Publications by authors named "Yu Di"

257 Publications

Flow cytometric analysis of T lymphocytes and cytokines in aqueous humor of patients with varicella zoster virus-mediated acute retinal necrosis.

BMC Ophthalmol 2021 May 1;21(1):193. Epub 2021 May 1.

Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Background: The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder.

Methods: Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed.

Results: VZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = - 0.834).

Conclusion: The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12886-021-01951-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088617PMC
May 2021

Clinical features and treatment outcomes of intraocular lymphoma: a single-center experience in China.

Int J Ophthalmol 2021 18;14(4):574-581. Epub 2021 Apr 18.

Department of Ophthalmology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.

Aim: To investigate the clinical manifestations, diagnostic approaches, treatments, and outcomes of intraocular lymphoma.

Methods: In this retrospective study, 16 patients (28 eyes) with intraocular lymphoma were recruited in the Department of Ophthalmology, Peking Union Medical College Hospital, from 2004 to 2019. All patients underwent comprehensive ophthalmic examinations. Vitreous specimens of 13 patients were sent for cytopathology examination and other adjunctive diagnostic procedures. Three patients were diagnosed with intraocular lymphoma according to analysis of the histopathological results of systemic lymphoma by one clinician. Twenty-three eyes were treated with intravitreal administration of methotrexate, 4 eyes could not receive ocular treatment due to life-threatening lymphoma, and 1 eye did not require ocular treatment because the fundus lesions regressed after systematic chemotherapy.

Results: In 28 eyes, 25 eyes were diagnosed with vitreoretinal lymphoma, and 3 eyes were diagnosed with ciliary body lymphoma, all of which were non-Hodgkin diffuse large B cell lymphomas. The final visual acuity improved in 15 eyes (54%), remained unchanged in 5 eyes (18%), and decreased in 8 eyes (29%). Anterior segment inflammation disappeared or reduced in 8 and 5 eyes, respectively; and 15 eyes had no anterior segment reaction. Twenty eyes had mild vitreous opacity, 1 eye had mild vitritis, and 7 eyes had pars plana vitrectomy combined with silicone oil tamponade. Fundus lesions disappeared in 9 eyes and were relieved in 5 eyes; 4 eyes showed no changes, and the remaining 10 eyes' fundus were normal.

Conclusion: The clinical manifestations of intraocular lymphoma are diverse, and the misdiagnosis rate is high. Cytopathological analysis of vitreous is one of the gold standards for the diagnosis. Immunohistochemistry, gene rearrangement and flow cytometric immunophenotypic analysis can improve the diagnostic rate. Ocular chemotherapy or radiotherapy regimens may preserve visual acuity, and a multidisciplinary team can provide individualized treatment for the patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18240/ijo.2021.04.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025169PMC
April 2021

IFN-I-tolerant oncolytic Semliki Forest virus in combination with anti-PD1 enhances T cell response against mouse glioma.

Mol Ther Oncolytics 2021 Jun 17;21:37-46. Epub 2021 Mar 17.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Oncolytic virotherapy holds promise of effective immunotherapy against otherwise nonresponsive cancers such as glioblastoma. Our previous findings have shown that although oncolytic Semliki Forest virus (SFV) is effective against various mouse glioblastoma models, its therapeutic potency is hampered by type I interferon (IFN-I)-mediated antiviral signaling. In this study, we constructed a novel IFN-I-resistant SFV construct, SFV-AM6, and evaluated its therapeutic potency , , and in the IFN-I competent mouse GL261 glioma model. analysis shows that SFV-AM6 causes immunogenic apoptosis in GL261 cells despite high IFN-I signaling. MicroRNA-124 de-targeted SFV-AM6-124T selectively replicates in glioma cells, and it can infect orthotopic GL261 gliomas when administered intraperitoneally. The combination of SFV-AM6-124T and anti-programmed death 1 (PD1) immunotherapy resulted in increased immune cell infiltration in GL261 gliomas, including an increased tumor-reactive CD8 fraction. Our results show that SFV-AM6-124T can overcome hurdles of innate anti-viral signaling. Combination therapy with SFV-AM6-124T and anti-PD1 promotes the inflammatory response and improves the immune microenvironment in the GL261 glioma model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omto.2021.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042242PMC
June 2021

Metabolome-Genome-Wide Association Study (mGWAS) Reveals Novel Metabolites Associated with Future Type 2 Diabetes Risk and Susceptibility Loci in a Case-Control Study in a Chinese Prospective Cohort.

Glob Chall 2021 Apr 23;5(4):2000088. Epub 2021 Mar 23.

CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China.

In a Chinese prospective cohort, 500 patients with new-onset type 2 diabetes (T2D) within 4.61 years and 500 matched healthy participants are selected as case and control groups, and randomized into discovery and validation sets to discover the metabolite changes before T2D onset and the related diabetogenic loci. A serum metabolomics analysis reveals that 81 metabolites changed significantly before T2D onset. Based on binary logistic regression, eight metabolites are defined as a biomarker panel for T2D prediction. Pipecolinic acid, carnitine C14:0, epinephrine and phosphatidylethanolamine 34:2 are first found associated with future T2D. The addition of the biomarker panel to the clinical markers (BMI, triglycerides, and fasting glucose) significantly improves the predictive ability in the discovery and validation sets, respectively. By associating metabolomics with genomics, a significant correlation ( < 5.0 × 10) between eicosatetraenoic acid and the FADS1 (rs174559) gene is observed, and suggestive correlations ( < 5.0 × 10) between pipecolinic acid and CHRM3 (rs535514), and leucine/isoleucine and WWOX (rs72487966) are discovered. Elevated leucine/isoleucine levels increased the risk of T2D. In conclusion, multiple metabolic dysregulations are observed to occur before T2D onset, and the new biomarker panel can help to predict T2D risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gch2.202000088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025395PMC
April 2021

FcRn is not the receptor mediating the transfer of serum IgG to colostrum in pigs.

Immunology 2021 Mar 19. Epub 2021 Mar 19.

State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

In contrast to humans or rabbits, in which maternal IgG is transmitted to offspring prenatally via the placenta or the yolk sac, large domestic animals such as pigs, cows and sheep transmit IgG exclusively through colostrum feeding after delivery. The extremely high IgG content in colostrum is absorbed by newborns via the small intestine. Although it is widely accepted that the neonatal Fc receptor, FcRn, is the receptor mediating IgG transfer across both the placenta and small intestine, it remains unclear whether FcRn also mediates serum IgG transfer across the mammary barrier to colostrum/milk, especially in large domestic animals. In this study, using a FcRn knockout pig model generated with a CRISPR-Cas9-based approach, we clearly demonstrate that FcRn is not responsible for the IgG transfer from serum to colostrum in pigs, although like in other mammals, it is involved in IgG homeostasis and mediates IgG absorption in the small intestine of newborns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imm.13328DOI Listing
March 2021

High levels of soluble CD25 in COVID-19 severity suggest a divergence between anti-viral and pro-inflammatory T-cell responses.

Clin Transl Immunology 2021 15;10(2):e1251. Epub 2021 Feb 15.

The University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD Australia.

Objectives: We aimed to gain an understanding of the paradox of the immunity in COVID-19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation.

Methods: A total of 280 hospitalised patients with COVID-19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single-cell RNA sequencing (scRNA-seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID-19 patients.

Results: The levels of soluble CD25 (sCD25), IL-6, IL-8, IL-10 and TNF-α were higher in severe COVID-19 patients than non-severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV-infected mice with high levels of sCD25 demonstrated insufficient anti-viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25CD8 T cells that also expressed the highest level of PD-1 with pro-inflammatory potential. The counterpart human CD25PD-1 T cells were expanded in BALF of COVID-19 patients with severe disease compared to those with modest disease.

Conclusion: These results suggest that high levels of sCD25 in COVID-19 patients probably result from insufficient anti-viral immunity and indicate an expansion of pro-inflammatory T cells that contribute to disease severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cti2.1251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883478PMC
February 2021

Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy.

Nano Lett 2021 03 17;21(5):2224-2231. Epub 2021 Feb 17.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumor-associated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8 T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.nanolett.0c05039DOI Listing
March 2021

Comparison of Standard and Transepithelial Corneal Cross-Linking for the Treatment of Keratoconus: A Meta-analysis.

J Ophthalmol 2021 29;2021:6679770. Epub 2021 Jan 29.

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

Purpose: To compare the clinical results of standard corneal cross-linking (SCXL) with transepithelial corneal cross-linking (TECXL) in progressive keratoconus using a meta-analysis.

Methods: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched up to June 2020 to identify relevant studies. The PRISMA guidelines were followed. Primary outcomes were change in uncorrected distance visual acuity and maximum keratometry () after CXL. Secondary outcomes were change in corrected distance visual acuity, mean refractive spherical equivalent (MRSE), spherical and cylindrical error, endothelial cells density (ECD), and central corneal thickness (CCT).

Results: Sixteen studies with a total of 690 eyes (SCXL: 332 eyes; TECXL: 358 eyes) were included. At the last follow-up, SCXL provided a greater decrease in maximum keratometry () than TECXL (weighted mean difference (WMD) -1.12; 95% confidence interval (CI) -1.96, -0.29). For the other outcomes, there were no statistically significant differences.

Conclusions: Except for a greater decrease in Kmax with SCXL group, both groups have a comparable effect on visual, pachymetric, and endothelial parameters at 24 months after surgery. Larger studies with a longer follow-up time are necessary to determine whether these techniques are comparable in the long term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6679770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864754PMC
January 2021

Effects of long non-coding RNA myocardial infarction-associated transcript on retinal neovascularization in a newborn mouse model of oxygen-induced retinopathy.

Neural Regen Res 2021 Sep;16(9):1877-1881

Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.

Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarction-associated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China (approval No. 2016PS074K) on February 25, 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1673-5374.306098DOI Listing
September 2021

Serum soluble epoxide hydrolase related oxylipins and major depression in patients with type 2 diabetes.

Psychoneuroendocrinology 2021 Apr 19;126:105149. Epub 2021 Jan 19.

Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada; Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; University Health Network Toronto Rehabilitation Institute - Rumsey Centre Cardiac Rehabilitation, 347 Rumsey Rd, East York, Ontario M4G 2V6, Canada. Electronic address:

Background: People with type 2 diabetes mellitus (T2DM) are at increased risk for depression. Both conditions are associated with disturbances in polyunsaturated fatty acids. Omega-3 and omega-6 fatty acids can be converted into bioactive epoxides by cytochrome P450s (CYP450), which play pro-resolving roles in the inflammatory response; however, soluble epoxide hydrolase (sEH) metabolizes epoxides into diols, which lack pro-resolving functions and can be cytotoxic. Here, we survey serum CYP450- and sEH-derived metabolite concentrations in people with T2DM with and without a major depressive episode.

Methods: Sunnybrook Type 2 Diabetes Study (NCT04455867) participants experiencing a major depressive episode (research version of the Structured Clinical Interview for DSM-5 criteria) were matched 1:1 for gender, glycosylated hemoglobin A1c and body mass index to participants without a current depressive episode. Depression severity was assessed using the Beck Depression Inventory 2nd Edition (BDI-II). From fasting morning blood, unesterified serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass spectrometry following solid phase extraction, and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay.

Results: Between 20 depressed and 20 non-depressed participants (mean age 58.9 ± 8.5 years, 65% women) with T2DM, several sEH-derived fatty acid diols, but not IL-6, were higher among those with a depressive episode (effect sizes up to d = 0.796 for 17,18-DiHETE, a metabolite of eicosapentaenoic acid [EPA]; t = 2.516, p = 0.016). Among people with a depressive episode, two epoxides were correlated with lower BDI-II scores: 12(13)-EpOME (ρ = -0.541, p = 0.014) and 10(11)-EpDPE (ρ = -0.444, p = 0.049), metabolites of linoleic acid and docosahexaenoic acid (DHA), respectively, while the ratio of 12,13-DiHOME/12(13)-EpOME was correlated with higher BDI-II scores (ρ = 0.513, p = 0.021).

Conclusions: In people with T2DM, major depressive episodes and depressive symptom severity were associated with an oxylipin profile consistent with elimination of pro-resolving lipid mediators by sEH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2021.105149DOI Listing
April 2021

Preoperative thyroid hormone levels predict ICU mortality after cardiopulmonary bypass in congenital heart disease patients younger than 3 months old.

BMC Pediatr 2021 Jan 25;21(1):50. Epub 2021 Jan 25.

Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Jiangdong South No. 8 Road, 210008, Nanjing, China.

Background: We aimed to study the effectiveness of preoperative thyroid hormone levels in predicting intensive care unit (ICU) mortality after cardiopulmonary bypass (CPB) in infants with congenital heart disease (CHD).

Methods: We retrospectively reviewed and analyzed data from 133 patients younger than 3 months old who underwent cardiac surgery with CPB from June 2017 to November 2019. ICU mortality prediction was assessed by multivariate binary logistic regression analysis and area under the curve (AUC) analysis.

Results: Non-survivors were younger (17.46 ± 17.10 days vs. 38.63 ± 26.87 days, P = 0.006), with a higher proportion of neonates (9/13 vs. 41/120, P = 0.017) and a higher proportion of individuals with a Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score ≥ 4 (8/13 vs. 31/120, P = 0.020). No significant difference was found in CPB and aortic cross-clamping (ACC) time. The levels of free triiodothyronine (FT3) (3.91 ± 0.99 pmol/L vs. 5.11 ± 1.55 pmol/L, P = 0.007) and total triiodothyronine (TT3) (1.55 ± 0.35 nmol/L vs. 1.90 ± 0.57 nmol/L, P = 0.032) were higher in survivors than in non-survivors. In the ICU mortality prediction assessment, FT3 was an independent mortality predictor and showed a high AUC (0.856 ± 0.040).

Conclusions: The preoperative FT3 level was a powerful and independent predictor of ICU mortality after CPB in infants with CHD younger than 3 months old.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-021-02513-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831186PMC
January 2021

Cytokines/Chemokines: Potential Biomarkers for Non-paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Front Neurol 2020 21;11:582296. Epub 2020 Dec 21.

Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study focuses on finding new biomarkers to evaluate the clinical condition and provide new directions for treatment. A total of 44 cytokines/chemokines in the cerebrospinal fluid of 10 non-paraneoplastic patients and nine controls were measured. We selected some of the cytokines/chemokines that significantly increased in patients. Six selected cytokines/chemokines, including IL-10, CXCL10, CCL22, CCL3, IL-7, TNF-α, and three previously reported (IL-2, IL-6, and IL-17A), were measured in seven other patients who provided repeat samples. We compared their levels and explored correlations with severity of disease and antibody titers. The levels of Th1 axis (CXCL10, TNF-α, IFN-γ, CCL3), Th2 axis (CCL1, CCL8, CCL17, CCL22), Treg axis (IL-10), Th17 axis (IL-7), and B cell axis (CXCL13) cytokines, as well as IL-12 p40 and IL-16, were significantly higher in patients compared to those in controls. The level of IL-2 was significantly decreased at the intermediate stage of treatment compared with that before treatment. The severity of disease is positively correlated with levels of CXCL10, CCL3, IL-10, CCL22, and IL-6. The level of CCL3 in the high antibody titer group was greater than that in the low antibody titer group. The pathogenesis of anti-NMDAR encephalitis involves T cell and B cell cytokines. T cells likely assist B cells to produce antibodies. IL-2, CXCL10, CCL3, IL-10, CCL22, and IL-6 may represent new biomarkers in anti-NMDAR encephalitis. Given the lack of research on IL-10, CCL3, and CCL22 in this disease, it will be informative to explore their potential role in pathogenesis in larger studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.582296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779630PMC
December 2020

Output-Based Event-Triggered Cooperative Robust Regulation for Constrained Heterogeneous Multiagent Systems.

IEEE Trans Cybern 2020 Dec 30;PP. Epub 2020 Dec 30.

The output-based event-triggered cooperative output regulation problem is addressed for constrained linear heterogeneous multiagent system in this article. In light of the robust control theory, H∞ leader-following consensus with respect to exogenous signals, including both disturbance to be rejected and reference state of leader to be tracked, is guaranteed. Meanwhile, the system performance alleviates degradation through a model recovery anti-windup technique while encountering input saturation. Furthermore, the follower's self-state observer, the leader-state observer, and the anti-windup auxiliary system are integrated into a comprehensive system, and a unified event-triggering mechanism of full states is addressed. A fixed lower bound of sampled interval is adopted such that the frequency of data transmission gets reduced and no Zeno-behavior happens. Both the input and output of the follower's controller and anti-windup compensator hold constant, respectively, during the event-triggered intervals such that the resulting output-based event-triggered controller can be directly implemented in a digital platform. Finally, a simulation example is provided to illustrate the effectiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCYB.2020.3041267DOI Listing
December 2020

Chlorinated Flame-Retardant Dechlorane 602 Potentiates Type 2 Innate Lymphoid Cells and Exacerbates Airway Inflammation.

Environ Sci Technol 2021 01 30;55(2):1099-1109. Epub 2020 Dec 30.

Laboratory of Immunology for Environment and Health, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China.

Chlorinated flame-retardant dechloranes are emerging substitutes for restricted flame retardants. Recent studies have demonstrated that they are accumulated in wildlife and detectable in humans; however, their effects on human health are poorly understood. Here, for the first time, we revealed that widely used chlorinated flame-retardant dechlorane 602 (Dec 602) exacerbated airway inflammation in two mouse models induced by house dust mite (HDM) or IL-33, respectively. Deteriorated airway inflammation by Dec 602 was associated with a higher production of type 2 cytokines including IL-4, IL-5, and IL-13, and IgE, accompanied by enhanced mRNA expression of proinflammatory cytokines such as TNF-α and IL-6. Mechanistically, we found that Dec 602 directly potentiated mouse and human group 2 innate lymphoid cells and, as such, promoted airway inflammation even in the absence of conventional T cells in mice. These findings provide novel immunological insights necessary for further studies of the health impact of emerging flame-retardant dechloranes including Dec 602.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.0c03758DOI Listing
January 2021

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes.

Int J Mol Sci 2020 Dec 23;22(1). Epub 2020 Dec 23.

Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China.

The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literature on different T subtypes (regulatory T cells, helper T cells, cytotoxic T cells, γδ T cells, and natural killer T cells) in human and animal testes that support their regulatory roles in infertility and the orchitis pathology. While many in vitro studies have indicated the regulation potential of functional T cell subsets and their possible interaction with Sertoli cells, Leydig cells, and spermatogenesis, both under physiological and pathological processes, there have been no in situ studies to date. Nevertheless, the normal distribution and function of T cell subsets are essential for the immune privilege of the testes and intact spermatogenesis, and T cell-mediated immune response drives testicular inflammation. The distinct function of different T cell subsets in testicular homeostasis and the orchitis pathology suggests a considerable potential of targeting specific T cell subsets for therapies targeting chronic orchitis and immune infertility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22010057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793097PMC
December 2020

Defective STING expression potentiates IL-13 signaling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps.

J Allergy Clin Immunol 2021 May 17;147(5):1692-1703. Epub 2020 Dec 17.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown.

Objective: Our aim was to explore the expression, regulation, and function of STING in CRSwNP.

Methods: STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro.

Results: STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP.

Conclusions: Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.12.623DOI Listing
May 2021

Association of low blood arsenic exposure with level of malondialdehyde among Chinese adults aged 65 and older.

Sci Total Environ 2021 Mar 19;758:143638. Epub 2020 Nov 19.

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address:

High environmental arsenic exposure can increase chronic oxidative stress in experimental studies and in occupational epidemiology studies. Many regulatory agencies have put forth arsenic exposure limits, it is still unclear that whether low environmental arsenic exposure was associated with adverse health outcome in general population. This study aimed to explore the association of low blood arsenic with malondialdehyde in community-dwelling older adults. We used a cross-sectional study of 2384 older adult individuals aged ≥65 years (mean age: 85 years) from the Healthy Aging and Biomarkers Cohort Study in 2017. The median blood arsenic level was 1.41 μg/L. High oxidative stress was categorized according to the 95th percentile of MDA levels (7.47 nmol/mL). Restricted cubic spline models showed that blood arsenic levels were positively associated with malondialdehyde levels (P < 0.01); and the risk of high oxidative stress was no longer significantly increased when blood arsenic level up to 8.74 μg/L. After adjusting for potential confounders, the odds ratios of high oxidative stress for the second, third, and fourth quartiles of blood arsenic were 2.35 (1.11-4.96), 3.87 (1.90-7.91), and 4.18 (2.00-8.72) (P < 0.01), compared with the first quartile. We concluded that even low arsenic exposure was associated with higher risk of oxidative stress, in a nonlinear dose-response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.143638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897719PMC
March 2021

Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses.

Metabolites 2020 Nov 24;10(12). Epub 2020 Nov 24.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Gliomas are the most aggressive phenotypes of brain tumors and are classified into four grades according to the malignancy degree by the World Health Organization. Metabolic profiling can provide an overview of metabolic reprogramming at a specific stage of tumor initiation and development. Studies about metabolic alterations related to different grades of gliomas are helpful to understand the molecular mechanism for progression of glioma. In the current study, metabolomics and lipidomics analyses based on chromatography-mass spectrometry were performed on different grades of glioma tissues. Differential metabolites between glioma and para-tumor tissues were studied and used as the basis to explore metabolic alterations related to glioma grading. It was found that short-chain acylcarnitines were elevated, whereas lysophosphatidylethanolamines (LPEs) were decreased in high-grade gliomas. Furthermore, the gene expression of short/branched-chain acyl-coenzyme dehydrogenase (ACADSB), which is involved in fatty acid oxidation, was found down-regulated with glioma progression by analyzing related genes and pathways. In addition, LPE metabolism showed a significant difference among different grades of gliomas. These important metabolic pathways related to glioma progression may provide potential clues for further study on the mechanisms and treatment of glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo10120478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760389PMC
November 2020

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model.

J Vis Exp 2020 10 27(164). Epub 2020 Oct 27.

Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University;

Ischemia/reperfusion-derived myocardial dysfunction is a common clinical scenario in patients after cardiac surgery. In particular, the sensitivity of cardiomyocytes to ischemic injury is higher than that of other cell populations. At present, hypothermia affords considerable protection against an expected ischemic insult. However, investigations into complex hypothermia-induced molecular changes remain limited. Therefore, it is essential to identify a culture condition similar to in vivo conditions that can induce damage similar to that observed in the clinical condition in a reproducible manner. To mimic ischemia-like conditions in vitro, the cells in these models were treated by oxygen/glucose deprivation (OGD). In addition, we applied a standard time-temperature protocol used during cardiac surgery. Furthermore, we propose an approach to use a simple but comprehensive method for the quantitative analysis of myocardial injury. Apoptosis and expression levels of apoptosis-associated proteins were assessed by flow cytometry and using an ELISA kit. In this model, we tested a hypothesis regarding the effects of different temperature conditions on cardiomyocyte apoptosis in vitro. The reliability of this model depends on strict temperature control, controllable experimental procedures, and stable experimental results. Additionally, this model can be used to study the molecular mechanism of hypothermic cardioprotection, which may have important implications for the development of complementary therapies for use with hypothermia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3791/61837DOI Listing
October 2020

Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy.

Allergy 2021 02 4;76(2):456-470. Epub 2020 Nov 4.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Allergic diseases are characterized by overactive type 2 immune responses to allergens and immunoglobulin E (IgE)-mediated hypersensitivity. Emerging evidence suggests that follicular helper T (T ) cells, rather than type 2 T-helper (T 2) cells, play a crucial role in controlling IgE production. However, follicular regulatory T (T ) cells, a specialized subset of regulatory T (T ) cells resident in B-cell follicles, restricts T cell-mediated help in extrafollicular antibody production, germinal center (GC) formation, immunoglobulin affinity maturation, and long-lived, high-affinity plasma and memory B-cell differentiation. In mouse models of allergic asthma and food allergy, CXCR5 T cells, not CXCR5 conventional T 2 cells, are needed to support IgE production, otherwise exacerbated by CXCR5 T cell deletion. Upregulation of T cell activities, including a skewing toward type 2 T (T 2) and IL-13 producing T (T 13) phenotypes, and defects in T cells have been identified in patients with allergic diseases. Allergen immunotherapy (AIT) reinstates the balance between T and T cells in patients with allergic diseases, resulting in clinical benefits. Collectively, further understanding of T and T cells and their role in the immunopathogenesis of allergic diseases creates opportunities to develop novel therapeutic approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14639DOI Listing
February 2021

Low-dose IL-2 therapy compensates for metabolic shifts and reverses anxiety-like behavior in PD-1 deficiency-induced autoimmunity.

Cell Mol Immunol 2021 May 16;18(5):1336-1338. Epub 2020 Oct 16.

School of Pharmaceutical Sciences, Shandong Analysis and Test Center, Laboratory of Immunology for Environment and Health, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-020-00562-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093245PMC
May 2021

Effects of ozone autohemotherapy on blood VEGF, TGF-β and PDGF levels after finger replantation.

Ann Palliat Med 2020 Sep;9(5):3332-3339

Department of Orthopedics, The Third People's Hospital of Cixi City, Cixi, China.

Background: The study aimed to confirm the important role of ozone autologous blood therapy (autohemotherapy) in promoting successful finger replantation and its possible influence mechanism.

Methods: A total of 150 patients with severed finger replantation admitted to our hospital from March 2018 to March 2019 were selected. Patients were divided into observation group and control group according to different treatment methods. The observation group received additional ozone autologous blood treatment in the control group. We compared the number of white blood cells, visual analogue scale (VAS) scores, and the expression levels of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet-derived growth factor (PDGF) in the two groups of patients before and after intervention. We also assessed the hospitalization time and survival time of the replanted finger in the two groups, as well as blood flow values (Vbcf).

Results: Compared with the observation group on the 1st day after the operation and the control group on the 7th day after the operation, the average white blood cell count of the observation group on the 7th day after the operation was significantly increased (P<0.05), and the VAS score was significantly decreased (P<0.05).48 hours after the operation, the average Vbcf value of the replanted finger was lower than that of the contralateral healthy finger (P<0.05). Compared with the control group, the Vbcf value of the replanted fingers in the observation group was higher, and the hospitalization time and finger survival time were shorter (P<0.05). At 7 days after operation, the serum VEGF, TGF-β and PDGF levels in the observation group were significantly higher than the 1 day after operation, before the operation and the control group (P<0.05).

Conclusions: Intervention with ozone autohemotherapy after severed finger replantation can significantly increase the number of white blood cells, relieve postoperative pain, and improve the survival rate of the finger body. Ozone autohemotherapy also improves the microcirculation after anastomosis of the severed finger by up-regulating the expression of VEGF, TGF-β and PDGF in blood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-1467DOI Listing
September 2020

Surgery combined with antibiotics for the treatment of endogenous endophthalmitis caused by liver abscess.

BMC Infect Dis 2020 Sep 7;20(1):661. Epub 2020 Sep 7.

Department of Ophthalmology, Shengjing Hospital of China Medical University, Heping district, Sanhao Road 36, Shenyang, 110004, People's Republic of China.

Backgrounds: Endogenous endophthalmitis is a serious disease caused by intraocular infection that can rapidly progress to cause blindness. This study evaluated the clinical features, surgical and antibiotics treatment strategies, and treatment outcomes in patients with endophthalmitis caused by liver abscess.

Methods: Between April 2014 and April 2019, the clinical data of 16 patients (19 eyes) with endophthalmitis associated with liver abscess who underwent surgery at Shengjing Hospital were retrospectively analyzed. Furthermore, we evaluated the final visual outcomes in the patients to determine the efficacy of surgery.

Results: Fifteen patients (18 eyes) underwent intravitreal injection followed by vitrectomy after admission. One patient (1 eye) only underwent intravitreal injection. Of the 16 patients, 3 patients (3 eyes) had recurrent intraocular inflammation and eventually underwent evisceration. Systemic antibiotics were administered for all patients based on the results of vitreous humor culture, blood culture, and antibiotic susceptibility tests. Outpatient follow-ups were performed until the patients were stable (6 months). Of the 19 eyes, 1 eye (5%) had visual acuity restored to 20/200, 6 eyes (31%) had visual acuity restored to counting fingers (CF), 2 eyes (11%) had visual acuity restored to hand motion (HM), 4 eyes (22%) showed only light perception (LP), and the remaining 6 eyes (31%) showed no light perception (NLP). Drug susceptibility tests suggested that the carbapenems exhibited significant effects in the inflammatory reaction.

Conclusion: Endogenous endophthalmitis caused by liver abscess is a very serious condition, and the final visual outcome is poor. Timely surgical intervention combined with antibiotic treatment is essential, and the primary disease must be treated to control disease progression at the earliest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-020-05390-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487656PMC
September 2020

Pressure Drop with Moving Contact Lines and Dynamic Contact Angles in a Hydrophobic Round Minichannel: Visualization via Synchrotron X-ray Imaging and Verification of Experimental Correlations.

Langmuir 2020 Sep 16;36(38):11207-11214. Epub 2020 Sep 16.

Department of Mechanical Design Engineering, Pukyong National University, Busan 48547, Republic of Korea.

In hydrophobic mini- and microchannels, slug flow with moving contact lines is typically generated under various two-phase flow conditions. There is a significant pressure drop in this flow pattern with moving contact lines, which is closely related to the dynamic contact angles. Researchers have investigated dynamic contact angles experimentally for decades, but due to the limitations of visualization techniques, these experiments have typically been conducted in low Weber number regions ( < 10). In this study, we clearly visualized the dynamic contact angles of a liquid slug in high Weber number regions (10 < <1) via synchrotron X-ray imaging with high temporal (∼1000 fps) and spatial (∼2 μm/pixel) resolutions. We precisely measured the pressure drop with moving contact lines in a hydrophobic minichannel (inner diameter = 1.018 mm). On the basis of our experimental data, we verified previous correlations for dynamic contact angles and explored the relationship between pressure drop with moving contact lines and dynamic contact angles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.0c01014DOI Listing
September 2020

Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals.

J Clin Invest 2020 12;130(12):6588-6599

Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.

BACKGROUNDMarked progress is achieved in understanding the physiopathology of coronavirus disease 2019 (COVID-19), which caused a global pandemic. However, the CD4+ T cell population critical for antibody response in COVID-19 is poorly understood.METHODSIn this study, we provided a comprehensive analysis of peripheral CD4+ T cells from 13 COVID-19 convalescent patients, defined as confirmed free of SARS-CoV-2 for 2 to 4 weeks, using flow cytometry and magnetic chemiluminescence enzyme antibody immunoassay. The data were correlated with clinical characteristics.RESULTSWe observed that, relative to healthy individuals, convalescent patients displayed an altered peripheral CD4+ T cell spectrum. Specifically, consistent with other viral infections, cTfh1 cells associated with SARS-CoV-2-targeting antibodies were found in COVID-19 covalescent patients. Individuals with severe disease showed higher frequencies of Tem and Tfh-em cells but lower frequencies of Tcm, Tfh-cm, Tfr, and Tnaive cells, compared with healthy individuals and patients with mild and moderate disease. Interestingly, a higher frequency of cTfh-em cells correlated with a lower blood oxygen level, recorded at the time of admission, in convalescent patients. These observations might constitute residual effects by which COVID-19 can impact the homeostasis of CD4+ T cells in the long-term and explain the highest ratio of class-switched virus-specific antibody producing individuals found in our severe COVID-19 cohort.CONCLUSIONOur study demonstrated a close connection between CD4+ T cells and antibody production in COVID-19 convalescent patients.FUNDINGSix Talent Peaks Project in Jiangsu Province and the National Natural Science Foundation of China (NSFC).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI141054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685722PMC
December 2020

Effect and mechanism of the long noncoding RNA MALAT1 on retinal neovascularization in retinopathy of prematurity.

Life Sci 2020 Nov 19;260:118299. Epub 2020 Aug 19.

Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. Electronic address:

Aims: The most typical pathological manifestation of retinopathy of prematurity (ROP) is Retinal neovascularization (RNV). Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to mediate angiogenesis. Our experiment aimed to research the effect and mechanism of the MALAT1 on RNV in ROP.

Main Methods: C57 mice was used to establish oxygen-introduced retinopathy (OIR), and divided into control, hyperoxia, hyperoxia control siRNA, and hyperoxia MALAT1 siRNA groups.

Key Findings: It was shown that MALAT1 mRNA was high expressed in the retinas of OIR mice. Further studies revealed that after intravitreal injection of MALAT1 siRNA, the degree of retinopathy was significantly reduced compared with OIR group. In addition, the protein and mRNA expression levels of CCN1, AKT and VEGF were significantly decreased. This was accompanied by a decrease in inflammatory genes including IL-1β, IL-6, and TNF-α compared with the hyperoxia control siRNA mice.

Significance: The result suggested that MALAT1 may be involved in the process of RNV in ROP and MALAT1 siRNA may be a promising agent for the treatment of ROP by inhibiting RNV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118299DOI Listing
November 2020

A light- and heat-driven glycal diazidation approach to nitrogenous carbohydrate derivatives with antiviral activity.

Org Biomol Chem 2020 Aug;18(31):6155-6161

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

The aminated mimetics of 2-keto-3-deoxy-sugar acids such as the anti-influenza clinical drugs oseltamivir (Tamiflu) and zanamivir (Relenza) are important bioactive molecules. Development of synthetic methodologies for accessing such compound collections is highly desirable. Herein, we describe a simple, catalyst-free glycal diazidation protocol enabled by visible light-driven conditions. This new method requires neither acid promoters nor transition-metal catalysts and takes place at ambient temperature within 1-2 hours. Notably, the desired transformations could be promoted by thermal conditions as well, albeit with lower efficacy compared to the light-induced conditions. Different sugar acid-derived glycal templates have been converted into a range of 2,3-diazido carbohydrate analogs by harnessing this mild and scalable approach, leading to the discovery of new antiviral agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0ob01172jDOI Listing
August 2020

Neutrophil activation in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of protein markers in blood and cerebrospinal fluid.

Ageing Res Rev 2020 09 23;62:101130. Epub 2020 Jul 23.

Department of Pharmacology & Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada; KITE UHN Toronto Rehabilitation Institute, 347 Rumsey Rd, East York, ON, M4G 2V6, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada. Electronic address:

Inflammation is involved in the pathophysiology of Alzheimer's disease (AD), with multiple inflammatory processes implicated in its risk and progression. This review included original peer-reviewed studies measuring the cerebrospinal fluid or peripheral blood concentrations of protein markers specifically related to neutrophil activity in healthy controls (HC) and in patients with AD or mild cognitive impairment (MCI). A total of 35 studies (N = 3095, N = 2596, N = 1203) were included. Random-effects meta-analyses were used to estimate between-groups standardized mean differences (SMD) and 95 % confidence intervals. In blood, concentrations of myeloperoxidase (MPO; N/N = 271/209, SMD = 0.41 [0.20, 0.62]; I = 15.7 %) and neutrophil gelatinase associated lipocalin (NGAL; N/N = 273/185, SMD = 0.30 [0.11, 0.49]; I < 0.005 %) were significantly higher in AD relative to HC. Peripheral blood concentrations of NGAL were also higher in MCI compared to HC (N/N = 489/145, SMD = 0.39 [0.11, 0.67]; I = 38.6 %). None of the protein markers exhibited a significant difference between HC, MCI, or AD groups in the cerebrospinal fluid. The evidence suggests that peripheral neutrophil activation, as indicated by blood concentrations of NGAL and MPO, may be a pathological feature of cognitive impairment due to AD, evident at stages of MCI and AD dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arr.2020.101130DOI Listing
September 2020

Analysis of the Chinese Alligator TCRα/δ Loci Reveals the Evolutionary Pattern of Atypical TCRδ/TCRμ in Tetrapods.

J Immunol 2020 08 26;205(3):637-647. Epub 2020 Jun 26.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People's Republic of China;

Atypical TCRδ found in sharks, amphibians, birds, and monotremes and TCRμ found in monotremes and marsupials are TCR chains that use Ig or BCR-like variable domains (VHδ/Vμ) rather than conventional TCR V domains. These unconventional TCR are consistent with a scenario in which TCR and BCR, although having diverged from each other more than 400 million years ago, continue to exchange variable gene segments in generating diversity for Ag recognition. However, the process underlying this exchange and leading to the evolution of these atypical TCR receptor genes remains elusive. In this study, we identified two TCRα/δ gene loci in the Chinese alligator (). In total, there were 144 V, 154 Jα, nine Jδ, eight Dδ, two Cα, and five Cδ gene segments in the TCRα/δ loci of the Chinese alligator, representing the most complicated TCRα/δ gene system in both genomic structure and gene content in any tetrapod examined so far. A pool of 32 VHδ genes divided into 18 subfamilies was found to be scattered over the two loci. Phylogenetic analyses revealed that these VHδ genes could be related to bird VHδ genes, VHδ/Vμ genes in platypus or opossum, or alligator VH genes. Based on these findings, a model explaining the evolutionary pattern of atypical TCRδ/TCRμ genes in tetrapods is proposed. This study sheds new light on the evolution of TCR and BCR genes, two of the most essential components of adaptive immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2000257DOI Listing
August 2020

PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland.

Int J Ophthalmol 2020 18;13(6):860-869. Epub 2020 Jun 18.

Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.

Aim: To investigate the regulatory roles of the members of the peroxisome proliferator-activated receptor (PPAR) family in lacrimal gland dysfunction under conditions of desiccating stress or diabetes.

Methods: Quantitative polymerase chain reaction (qPCR) was used to examine the expression of PPARs in the cornea, conjunctiva, meibomian gland, and lacrimal gland in adult rats. The rats were divided into 3 groups: a control group, dry eye group, and diabetic group. The phenol red threads test, tear film break-up time (BUT) test and fluorescein staining were carried out to evaluate the development of dry eye. Based on bioinformatics research, qPCR was used to examine the expression level of PPARγ, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), sirtuin 1 (Sirt1), myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β) in the lacrimal glands.

Results: PPARα and PPARβ/δ were mainly expressed in the conjunctiva and the lacrimal gland, respectively. However, PPARγ was expressed in both the conjunctiva and lacrimal gland, at much higher levels than those measured for PPARα and PPARβ/δ. Dry eye rats and diabetic rats both showed decreased tear secretion, shortened BUT, and increased corneal staining. Significant changes in gene expression were observed compared with the control group. In the lacrimal glands of dry eye rats and diabetic rats, expression of PPARγ decreased (<0.05), expression of Sirt1 also decreased (<0.01), whereas expression of TNF-α, IL-1β, IL-6, MyD88, and TGF-β increased (<0.05).

Conclusion: Among PPARs, PPARγ might play a dominant role in the regulation of metabolic- and inflammatory-signaling pathways on the ocular surfaces and in lacrimal glands. Down-regulation of PPARγ is highly relevant to lacrimal gland dysfunction under desiccating-stress and diabetic conditions. PPARγ, thus, is a potential therapeutic target in the treatment of environment- or diabetes-induced dry eye diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18240/ijo.2020.06.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270247PMC
June 2020