Dermal papilla (DP) cells are specialized mesenchymal cells that play a crucial role in regulating hair morphology, colour and growth through the secretion of specific factors. It is still unclear wha Show more
Dermal papilla (DP) cells are specialized mesenchymal cells that play a crucial role in regulating hair morphology, colour and growth through the secretion of specific factors. It is still unclear what the source of progenitor cells is for dermal cell regeneration during wound healing, and whether DP cells are involved in this process. We analyzed the gene expression profile of various skin cell populations using existing datasets and found that the Hey2 gene was predominantly expressed in DP cells. We introduced Hey2-CreERT2 knockin mice and crossed them with Rosa26-ZsGreen reporter mice. After induction in the double transgenic mice by administration of tamoxifen, the reporter ZsGreen was found to be predominantly expressed in DP cells both at anagen and telogen phases, and broadly expressed in some other dermal cells at anagen. We also created a wound after tamoxifen induction, and found there were abundant ZsGreen Show less
Necroptosis is a programmed necrotic cell death, in which dying cells rupture and release intracellular components that trigger a proinflammatory response. The current study aimed at probing the circu Show more
Necroptosis is a programmed necrotic cell death, in which dying cells rupture and release intracellular components that trigger a proinflammatory response. The current study aimed at probing the circular RNA (circRNA)-mediated regulatory mechanisms in necroptosis in premature ovarian failure (POF). CircRNA sequencing analysis was conducted in ovarian tissues of control and POF rats and transcriptome microarrays were acquired from the GSE33423 dataset. Differential expression analysis of circRNAs and mRNAs was executed between the POF and control data. Both a necroptosis-based circRNA-microRNA (miRNA)-mRNA network and a protein-protein interaction (PPI) network were established. Then, the functional annotation and immunological traits were analyzed. Totally, 1266 upregulated and 1283 downregulated circRNAs as well as 1101 upregulated and 1168 downregulated mRNAs were determined in the POF rats versus the controls. The differentially expressed mRNAs predominantly correlated with necroptosis. The circRNA-miRNA-mRNA networks of downregulated necroptosis genes (comprising rno_circRNA₀₀₄₉₉₅₋rno-miR-148b-5p-H2afy2, rno_circRNA₀₁₆₉₉₈₋rno-miR-29a-5p-Hmgb1, and rno_circRNA₀₁₇₅₉₃₋rno-miR-29a-5p-Hmgb1) and upregulated necroptosis genes (comprising rno_circRNA₀₁₅₉₀₀₋rno-miR-935-Stat1, rno_circRNA₀₀₇₉₄₆₋rno-miR-328a-3p-Stat5a, rno_circRNA₀₀₇₉₄₇₋rno-miR-328a-3p-Stat5a, rno_circRNA₀₀₅₀₆₄₋rno-miR-18a-5p-Stat1, rno_circRNA₀₀₅₀₆₄₋rno-miR-18a-5p-Stat5a, rno_circRNA₀₀₅₁₁₅₋rno-miR-22-3p-Stat1, rno_circRNA₀₀₉₀₂₈₋rno-miR-342-5p-Stat1, rno_circRNA₀₁₁₂₄₀₋rno-miR-1224-Stat5a, rno_circRNA₀₁₆₀₇₈₋rno-miR-711-Stat5a) were built. POF-specific necroptosis genes ( Altogether, we proposed the presence of widespread regulatory mechanisms of circRNAs in necroptosis and demonstrated that altered circRNA biogenesis might contribute to POF by affecting necroptosis. Show less
The purpose of the network meta-analysis was to make a more comprehensive comparison of different interleukins in the detection of neonatal sepsis and to pose clues in the field of clinical practice. Show more
The purpose of the network meta-analysis was to make a more comprehensive comparison of different interleukins in the detection of neonatal sepsis and to pose clues in the field of clinical practice. Electronic databases of PubMed, Web of Science and Embase were systematically searched. Eligible studies included diagnostic tests utilizing interleukins to detect neonatal sepsis. We calculated pooled sensitivity, specificity, positive Likelihood Ratio (PLR) and negative Likelihood Ratio (NLR), diagnostic odds ratio (DOR), and superiority index. Fifteen studies including 1,369 neonates diagnosed of sepsis were included in this meta-analysis. For the detection of early-onset sepsis in neonates, the pooled sensitivity was 0.91 (95% CI: 0.81, 0.97; Findings of this network meta-analysis suggest that interleukins including IL-6, IL-8, IL-10, and IL-27 may have favorable performance in the detection of neonatal sepsis. IL-8 was more accurate in the detection of early-onset sepsis in neonates. IL-27 was more accurate in the detection of late-onset neonatal sepsis. Show less
Intravenous immunoglobulin (IVIG) is a first-line drug prepared from human plasma for the treatment of autoimmune diseases (AIDs), especially immune thrombocytopenia (ITP). Significant differences exi Show more
Intravenous immunoglobulin (IVIG) is a first-line drug prepared from human plasma for the treatment of autoimmune diseases (AIDs), especially immune thrombocytopenia (ITP). Significant differences exist in protein types and expression levels between male and female plasma, and the prevalence of autoimmune diseases varies between sexes. The present study seeks to explore potential variations in IVIG sourced from distinct sex-specific plasma (DSP-IVIG), including IVIG sourced from female plasma (F-IVIG), IVIG sourced from male plasma (M-IVIG), and IVIG sourced from a blend of male and female plasma (Mix-IVIG). To address this question, we used an ITP mouse model and a monocyte-macrophage inflammation model treated with DSP IVIG. The analysis of proteomics in mice suggested that the pathogenesis and treatment of ITP may involve FcγRs mediated phagocytosis, apoptosis, Th17, cytokines, chemokines, and more. Key indicators, including the mouse spleen index, CD16 Show less
Antigen-presenting cells (APCs) constantly express major histocompatibility complex II (MHC II), including macrophages and dendritic cells (DCs) which deliver antigens to CD4
The pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflamm Show more
The pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown. In this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA. Summary statistics for RA (14,361 RA cases and 43,923 healthy controls) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. Then we used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality. MR and MVMR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods, which were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC, and IL-17D/IL-17RD and RA. For assessing the robustness of the results, we also carried out a sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO). Two-sample MR Analysis showed the causal relationship between IL-17A/IL-17RA and RA. The presence of genetically high IL-17A/IL-17RA may increase the risk of RA (IL-17A(OR = 1.095; 95% C.I., 0.990-1.210, p.adj = 0.013), IL-17RA(OR = 1.113, 95%CI = 1.006-1.231, p.adj = 0.006)). However, the results indicated that IL-17C/IL-17RC, and IL-17D/IL-17RD demonstrated no causal impact on RA (IL-17C(OR = 1.007, 95%CI = 0.890-1.139, p.adj = 0.152), IL-17RC(OR = 1.006, 95%CI = 0.904-1.119, p.adj = 0.152), IL-17D(OR = 0.979, 95%CI = 0.843-1.137, p.adj = 0.130), IL-17RD(OR = 0.983, 95%CI = 0.876-1.104, p.adj = 0.129)). Furthermore, MVMR analysis shown that IL-17RA(OR = 1.049, 95% CI: 0.997-1.102, p.adj = 0.014) was associated with increased risk of RA. Sensitivity analysis showed no heterogeneity and pleiotropy, suggesting that the above results were robust and reliable. The MR analysis provides evidence that IL-17A/IL-17RA are risk factors for RA. This emphasizes the importance of intervention on IL-17A/IL-17RA in patients with RA. Developing drugs that limit IL-17A may reduce the risk of RA. Show less
Recurrent pregnancy loss (RPL) and pre-eclampsia (PE) are immune-related pregnancy complications that have been linked to CD4 All eligible case-control studies published up to February 2023 were ident Show more
Recurrent pregnancy loss (RPL) and pre-eclampsia (PE) are immune-related pregnancy complications that have been linked to CD4 All eligible case-control studies published up to February 2023 were identified by searching PubMed, EMBASE, Cochrane, Web of Science, and Google Scholar. The risk of recurrent pregnancy loss and PE associated with the IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were estimated for each study. The meta-analysis incorporated a total of 13 studies. The overall analysis indicated that IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with immune-related pregnancy complications, including RPL and PE. However, when the analysis was stratified by disease type, the IL-17 rs2275913 polymorphism was found to be associated with an increased risk of RPL (recessive model AA/GA + GG: OR = 1.68, 95% confidence interval [CI]: 1.13-2.49, p = .01). The IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with RPL and PE, whereas the IL-17 rs2275913 polymorphism was associated with the susceptibility to recurrent miscarriage. Show less
In rheumatoid arthritis (RA), hyperproliferative fibroblast-like synoviocytes (FLS) can secrete a variety of tissue hydrolases, such as matrix metalloproteinases (MMPs), causing the destruction of cho Show more
In rheumatoid arthritis (RA), hyperproliferative fibroblast-like synoviocytes (FLS) can secrete a variety of tissue hydrolases, such as matrix metalloproteinases (MMPs), causing the destruction of chondrocytes. Mesenchymal stem cells (MSCs) can directly affect FLS through extracellular vesicles (EVs). Interleukin-27 (IL-27) is a pleiotropic immune regulator frequently overexpressed in RA. The study intended to examine the effects of IL-27-induced exosomes from bone-marrow mesenchymal stem cells (BM-MSCs) and to determine if they promote the secretion of MMP3 in synovial cells. The research team performed a genetic study. The study took place at the First Affiliated Hospital of Hainan Medical University in Haikou City, Hainan, China. The research team: (1) determined if IL-27 expression had occurred in the synovial fluid; (2) co-cultured IL-27-induced MSCs with FLS to detect the expression of MMP3 in the FLS; (3) Under IL-27 induction, MSC-derived exosomes with IL-27R knockdown were collected to detect the expression of microRNAs(miRNAs) associated with RA; (4) screened the miRNAs to determine the most significant differences in expression; (5) determined the miRNA target genes in arthritis, using Western blot (WB) and qRT-PCR; and (6) Dual luciferase and ChIP experiments confirm regulation of MMP3 by L3MBTL4. IL-27 was highly expressed in RA, and the IL-27-induced, MSC-derived exosomes promoted the expression of MMP3 in FLS. The IL-27-induced MSC-derived exosomes significantly upregulated the expression of miR-206-3p, and the miR-206-3p target, miR-206/ lethal(3) malignant brain tumor-like protein 4 (L3MBTL4), regulated the MMP3 transcription. The IL-27-induced, MSC-derived exosomes promoted MMP3 expression in the FLS through the miR-206-3p/L3MBTL4 axis, thereby promoting chondrocyte degradation and aggravating RA. IL-27 can induce the expression of miR-206 in MSCs, and miR-206 can be transported into FLS through MSC-EVs to promote FLS migration and MMP3 expression and aggravate articular cartilage damage. Patients with RA who have a high IL-27 expression may not be suitable to receive treatment with MSCs, and clinicians can use MSCs that knock down or delete IL-27R to treat RA patients who have a high IL-27 expression. Show less
The level of serum interleukin-27 (IL-27) was significantly decreased in the obesity group. After injection of IL-27, obese mice showed significant weight loss,reduced fat accumulation, improved insul Show more
The level of serum interleukin-27 (IL-27) was significantly decreased in the obesity group. After injection of IL-27, obese mice showed significant weight loss,reduced fat accumulation, improved insulin resistance and hepatic steatosis.IL-27 plays a key role in the regulation of metabolic processes, but there are scarce data on circulating IL-27 levels in hypothyroidism. The purpose of this study was to assess the serum levels of IL-27 in patients with hypothyroidism and its relationship with NAFLD. 185 participants were included in this cross-sectional survey. According to thyroid function, the subjects were classified into three groups: euthyroidism (n = 55), subclinical hypothyroidism (n = 53), and hypothyroidism (n = 77). Serum IL-27 concentrations were measured by ELISA. Serum IL27 levels were significantly higher in subclinical hypothyroidism and hypothyroidism groups than in the euthyroidism group. Serum IL27 levels had a negative correlation with HOMA-IR,FBG,TG, subcutaneous fat,and visceral fat, and had a positive correlation with HDL-C ( Serum IL-27 levels demonstrated a compensatory increase in patients with subclinical hypothyroidism or hypothyroidism and showed an independent association with NAFLD. Circulating IL-27 levels could predict the occurrence of NAFLD in hypothyroidism. These results suggested that altering the circulating levels of IL-27 may be a potential therapeutic target for NAFLD. Show less
Vaccination is an effective means of preventing pneumococcal disease and SPY1 is a live attenuated pneumococcal vaccine we obtained earlier. We found IL-27 and its specific receptor (WSX-1) were incre Show more
Vaccination is an effective means of preventing pneumococcal disease and SPY1 is a live attenuated pneumococcal vaccine we obtained earlier. We found IL-27 and its specific receptor (WSX-1) were increased in SPY1 vaccinated mice. Bacterial clearance and survival rates were decreased in SPY1 vaccinated IL-27Rα Show less
Primary Sjogren's Syndrome (pSS) is a chronic autoimmune disease, with unclear pathogenies. Lysine-malonylation (Kmal) as a novel post-translational modification (PTMs) was found associated with metab Show more
Primary Sjogren's Syndrome (pSS) is a chronic autoimmune disease, with unclear pathogenies. Lysine-malonylation (Kmal) as a novel post-translational modification (PTMs) was found associated with metabolic, immune, and inflammatory processes. For purpose of investigating the proteomic profile and functions of kmal in pSS, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based analysis and bioinformatics analysis are performed based on twenty-eight pSS patients versus twenty-seven healthy controls (HCs). A total of 331 down-regulated proteins and 289 up-regulated proteins are observed in differentially expressed proteins (DEPs) of pSS. We discover the expression of transforming growth factor beta-1 (TGFB1) and CD40 ligand downregulate which enriches in the inflammatory associated pathway. Expression of signal transducer and activator of transcription 1-alpha/beta (STAT1) show upregulation and enrich in type I interferon signaling pathway and IL-27-mediated signaling pathway. In differentially malonylated proteins (DMPs) of pSS, we identify 3 proteins are down-regulated in 7 sites and 18 proteins are up-regulated in 19 sites. Expression of malonylated integrin-linked kinase (ILK) significantly enrich in the focal adhesion pathway. Together, our data provide evidence that downregulation of TGFB1 and CD40LG play a critical role in the inflammatory process of pSS, while upregulation of STAT1 may be associated with IL-27 immunity and pSS immune dysfunction. Moreover, kmal modification at the kinase domain of ILK may destabilize ILK that thus contributing to pSS pathogenies by regulating the focal adhesion pathway. SIGNIFICANCE: Our research offered the first characterization of Kmal, a newly identified form of lysine acylation in pSS, as well as proteomic data on individuals with pSS. In this study, we found that several key DMPs were associated with focal adhesion pathway, which contributes to the development of pSS. The present results provide an informative dataset for the future exploration of Kmal in pSS. Show less
Different subtypes of dendritic cells (DCs) can induce different types of immune responses. Our previous study found that Echinococcus granulosus (E. granulosus) antigens (Eg.ferritin, Eg.mMDH and Eg. Show more
Different subtypes of dendritic cells (DCs) can induce different types of immune responses. Our previous study found that Echinococcus granulosus (E. granulosus) antigens (Eg.ferritin, Eg.mMDH and Eg.10) stimulated DC differentiation to different subtypes and produced different immune responses. To further understand whether Eg.ferritin, Eg.mMDH and Eg.10 affect the DC-mediated immune response by promoting the differentiation of monocytes to DCs. Bone marrow-derived monocytes were exposed to three antigens of E. granulosus on days 0, 3, 5, and 7. The percentage of monocyte-derived DCs (moDCs), DCs subsets, and the expression of surface molecules of DCs at different time points in different groups were assessed by flow cytometry. The levels of cytokines of IL-1β, IL-4, IL-6, IL-10, IL-13, IFN-γ, TNF-α, IL-12p70, IL-18, IL-23, and IL-27 in the cell culture supernatant were detected by multi-factorial detection technology. The percentage of moDCs revealed that none of the three antigens blocked monocyte differentiation to DCs. The monocytes of 7-day-old cultures showed increased sensitivity to these antigens. The Eg.ferritin induced more mature DCs, which expressed high levels of MHC II and costimulatory molecules, and secreted Th1 cytokines. Eg10 and Eg.mMDH induced lower degrees of DC maturation, however differentiated DCs were in a semi-mature state due to low expression of MHC II and costimulatory molecules and secretion of higher Th2 and lower Th1 cytokines. Eg.ferritin promotes full maturation of DCs and induces Th1 immune response, whereas Eg.10 and Eg.mMDH induce semi-mature DCs producing higher levels of Th2 cytokines. Show less
Yiran Sun, Feng Wang, Shuwen Li · 2023 · Heart & lung : the journal of critical care · Elsevier · added 2026-04-24
Peripheral inflammation plays an potential role in both pathogenesis and outcomes of sleep apnea syndrome (SAS). However, this topic has not been explored at the genetic level. The aim of the study wa Show more
Peripheral inflammation plays an potential role in both pathogenesis and outcomes of sleep apnea syndrome (SAS). However, this topic has not been explored at the genetic level. The aim of the study was to investigate the genetic interaction between a total of 56 peripheral inflammatory regulators and SAS, and to further reveal the genetic association of SAS-related inflammatory regulators with several neurological disorders. Summary data for SAS, cerebral atherosclerosis, vascular dementia and peripheral concentrations of these inflammatory regulators were collected from genome-wide association studies. Instrumental variables were extracted from these data for causal inference of exposure and outcome using Two-sample Mendelian randomization methods. All analyses were performed using R (version 3.5.2). First, of the included 56 inflammatory regulators, higher IL-25 level and lower IL-23, IL-24, IL-36γ and MIP-1a levels in peripheral circulation significantly increased the risk of SAS (P<0.05). Second, SAS significantly decreased the peripheral levels of IL-17A, IL-23, IL-27, IL-36α and TRAIL (P<0.05). Third, there was no genetic relationship between SAS and other inflammatory regulators (P>0.05). Fourth, in the SAS-related inflammatory regulators mentioned above, decreased levels of IL-17A and IL-27 in peripheral circulation were significantly associated with the increased risk of cerebral atherosclerosis, and decreased level of TRAIL promoted the elevation of vascular dementia risk (P<0.05). There was a interaction between peripheral inflammation and SAS at the genetic level. Furthermore, peripheral inflammation might involved in the mechanism for SAS causing some neurological diseases mentioned above. Show less
Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by severe liver function impairment, coagulation disorder, and multiple organ function impairment. T Show more
Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by severe liver function impairment, coagulation disorder, and multiple organ function impairment. The aim of this study was to explore the predictive value of antithrombin Ⅲ activity to the prognosis of HBV-ACLF patients. A total of 186 HBV-ACLF patients were included in the analysis, and the baseline clinical data of patients were recorded to analyze the risk factors affecting the 30-day survival outcome of patients. Bacterial infection, sepsis, and hepatic encephalopathy were observed in ACLF patients. Antithrombin Ⅲ activity and serum cytokine levels were determined. The antithrombin Ⅲ activity of ACLF patients in the death group was significantly lower than that in the survival group, and antithrombin Ⅲ activity was independent factors affecting the 30-day outcome. The areas under the receiver operation characteristic (ROC) curve of antithrombin Ⅲ activity to predict the 30-day mortality of ACLF was 0.799. Survival analysis showed that the mortality of patients with antithrombin Ⅲ activity less than 13% was significantly increased. Patients with bacterial infection and sepsis had lower antithrombin Ⅲ activity than those without infection. Antithrombin Ⅲ activity was positively correlated with platelet count, fibrinogen, interferon (IFN)-γ, interleukin (IL)-13, IL-1β, IL-4, IL-6, tumor necrosis factor-α, IL-23, IL-27, and IFN-α, but negatively correlated with C-reactive protein, D dimer, total bilirubin, and creatinine levels. As a natural anticoagulant, antithrombin Ⅲ can be regarded as a marker of inflammation and infection in patients with HBV-ACLF, and as a predictor of survival outcome in patients with ACLF. Show less
Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational resear Show more
Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational research was not able to address problems with residual confusion and reverse causality. We summarized and retrieved 28 inflammatory cytokines associated with RA, depression, or RA with depression through a literature search. The summary statistics from genome-wide association studies for RA, inflammatory biomarkers, broad depression, and major depression disease phenotypes were used. Mendelian randomization was performed to assess the causal association between RA and inflammatory biomarkers, as well as the effects of inflammatory biomarkers on depression. Bonferroni correction was used to reduce the possibility of false positive results. The study found that evidence for associations of genetically predicted RA was associated with higher levels of interleukin (IL)-9 (OR = 1.035, 95%CI = 1.002-1.068, P = 0.027), IL-12 (OR = 1.045, 95%CI = 1.045-1.014, P = 0.004), IL-13 (OR = 1.060, 95%CI = 1.028-1.092, P = 0.0001), IL-20 (OR = 1.037, 95%CI = 1.001-1.074, P = 0.047), and IL-27 (OR = 1.017, 95%CI = 1.003-1.032, P = 0.021). The level of IL-7 (OR = 1.029, 95%CI = 1.018-1.436, P = 0.030) was significantly related to RA. Only the analysis results between RA and IL-13 were satisfied with the statistical significance threshold corrected by Bonferroni (P < 0.002). However, a causal effect was not found between inflammatory biomarkers and depression. In the current study the inflammatory cytokines associated with RA comorbid depression may not be the mediators that directly lead to the co-pathogenesis of RA and depression. Show less
The aim of this meta-analysis is to evaluate the association of interleukin-27 gene rs153109 and rs17855750 polymorphisms with preeclampsia susceptibility and severity. Web of Science, PubMed, Embase, Show more
The aim of this meta-analysis is to evaluate the association of interleukin-27 gene rs153109 and rs17855750 polymorphisms with preeclampsia susceptibility and severity. Web of Science, PubMed, Embase, CBM, WanFang Data, CNKI, and VIP database were used for retrieving. After screening with our inclusion and exclusion criteria, data extraction and quantity evaluation were performed by 2 independent authors. Included case-control studies were used for meta-analysis by RevMan 5.4, and sensitivity analysis was carried out through 1-by-1 exclusion procedure. If heterogeneity exists, then random effects model was used; otherwise, fixed effect model was used. Publication bias analysis was performed using Begg test and Egger test. Trial sequential analysis was performed using trial sequential analysis 0.9.5.10 Beta. A total of 5 articles were included. The heterogeneity was high across most models during the meta-analysis. Meta-analysis results related to preeclampsia susceptibility showed that P values of all the models were higher than .05, while for meta-analysis results related to preeclampsia severity showed that P values of all the models were higher than .05 except for TT versus TG + GG and TT versus TG models of rs17855750 group. The sensitivity of the meta-analysis was high, and trial sequential analysis showed the possibility of false negative results. No obvious publication bias was found. There is no obvious association between interleukin-27 gene rs153109 and rs17855750 polymorphisms and preeclampsia susceptibility or severity. However, more multi-center and large sample case-control studies are expected to be carried out to verify our conclusion in the future. Show less
Human newborns exhibit increased vulnerability and risk of mortality from infection that is consistent with key differences in the innate and adaptive immune responses relative to those in adult cells Show more
Human newborns exhibit increased vulnerability and risk of mortality from infection that is consistent with key differences in the innate and adaptive immune responses relative to those in adult cells. We have previously shown an increase in the immune suppressive cytokine, IL-27, in neonatal cells and tissues from mice and humans. In a murine model of neonatal sepsis, mice deficient in IL-27 signaling exhibit reduced mortality, increased weight gain, and better control of bacteria with reduced systemic inflammation. To explore a reprogramming of the host response in the absence of IL-27 signaling, we profiled the transcriptome of the neonatal spleen during Show less
The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state accor Show more
The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state according to their respective environment. Show less
Several interleukins (ILs) have been demonstrated to participate in cardiac injury. This study aimed to investigate whether IL-27p28 plays a regulatory role in doxorubicin (DOX)-induced cardiac injury Show more
Several interleukins (ILs) have been demonstrated to participate in cardiac injury. This study aimed to investigate whether IL-27p28 plays a regulatory role in doxorubicin (DOX)-induced cardiac injury by regulating inflammation and oxidative stress. Dox was used to establish a mouse cardiac injury model, and IL-27p28 was knocked out to observe its role in cardiac injury. In addition, monocytes were adoptively transferred to clarify whether monocyte-macrophages mediate the regulatory role of IL-27p28 in DOX-induced cardiac injury. IL-27p28 knockout significantly aggravated DOX-induced cardiac injury and cardiac dysfunction. IL-27p28 knockout also upregulated the phosphorylation levels of p65 and STAT1 and promoted M1 macrophage polarization in DOX-treated mice, which increased cardiac inflammation and oxidative stress. Moreover, IL-27p28-knockout mice that were adoptively transferred WT monocytes exhibited worse cardiac injury and cardiac dysfunction and higher cardiac inflammation and oxidative stress. IL-27p28 knockdown aggravates DOX-induced cardiac injury by worsening the M1 macrophage/M2 macrophage imbalance and its associated inflammatory response and oxidative stress. Show less
Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM Show more
Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-κB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules interleukin-27 receptor-α (IL-27Rα) and the adhesion molecule JAM2 to be responsive to RELA at the messenger RNA and protein levels. IL-27Rα and JAM2 were expressed on primary MM cells at higher levels than on healthy long-lived plasma cells (PCs) in the bone marrow. IL-27 activated STAT1, and to a lesser extent STAT3, in MM cell lines and in PCs generated from memory B cells in an IL-21-dependent in vitro PC differentiation assay. Concomitant activity of IL-21 and IL-27 enhanced differentiation into PCs and increased the cell-surface expression of the known STAT target gene CD38. In accordance, a subset of MM cell lines and primary MM cells cultured with IL-27 upregulated CD38 cell-surface expression, a finding with potential implications for enhancing the efficacy of CD38-directed monoclonal antibody therapies by increasing CD38 expression on tumor cells. The elevated expression of IL-27Rα and JAM2 on MM cells compared with that on healthy PCs may be exploited for the development of targeted therapeutic strategies that modulate the interaction of MM cells with the TME. Show less
IL-21 is essential for type 1 diabetes (T1D) development in the NOD mouse model. IL-21-expressing CD4 T cells are present in pancreatic islets where they contribute to T1D progression. However, little Show more
IL-21 is essential for type 1 diabetes (T1D) development in the NOD mouse model. IL-21-expressing CD4 T cells are present in pancreatic islets where they contribute to T1D progression. However, little is known about their phenotype and differentiation states. To fill this gap, we generated, to our knowledge, a novel IL-21 reporter NOD strain to further characterize IL-21+ CD4 T cells in T1D. IL-21+ CD4 T cells accumulate in pancreatic islets and recognize β cell Ags. Single-cell RNA sequencing revealed that CD4 T effector cells in islets actively express IL-21 and they are highly diabetogenic despite expressing multiple inhibitory molecules, including PD-1 and LAG3. Islet IL-21+ CD4 T cells segregate into four phenotypically and transcriptionally distinct differentiation states, that is, less differentiated early effectors, T follicular helper (Tfh)-like cells, and two Th1 subsets. Trajectory analysis predicts that early effectors differentiate into both Tfh-like and terminal Th1 cells. We further demonstrated that intrinsic IL-27 signaling controls the differentiation of islet IL-21+ CD4 T cells, contributing to their helper function. Collectively, our study reveals the heterogeneity of islet-infiltrating IL-21+ CD4 T cells and indicates that both Tfh-like and Th1 subsets produce IL-21 throughout their differentiation process, highlighting the important sources of IL-21 in T1D pathogenesis. Show less
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestina Show more
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier. Show less
Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects betwee Show more
Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them. We conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively. The odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it. Show less
Renal ischemia/reperfusion (I/R) injury is one of the crucial factors affecting the outcome of renal transplantation. In recent years, myeloid-derived growth factor (MYDGF) has received a lot of atten Show more
Renal ischemia/reperfusion (I/R) injury is one of the crucial factors affecting the outcome of renal transplantation. In recent years, myeloid-derived growth factor (MYDGF) has received a lot of attention for its extensive beneficial effects on cardiac repair and protection of cardiomyocytes from cell death. Therefore, we hypothesized that the recombinant human MYDGF (rhMYDGF) protein might play an essential role in safeguarding renal I/R injury. In vivo experiments were conducted using a mouse unilateral I/R model. Mice were pretreated with rhMYDGF by intraperitoneal injection to study the potential mechanism of renal protection. In vitro, we established hypoxia/reoxygenation and H 2 O 2 treatment models to pretreat cells with rhMYDGF. The expression levels of oxidative stress, inflammation, and apoptosis-related factors in tissues and cells were detected. Finally, we explored the role of the protein kinase B (Akt) pathway in the renal protective mechanism of rhMYDGF. In this study, we found that intraperitoneal injection of 1.25 μg rhMYDGF could significantly improve renal function of I/R mice, and reduce oxidative stress, inflammation, and apoptosis. For the human proximal tubular epithelial cell line and human kidney cell line, pretreatment with 0.3 μg/mL rhMYDGF for 24 h significantly downregulated oxidative stress, inflammation, and apoptosis via the phosphorylation of Akt, which could be ameliorated by LY294002. rhMYDGF protects kidney from I/R injury by attenuating oxidative stress, inflammation, and apoptosis through the activation of the Akt pathway. Show less
Interleukin (IL)-12 family cytokines including IL-12, IL-23, IL-27, IL-35 and IL-39 are heterodimeric cytokines composed of two subunits, an α-chain (entitled p35, p19 and p28) and a β-chain (namely p Show more
Interleukin (IL)-12 family cytokines including IL-12, IL-23, IL-27, IL-35 and IL-39 are heterodimeric cytokines composed of two subunits, an α-chain (entitled p35, p19 and p28) and a β-chain (namely p40 and Epstein-Barr virus-induced gene 3, EBI3). Unlike in mammals, specific whole genome duplication events in fish may generate more paralogues of these subunits as the components of IL-12 family cytokines. Although all subunit genes of IL-12 family have been isolated and identified in various fish species, some important issues on fish IL-12 family are needed to be addressed compared to the extensive study in mammals: Whether the expansion of these subunit genes results in the generation of multiple isoforms of the family cytokines; Whether the related receptor genes have similar complex repertoire corresponding to their ligands; How about the expression kinetics of these subunit paralogues particularly under the circumstance of pathogen infection and immune stimulation; How about the functional properties of IL-12 family in fish. In the past ten years, these concerns have received increasing attentions to establish the biological significance of this family cytokines in fish immunity. In this review, we summarized the current understanding of IL-12 family with a special focus on the molecular structures, inducible expression profiles and functions of IL-12 family members in fish. Show less