. Here, we analyzed how the ITIMs of LILRB4 in AML cells mediate its function. Our in vitro and in vivo data show that Y and Y, but not Y, of LILRB4 are required for T-cell inhibition, and all three ITIMs are needed for leukemia cell infiltration. We constructed chimeric proteins containing the extracellular domain of LILRB4 and the intracellular domain of LILRB1 and vice versa. The intracellular domain of LILRB4, but not that of LILRB1, mediates T-cell suppression and AML cell migration. Our studies thus defined the unique signaling roles of LILRB4 ITIMs in AML cells.
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http://dx.doi.org/10.1038/s41423-019-0321-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052276PMC
March 2020