Publications by authors named "Liqing Cheng"

15 Publications

  • Page 1 of 1

Knockout of immunotherapy prognostic marker genes eliminates the effect of the anti-PD-1 treatment.

NPJ Precis Oncol 2021 May 7;5(1):37. Epub 2021 May 7.

Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing, China.

The efficacy of immunotherapy is largely patient-specific due to heterogeneity in tumors. Combining statistic power from a variety of immunotherapies across cancer types, we found four biological pathways significantly correlated with patient survival following immunotherapy. The expression of immunotherapy prognostic marker genes (IPMGs) in these pathways can predict the patient survival with high accuracy not only in the TCGA cohort (89.36%) but also in two other independent cohorts (80.91%), highlighting that the activity of the IPMGs can reflect the sensitivity of the tumor immune microenvironment (TIME) to immunotherapies. Using mouse models, we show that knockout of one of the IPMGs, MALT1, which is critical for the T-cell receptor signaling, can eliminate the antitumor effect of anti-PD-1 treatment completely by impairing the activation of CD8 T cells. Notably, knockout of another IPMG, CLEC4D, a C-type lectin receptor that expressed on myeloid cells, also reduced the effect of anti-PD-1 treatment potentially through maintaining the immunosuppressive effects of myeloid cells. Our results suggest that priming TIME via activating the IPMGs may increase the response rate and the effect of immune checkpoint blockers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41698-021-00175-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105367PMC
May 2021

Intrinsic Abnormalities of Keratinocytes Initiate Skin Inflammation through the IL-23/T17 Axis in a MALT1-Dependent Manner.

J Immunol 2021 Feb 8;206(4):839-848. Epub 2021 Jan 8.

Institute for Immunology, Tsinghua University School of Medicine, Beijing 100084, China;

Increasing evidence has supported the crucial role of CARD14 in the pathogenesis of psoriasis, whereas the precise cellular signaling involved in skin physiopathology remains poorly understood. In this article, we show that neither genetic ablation of nor elimination of T cells was sufficient to restrain the skin inflammation in a CARD14-E138A-mutation-induced psoriasis-like mouse model, whereas depletion of , which extremely blocked the IL-23/T17 axis, was more effective. Targeting CBM complex by conditional deletion of MALT1 or BCL10 in keratinocytes abrogated both the cutaneous and systemic inflammation of heterozygous mice. Selective inactivation of keratinocyte-specific MALT1 proteolytic activity strongly ameliorated the - and -induced skin disease, which was reproduced by using the imiquimod-induced mouse model. Together, our results suggest a sequence of events under CARD14-mutation-induced psoriasis condition that keratinocyte-intrinsic activation of CBM complex initiates the skin inflammation depending on the IL-23/T17 axis. Targeting keratinocytes by inactivation of MALT1 paracaspase activity might be a promising therapeutic target for early psoriasis treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2001031DOI Listing
February 2021

Association of miR-146a polymorphism rs2910164 and type 2 diabetes risk: a meta-analysis.

J Int Med Res 2020 Aug;48(8):300060520931313

Department of Endocrinology and Metabolism, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Objective: Circulating miR-146a is aberrantly expressed in patients with type 2 diabetes (T2D), probably resulting from gene polymorphisms. However, the role of polymorphism rs2910164 in T2D pathogenesis remains controversial. Thus, we designed a meta-analysis to investigate the association between rs2910164 and T2D.

Methods: PubMed and Embase were searched for eligible papers in English published through September 2, 2019. Random or fixed effect models were used to determine risk estimates according to heterogeneities.

Results: Four studies, involving 2,069 patients and 1,950 controls, were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. The pooled ORs and 95% CIs were 1.501 (0.887-2.541), 1.102 (0.931-1.304), 1.276 (0.900-1.811), 1.204 (0.878-1.652), 1.238 (0.880-1.740), and 1.350 (0.904-2.016) under the homozygote, heterozygote (CG vs. GG and CC vs. CG), dominant, allele, and recessive models, respectively. Heterogeneity was detected in most genetic models, with subgroup analyses performed by ethnicity, genotyping method, and disease duration. The co-dominant model was determined to be the most appropriate genetic model.

Conclusions: Our findings suggested that polymorphism rs2910164 is not correlated with T2D susceptibility. However, the results should be interpreted with caution because of confounding factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060520931313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441291PMC
August 2020

Epidemiological, comorbidity factors with severity and prognosis of COVID-19: a systematic review and meta-analysis.

Aging (Albany NY) 2020 07 13;12(13):12493-12503. Epub 2020 Jul 13.

Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.

A systematic review and meta-analysis was conducted in an attempt to systematically collect and evaluate the associations of epidemiological, comorbidity factors with the severity and prognosis of coronavirus disease 2019 (COVID-19). The systematic review and meta-analysis was conducted according to the guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Sixty nine publications met our study criteria, and 61 studies with more than 10,000 COVID-19 cases were eligible for the quantitative synthesis. We found that the males had significantly higher disease severity (RR: 1.20, 95% CI: 1.13-1.27, P <0.001) and more prognostic endpoints. Older age was found to be significantly associated with the disease severity and six prognostic endpoints. Chronic kidney disease contributed mostly for death (RR: 7.10, 95% CI: 3.14-16.02), chronic obstructive pulmonary disease (COPD) for disease severity (RR: 4.20, 95% CI: 2.82-6.25), admission to intensive care unit (ICU) (RR: 5.61, 95% CI: 2.68-11.76), the composite endpoint (RR: 8.52, 95% CI: 4.36-16.65,), invasive ventilation (RR: 6.53, 95% CI: 2.70-15.84), and disease progression (RR: 7.48, 95% CI: 1.60-35.05), cerebrovascular disease for acute respiratory distress syndrome (ARDS) (RR: 3.15, 95% CI: 1.23-8.04), coronary heart disease for cardiac abnormality (RR: 5.37, 95% CI: 1.74-16.54). Our study highlighted that the male gender, older age and comorbidities owned strong epidemiological evidence of associations with the severity and prognosis of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.103579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377860PMC
July 2020

Malt1 Protease Is Critical in Maintaining Function of Regulatory T Cells and May Be a Therapeutic Target for Antitumor Immunity.

J Immunol 2019 05 12;202(10):3008-3019. Epub 2019 Apr 12.

Institute for Immunology, Tsinghua University School of Medicine, Beijing 100084, China;

The paracaspase Malt1 is a key molecule in mediating Ag receptor-induced NF-κB activation in lymphocytes, but the role of Malt1 in the function of regulatory T (Treg) cells is still unclear. In this article, we reported that specific deletion of Malt1 in Treg cells would lead to -like lethal autoimmune disease, which was caused by Treg cell dysfunction but not number loss. Interestingly, mice, in which Malt1 protease was specifically inactivated in Treg cells, also displayed spontaneous inflammatory disorders, with severe hair loss and skin hyperplasia. Consistently, mice showed enhanced antitumor response because of their decreased function and infiltration of Treg cells, as well as reduced CD8 T cell exhaustion. Gene expression profiling analysis revealed dysregulated expression pattern of Treg effector genes upon Malt1 deletion or its protease inactivation. Together, our data unraveled a critical role of Malt1, especially its protease activity, in maintaining homeostasis and function of Treg cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1801614DOI Listing
May 2019

C-Type Lectin Receptor CD23 Is Required for Host Defense against and Infection.

J Immunol 2018 10 5;201(8):2427-2440. Epub 2018 Sep 5.

Institute for Immunology, Tsinghua University School of Medicine, Beijing 100084, China;

Infection by invasive fungi, such as , , and , is one of the leading death causes for the increasing population of immunocompromised and immunodeficient patients. Several C-type lectin receptors (CLRs), including Dectin-1, -2, and -3 and Mincle can recognize fungal surface components and initiate the host antifungal immune responses. Nevertheless, it remains to be determined whether other CLRs are involved in antifungal immunity. Our recent study suggests that CD23 (CLEC4J), a CLR and also a well-known B cell surface marker, may function to sense components in antifungal immunity. However, it is not clear how CD23 functions as a fungal pattern recognition receptor and whether the antifungal role of CD23 is specific to or not. In this study, we show that CD23 can recognize both α-mannan and β-glucan from the cell wall of or but cannot recognize glucuronoxylomannan from Through forming a complex with FcRγ, CD23 can induce NF-κB activation. Consistently, CD23-deficient mice were highly susceptible to and but not to infection. The expression of CD23 in activated macrophages is critical for the activation of NF-κB. CD23 deficiency results in impaired expression of NF-κB-dependent genes, especially , which induces NO production to suppress fungal infection. Together, our studies reveal the CD23-induced signaling pathways and their roles in antifungal immunity, specifically for and , which provides the molecular basis for designing potential therapeutic agents against fungal infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1800620DOI Listing
October 2018

Gangrene caused by topically applied home-prepared aconite liniment.

Contact Dermatitis 2017 Jun;76(6):368-369

Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.12722DOI Listing
June 2017

Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation.

Exp Ther Med 2016 Sep 15;12(3):1509-1514. Epub 2016 Jun 15.

Department of Endocrinology and Metabolism, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.

Zinc transporter 8 (ZnT8) is exclusively expressed in the pancreatic islet and is essential for insulin crystallization, hexamerization and secretion. Tumor necrosis factor α-induced protein-3 (TNFAIP3) is a zinc finger protein that serves a major role in the negative feedback regulation of NF-κB signaling in response to multiple stimuli, and is a central regulator of immunopathology. Although the role of TNFAIP3 in diabetes has been extensively studied, its effect on ZnT8 has not been fully elucidated. The present study aimed to verify whether proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), are able to affect ZnT8 expression in islet cells. In addition, the study aimed to determine the effect of TNFAIP3 overexpression on cytokine-altered ZnT8 activity, considering its effect on NF-κB signaling. Cell-based studies using NIT-1 cells overexpressing TNFAIP3 were used to assess the effect of cytokines on ZnT8 and NF-κB activation, as well as the effect of TNFAIP3 on ZnT8 expression. Western blot analysis and immunofluorescence staining were employed to determine the protein expression and NF-κB activation, respectively. The results indicated that cytokine stimulation led to TNFAIP3 upregulation, ZnT8 downregulation and NF-κB activation. Furthermore, TNFAIP3 overexpression protected ZnT8 from cytokine-induced downregulation. In conclusion, the current results suggest that inflammation or TNFAIP3 dysfunction may be involved in the pathogenesis of diabetes via ZnT8 expression, besides from islet cell apoptosis. In addition, restricting inflammation and enhancing TNFAIP3 expression may exert a positive effect in diabetes prevention, treatment and pancreatic cell transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2016.3457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997978PMC
September 2016

Compounds with Antifouling Activities from the Roots of Notopterygium franchetii.

Nat Prod Commun 2015 Dec;10(12):2119-21

In antifouling screening, the extract of Notopterygium franchetii de Boiss showed obvious activity. Two new phenylpropanoids (1-2) and five known coumarins (3-7) were isolated from the methanol extract of the roots of this species. The structures of the isolated compounds were determined on the basis of spectroscopic analysis. Compounds 1-2 showed definite antifouling activity against larval settlement of Bugula neritina.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2015

Prokaryotic Expression of Bioactive Zinc Transporter 8 Antigens and Detection of Diabetes Specific Autoantibodies in a Single Dot Immunogold Filtration Assay.

Clin Lab 2015 ;61(10):1445-52

Background: Type 1 diabetes mellitus is an autoimmune disease, and islet autoantibodies secreted by auto-reactive plasma cells are diagnostic indicators of the immune processes. Autoantibodies to zinc transporter 8 (ZnT8) have been identified as a novel reliable biomarker for the prediction, diagnosis, monitoring, and prognosis of autoimmune diabetes, complementing the panel of existing diagnostic autoantibodies. Although the enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay are the most frequently used testing methods, they do not allow simultaneous detection of multiple autoantibodies. Another obstacle is the cost of ZnT8 production for antibody assays. This study aimed to develop a cost-effective expression system for the production of two ZnT8 C-terminal fragments containing main ZnT8 antigen epitopes and establish an improved reliable and rapid assay for the detection of anti-ZnT8 antibodies with a potential to simultaneously measure multiple autoantibodies.

Methods: The coding codons of the human ZnT8 were optimized for prokaryotic expression and the mutation was achieved using site-directed mutagenesis. A total of 42 newly diagnosed type 1 diabetes patients (16 males and 26 females) and 100 healthy controls (57 males and 43 females) were enrolled for sera. The dot immunogold filtration assay (DIGFA) was evaluated by comparing with ELISA as the "gold standard".

Results: Two ZnT8 antigens (arginine and tryptophan ZnT8 at position 325) were successfully produced. We established a rapid DIGFA method for the simultaneous detection of anti-ZnT8 antibodies, with the sensitivity, specificity, accuracy, Youden index, and positive and negative likelihood ratio being 64.3%, 96.4%, 85.7%, 0.607, 18.0, and 0.370, respectively, and the results did not significantly differ from those for ELISA (p = 0.22).

Conclusions: These results demonstrate that the pColdII expression system is suitable for the production of bioactive ZnT8 antigens and that DIGFA can be a rapid, reliable, and highly specific method for the detection of ZnT8 antibodies, which can be potentially applied to identify a panel of diabetes-specific autoantibodies simultaneously.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/clin.lab.2015.150220DOI Listing
December 2015

Association between SLC30A8 rs13266634 Polymorphism and Type 2 Diabetes Risk: A Meta-Analysis.

Med Sci Monit 2015 Jul 27;21:2178-89. Epub 2015 Jul 27.

Department of Endocrinology and Metabolism, Southwest Hospital, Third Military Medical University, Chongqing, China (mainland).

Background: Accumulating but inconsistent data about the role of rs13266634 variant of SLC30A8 in type 2 diabetes have been reported, partly due to small sample sizes and non-identical ethnicity.

Material And Methods: We searched PubMed and Cochrane Library to identify eligible studies and extract data of baseline characteristics, genotype count, odds ratio (OR), and 95% confidence interval (CI). Both adjusted OR with 95% CI and genotype counts were employed to assess the association. Genotype data were further pooled to provide estimates under different genetic models and the most appropriate model was determined. Sensitivity and cumulative analysis were conducted to assure the strength of results.

Results: Fifty-five datasets of 39 studies (including 38 of 24 with genotype count) were included. Significant associations were found in allelic contrasts using adjusted ORs and raw genotype count, respectively, overall in Asian and European populations (overall: OR=1.147/1.157, 95% CI 1.114-1.181/1.135-1.180; Asian: OR=1.186/1.165, 95% CI 1.150-1.222/1.132-1.198; European: OR=1.100/1.151, 95% CI 1.049-1.153/1.120-1.183; All p=0.00), but not in African populations (African: OR=1.255/1.111, 95% CI 0.964-1.634/0.908-1.360, p=0.091/0.305). Further analysis with genotype count under different genetic models all showed that individuals with CC genotype had 33.0% and 16.5% higher risk of type 2 diabetes than those carrying TT and CT genotypes, respectively, under the most likely codominant model. Cumulative analysis indicated gradually improved precision of estimation after studies accumulated.

Conclusions: Our results suggest that rs13266634 may be an important genetic factor of type 2 diabetes risk among Asian and European but not African populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.894052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527121PMC
July 2015

Declined plasma sfrp5 concentration in patients with type 2 diabetes and latent autoimmune diabetes in adults.

Pak J Med Sci 2015 ;31(3):602-5

Bing Chen, Department of Endocrinology and Metabolism, Southwest Hospital, Third Military Medical University, Chongqing, China, 400038.

Objective: Secreted frizzled-related protein 5 (sfrp5), like adiponectin, has been identified as a novel insulin-sensitising and anti-inflammatory adipokine. Our objective was to determine whether differences of circulating plasma sfrp5 concentration exist among type 2 diabetes (T2D), latent autoimmune diabetes in adults (LADA) and healthy population.

Methods: Enzyme-linked immuno sorbent assay was employed to detect the circulating sfrp5 level in plasma, and other lab tests such as fasting glucose and creatinine were also examined. Correlation analysis between sfrp5 and characteristics of subjects was conducted IBM SPSS Statistics and GraphPad Prism.

Results: Circulating sfrp5 level was significantly decreased in T2D and LADA patients plasma compared with that in healthy control (14.14±11.91ng/mL, 14.82±11.27ng/mL, 22.98±12.36ng/mL, respectively), although no differences was observed between LADA and T2D groups. Furthermore, we found sfrp5 was correlated with homeostasis model assessment of insulin resistance (HOMA-IR), diabetes duration and BMI. Finally we found sfrp5 was still negatively correlated with HOMA-IR after being adjusted for disease duration and BMI(r= -0.315, P< 0.05).

Conclusions: Our results support a role for SFRP5 as a protective factor in the pathogenesis of autoimmune diabetes and facilitate a novel aspect for diabetes research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12669/pjms.313.6964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485279PMC
July 2015

Decreased A20 mRNA and protein expression in peripheral blood mononuclear cells in patients with type 2 diabetes and latent autoimmune diabetes in adults.

Diabetes Res Clin Pract 2014 Dec 2;106(3):611-6. Epub 2014 Oct 2.

Department of Endocrinology and Metabolism, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address:

Aims: A20 is a negative regulator of nuclear factor kappa B activation and the central gatekeeper in inflammation and immunity. While its role in type 1 diabetes has been widely studied, its expression level in immune cells from type 2 diabetes (T2D) and latent autoimmune diabetes in adult (LADA) patients remains unclear. This study aimed to clarify whether the expression of A20 is altered in patients with T2D or LADA.

Methods: Quantitative real-time polymerase chain reaction and western blotting were utilized to determine the expression of A20 mRNA and protein respectively in peripheral blood mononuclear cells (PBMCs) from patients with T2D (n=36) or LADA (n=17) and sex- and age-matched healthy controls (n=34).

Results: The mRNA and protein expression of A20 in PBMCs from T2D and LADA patients was significantly decreased compared with healthy controls (P<0.05). Furthermore, A20 mRNA and protein expression was significantly lower in newly diagnosed T2D patients (≤1 year since diagnosis) than in patients with a long T2D duration (>1 year since diagnosis) (P<0.05).

Conclusions: Our results suggest that decreased expression of A20 in PBMCs may be involved in the pathogenesis of diabetes, and targeting A20 may offer a potential therapeutic tool in the treatment of diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2014.09.014DOI Listing
December 2014

A novel watery diarrhoea caused by the co-infection of neonatal piglets with Clostridium perfringens type A and Escherichia coli (K88, 987P).

Vet J 2013 Sep 9;197(3):812-6. Epub 2013 Jul 9.

College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China.

In 2011, a novel watery diarrhoea in 1-7 day-old piglets occurred in Changchun, China, characterized by high pathogenicity and mortality. Investigation of clinical signs, examination for viruses, and isolation and identification of bacteria showed that co-infection by Clostridium perfringens type A and Escherichia coli (K88, 987P) was the most likely cause of the disease. Newborn piglets challenged with a mixture of Clostridium perfringens type A and Escherichia coli (K88, 987P) died within 3 days with clinical signs and gross lesions similar to those in the piglets that died in the outbreak. A subsequent study showed that the use in sows of an inactivated vaccine against the two causal bacteria was effective at reducing the incidence of the watery diarrhoea in piglets. Piglets from sows given the inactivated vaccine had a incidence of watery diarrhoea of 8% (14/175), much lower than the 95% (192/201) seen in piglets from control sows. This is the first report of diarrhoea in piglets resulting from co-infection of Clostridium perfringens type A and Escherichia coli (K88, 987P). Further studies are required to better understand the pathogenesis of this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tvjl.2013.05.023DOI Listing
September 2013

Molecular characterization, structural analysis and determination of host range of a novel bacteriophage LSB-1.

Virol J 2010 Sep 28;7:255. Epub 2010 Sep 28.

Department of Epidemiology, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.

Background: Bacteriophages (phages) are widespread in the environment and play a crucial role in the evolution of their bacterial hosts and the emergence of new pathogens.

Results: LSB-1, a reference coliphage strain, was classified as a member of the Podoviridae family with a cystic form (50 ± 5 nm diameter) and short tail (60 ± 5 nm long). The double stranded DNA was about 30 kilobase pairs in length. We identified its host range and determined the gp17 sequences and protein structure using shotgun analysis and bioinformatics technology.

Conclusions: Coliphage LSB-1 possesses a tailspike protein with endosialidase activity which is probably responsible for its specific enteroinvasive E.coli host range within the laboratory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1743-422X-7-255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955717PMC
September 2010