Publications by authors named "Ping Jia"

103 Publications

Semaphorin 3E Promotes Susceptibility to Infection in Mice by Suppressing CD4 Th1 Cell Response.

J Immunol 2021 Feb 21;206(3):588-598. Epub 2020 Dec 21.

Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada;

Protective immunity to cutaneous leishmaniasis is mediated by IFN-γ-secreting CD4 Th1 cells. IFN-γ binds to its receptor on -infected macrophages, resulting in their activation, production of NO, and subsequent destruction of parasites. This study investigated the role of Semaphorin 3E (Sema3E) in host immunity to infection in mice. We observed a significant increase in Sema3E expression at the infection site at different timepoints following infection. Sema3E-deficient (Sema3E knockout [KO]) mice were highly resistant to infection, as evidenced by significantly ( < 0.05-0.01) reduced lesion sizes and lower parasite burdens at different times postinfection when compared with their infected wild-type counterpart mice. The enhanced resistance of Sema3E KO mice was associated with significantly ( < 0.05) increased IFN-γ production by CD4 T cells. CD11c cells from Sema3E KO mice displayed increased expression of costimulatory molecules and IL-12p40 production following infection and were more efficient at inducing the differentiation of -specific CD4 T cells to Th1 cells than their wild-type counterpart cells. Furthermore, purified CD4 T cells from Sema3E KO mice showed increased propensity to differentiate into Th1 cells in vitro, and this was significantly inhibited by the addition of recombinant Sema3E in vitro. These findings collectively show that Sema3E is a negative regulator of protective CD4 Th1 immunity in mice infected with and suggest that its neutralization may be a potential therapeutic option for treating individuals suffering from cutaneous leishmaniasis.
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http://dx.doi.org/10.4049/jimmunol.2000516DOI Listing
February 2021

The Long Pentraxin 3 (PTX3) Suppresses Immunity to Cutaneous Leishmaniasis by Regulating CD4 T Helper Cell Response.

Cell Rep 2020 Dec;33(11):108513

Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. Electronic address:

The long pentraxin 3 (PTX3) plays a critical role in inflammation, tissue repair, and wound healing. Here, we show that PTX3 regulates disease pathogenesis in cutaneous leishmaniasis (CL). PTX3 expression increases in skin lesions in patients and mice during CL, with higher expression correlating with severe disease. PTX3-deficient (PTX3) mice are highly resistant to L. major and L. braziliensis infections. This enhanced resistance is associated with increases in Th17 and IL-17A responses. The neutralization of IL-17A abolishes this enhanced resistance, while rPTX3 treatment results in decrease in Th17 and IL-17A responses and increases susceptibility. PTX3 CD4 T cells display increased differentiation to Th17 and expression of Th17-specific transcription factors. The addition of rPTX3 suppresses the expression of Th17 transcription factors, Th17 differentiation, and IL-17A production by CD4 T cells from PTX3 mice. Collectively, our results show that PTX3 contributes to the pathogenesis of CL by negatively regulating Th17 and IL-17A responses.
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http://dx.doi.org/10.1016/j.celrep.2020.108513DOI Listing
December 2020

Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats.

Nutr Metab (Lond) 2020 26;17:91. Epub 2020 Oct 26.

Division of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China.

Background: Ketogenic diet (KD) has been proposed to be an effective lifestyle intervention in metabolic syndrome. However, the effects of KD on cardiac remodeling have not been investigated. Our aim was to investigate the effects and the underling mechanisms of KD on cardiac remodeling in spontaneously hypertensive rats (SHRs).

Methods: 10-week-old spontaneously hypertensive rats were subjected to normal diet or ketogenic diet for 4 weeks. Then, their blood pressure and cardiac remodeling were assessed. Cardiac fibroblasts were isolated from 1- to 3-day-old neonatal pups. The cells were then cultured with ketone body with or without TGF-β to investigate the mechanism in vitro

Results: 4 weeks of KD feeding aggravated interstitial fibrosis and cardiac remodeling in SHRs. More interestingly, ketogenic diet feeding increased the activity of mammalian target of rapamyoin (mTOR) complex 2 pathway in the heart of SHRs. In addition, β-hydroxybutyrate strengthened the progression of TGF-β-induced fibrosis in isolated cardiac fibroblasts. mTOR inhibition reversed this effect, indicating that ketone body contributes to cardiac fibroblasts via mTOR pathway.

Conclusions: These data suggest that ketogenic diet may lead to adverse effects on the remodeling in the hypertensive heart, and they underscore the necessity to fully evaluate its reliability before clinical use.
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http://dx.doi.org/10.1186/s12986-020-00510-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586698PMC
October 2020

Definition and retrospective application of a clinical scoring system for COVID-19 triage at presentation.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620963019

Department of Respiratory and Critical Care Medicine, the People's Hospital of Changshou District, Beiguan Road 16, Fengcheng Street, Changshou District, Chongqing, 401220, China.

Background: A simple scoring system for triage of suspected patients with COVID-19 is lacking.

Methods: A multi-disciplinary team developed a screening score taking into account epidemiology history, clinical feature, radiographic feature, and routine blood test. At fever clinics, the screening score was used to identify the patients with moderate to high probability of COVID-19 among all the suspected patients. The patients with moderate to high probability of COVID-19 were allocated to a single room in an isolation ward with level-3 protection. And those with low probability were allocated to a single room in a general ward with level-2 protection. At the isolation ward, the screening score was used to identify the confirmed and probable cases after two consecutive real-time reverse transcription polymerase chain reaction (RT-PCR) tests. The data in the People's Hospital of Changshou District were used for internal validation and those in the People's Hospital of Yubei District for external validation.

Results: We enrolled 76 and 40 patients for internal and external validation, respectively. In the internal validation cohort, the area under the curve of receiver operating characteristics (AUC) was 0.96 [95% confidence interval (CI): 0.89-0.99] for the diagnosis of moderate to high probability of cases among all the suspected patients. Using 60 as cut-off value, the sensitivity and specificity were 88% and 93%, respectively. In the isolation ward, the AUC was 0.94 (95% CI: 0.83-0.99) for the diagnosis of confirmed and probable cases. Using 90 as cut-off value, the sensitivity and specificity were 78% and 100%, respectively. These results were confirmed in the validation cohort.

Conclusion: The scoring system provides a reference on COVID-19 triage in fever clinics to reduce misdiagnosis and consumption of protective supplies.
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http://dx.doi.org/10.1177/1753466620963019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570777PMC
October 2020

Identification of a Protective Antigen Dihydrolipoyl Dehydrogenase and Its Responding CD4 T Cells at Clonal Level.

J Immunol 2020 09 29;205(5):1355-1364. Epub 2020 Jul 29.

Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada;

There is currently no clinically effective vaccine against cutaneous leishmaniasis because of poor understanding of the Ags that elicit protective CD4 T cell immunity. In this study, we identified a naturally processed peptide (DLD) that is derived from dihydrolipoyl dehydrogenase (DLD) protein. DLD is conserved in all pathogenic species, is expressed by both the promastigote and amastigote stages of the parasite, and elicits strong CD4 T cell responses in mice infected with We generated I-A-DLD tetramer and identified DLD-specific CD4 T cells at clonal level. Following infection, DLD-specific CD4 T cells massively expanded and produced effector cytokines (IFN-γ and TNF). This was followed by a gradual contraction, stable maintenance following lesion resolution, and display of memory (recall) response following secondary challenge. Vaccination with rDLD protein induced strong protection in mice against virulent challenge. Identification of Ags that elicit protective immunity and their responding Ag-specific T cells are critical steps necessary for developing effective vaccines and vaccination strategies against infectious agents, including protozoan parasites.
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http://dx.doi.org/10.4049/jimmunol.2000338DOI Listing
September 2020

Ketogenic diet aggravates hypertension via NF-κB-mediated endothelial dysfunction in spontaneously hypertensive rats.

Life Sci 2020 Oct 21;258:118124. Epub 2020 Jul 21.

Division of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:

Aims: Ketogenic diet (KD) has been proposed to be an effective lifestyle intervention for metabolic syndrome. However, the effects of KD on hypertension have not been well investigated. The present study aimed to investigate the effects and underling mechanisms of KD on hypertension in spontaneously hypertensive rats (SHRs).

Materials And Methods: SHRs were subjected to normal diet or KD for 4 weeks, starting at the age of 10 weeks. Then, the blood pressure and vascular function were assessed. Next, the eNOS expression, inflammatory factors and relative signaling pathway were examined. Human umbilical vein endothelial cells were used to investigate the underlying mechanism account for the effect of ketone on inflammation and eNOS expression.

Key Findings: Compared with the normal diet, KD was indicated to aggravate hypertension and impaire endothelium-dependent relaxation in mesenteric arteries of SHRs. eNOS and CD31 expression in mesenteric arteries were also significantly suppressed by KD. In addition, KD markedly increased the activation of NF-κB pathway and the expression of IL1-β and TNF-α. In vitro, results showed that inhibition of NF-κB could rescue the adverse effects of ketone body and TGF-β on eNOS expression and inflammation response.

Significance: Our study indicated that KD impaired endothelium-dependent relaxation in mesenteric arteries and aggravated the development of hypertension in SHRs, suggesting that it should be more cautious to apply KD into clinical application in hypertensive individuals.
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http://dx.doi.org/10.1016/j.lfs.2020.118124DOI Listing
October 2020

Depletion of miR-21 in dendritic cells aggravates renal ischemia-reperfusion injury.

FASEB J 2020 09 15;34(9):11729-11740. Epub 2020 Jul 15.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Dendritic cells (DCs) play an important role in the pathophysiology of renal ischemia-reperfusion injury (IRI). The mechanisms underlying DCs phenotypic modulation and their function are not fully understood. In this study, we examined the effect of miR-21 on the phenotypic modulation of DCs in vitro and in vivo, and further investigated the impact of miR-21-overexpression DC or miR-21-deficient DC on renal IRI. We found that treatment with hypoxia/reoxygenation (H/R) suppressed miR-21 expression in bone marrow-derived dendritic cells (BMDCs), and significantly increased the percentage of mature DCs (CD11c /MHC-II /CD80 ). Using a selection of microRNA mimics, we successfully induced the upregulation of miR-21 in BMDCs, which induced immature DC phenotype and an anti-inflammatory DC response. However, deletion of miR-21 in BMDCs promoted maturation of DCs under H/R. Adoptive transfer of miR-21-overexpression BMDCs could alleviate renal IR-induced pro-inflammatory cytokines production and acute kidney injury (AKI). Mice with miR-21 deficiency in DCs subjected to renal IR showed more severe renal dysfunction and inflammatory response compared with wild-type mice. In addition, chemokine C receptor 7 (CCR7), a surface marker of mature DC, was a target gene of miR-21, and silencing of CCR7 in BMDCs led to reduced mature DCs under H/R. In conclusion, our findings highlight miR-21 as a key regulator of DCs subset phenotype and a potential therapeutic target in renal IRI.
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http://dx.doi.org/10.1096/fj.201903222RRDOI Listing
September 2020

Terminal Sliding Mode Control with a Novel Reaching Law and Sliding Mode Disturbance Observer for Inertial Stabilization Imaging Sensor.

Sensors (Basel) 2020 May 31;20(11). Epub 2020 May 31.

Information Engineering School, Inner Mongolia University of Science and Technology, Baotou 014010, China.

High-performance control of inertial stabilization imaging sensors (ISISs) is always challenging because of the complex nonlinearities induced by friction, mass imbalance, and external disturbances. To overcome this problem, a terminal sliding mode controller (TSMC) based on a novel exponential reaching law (NERL) method with a high-order terminal sliding mode observer (HOTSMO) is suggested. First, the TSMC based on NERL is adopted to improve system performance. The NERL incorporates the power term and switching gain term of the system state variables into the conventional exponential reaching law, and the convergent speed of the TSMC is accelerated. Then, an HOTSMO is designed, which considers the speed and lumped disturbances of the system as the observation object. The estimated disturbance is then provided as a compensation for the controller, which enhances the disturbance rejection ability of the system. Comparative simulation and experimental results show that the proposed method achieves the best tracking performance and the strongest robustness than PID and the traditional TSMC methods.
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http://dx.doi.org/10.3390/s20113107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308983PMC
May 2020

Sinusoidal Single-Pixel Imaging Based on Fourier Positive-Negative Intensity Correlation.

Sensors (Basel) 2020 Mar 17;20(6). Epub 2020 Mar 17.

Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

Single-pixel imaging techniques extend the time dimension to reconstruct a target scene in the spatial domain based on single-pixel detectors. Structured light illumination modulates the target scene by utilizing multi-pattern projection, and the reflected or transmitted light is measured by a single-pixel detector as total intensity. To reduce the imaging time and capture high-quality images with a single-pixel imaging technique, orthogonal patterns have been used instead of random patterns in recent years. The most representative among them are Hadamard patterns and Fourier sinusoidal patterns. Here, we present an alternative Fourier single-pixel imaging technique that can reconstruct high-quality images with an intensity correlation algorithm using acquired Fourier positive-negative images. We use the Fourier matrix to generate sinusoidal and phase-shifting sinusoid-modulated structural illumination patterns, which correspond to Fourier negative imaging and positive imaging, respectively. The proposed technique can obtain two centrosymmetric images in the intermediate imaging course. A high-quality image is reconstructed by applying intensity correlation to the negative and positive images for phase compensation. We performed simulations and experiments, which obtained high-quality images, demonstrating the feasibility of the methods. The proposed technique has the potential to image under sub-sampling conditions.
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http://dx.doi.org/10.3390/s20061674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146428PMC
March 2020

Efficacy and safety of Zaoren Anshen capsules in the treatment of insomnia: A meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2020 Feb;99(6):e19033

The First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, P.R. China.

Background: Zaoren Anshen capsules (ZRAS) have been widely used to treat patients with insomnia. However, the efficacy and safety of ZRAS for insomnia treatment is not entirely clear. Therefore, it is necessary to clarify the effect of ZRAS for the treatment of insomnia by a systematic meta-analysis.

Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases and performed a manual search to retrieve relevant articles (available through January 2019) describing randomized controlled trials (RCTs) of ZRAS for the treatment of insomnia. The quality of the selected articles was assessed with the Cochrane risk-of-bias tool. A meta-analysis of the selected articles was performed with RevMan 5.3 software.

Results: A total of 13 articles including 1175 patients were included in the study. Overall, our results showed that ZRAS was slightly higher than that of the conventional Western medicine for insomnia in terms of clinical efficacy rate; but there was no statistical difference between the 2 groups (relative risk [RR] = 1.03, 95% confidence interval [CI] = [0.97, 1.09], P = .34). However, it should be noted that ZRAS treatment causes far fewer adverse reaction than treatment with conventional Western medicine (RR = 0.20, 95% CI = [0.14, 0.28], P < .00001).

Conclusion: Our results suggested that ZRAS is an effective and safe treatment for insomnia, especially in adverse reaction. However, multi-regional and well-designed RCTs studies are needed in the future to validate the results.
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http://dx.doi.org/10.1097/MD.0000000000019033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015645PMC
February 2020

[Effect of Naoshuming decoction on expression of NF-κB, TNF-α, and IL-1β in focal cerebral ischemia rats].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019 Nov;44(11):1222-1229

Shenzhen Beikelian Pharmaceutical Technology Limited Liability Company, Shenzhen 518000, China.

Objective: To explore the effect of Naoshuming decoction on cerebral ischemic rats.
 Methods: The model of cerebral ischemia in rats was established via middle cerebral artery occlusion (MCAO). The MCAO model rats were randomly divided into a model group (n=36), a Naoshuming decoction at high dose group (n=36), a Naoshuming decoction at middle dose group (n=36) and a Naoshuming decoction at low dose group (n=36). In addition, a normal group (n=12) and a sham operation group (n=12) were included. Rats in each group were killed on the 3rd, 7th, and 14th day to detect relevant indicators. The Ayelet Levy 14 method was used to score the neurological function. Immunohistochemical method was used to detect the protein expression of nuclear factor kappa-B (NF-κB)/p50, NF-κB/p65, tumor necrosis factor-α (TNF-α), and IL-1β. The quantitative real-time PCR were used to detect the mRNA expression of NF-κB, TNF-α and IL-1β. 
 Results: Compared with the sham group, at each time point, the inflammation indexes in the model group and different dose of Naoshuming decoction groups were significantly enhanced, and all of them showed neurological dysfunction. But the inflammatory indexes and neurological function scores would were gradually improved with the pass of time. Compared with the model group, the neurological dysfunction, the protein levels of NF-κB/p50, NF-κB/p65, TNF-α and IL-1β, and the mRNA of NF-κB, TNF-α and IL-1β in the high, middle and low dose of Naoshuming decoction groups were reduced at 3, 7 and 14 d, with statistical difference (all P<0.05 or P<0.01). 
 Conclusion: Naoshuming decoction can alleviate the cerebral ischemic injury in rats.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2019.190459DOI Listing
November 2019

TLR-2 and MyD88-Dependent Activation of MAPK and STAT Proteins Regulates Proinflammatory Cytokine Response and Immunity to Experimental Infection.

Front Immunol 2019 22;10:2673. Epub 2019 Nov 22.

Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.

It is known that infection in mice is associated with increased production of proinflammatory cytokines by macrophages and monocytes. However, the intracellular signaling pathways leading to the production of these cytokines still remain unknown. In this paper, we have investigated the innate receptors and intracellular signaling pathways that are associated with -induced proinflammatory cytokine production in macrophages. We show that the production of IL-6, IL-12, and TNF-α by macrophages and following interaction with is dependent on phosphorylation of mitogen-activated protein kinase (MAPK) including ERK, p38, JNK, and signal transducer and activation of transcription (STAT) proteins. Specific inhibition of MAPKs and STATs signaling pathways significantly inhibited -induced production of proinflammatory cytokines in macrophages. We further show that induced proinflammatory cytokine production in macrophages is mediated via Toll-like receptor 2 (TLR2) and involves the adaptor molecule, MyD88. Deficiency of MyD88 and TLR2 leads to impaired cytokine production by macrophages and acute death of -infected relatively resistant mice. Collectively, our results provide insight into -induced activation of the immune system that leads to the production of proinflammatory cytokines and resistance to the infection.
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http://dx.doi.org/10.3389/fimmu.2019.02673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883972PMC
November 2020

Understanding unipolar electrograms and global activation from noninvasive mapping for diagnosing arrhythmias.

Authors:
Ping Jia

J Electrocardiol 2019 Nov - Dec;57S:S10-S14. Epub 2019 Oct 15.

Medtronic, Inc., Independence, OH, USA. Electronic address:

In the past several decades Electrocardiographic Imaging has been developed, validated, and recently commercialized for clinical use (Medtronic CardioInsight™). The technology noninvasively maps cardiac electrical potentials by combining multi-channel body surface electrocardiograms and patient specific heart-torso geometry. Unlike contact catheter mapping where bipolar electrograms are commonly used, noninvasive mapping is unipolar in nature. While bipolar electrograms reflect local activation time, noninvasive mapping reflects both local and global information. Characterizing arrhythmias using noninvasive mapping requires a different approach than what is used with bipolar mapping during electrophysiological studies. With multiple example cases, this article aims to demonstrate how in-depth analysis of noninvasive electrogram features and global activation patterns can reveal clinically important characteristics of arrhythmias, which may not be evident on the automatically generated maps. These characteristics include transmural location of the ectopic focus, differential locations within structural proximity, engagement of bundle or specific tissue, and substrate properties. The analysis approach involves applying unipolar potential fundamentals and relating electrogram features, global activation with underlying electrophysiology and cardiac anatomy to explain specific mapping phenomenon. If validated, easy-to-use diagnostic criteria or algorithms can be built and automated as product features in the commercial system to facilitate future noninvasive mapping in patients.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.09.011DOI Listing
October 2019

Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury.

EBioMedicine 2019 Nov 31;49:331-340. Epub 2019 Oct 31.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Medical Center of Kidney, Shanghai, China; Kidney and Dialysis Institute of Shanghai, Shanghai, China; Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China; Hemodialysis quality control center of Shanghai, Shanghai, China. Electronic address:

Background: Uncoupling protein 1 (UCP1) is predominantly found in brown adipose tissue mitochondria, and mediates energy dissipation to generate heat rather than ATP via functional mitochondrial uncoupling. However, little is known about its expression and function in kidney.

Methods: We carried out a mRNA microarray analysis in mice kidneys with ischemia reperfusion (IR) injury. The most dramatically downregulated gene UCP1 after IR was identified, and its role in generation of mitochondrial reactive oxygen species (ROS) and oxidative stress injury was assessed both in vitro and in vivo. Genetic deletion of UCP1 was used to investigate the effects of UCP1 on ischemia or cisplatin-indued acute kidney injury (AKI) in mice.

Findings: UCP1 was located in renal tubular epithelial cells in kidney and downregulated in a time-dependent manner during renal IR. Deletion of UCP1 increased oxidative stress in kidneys and aggravated ischemia or cisplatin induced AKI in mice.Viral-based overexpression of UCP1 reduced mitochondrial ROS generation and apoptosis in hypoxia-treated tubular epithelial cells. Furthermore, UCP1 expression was regulated by peroxisome proliferator-activator receptor (PPAR) γ in kidneys during renal IR. Overexpression of PPAR-γ resembled UCP1-overexpression phenotype in vitro. Treatment with PPAR-γ agonist could induce UCP1 upregulation and provide protective effect against renal IR injury in UCP1mice, but not in UCP1mice.

Interpretation: UCP1 protects against AKI likely by suppressing oxidative stress, and activation of UCP1 represents a potential therapeutic strategy for AKI. FUND: National Natural Science Foundation of China grants, Science and Technology Commission of Shanghai.
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http://dx.doi.org/10.1016/j.ebiom.2019.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945195PMC
November 2019

Paeonol ameliorates monosodium urate-induced arthritis in rats through inhibiting nuclear factor-κB-mediated proinflammatory cytokine production.

Phytother Res 2019 Nov 12;33(11):2971-2978. Epub 2019 Aug 12.

Key Laboratory of Natural Medicine Research of Chongqing Education Commission, College of Environment and Resources, Chongqing Technology and Business University, Chongqing, 400067, China.

Moutan Cortex has been widely used to treat various types of arthritis in traditional Chinese medicine. Paeonol is isolated as an active ingredient from Moutan Cortex. However, the effect and potential mechanism of paeonol on gouty arthritis have not been evaluated. In this study, rats were treated intragastrically with paeonol for consecutive 7 days. On Day 5, rats were intra-articularly injected with monosodium urate (MSU) crystals in the ankle joints to induce MSU-induced arthritis (MIA). Paw volume was detected at various time points. Gait score was measured at 24 hr after MSU crystal injection. Ankle joints were collected for evaluation of histological score and expression of proinflammatory cytokines using hematoxylin and eosin staining and immunohistochemistry staining, respectively. Nuclear level of nuclear factor (NF)-κBp65 in synovial tissues was analyzed by western blot assay. NF-κB DNA-binding activity was measured by enzyme linked immunosorbent assay. Paeonol markedly lowered the paw volume, gait score, and histological score in MIA rats. Mechanistically, paeonol markedly reduced the expression of TNF-α, IL-1β, and IL-6 in synovial tissues of MIA rats. In addition, the elevated level of p65 in nucleus and NF-κB DNA-binding activity in synovial tissues of MIA rats were reduced significantly by paeonol treatment. These findings suggest that paeonol exerts anti-inflammatory effect in MIA rats through inhibiting expression of proinflammatory cytokines and NF-κB activation.
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http://dx.doi.org/10.1002/ptr.6472DOI Listing
November 2019

Impact of Thermal Control Measures on the Imaging Quality of an Aerial Optoelectronic Sensor.

Sensors (Basel) 2019 Jun 19;19(12). Epub 2019 Jun 19.

Key Laboratory of Airborne Optical Imaging and Measurement, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

The image resolution is the most important performance parameter for an aerial optoelectronic sensor. Existing thermal control methods cannot eliminate the sensor's temperature gradient, making the image resolution difficult to further improve. This article analyzes the different impacts of temperature changes on the imaging resolution and proposes modifications. Firstly, the sensor was subjected to thermo-optical simulation by means of finite element analysis, and the different impacts of temperature changes on the imaging quality were analyzed. According to the simulation results, an active thermal control method is suggested to enhance the temperature uniformity of the sensor. Considering the impacts of active and passive thermal control measures, thermal optical analysis was carried out to predict the performance of the sensor. The results of the analysis show that the imaging quality of the sensor has been significantly improved. The experimental results show that the image resolution of the optoelectronic sensor improved from 47 to 59 lp/mm, which demonstrates that the sensor can produce a high image quality in a low-temperature environment.
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http://dx.doi.org/10.3390/s19122753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631959PMC
June 2019

Value of N-terminal pro-brain natriuretic peptide and aortic diameter in predicting in-hospital mortality in acute aortic dissection.

Cytokine 2019 07 20;119:90-94. Epub 2019 Mar 20.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address:

Objective: To determine the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and aortic diameter in predicting in-hospital mortality in acute aortic dissection (AD).

Methods: A single-center prospective study was designed in the setting of University hospital in China. 122 patients with acute AD were enrolled. Admission plasma NT-proBNP levels and aortic diameter were measured.

Results: Plasma NT-proBNP concentrations (P < 0.001), aortic diameter (P = 0.002), and admission systolic blood pressure (SBP) (P = 0.011) were significantly increased in patients who died compared to those who survived during hospitalization. Furthermore, aortic diameter had positive correlations with NT-proBNP levels (r = 0.270, P = 0.003) and admission diastolic blood pressure (DBP) (r = 0.202, P = 0.025), respectively. Multiple logistic regression analysis demonstrated that NT-proBNP ≥569.75 pg/ml and aortic diameter ≥40 mm were strongly associated with in-hospital mortality. The odds ratio (OR) and 95% confidence interval (CI) were 3.246, 1.212-8.693 (P = 0.019); and 2.917, 1.102-7.722 (P = 0.031), respectively. Moreover, when NT-proBNP ≥1325.6 pg/ml, the sensitivity and specificity of NT-proBNP in predicting in-hospital mortality risk were 55.2% and 95.7% (95% CI, 0.707-0.891; P < 0.001), respectively. In addition, when aortic diameter ≥47 mm, the sensitivity and specificity were 58.6% and 88.2% (95% CI, 0.607-0.841; P < 0.001), respectively.

Conclusions: NT-proBNP ≥569.75 pg/ml and aortic diameter ≥40 mm were important risk factors and independently associated with acute AD in-hospital mortality. NT-proBNP ≥1325.6 pg/ml or aortic diameter ≥47 mm showed higher specificity in predicting in-hospital mortality. Using NT-proBNP and aortic diameter together showed better performance in predicting in-hospital mortality with higher sensitivity.
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http://dx.doi.org/10.1016/j.cyto.2019.03.004DOI Listing
July 2019

Delayed Remote Ischemic Preconditioning ConfersRenoprotection against Septic Acute Kidney Injury via Exosomal miR-21.

Theranostics 2019 1;9(2):405-423. Epub 2019 Jan 1.

Department of Nephrology, Zhongshan Hospital, Fudan University.

Sepsis is a common and life-threatening systemic disorder, often leading to acute injury of multiple organs. Here, we show that remote ischemic preconditioning (rIPC), elicited by brief episodes of ischemia and reperfusion in femoral arteries, provides protective effects against sepsis-induced acute kidney injury (AKI). Limb rIPC was conducted on mice 24 h before the onset of cecal ligation and puncture (CLP), and serum exosomes derived from rIPC mice were infused into CLP-challenged recipients. , we extracted and identified exosomes from differentiated C2C12 cells (myotubes) subjected to hypoxia and reoxygenation (H/R) preconditioning, and the exosomes were administered to lipopolysaccharide (LPS)-treated mouse tubular epithelial cells (mTECs) or intravenously injected into CLP-challenged miR-21 knockout mice for rescue experiments. Limb rIPC protected polymicrobial septic mice from multiple organ dysfunction, systemic accumulation of inflammatory cytokines and accelerated parenchymal cell apoptosis through upregulation of miR-21 in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner in the ischemic limbs of mice. However, in miR-21 knockout mice or mice that received HIF-1α siRNA injection into hind limb muscles, the organ protection conferred by limb rIPC was abolished. Mechanistically, we discovered that miR-21 was transported from preischemic limbs to remote organs via serum exosomes. In kidneys, the enhanced exosomal miR-21 derived from cultured myotubes with H/R or the serum of mice treated with rIPC integrated into renal tubular epithelial cells and then targeted the downstream PDCD4/NF-κB and PTEN/AKT pathways, exerting anti-inflammatory and anti-apoptotic effects and consequently attenuating sepsis-induced renal injury both and . This study demonstrates a critical role for exosomal miR-21 in renoprotection conferred by limb rIPC against sepsis and suggests that rIPC and exosomes might serve as the possible therapeutic strategies for sepsis-induced kidney injury.
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http://dx.doi.org/10.7150/thno.29832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376188PMC
December 2019

Pacing prescription for cardiac resynchronization therapy: When RV stimulation matters.

J Cardiovasc Electrophysiol 2019 05 29;30(5):769-770. Epub 2019 Jan 29.

Cardiac Bioelectricity Research and Training Center, Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.

Background: Cardiac resynchronization therapy (CRT) aims to correct delayed left ventricle (LV) activation resulting from left bundle branch block (LBBB). The source of LV activation delay resides in the septum and/or anterior LV. LV pacing, timed with intrinsic right bundle branch (RBB) conduction, may restore "physiological" biventricular activation. This is not assured because LV paced wavefronts themselves propagate unpredictably. Less studied are effects of right ventricle (RV) pacing on LV activation in heart failure (HF) patients with LBBB.

Methods And Results: In this case RV pacing pre-excited precisely the region left behind during LV pacing. Consequently, biventricular pacing produced confluent LV depolarization (the patient "responded" to this with reverse remodeling).

Conclusion: Successful electrical resynchronization requires best combination and timing of paced/intrinsic wavefront(s). This demands individualization. Sometimes, an RV paced wavefront may be valuable to resynchronization.
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http://dx.doi.org/10.1111/jce.13850DOI Listing
May 2019

Changchun Institute of Optics, Fine Mechanics and Physics (CIOMP): introduction to the feature issue.

Authors:
Ping Jia

Appl Opt 2018 Dec;57(34):CIO1

The Changchun Institute of Optics, Fine Mechanics and Physics (CIOMP), Chinese Academy of Sciences (CAS) is the first national research institute in modern China with optics as its primary research focus. Focusing on luminescence, applied optics, optical engineering, precision mechanics, and intelligent manufacturing as its main research areas, CIOMP has made many significant achievements in the international optical community. The articles in this feature issue present the latest research findings on CIOMP's specific topics.
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http://dx.doi.org/10.1364/AO.57.00CIO1DOI Listing
December 2018

Diminazene aceturate (Berenil) downregulates Trypanosoma congolense-induced proinflammatory cytokine production by altering phosphorylation of MAPK and STAT proteins.

Immunol Res 2019 02;67(1):84-92

Parasite Vaccines Development Laboratory, Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB, R3E 0T5, Canada.

Diminazene aceturate (Berenil) is the most commonly used trypanolytic agent in livestock. We previously showed that Berenil downregulates Trypanosoma congolense (T. congolense)-induced cytokine production in macrophages both in vitro and in vivo. Here, we investigated the molecular mechanisms through which the drug alters T. congolense-induced cytokine production in macrophages. We show that pretreatment of macrophages with Berenil significantly downregulated T. congolense-induced phosphorylation of mitogen-activated protein kinase (p38), signal transducer and activator of transcription (STAT) proteins including STAT1 and STAT3, and NFκB activity both in vitro and in vivo. Collectively, our results reveal a mechanistic insight through which Berenil downregulates T. congolense-induced cytokine production in macrophages by inhibiting key signaling molecules and pathways associated with proinflammatory cytokine production.
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http://dx.doi.org/10.1007/s12026-018-9040-5DOI Listing
February 2019

Optimization of cardiac resynchronisation therapy: LV Lead position, qLV, or paced effects?

Europace 2019 Mar;21(3):360

Cardiac Bioelectricity Research and Training Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA.

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http://dx.doi.org/10.1093/europace/euy247DOI Listing
March 2019

HIF-1α-induced autophagy contributes to cisplatin resistance in ovarian cancer cells.

Pharmazie 2018 09;73(9):533-536

In this study, the viability and apoptosis of ovarian cancer cell line OVCAR-3 were assessed using MTT and flow cytometry analysis. GFP-tagged LC3 plasmid transfection was utilized to demonstrate the occurrence of autophagy. The expression of HIF-1α, Beclin1, LC3 and β-actin were determined with Western blot analysis. We found that hypoxia could inhibit cisplatin induced apoptosis in OVCAR-3 cells and enhance the chemoresistance to cisplatin. Furthermore, GFP-tagged LC3 plasmid transfection and western blot were used to demonstrate that hypoxia induced chemoresistance of OVCAR-3 cells to cisplatin is related to HIF-1α-induced autophagy. All these findings suggest that the cisplatin resistance of ovarian cancer cells is associated with HIF-1α-induced autophagy.
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http://dx.doi.org/10.1691/ph.2018.8514DOI Listing
September 2018

Total Flavonoids from Leaves of Carya Cathayensis Ameliorate Renal Fibrosis via the miR-21/Smad7 Signaling Pathway.

Cell Physiol Biochem 2018 13;49(4):1551-1563. Epub 2018 Sep 13.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background/aims: Renal tubulointerstitial fibrosis is the most common pathway of progressive kidney injury, leading to end-stage renal disease. At present, no effective prophylactic treatment method is available. This study investigated the anti-fibrotic effects of total flavonoids (TFs) extracted from leaves of Carya Cathayensis in vivo and in vitro, and explored the underlying mechanisms.

Methods: Anti-fibrotic effects of TFs were measured using a mouse model of unilateral ureteral obstruction (UUO) and in transforming growth factor-β1 (TGF-β1)-treated mouse tubular epithelial cells (mTECs). mRNA expression and protein levels of Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also tested by real-time reverse transcription PCR and western blot analysis. To elucidate the underlying mechanisms, expression of miR-21 was examined in mTECs treated with TFs using miR-21 mimics transfected into mTECs before TGF-β1 and TFs treatment. Regulation of mothers against decapentaplegic homolog (Smad) signaling by miR-21 was subsequently validated via overexpression and deletion of miR-21 followed by a luciferase assay.

Results: TFs treatment attenuated renal fibrosis, and inhibited expression of collagens and α-SMA in the kidneys of mice subjected to UUO. In vitro, the TFs significantly decreased expression of fibrotic markers in TGF-β1-treated mTECs. Moreover, TFs reduced miR-21 expression in a time- and dose-dependent manner in mTECs, increased expression of Smad7, and decreased phosphorylation of Smad3. Treatment with miR-21 mimics abolished the anti-fibrotic effects of the TFs on the TGF-β1-treated mTECs. In addition, genetic deletion of miR-21 upregulated expression of Smad7 and suppressed phosphorylation of Smad3, attenuating renal fibrosis in mice. Bioinformatics predictions revealed the potential binding site of miR-21 in the 3'-untranslated region of Smad7, and this was further confirmed by the luciferase assay.

Conclusion: TFs ameliorate renal fibrosis via a miR-21/Smad7 signaling pathway, indicating a potential therapy for the prevention of renal fibrosis.
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http://dx.doi.org/10.1159/000493458DOI Listing
October 2018

Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.

Oxid Med Cell Longev 2018 13;2018:4895913. Epub 2018 Aug 13.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs. O-linked -N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions. Growing evidence indicates that stress can induce an acute increase in O-GlcNAc levels, which can be cytoprotective. The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling. We established a stable model of CI-AKI using 5/6 nephrectomized rats exposed to dehydration followed by iohexol injection via the tail vein. We found that RIPC increased UDP-GlcNAc levels through the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation. RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species. In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis. In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
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http://dx.doi.org/10.1155/2018/4895913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112094PMC
January 2019

Effect of long non-coding RNA growth arrest-specific 5 on apoptosis in renal ischaemia/reperfusion injury.

Nephrology (Carlton) 2019 Apr;24(4):405-413

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Aim: Long non-coding RNA (lncRNAs) have been shown to play a critical role in a variety of pathophysiological processes, such as cell proliferation, apoptosis and migration. However, there were few studies addressing the function of lncRNAs in renal ischaemia/reperfusion (I/R) injury. Apoptosis is an important pathogenesis during I/R injury. Here, we identified the effect of hypoxia-responsive lncRNA growth arrest-specific 5 (GAS5) on apoptosis in renal I/R injury.

Methods: Ischaemia/reperfusion injury in mice or hypoxia/re-oxygenation (H/R) in human proximal renal tubular epithelial cells (HK-2) was practiced to induce apoptosis. The kidneys and blood were collected at 24 h after reperfusion. The GAS5 messenger RNA (mRNA) expression and apoptosis-related gene mRNA and protein levels, including p53, cellular inhibitor of apoptosis protein 2 (cIAP2) and thrombospondin-1 (TSP-1), were analysed. GAS5 small-interfering RNA was transfected with H/R induced cells. Over-expression of GAS5 was performed by plasmid transfection.

Results: Apoptotic cells significantly increased in I/R-injured kidneys. GAS5 could be up-regulated in kidneys at 24 h after reperfusion and 3 h after re-oxygenation, combined with increased expression of its downstream apoptosis-related proteins p53 and cIAP2. GAS5 small-interfering RNA treatment down-regulated the mRNA and protein levels of p53 and TSP-1, and attenuated apoptosis induced by H/R in HK-2 cells. Conversely, over-expression of GAS5 up-regulated the mRNA and protein levels of p53 and TSP-1, and promoted apoptosis in HK-2 cells.

Conclusion: Long non-coding RNA GAS5 induced by I/R injury could promote apoptosis in kidney. TSP-1 might be one of the downstream effectors of GAS5, which will be explored in the future.
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http://dx.doi.org/10.1111/nep.13476DOI Listing
April 2019

miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation.

Front Physiol 2018 26;9:790. Epub 2018 Jun 26.

Division of Nephrology, Zhongshan Hospital,Fudan University, Shanghai, China.

Renal tubular injury and innate immune responses induced by hypoxia contribute to acute kidney injury. Accumulating evidence suggests that miR-21 overexpression protects against kidney ischemia injury. Additionally, miR-21 emerges as a key inhibitor in dendritic cell maturation. Thus, we hypothesized that miR-21 protects the kidney from IR injury by suppressing epithelial cell damage and inflammatory reaction. In this study, we investigated effects of miR-21 and its signaling pathways (PTEN/AKT/mTOR/HIF, PDCD4/NFκ-B) on kidney ischemia/reperfusion (IR) injury and . The results revealed that IR increased miR-21, HIF1α, and 2α expression and . MiR-21 interacted with HIF1α and 2α through the PTEN/AKT/mTOR pathway. Moreover, inhibition of miR-21 activated PDCD4/NFκ-B pathways, which are critical for dendritic cell maturation. Renal IR triggers local inflammation by inducing the dendritic cell maturation and promoting the secretion of IL-12, IL-6, and TNF-α cytokines. Knockdown of miR-21 intensified the effect of IR on tubular epithelial cell apoptosis and dendritic cell maturation. Our results suggested that IR-inducible miR-21 protects epithelial cells from IR injury via a feedback interaction with HIF (PTEN/AKT/mTOR/HIF/miR-21) and by inhibiting maturation of DCs through the PDCD4/NF-κB pathway. These findings highlight new therapeutic opportunities in AKI.
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http://dx.doi.org/10.3389/fphys.2018.00790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036242PMC
June 2018

Myeloid-Derived Suppressor Cells Contribute to Susceptibility to Infection by Suppressing CD4 T Cell Proliferation and IFN-γ Production.

J Immunol 2018 07 13;201(2):507-515. Epub 2018 Jun 13.

Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada; and

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of bone marrow-derived myeloid cells that have immune-suppressive activities. These cells have been reported to suppress T cell immunity against tumors as well as in some parasitic and bacterial infections. However, their role during infection has not been studied. Given that immunosuppression is a hallmark of African trypanosomiasis, we investigated the role of MDSCs in immunity to infection. We found increased numbers of MDSCs in the spleen and liver of infected mice, which correlated with increased parasitemia. Depletion of MDSCs significantly increased the percentage of proliferating and IFN-γ-producing CD4 T cells from the spleen of infected mice. Furthermore, MDSCs from infected mice directly suppressed CD4 T cell proliferation in a coculture setting. This suppressive effect was abolished by the arginase-1 inhibitor, N-hydroxy-nor-l-arginine (nor-NOHA), indicating that MDSCs suppress CD4 T cell proliferation and function in an arginase-1-dependent manner. Indeed, depletion of MDSCs during infection led to control of the first wave of parasitemia and prolonged survival of infected mice. This was also associated with increased CD4 T cell proliferation and IFN-γ production. Taken together, our findings identify an important role of MDSCs in the pathogenesis of experimental infection via suppression of T cell proliferative and effector cytokine responses in an arginase-1-dependent manner.
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http://dx.doi.org/10.4049/jimmunol.1800180DOI Listing
July 2018

The p110δ isoforme of phosphatidylinositol 3-kinase plays an important role in host defense against chlamydial lung infection through influencing CD4+ T-cell function.

Pathog Dis 2018 08 1;76(6). Epub 2018 Aug 1.

Department of Immunology, Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E0T5, Canada.

PI3Ks display integrant significance in T-cell development and differentiation, which is related to host defense against infections. Here, we investigated the role of p110δ isoform of PI3Ks in host defense against chlamydial lung infection in a mouse model. Our data showed that lung infection with Chlamydia muridarum (Cm) activated PI3K/AKT signaling pathway. Compared to WT mice, p110δD910A mice, mice with an inactivating knockin mutation in the p110δ Isoform of PI3Ks, showed more sever disease phenotype and slower recovery, which was associated with reduced Chlamydia-specific Th1 and Th17 immune responses following infection. Further adoptive transfer experiment showed that mice which received CD4+ T cells from infected p110δD910A mice exhibited greater body weight loss and higher bacterial loads in the lung than those which received CD4+ T cells from WT mice following challenge infection. These results provide in vivo evidence that p110δ isoform of PI3Ks plays an important role in host defense against chlamydial infection by promoting CD4+ T-cell immunity.
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http://dx.doi.org/10.1093/femspd/fty053DOI Listing
August 2018

The human breast cancer-associated protein, the prolactin-inducible protein (PIP), regulates intracellular signaling events and cytokine production by macrophages.

Immunol Res 2018 04;66(2):245-254

Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.

The prolactin-inducible protein (PIP) is considered a valuable biomarker that is associated with both benign and malignant pathological conditions of the mammary gland. The function of PIP in breast tumorigenesis remains unknown; however, evidence from our laboratory and others suggest that it regulates host immunity. Studies with PIP-deficient (PIP) mice demonstrated significantly lower numbers of CD4 T cells in their secondary lymphoid organs, impaired Th1 response, and impaired nitric oxide (NO) production. To further delineate the immunoregulatory role of PIP, we compared the expression of IFN-γR and TLR4, pro-inflammatory cytokine production, and intracellular signaling events by IFN-γ and lipopolysaccharide (LPS)-stimulated macrophages from wild-type (WT) and PIP mice. We showed that although the expressions of IFN-γR and TLR4 were comparable, productions of pro-inflammatory cytokines were decreased in PIP macrophages. This was associated with decreased phosphorylation of mitogen-activated protein kinase (MAPK) and signal transducer of activation of transcription (STAT) proteins in macrophages from PIP mice. Interestingly, the expression of suppressors of cytokine signaling (SOCS) 1 and 3 proteins, known to suppress IFN-γ and LPS signaling, was higher in PIP macrophages compared to those from WT mice. Collectively, our studies show that deficiency of PIP significantly affects intracellular signaling events leading to decreased pro-inflammatory cytokine production, and further confirms a role for PIP as an important immunoregulatory protein. This direct link between PIP and cell-mediated immunity, a key component of the immune system that is critical for cancer control, may have significant therapeutic implications.
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http://dx.doi.org/10.1007/s12026-018-8987-6DOI Listing
April 2018