The overall survival of metastatic colon adenocarcinoma (COAD) remains poor, so it is important to explore the mechanisms of metastasis and invasion. This study aimed to identify invasion-related gene Show more
The overall survival of metastatic colon adenocarcinoma (COAD) remains poor, so it is important to explore the mechanisms of metastasis and invasion. This study aimed to identify invasion-related genetic markers for prognosis prediction in patients with COAD. Three molecular subtypes (C1, C2, and C3) were obtained based on 97 metastasis-related genes in 365 COAD samples from The Cancer Genome Atlas (TCGA). A total of 983 differentially expressed genes (DEGs) were identified among the different subtypes by using the limma package. A 6-gene signature (ITLN1, HOXD9, TSPAN11, GPRC5B, TIMP1, and CXCL13) was constructed via Lasso-Cox analysis. The signature showed strong robustness and could be used in the training, testing, and external validation (GSE17537) cohorts with stable predictive efficiency. Compared with other published signatures, our model showed better performance in predicting outcomes. Pan-cancer expression analysis results showed that ITLN1, TSPAN11, CXCL13, and GPRC5B were downregulated and TIMP1 was upregulated in most tumor samples, including COAD, which was consistent with the results of the TCGA and GEO cohorts. Western blot analysis and immunohistochemistry were performed to validate protein expression. Tumor immune infiltration analysis results showed that TSPAN11, GPRC5B, TIMP1, and CXCL13 protein levels were significantly positively correlated with CD4+ T cells, macrophages, neutrophils, and dendritic cells. Further, the TIMP1 and CXCL13 proteins were significantly related to the tumor immune infiltration of CD8+ T cells. We recommend using our signature as a molecular prognostic classifier to assess the prognostic risk of patients with COAD. Show less
Genome-wide association studies (GWAS) have revealed sixteen risk loci for endoemtrial cancer but the identification of candidate susceptibility genes remains challenging. Here, we perform transcripto Show more
Genome-wide association studies (GWAS) have revealed sixteen risk loci for endoemtrial cancer but the identification of candidate susceptibility genes remains challenging. Here, we perform transcriptome-wide association study (TWAS) analyses using the largest endometrial cancer GWAS and gene expression from six relevant tissues, prioritizing eight candidate endometrial cancer susceptibility genes, one of which (EEFSEC) is located at a potentially novel endometrial cancer risk locus. We also show evidence of biologically relevant tissue-specific expression associations for CYP19A1 (adipose), HEY2 (ovary) and SKAP1 (whole blood). A phenome-wide association study demonstrates associations of candidate susceptibility genes with anthropometric, cardiovascular, diabetes, bone health and sex hormone traits that are related to endometrial cancer risk factors. Lastly, analysis of TWAS data highlights candidate compounds for endometrial cancer repurposing. In summary, this study reveals endometrial cancer susceptibility genes, including those with evidence of tissue specificity, providing insights into endometrial cancer aetiology and avenues for therapeutic development. Show less
The blood-brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer's disease (AD) Show more
The blood-brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer's disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ Show less
PKR, also known as EIF2AK2, is an IFN-stimulated gene (ISG) and shows a higher expression in probands with systemic lupus erythematosus (SLE), which is likely responsible for the impaired translationa Show more
PKR, also known as EIF2AK2, is an IFN-stimulated gene (ISG) and shows a higher expression in probands with systemic lupus erythematosus (SLE), which is likely responsible for the impaired translational and proliferative responses to mitogens in T cells from SLE patients. In this study, we overexpressed EIF2AK2 in HeLa cells to study EIF2AK2-regulated genes using RNA-seq technology, followed by bioinformatic analysis of target genes of EIF2AK2-regulated transcriptional factors (TFs). Overexpression of EIF2AK2 promotes HeLa cell apoptosis. EIF2AK2 selectively represses the transcription of histone protein genes associated with SLE, immune response genes and TF genes, which was validated by RT-qPCR experiments. Analysis of motifs overrepresented in the promoter regions of EIF2AK2-regulated genes revealed eighteen EIF2AK2-regulated TFs involved in establishing the EIF2AK2 network. Eight out of these predicted EIF2AK2-regulated TFs were further verified by RT-qPCR selectively in both HeLa and Jurkat cells, and most such as HEY2, TFEC, BATF2, GATA3 and ATF3 and FOXO6 are known to regulate immune response. Our results suggest that the dsRNA-dependent kinase EIF2AK2 selectively regulates the transcription of immune response and SLE-associated histone protein genes, and such a selectivity is likely to be operated by EIF2AK2-targeted TFs. The EIF2AK2-TFs axis potentially offers new therapeutic targets for counteracting immunological disease in the future. Show less
Testosterone (TS) is a critical androgenic steroid that regulates human metabolism and maintains secondary sexual characteristics. The biotransformation from 4-androstene-3,17-done (4-AD) to TS is lim Show more
Testosterone (TS) is a critical androgenic steroid that regulates human metabolism and maintains secondary sexual characteristics. The biotransformation from 4-androstene-3,17-done (4-AD) to TS is limited by the poor catalytic activity of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3). Herein, we explored the structural characteristics and catalytic mechanism of 17β-HSD3 and adopted the rational design strategy to improve its catalytic activity. Molecular docking and molecular dynamics simulations revealed the substrate-binding pocket and the binding mode of 4-AD to 17β-HSD3. We located the pivotal residues and regulated their hydrophobicity and polarity. The obtained G186R/Y195W variant formed additional electrostatic interaction and hydrogen bond with 4-AD, increasing the binding affinity between the variant and 4-AD. Therefore, the G186R/Y195W variant produced 3.98 g/L of TS, which increased to 297%. The combination of structural and mechanism resolution drives the implementation of the rational design strategy, which provides guidance for bioproduction of TS catalyzed by 17β-HSD3. Show less
The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyro Show more
The occurrence and development of rheumatoid arthritis (RA) is regulated by numerous cytokines. Interleukin 27 (IL-27) is a soluble cytokine that exerts biological effects by regulating the Janus tyrosine kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway Show less
To investigate the correlation between changes in serum RBP4, hs-CRP, and IL-27 levels and rosuvastatin in the treatment of coronary heart disease (CHD). One hundred and twenty patients with CHD admit Show more
To investigate the correlation between changes in serum RBP4, hs-CRP, and IL-27 levels and rosuvastatin in the treatment of coronary heart disease (CHD). One hundred and twenty patients with CHD admitted in our hospital were selected as the research object, including 60 patients with acute coronary syndrome as the ACS group, and 60 patients with stable angina as the SA group. Another 60 patients without CHD who were examined in our hospital at the same time were included in the non-CHD group. The patients with CHD were further divided into the control group (CG) ( After retrospective analysis, no significant difference was found among the ACS group, the SA group, and the non-CHD group ( Serum RBP4, hs-CRP, and IL-27 play an important role in the occurrence and development of CHD, with a positive correlation to the Gensini score, which can indicate the severity of cardiovascular disease to a certain extent. Meanwhile, rosuvastatin can remarkably reduce serum RBP4, hs-CRP, and IL-27 levels, which is of significance for prognosis. Show less
Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes
Immune disorders play an important role in the pathogenesis of Crohn's disease (CD). Notably, the increased immune response of Th1 cells and related cytokines is associated with the onset of CD. IL-27 Show more
Immune disorders play an important role in the pathogenesis of Crohn's disease (CD). Notably, the increased immune response of Th1 cells and related cytokines is associated with the onset of CD. IL-27 is a newly discovered IL-12-related cytokine, but its expression and clinical significance in CD patients are still controversial. This study is aimed at evaluating the serum levels of IL-27 in CD patients and analyzing their clinical significance. The results indicated that serum levels of IL-27 in CD patients were significantly higher than those in control subjects (median (interquartile range (IQR)): 110.0 (95.0, 145.0) vs. 85.0 (80.0, 95.0) pg/ml, Show less
RNA-seq data, drug sensitivity data, and clinical data were obtained from TCGA, GEO, CCLE, and CTRP. Log-rank test was used to determine the survival value of Clinically,
Autoimmune regulator (Aire) is a transcription factor that plays a pivotal role in the maintenance of immune tolerance. However, little is known about its roles in peripheral immune tolerance. Aire is Show more
Autoimmune regulator (Aire) is a transcription factor that plays a pivotal role in the maintenance of immune tolerance. However, little is known about its roles in peripheral immune tolerance. Aire is predominantly expressed in dendritic cells (DCs) in the periphery. DCs with higher inducible costimulatory ligand (ICOSL) expression and interleukin (IL)-27 production have been reported highly suggesting its roles in inducing follicular helper T cells (TFH). Here we use Aire-overexpressing DC2.4 cells in a coculture system composed of naïve CD4 Show less
Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurre Show more
Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m Show less
Psoriasis is a severe skin disease with significant physical and psychological health consequences. As a typical type of immune disease, both innate and adaptive immunity disorders play key roles in t Show more
Psoriasis is a severe skin disease with significant physical and psychological health consequences. As a typical type of immune disease, both innate and adaptive immunity disorders play key roles in the development of psoriasis. Interleukin (IL)-30 was thought as a natural antagonist of gp130-mediated signaling that affects T helper type 1 and 17 cell polarization by inhibiting IL-6 and IL-27 signaling pathways. Here, we found that, in vitro, IL-30 reduced cytokine levels of HaCaT keratinocytes and dendritic cells (DCs), weakened the maturationS of DCs, inhibited DC-mediated T cell proliferation, and blocked the activation of nuclear factor-κB. In vivo, IL-30 inhibited the development of skin disease in two animal models: Krt14-Vegfa and imiquimod (IMQ)-induced psoriasis-like skin disease. Thus, IL-30 may be useful as a therapeutic agent for controlling psoriasis. Show less
B cell dysfunction and inflammatory cytokine over-production participate in the pathogenesis of rheumatoid arthritis (RA). Here we compared peripheral B cell homeostasis and immune functions between R Show more
B cell dysfunction and inflammatory cytokine over-production participate in the pathogenesis of rheumatoid arthritis (RA). Here we compared peripheral B cell homeostasis and immune functions between RA patients and healthy controls (HC) and explored vital signaling pathways involved in altered RA B cells. We found that RA patients showed significantly decreased frequencies of peripheral CD19 Show less
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients Show more
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany ( We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funded by Roche Sequencing Solutions, Inc. Show less
Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) Show more
Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) to promote tissue repair after acute myocardial infarction. We hypothesized that MYDGF has a role in cardiac adaptation to persistent pressure overload. We defined the cellular sources and function of MYDGF in wild-type (WT), MYDGF protein abundance increased in the left ventricular myocardium and in blood plasma of pressure-overloaded mice. Patients with severe aortic stenosis also had elevated MYDGF plasma concentrations, which declined after transcatheter aortic valve implantation. Monocytes and macrophages emerged as the main MYDGF sources in the pressure-overloaded murine heart. While These findings establish a MYDGF-based adaptive crosstalk between inflammatory cells and cardiomyocytes that protects against pressure overload-induced heart failure. Show less
Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA. Asthmatics (n = 115) and healthy controls (n = 28) underwent Show more
Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA. Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1β, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1β in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1β mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells. NA had increased baseline sputum cell IL-1β expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV IL-1β level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT through MAPK signaling pathways. This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406). Show less
Immune thrombocytopenia (ITP) is an autoimmune-mediated disease characterized by decreased platelet counts. Cytokines play important roles in modulating the immune response and are involved in the pat Show more
Immune thrombocytopenia (ITP) is an autoimmune-mediated disease characterized by decreased platelet counts. Cytokines play important roles in modulating the immune response and are involved in the pathogenesis of many autoimmune diseases. This study aimed at exploring the serum levels of a core set of cytokines that exert immune-regulatory functions in newly diagnosed ITP patients (both before and after treatment) and splenectomized ITP patients. Using the Bio-Plex suspension array system and ELISA, the serum levels of IL-10, IL-21, IL-27, IL-33, IL-35, IL-37, and TGF-β Show less
The strong genetic association between autoimmune regulator (AIRE) and autoimmune diseases indicates its critical role in immune tolerance. AIRE deficiency is thought to promote the development of fol Show more
The strong genetic association between autoimmune regulator (AIRE) and autoimmune diseases indicates its critical role in immune tolerance. AIRE deficiency is thought to promote the development of follicular helper T (T Show less
Interleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is repo Show more
Interleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is reported that IL-27 suppresses autophagy in Mycobacterium tuberculosis-infected macrophages; however, a role for IL-27 on autophagy induction has been less studied. In this study, we investigated the impact of IL-27 in both autophagy induction and HIV-1 infection in macrophages. Primary human monocytes were differentiated into macrophages using human AB serum (huAB) alone, macrophage-colony stimulating factor (M-CSF) alone, or a combination of IL-27 with huAB or M-CSF. Electron microscopy and immunofluorescence staining demonstrated that a 20-fold increase in autophagosome formation was only detected in IL-27 + huAB-induced macrophages. Western blot analysis indicated that the autophagosome induction was not linked to either dephosphorylation of the mammalian target of rapamycin (mTOR) or lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3), an autophagosomal marker, implying that IL-27 can induce autophagy through a novel non-canonical pathway. Here we show for the first time that IL-27 induces autophagy during monocyte-to-macrophage differentiation in a subtype-dependent manner. Show less
Our previous studies have identified miR-483-3p to be highly expressed in synoviocytes from patients with rheumatoid arhtirits (RA); however, its effects on inflammation of RA fibroblast-like synovioc Show more
Our previous studies have identified miR-483-3p to be highly expressed in synoviocytes from patients with rheumatoid arhtirits (RA); however, its effects on inflammation of RA fibroblast-like synoviocytes (FLSs) have remained unclear. The expression of miR-483-3p and cytokines in RA FLSs was detected using quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent was conducted to determine interleukin (IL)-33 production from RA FLSs. Western blotting was employed to quantify the levels of p-ERK and total ERK. Overexpressed miR-483-3p significantly increased the mRNA and protein expression of IL-33, but not of IL-27 or IL-34, in RA FLSs, whereas miR-483-3p suppression showed the opposite effects. Furthermore, miR-483-3p upregulation activated the ERK signaling pathway. The ERK signaling inhibitor PD98059 partly reversed the elevation of IL-33 levels mediated by miR-483-3p overexpression. Our results reveal that miR-483-3p promotes IL-33 expression by regulating the ERK signaling pathway in RA FLSs. Thus, miR-483-3p may be a potential effective target for RA treatment. Show less
The pathogenesis of ankylosing spondylitis (AS) remains unclear but appears to be associated with heredity and the environment. The mouth links the external environment to the gut and lungs. In the pr Show more
The pathogenesis of ankylosing spondylitis (AS) remains unclear but appears to be associated with heredity and the environment. The mouth links the external environment to the gut and lungs. In the present study, compared to that observed in healthy controls (HCs), AS saliva was depleted of Bacilli such as Streptococcus, enriched with Clostridia such as Show less
Colorectal cancer (CRC) remains a leading cause of cancer mortality. Here, we define the colonic epithelial expression of cathelicidin (LL-37) in CRC. Cathelicidin exerts pleotropic effects including Show more
Colorectal cancer (CRC) remains a leading cause of cancer mortality. Here, we define the colonic epithelial expression of cathelicidin (LL-37) in CRC. Cathelicidin exerts pleotropic effects including anti-microbial and immunoregulatory functions. Genetic knockout of cathelicidin led to increased size and number of colorectal tumours in the azoxymethane-induced murine model of CRC. We aimed to translate this to human disease. The expression of LL-37 in a large (n = 650) fully characterised cohort of treatment-naïve primary human colorectal tumours and 50 matched normal mucosa samples with associated clinical and pathological data (patient age, gender, tumour site, tumour stage [UICC], presence or absence of extra-mural vascular invasion, tumour differentiation, mismatch repair protein status, and survival to 18 years) was assessed by immunohistochemistry. The biological consequences of LL-37 expression on the epithelial barrier and immune cell phenotype were assessed using targeted quantitative PCR gene expression of epithelial permeability (CLDN2, CLDN4, OCLN, CDH1, and TJP1) and cytokine (IL-1β, IL-18, IL-33, IL-10, IL-22, and IL-27) genes in a human colon organoid model, and CD3 Show less
The present study was aimed to investigate the value of blood interleukin-27 (IL-27) as a diagnostic biomarker of sepsis. We searched PubMed, EMBASE, the Cochrane Library, and the reference lists of r Show more
The present study was aimed to investigate the value of blood interleukin-27 (IL-27) as a diagnostic biomarker of sepsis. We searched PubMed, EMBASE, the Cochrane Library, and the reference lists of relevant articles. All studies published up to October 21, 2020, which evaluated the accuracy of IL-27 levels for the diagnosis of sepsis were included. All the selected papers were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We used a bivariate random effects model to estimate sensitivity, specificity, diagnostic odds ratios (DOR), and a summary receiver operating characteristic curve (SROC). Deeks' funnel plot was used to illustrate the potential presence of publication bias. This meta-analysis included seven articles. The pooled sensitivity, specificity, and DOR were 0.85 (95% CI, 0.72-0.93), 0.72 (95% CI, 0.42-0.90), and 15 (95% CI, 3-72), respectively. The area under the summary receiver operating characteristic curve was 0.88 (95% CI, 0.84-0.90). The pooled The present results showed that IL-27 is a reliable diagnostic biomarker of sepsis, but it should be investigated in combination with other clinical tests and results. Show less
The interleukin (IL)-17 family, consisting of six members, promotes host defense but can in some context promote the development of autoimmune disease. Here, we examined the role of IL-17D, a poorly u Show more
The interleukin (IL)-17 family, consisting of six members, promotes host defense but can in some context promote the development of autoimmune disease. Here, we examined the role of IL-17D, a poorly understood member in the IL-17 family. IL-17D was expressed primarily by colonic epithelial cells. Il17d Show less
Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy Show more
Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other. Show less
Some evidence supports that the significance of inflammation is linked to a variety of tumors, including thyroid carcinoma. This work measured the preoperative serum inflammatory factors in thyroid tu Show more
Some evidence supports that the significance of inflammation is linked to a variety of tumors, including thyroid carcinoma. This work measured the preoperative serum inflammatory factors in thyroid tumors to explore their diagnostic values. Altogether 487 thyroid tumor patients were recruited, their neutrophil (NE), white blood cell (WBC), monocyte (MO), lymphocyte (LY), platelet (PLT) counts, together with monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), interleukin (IL)-1β, IL-2, IL-27, and tumor necrosis factor-α (TNF-α) levels were compared with controls. Afterward, the receiver operating characteristics (ROC) curve was plotted to further evaluate the values of these inflammatory markers in diagnosis. In addition, multivariable regression analysis was conducted to analyze all these inflammatory factors. Serum PLR, NLR, CRP, and IL-27 levels in thyroid adenoma (TA) and differentiated thyroid carcinoma (DTC) patients were higher than those in controls. Only the areas under the curve (AUC) for CRP and IL-27 were significant in the context of DTC. Besides, the AUC for IL-27 was significant between papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) groups, while that for NLR+PLR was also significant between PTC and healthy control groups. According to multivariable logistic regression analysis, IL-27 and CRP were associated with DTC. Inflammation plays an important role in TA and DTC progression. Preoperative IL-27 and CRP levels help to differentially diagnose DTC. Moreover, IL-27 assists in distinguishing FTC from PTC, and NLR+PLR is important for the differential diagnosis of PTC. Show less
Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of Show more
Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10 Show less
Although integrated traditional Chinese medicine (TCM) has long been indicated to be effective in the treatment of sciatica and is widely used in the management of this condition, the mechanism by whi Show more
Although integrated traditional Chinese medicine (TCM) has long been indicated to be effective in the treatment of sciatica and is widely used in the management of this condition, the mechanism by which integrated TCM alleviates sciatica has not yet been fully defined, and the effect of integrated TCM on gene expression in the peripheral blood of patients with sciatica is still unknown. We performed this study to investigate the effect of integrated TCM on peripheral blood gene expression in patients with sciatica and to explore new clues for studying the mechanism of integrated TCM in alleviating sciatica. We used a microarray to identify differentially expressed genes (DEGs) in the peripheral blood of patients with sciatica and healthy controls (DEGs-baseline), bioinformatic analysis to reveal the characteristics of DEGs-baseline, and the key genes that contribute to the gene dysregulation. A microarray was also used to identify DEGs in the peripheral blood of patients with sciatica after integrated TCM treatment compared with those at baseline, and the expression levels of DEGs were validated by qRT-PCR. We identified 153 DEGs-baseline, which included 131 upregulated genes and 22 downregulated genes. Bioinformatic analysis revealed that most of the DEGs-baseline were related to immunity and the inflammatory response and that TLR4, MMP9, MPO, CAMP, RETN, TLR5, and IL1RN were key genes involved in the dysregulation of genes in the peripheral blood of patients with sciatica. The expression levels of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 were decreased in the peripheral blood of patients after integrated TCM treatment compared with that at baseline, which was accompanied by relief of pain. Integrated TCM treatment relieved pain while regulating the gene expression of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 in the peripheral blood of patients with sciatica. Our study provides new clues for studying the mechanism of TCM in treating sciatica. Show less