G protein-coupled receptors are important regulators of contractility and differentiation in vascular smooth muscle cells (SMCs), but the specific function of SMC-expressed orphan G protein-coupled re Show more
G protein-coupled receptors are important regulators of contractility and differentiation in vascular smooth muscle cells (SMCs), but the specific function of SMC-expressed orphan G protein-coupled receptor class C group 5 member B (GPRC5B) is unclear. We studied the role of GPRC5B in the regulation of contractility and dedifferentiation in human and murine SMCs in vitro and in iSM- Mesenteric arteries from SMC-specific Taken together, our data show that GPRC5B regulates vascular SMC tone and differentiation by negatively regulating IP signaling. Show less
Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Show more
Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap. To identify and characterize artery- and vein-specific endothelial enhancers in the human genome, thereby gaining insights into mechanisms by which blood vessel identity is regulated. Using chromatin immunoprecipitation and deep sequencing for markers of active chromatin in human arterial and venous endothelial cells, we identified several thousand artery- and vein-specific regulatory elements. Computational analysis revealed that NR2F2 (nuclear receptor subfamily 2, group F, member 2) sites were overrepresented in vein-specific enhancers, suggesting a direct role in promoting vein identity. Subsequent integration of chromatin immunoprecipitation and deep sequencing data sets with RNA sequencing revealed that NR2F2 regulated 3 distinct aspects related to arteriovenous identity. First, consistent with previous genetic observations, NR2F2 directly activated enhancer elements flanking cell cycle genes to drive their expression. Second, NR2F2 was essential to directly activate vein-specific enhancers and their associated genes. Our genomic approach further revealed that NR2F2 acts with ERG (ETS-related gene) at many of these sites to drive vein-specific gene expression. Finally, NR2F2 directly repressed only a small number of artery enhancers in venous cells to prevent their activation, including a distal element upstream of the artery-specific transcription factor, By leveraging a genome-wide approach, we revealed mechanistic insights into how NR2F2 functions in multiple roles to maintain venous identity. Importantly, characterization of its role at a crucial artery enhancer upstream of Show less
The zebrafish has become a popular vertebrate animal model in biomedical research. However, it is still challenging to make conditional gene knockout (CKO) models in zebrafish due to the low efficienc Show more
The zebrafish has become a popular vertebrate animal model in biomedical research. However, it is still challenging to make conditional gene knockout (CKO) models in zebrafish due to the low efficiency of homologous recombination (HR). Here we report an efficient non-HR-based method for generating zebrafish carrying a CKO and knockin (KI) switch (zCKOIS) coupled with dual-color fluorescent reporters. Using this strategy, we generated hey2 Show less
Fatty acids are involved in the development and progression of colorectal cancer (CRC). However, genetic effects of fatty acid biosynthesis pathway on CRC outcome are unclear. Cox regression model was Show more
Fatty acids are involved in the development and progression of colorectal cancer (CRC). However, genetic effects of fatty acid biosynthesis pathway on CRC outcome are unclear. Cox regression model was used to evaluate genetic effects on CRC overall survival (OS) and progression-free survival (PFS), accompanied by calculating hazard ratios (HRs) and confidence intervals (CIs). Differential expression analysis, expression quantitative trait loci analysis, dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to explore the genetically biological mechanism. The rs10838164 C>T in HSD17B12 was significantly associated with an increased risk of death and progression of CRC (OS, HR = 2.12, 95% CI = 1.40-3.22, P = 4.03 × 10 Show less
Gonadotropin-releasing hormone (GnRH) controls synthesis of sex steroid hormones through hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. But in mollusks, research on GnRH and steroidogenesis Show more
Gonadotropin-releasing hormone (GnRH) controls synthesis of sex steroid hormones through hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. But in mollusks, research on GnRH and steroidogenesis pathways is still limited. In this study, we first identified two gonadotropin receptor like genes (LGR and LGR5L) and four steroidogenesis-related genes (CYP17A, HSD17B12, HSD3B1 and HSD3B2) in the scallop Patinopecten yessoensis. By examining the expression of 11 genes in the ganglia and/or gonad as well as the concentration of progesterone, testosterone and estradiol in the gonad, we postulate that a potential GnRH signaling pathway (GnRH-GnRHR-GPB5-LGR/LGR5L) in the cerebral and pedal ganglia (CPG) and steroidogenesis pathway (CYP17A, HSD17B12 and HSD3B1) in the gonad are involved in regulating sex steroid hormones. E Show less
The advent of base editors (BEs) holds great potential for correcting pathogenic-related point mutations to treat relevant diseases. However, Cas9 nickase (nCas9)-derived BEs lead to DNA double-strand Show more
The advent of base editors (BEs) holds great potential for correcting pathogenic-related point mutations to treat relevant diseases. However, Cas9 nickase (nCas9)-derived BEs lead to DNA double-strand breaks, which can trigger unwanted DNA damage response (DDR). Here, we show that the original version of catalytically dead Cas12a (dCas12a)-conjugated BEs induce a basal level of DNA breaks and minimally activate DDR proteins, including H2AX, ATM, ATR, and p53. By fusing dCas12a with engineered human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A), we further develop the BEACON (base editing induced by human APOBEC3A and Cas12a without DNA break) system to achieve enhanced deamination efficiency and editing specificity. Efficient C-to-T editing is achieved by BEACON in mammalian cells at levels comparable to AncBE4max, with only low levels of DDR and minimal RNA off-target mutations. Importantly, BEACON induces in vivo base editing in mouse embryos, and targeted C-to-T conversions are detected in F0 mice. Show less
Cadmium (Cd) a highly toxic metal to human and wildlife health and it is hazardous to both terrestrial and aquatic life. In this study, we used RNA sequencing analysis to examine the effects of chroni Show more
Cadmium (Cd) a highly toxic metal to human and wildlife health and it is hazardous to both terrestrial and aquatic life. In this study, we used RNA sequencing analysis to examine the effects of chronic cadmium exposure on liver lipid metabolism of Bufo gargarizans larvae. Tadpoles were exposed to cadmium concentrations at 0, 5, 10, 50, 100 and 200 μg L Show less
The Jianchang duck is mainly distributed in Southwest China, and has the characteristics of fast growth rate and strong abilities in lipid deposition in the liver. In order to investigate the effects Show more
The Jianchang duck is mainly distributed in Southwest China, and has the characteristics of fast growth rate and strong abilities in lipid deposition in the liver. In order to investigate the effects of domestication process on formation of the unique characteristics of Jianchang duck, the whole genome of sixteen individuals and three pooling of Jianchang duck were re-sequenced, and genome data of 70 mallards and 83 domestic ducks from thirteen different places in China were obtained from NCBI. The population stratification and evolution analysis showed gene exchanges existed between the Jianchang and other domestic duck populations, as well as Jianchang ducks and mallards. Genomic comparison between mallards and Jianchang ducks showed genes, including Show less
Interleukin-27 (IL-27) has been reported to inhibit type 2 T helper cell (Th2) response in allergic rhinitis (AR). However, its effects on group II innate lymphoid cells (ILC2) in AR are not fully und Show more
Interleukin-27 (IL-27) has been reported to inhibit type 2 T helper cell (Th2) response in allergic rhinitis (AR). However, its effects on group II innate lymphoid cells (ILC2) in AR are not fully understood. Nineteen patients with AR and nineteen controls were enrolled in this study. The effects of IL-27 on ILC2 differentiation and function as well as the regulation of the IL-27 receptor (IL-27R) were analyzed by tritiated thymidine incorporation, enzyme-linked immunosorbent assay (ELISA), and real-time polymerase chain reaction (PCR), respectively. AR mice were used to confirm the role of IL-27 The serum IL-27 protein expression in AR patients was significantly lower compared with controls. IL-27 decreased the ILC2 proliferation and type II cytokine secretion through the interaction with IL-27R. IL-27 also inhibited systemic and nasal ILC2 response of AR mice. IL-27 inhibited the proliferation and function of ILC2 in AR, implying that IL-27 may be used as new treatment target in AR. Show less
Interleukin-27 (IL-27), which belongs to IL-12 family, influences the function of T cells (Tregs) through regulating the expression, and function of forkhead box P3 (FoxP3). In this study, we detected Show more
Interleukin-27 (IL-27), which belongs to IL-12 family, influences the function of T cells (Tregs) through regulating the expression, and function of forkhead box P3 (FoxP3). In this study, we detected the IL-27 serum levels in 59 myasthenia gravis (MG) patients and 35 healthy controls (HCs). Among them, 32 MG patients received immunoglobulin intravenous (IVIG) injections (0.4 g/kg per day for 5 consecutive days). IL-27 levels were collected before and after the treatments and subjected to a comparative study. Finally, we assessed the correlations of IL-27 levels with the clinical characteristics of MG. As a result, serum IL-27 levels were significantly higher in MG patients than those in the HCs. Meanwhile, significant reduction was detected after the IVIG treatment. IL-27 levels positively correlated with both MG activities of daily living and quantitative MG score. IL-27 may participate in the pathogenesis of MG and can be used as an early marker for the diagnosis and prognosis of MG. In addition, IL-27 can be used as a target for MG treatment through the regulation of specific immune signaling and maintaining immune homeostasis. Show less
To investigate the effect of IL-27 on Th17 cells in patients with henoch-schönlein purpura（HSP） in order to further elucidate the pathogenesis. Fifty patients with HSP treated in our hospital from Apr Show more
To investigate the effect of IL-27 on Th17 cells in patients with henoch-schönlein purpura（HSP） in order to further elucidate the pathogenesis. Fifty patients with HSP treated in our hospital from April 2019 to July 2019 were selected as HSP group, and 30 volunteers underwent physical examination at the same time were selected as control group. The proportion of Th17 cells in peripheral blood of HSP group and healthy control group was determined by flow cytometry (FCM). A total of 27 HSP patients were selected, and candidate peripheral blood mononuclear lymphocytes (PBMC) were co-cultured with exogenous rhIL-27, and the ratio of Th17 cells was detected by flow cytometry. The proportion of Th17 cells in the peripheral blood of HSP patients with acute phase was (1.57±0.54)%, which was significantly higher than that of the control group (0.86±0.40)% (t=-6.298, P<0.001), and the proportion of Th17 cells was decreased significantly after rhIL-27 co-culture (1.39%±0.52% vs 0.98%±0.44%)(P<0.05). IL-27 can reduce the level of Th17 cells in patients with HSP, which may be involved in the pathogenic process of HSP and play a protective role in the development of the disease. Show less
no PDFDOI: 10.19746/j.cnki.issn.1009-2137.2020.06.042
IL-27 attenuates allergic inflammation and improves lung function in mouse models of allergic asthma. However, plasma IL-27 levels of asthma patients and the association with clinical features remain Show more
IL-27 attenuates allergic inflammation and improves lung function in mouse models of allergic asthma. However, plasma IL-27 levels of asthma patients and the association with clinical features remain poorly understood. This study examined plasma IL-27 protein expression in untreated asthma patients and controls, analyzed its correlation with Th2 inflammation and lung function, and evaluated the effect of corticosteroids on IL-27 expression. Plasma IL-27 levels were lower in untreated asthma patients compared to controls. Plasma IL-27 levels were inversely correlated with sputum IL-5 mRNA expression in Th2 The results indicate that low levels of IL-27 in peripheral blood are closely related to Th2 inflammation and lung function of asthma patients. Low IL-27 levels in combination with high Th2 inflammation identify an asthma phenotype with high AHR and substantial response to corticosteroids. Understanding of this interaction could help to elucidate the inherent inflammation heterogeneity of asthma. Show less
What is the mechanism of Tim-3+ regulatory T (Treg)-cell accumulation in the decidua during early pregnancy and is its disruption associated with recurrent pregnancy loss (RPL)? IL-27 and Gal-9 secret Show more
What is the mechanism of Tim-3+ regulatory T (Treg)-cell accumulation in the decidua during early pregnancy and is its disruption associated with recurrent pregnancy loss (RPL)? IL-27 and Gal-9 secreted by trophoblasts activate the Tim-3 signaling pathway in CD4+ T cells and Treg cells and so promote accumulation of Tim-3+ Treg cells, the abnormal expression of IL-27 and Gal-9 is associated with impaired immunologic tolerance in RPL patients. Tim-3+ Treg cells are better suppressors of Teff cell proliferation, and display higher proliferative activity than Tim-3- Treg cells. Tim-3+ Treg cells are tissue-specific promoters of T-cell dysfunction in many tumors. These cells express a unique factor that influences and shapes the tumor microenvironment. The animal study included 80 normal pregnant mice. In human study, decidua tissues in the first trimester for flow cytometry analysis were collected from 32 normal pregnant women and 23 RPL patients. Placenta tissues for immunohistochemistry analysis were collected from 15 normal pregnant women. Placenta tissues for western blot analysis were collected from 5 normal pregnant women, 5 RPL patients and 5 women who have experienced one miscarriage. Blood samples for in vitro experiments were collected from 30 normal pregnant women. This study was performed between January 2017 and March 2019. In this study, we investigated the kinetics of Tim-3+ CD4+ T-cell accumulation, and the proportions of Tim-3+ Treg cells throughout murine pregnancies using flow cytometry. We compared Tim-3 expression on decidual CD4+ T cells and Treg cells during normal pregnancies with expression on the same cell populations in women suffering from RPL. IL-27 and Gal-9 transcription and protein expression in the placenta were determined by RT-PCR and western blot, respectively. An in vitro co-culture model consisting of peripheral CD4+ T cells and primary trophoblasts from early pregnancy was used to mimic the maternal-fetal environment. The percentage of Tim-3+ Treg cells present in mouse uteri fluctuates as gestation proceeds but does not change in the spleen. Levels of Tim3+ Treg cells in uteri peaked at pregnancy Day 6.5 (E 6.5), then progressively diminished, and fell to non-pregnant levels by E18.5. In pregnant mice, Tim-3+ Treg cells constituted 40-70% of Treg cells in uteri but were present at much lower abundance in spleens. About 60% of decidual Treg cells were Tim-3 positive at E6.5. Of these decidual Tim3+ Treg cells, nearly 90% were PD-1 positive. However, only about 16% of Tim3- Treg cells expressed PD-1. Blocking the Tim-3 signaling pathway decreased the proportion of Treg cells and led to embryo resorption. Moreover, much lower Tim-3 expression was observed on CD4+ T cells and Treg cells in women who had suffered from RPL at 6-9 gestational weeks compared with those who had normal pregnancies at matched gestations. In a normal pregnancy, Tim-3 expression on decidual CD4+ T cells is induced initially by IL-27. Then Gal-9-Tim-3 interaction promotes differentiation of decidual Tim-3+ CD4+ T cells into Treg cells. IL-27 and Gal-9 cooperatively induced Tim-3+ Treg cells in vitro. N/A. We did not investigate the kinetics of human decidual Tim-3+ CD4+ T and Tim-3+ Treg cell populations throughout pregnancy due to limited availability of second and third trimester decidua. In addition, functional suppressive data on the decidual Tim-3+ Treg cells are lacking due to limited and low quantities of these cells in decidua. These findings might have therapeutic clinical implications in RPL. This study was supported by research grants from the National Natural Science Foundation of China (No. 81871186) and National Key Research & Developmental Program of China (2018YFC1003900, 2018YFC1003904). The authors declare no conflict of interest. Show less
Tuberculosis (TB) is an infectious disease and its mortality rate ranks first. Latent tuberculosis infection (LTBI) means that a patient is infected with Mycobacterium tuberculosis, but has no relativ Show more
Tuberculosis (TB) is an infectious disease and its mortality rate ranks first. Latent tuberculosis infection (LTBI) means that a patient is infected with Mycobacterium tuberculosis, but has no relative clinical symptoms. It has been estimated that approximately 10% of patients with LTBI would develop into active tuberculosis. Therefore, it was urgent to search for more efficient biomarkers to discriminate LTBI from healthy population. The Luminex assay was employed to detect the quantity of cytokines secreted by mononuclear cells from peripheral blood stimulated with the ESAT6 protein among TB, LTBI and healthy controls. The cytokine profile was analyzed by principal components analysis and the receiver operating characteristic curve analysis. The principal components analysis indicated that LTBI and TB were clearly separated from healthy controls, and that LTBI was also successfully differentiated from healthy controls. The cytokine profiling method to distinguish LTBI from healthy controls has a sensitivity and specificity of 100%. Nine potential biomarkers, including IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-1β, IL-22 and IL-18, were identified, and these cytokines were considered as a potential cytokine complex for more effectively discriminating LTBI from healthy controls. IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-1β, IL-22 and IL-18 were demonstrated to be the potential cytokine complex for the assessment between LTBI and healthy controls. Show less
Tuberculosis pleural effusion (TPE) is common in clinical practice, and its diagnosis remains a challenge for clinicians. Ziehl-Neelsen staining, PE Mycobacterium tuberculosis culture, and biopsy are Show more
Tuberculosis pleural effusion (TPE) is common in clinical practice, and its diagnosis remains a challenge for clinicians. Ziehl-Neelsen staining, PE Mycobacterium tuberculosis culture, and biopsy are the gold standards for TPE diagnosis; however, they are time-consuming, invasive, observer-dependent, and insensitive. PE markers represent a rapid, low-cost, and non-invasive objective diagnostic tool for TPE. In the past decades, several PE biomarkers have been developed, and their diagnostic accuracy has been evaluated in many studies. Here, we reviewed the literature to summarize the diagnostic accuracy of these biomarkers, especially using the evidence from systematic review and meta-analysis. The current research strongly suggests that adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin 27 (IL-27) have extremely higher diagnostic accuracy for TPE, while the diagnostic accuracy of interferon gamma release assays (IGRAs), tumor necrosis factor-α (TNF-α), and interferon-γ-induced protein 10 kDa (IP-10) is moderate. Although some evidence supports C-X-C motif chemokine ligand 9 (CXCL9), CXCL11, CXCL12, sFas ligand, angiotensin-converting enzyme (ACE), calpain-1, spectrin breakdown products (SBDP), matrix metalloproteinase-1 (MMP-1), soluble CD26 (sCD26), soluble interleukin 2 receptor (sIL-2R) as useful diagnostic markers for TPE, more support is needed to validate their diagnostic accuracy. Finally, nucleic acid amplification tests (NAATs) have extremely high diagnostic specificity, but their sensitivity is low. Taken together, ADA is the preferred marker for TPE because its low cost and suitability for standardization. Show less
Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The Show more
Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)-mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by Show less
The aim of this study was to investigate the changes of tear secretion and inflammatory cytokines induced by aerobic exercise (AE) on healthy Chinese. A prospective, cross-sectional study. A total of Show more
The aim of this study was to investigate the changes of tear secretion and inflammatory cytokines induced by aerobic exercise (AE) on healthy Chinese. A prospective, cross-sectional study. A total of 73 eyes from 43 healthy participants were included in this study, which was composed of 2 parts. Thirty individuals were included to investigate the effect of AE on tear secretion. Tear samples from extra 13 healthy subjects were collected to explore the effect of AE on tear cytokines profiles. In the first section, both areas of lower tear meniscus and volume of lower tear meniscus showed significant increase at 10 minutes after AE (P < 0.01). In the second section, a total of 15 tear cytokines including interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-10, IL-12P70, IL-13, IL-15, IL-17A, IL-21, and IL-27 were significantly lower at 20 minutes after AE than that of baseline (P < 0.01), whereas CCL/MIP-3α persisted to decrease at 60 minutes after exercise (P = 0.031). However, there was no significant difference of IL-2 concentration between baseline and any time point after exercise (P > 0.05). AE could promote tear secretion and decrease inflammatory cytokines in healthy subjects. Show less
Ping Li, Yu Liu, Qiang He · 2020 · Drug design, development and therapy · added 2026-04-24
Hepatocellular carcinoma (HCC) is a primary liver cancer with a 5-year incidence of over 70%. Anisodamine (ANI), an alkaloid extracted from HepG2 cells were subcutaneously injected into BALB/C nude mi Show more
Hepatocellular carcinoma (HCC) is a primary liver cancer with a 5-year incidence of over 70%. Anisodamine (ANI), an alkaloid extracted from HepG2 cells were subcutaneously injected into BALB/C nude mice and the tumor tissue was subcutaneously inoculated to construct the transplanted tumor. Mice were randomly divided into 10 groups (n = 5): control group, ANI-10 group, ANI-50 group, ANI-200 group, ANI-200+pcDNA-NLRP3 group, ANI-200+EV group, sh-NLRP3 group, ANI-200 + sh-NLRP3 group, normal group and normal+ANI-200 group. Studies indicated that ANI inhibited the growth of HCC xenografts and reduced liver damage in a dose-dependent manner. Besides, ANI increased the survival rate of tumor-bearing mice and suppressed the expression of NLRP3 in a dose-dependent manner. It is worth noting that NLRP3 overexpression reversed the inhibitory effect of ANI on HCC xenografts. In addition, TUNEL analysis showed that ANI-induced apoptosis of tumor cells, and NLRP3 overexpression reversed the inhibitory effect of ANI on HCC. Moreover, ANI further regulated the levels of IFN-γ, TNF-α, IL-4 and IL-27. Notably, low expression of NLRP3 enhanced the inhibitory effect of ANI on the development of HCC xenografts in mice. These findings indicate that ANI suppressed the growth of HCC cells, induced apoptosis and regulated the levels of inflammatory factors by inhibiting NLRP3 inflammasome activation. Show less
IL-6 was associated with the severity of mycoplasma pneumoniae pneumonia (MPP). But the relationship between IL-27 and MPP was unknown. Ninety-eight patients with MPP < 14 years old were enrolled in t Show more
IL-6 was associated with the severity of mycoplasma pneumoniae pneumonia (MPP). But the relationship between IL-27 and MPP was unknown. Ninety-eight patients with MPP < 14 years old were enrolled in this study and divided into groups by severity (mild cases and severe cases), infection types (MP single infection group and MP mixed infection group) and DNA loads (low MP DNA loads group and high MP DNA loads group), respectively. Fifteen children with foreign bodies in bronchus were also enrolled as control. IL-6 s and IL-27 s in bronchoalveolar lavage fluids (BALFs) from these children were measured by ELISA. There were significant differences in IL-6 s of BALFs from patients between mild cases and severe cases, MP single infection group and MP mixed infection group, and low MP DNA loads group and high MP DNA loads group, respectively (P < 0.05). Compared with IL-6 s of BALFs from control, IL-6 s in BALFs from the 6 patient groups were significantly higher (P < 0.05). IL-27 s in BALFs from MP mixed infection group were significantly lower than those from MP single infection group and control (P < 0.05) respectively. IL-6 was firmly associated with MPP and had potential application in clinical practice while IL-27 was not related to MP infection. Show less
Mengjiao Li, Lin Jiao, Mengyuan Lyu+6 more · 2020 · Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · Elsevier · added 2026-04-24
Host immune response have a pivotal role in the course of Mycobacterium tuberculosis (Mtb) infection. IL27 plays both pro-inflammatory and anti-inflammatory activities in infectious diseases via STAT1 Show more
Host immune response have a pivotal role in the course of Mycobacterium tuberculosis (Mtb) infection. IL27 plays both pro-inflammatory and anti-inflammatory activities in infectious diseases via STAT1/STAT3 mechanism. To investigate the association of single nucleotide polymorphisms (SNPs) of IL27 and STAT3 on the susceptibility of tuberculosis, we conducted a large size of case-control study in western Chinese Han population. A total of seven SNPs were genotyped using multiplex ligation detection reaction method in 900 patients with tuberculosis and 1534 healthy controls. Variants of three SNPs (rs181206, rs17855750, rs26528) within IL27 gene, the genotype and allele frequencies of rs17855750 were significantly different (p = .013, p = .004, respectively) between the TB patients and healthy controls. Subjects carrying C allele for rs17855750 showed a decreased tuberculosis risk (OR = 0.75, 95% CI = 0.62-0.91, p = .004). Genetic model analysis revealed that dominant modal was associated with lower TB risk (OR = 0.74, 95% CI = 0.60-0.92, p = .042). Haplotype of ACG (representing rs181206, rs17855750 and rs26528) showed a reduced risk to TB (OR = 0.79, 95% CI = 0.65-0.96, p = .017). There were no significant differences between TB cases and healthy controls in the variants of four SNPs (rs1053005, rs2293152, rs744166, rs4796793) within STAT3 gene. The polymorphisms of IL27, rs17855750, but not rs181206 and rs26528, plays a protective role on the susceptibility to TB. Show less
Dietary L-proline (proline) supplementation during gestation enhances fetal survival and placental development in mice. The objective of the present study was to test the hypothesis that this benefici Show more
Dietary L-proline (proline) supplementation during gestation enhances fetal survival and placental development in mice. The objective of the present study was to test the hypothesis that this beneficial effect of proline was associated with alterations in inflammatory response at the placenta and fetus interface. Populations of immune cells present in peripheral blood mononuclear cells (PBMC) were determined by flow cytometry analysis. The concentrations of immunoglobulins in plasma, and the concentrations of cytokines in plasma, uterus, placenta, and amniotic fluid were measured using a bead-based immunoassay. The data showed that proline supplementation led to higher (P < 0.05) populations of B lymphocytes (CD3 Show less
Rheumatoid arthritis and juvenile idiopathic arthritis are two types of autoimmune diseases with inflammation at the joints, occurring to adults and children respectively. There are phenotypic overlap Show more
Rheumatoid arthritis and juvenile idiopathic arthritis are two types of autoimmune diseases with inflammation at the joints, occurring to adults and children respectively. There are phenotypic overlaps between these two types of diseases, despite the age difference in patient groups. To systematically compare the genetic architecture of them, we conducted analyses at gene and pathway levels and constructed protein-protein-interaction network based on summary statistics of genome-wide association studies of these two diseases. We examined their difference and similarity at each level. We observed extensive overlap in significant SNPs and genes at the human leukocyte antigen region. In addition, several SNPs in other regions of the human genome were also significantly associated with both diseases. We found significantly associated genes enriched in 32 pathways shared by both diseases. Excluding genes in the human leukocyte antigen region, significant enrichment is present for pathways like interleukin-27 pathway and NO2-dependent interleukin-12 pathway in natural killer cells. The identification of commonly associated genes and pathways may help in finding population at risk for both diseases, as well as shed light on repositioning and designing drugs for both diseases. Show less
Myeloid-derived growth factor (MYDGF), which is produced by bone marrow-derived cells, mediates cardiac repair following myocardial infarction by inhibiting cardiac myocyte apoptosis to subsequently r Show more
Myeloid-derived growth factor (MYDGF), which is produced by bone marrow-derived cells, mediates cardiac repair following myocardial infarction by inhibiting cardiac myocyte apoptosis to subsequently reduce the infarct size. However, the function of MYDGF in the incretin system of diabetes is still unknown. Here, loss-of-function and gain-of-function experiments in mice revealed that MYDGF maintains glucose homeostasis by inducing glucagon-like peptide-1 (GLP-1) production and secretion and that it improves glucose tolerance and lipid metabolism. Treatment with recombinant MYDGF increased the secretion and production of GLP-1 in STC-1 cells in vitro. Mechanistically, the positive effects of MYDGF are potentially attributable to the activation of protein kinase A/glycogen synthase kinase 3β/β-catenin (PKA/GSK-3β/β-catenin) and mitogen-activated protein kinase (MAPK) kinases/extracellular regulated protein kinase (MEK/ERK) pathways. Based on these findings, MYDGF promotes the secretion and production of GLP-1 in intestinal L-cells and potentially represents a potential therapeutic medication target for type 2 diabetes. Show less
The roles of the histone demethylase JMJD1C in cardiac hypertrophy remain unknown. JMJD1C was overexpressed in hypertrophic hearts of humans and mice, whereas the histone methylation was reduced.
Histone demethylases are promising therapeutic targets as they play fundamental roles for survival of Mixed lineage leukemia rearranged acute leukemia (MLLr AL). Here we focused on the catalytic Jumon Show more
Histone demethylases are promising therapeutic targets as they play fundamental roles for survival of Mixed lineage leukemia rearranged acute leukemia (MLLr AL). Here we focused on the catalytic Jumonji domain of histone H3 lysine 9 (H3K9) demethylase JMJD1C to screen for potential small molecular modulators from 149,519 natural products and 33,765 Chinese medicine components via virtual screening. JMJD1C Jumonji domain inhibitor 4 (JDI-4) and JDI-12 that share a common structural backbone were detected within the top 15 compounds. Surface plasmon resonance analysis showed that JDI-4 and JDI-12 bind to JMJD1C and its family homolog KDM3B with modest affinity. In vitro demethylation assays showed that JDI-4 can reverse the H3K9 demethylation conferred by KDM3B. In vivo demethylation assays indicated that JDI-4 and JDI-12 could induce the global increase of H3K9 methylation. Cell proliferation and colony formation assays documented that JDI-4 and JDI-12 kill MLLr AL and other malignant hematopoietic cells, but not leukemia cells resistant to JMJD1C depletion or cord blood cells. Furthermore, JDI-16, among multiple compounds structurally akin to JDI-4/JDI-12, exhibits superior killing activities against malignant hematopoietic cells compared to JDI-4/JDI-12. Mechanistically, JDI-16 not only induces apoptosis but also differentiation of MLLr AL cells. RNA sequencing and quantitative PCR showed that JDI-16 induced gene expression associated with cell metabolism; targeted metabolomics revealed that JDI-16 downregulates lactic acids, NADP Show less
Chromosomal translocations and generating fusion genes are closely associated with disease initiation and progression in acute myeloid leukemia (AML). In this study, we identified a novel t(X;17)(q28; Show more
Chromosomal translocations and generating fusion genes are closely associated with disease initiation and progression in acute myeloid leukemia (AML). In this study, we identified a novel t(X;17)(q28;q21) chromosomal rearrangement in a patient with acute monocytic leukemia. Using RNA-sequencing, we identified a KANSL1-MTCP1 and a KANSL1-CMC4 fusion gene. 5'-UTR sequences of the KANSL1 gene were found to become fused upstream of the coding sequence region of the MTCP1 and CMC4 genes, respectively, resulting in an aberrantly high expression of these genes. Functional studies revealed that overexpression of the MTCP1 gene induced an increased cell proliferation and partial blockage of cell differentiation, suggesting that the aberrant expression of MTCP1 is of critical importance in leukemogenesis. Show less
Neuroplasticity and connectivity in the central nervous system (CNS) are easily damaged after hypoxia. Long-term exposure to an anoxic environment can lead to neuropsychiatric symptoms and increases t Show more
Neuroplasticity and connectivity in the central nervous system (CNS) are easily damaged after hypoxia. Long-term exposure to an anoxic environment can lead to neuropsychiatric symptoms and increases the likelihood of depression. Demyelination is an important lesion of CNS injury that may occur in depression. Previous studies have found that the RhoA/ROCK pathway is upregulated in neuropsychiatric disorders such as multiple sclerosis, stroke, and neurodegenerative diseases. Therefore, the chief aim of this study is to explore the regulatory role of the RhoA/ROCK pathway in the development of depression after hypoxia by behavioral tests, Western blotting, immunostaining as well as electron microscopy. Results showed that HIF-1α, S100β, RhoA/ROCK, and immobility time in FST were increased, sucrose water preference ratio in SPT was decreased, and the aberrant activity of neurocyte and demyelination occurred after hypoxia. After the administration of Y-27632 and fluoxetine in hypoxia, these alterations were improved. Lingo1, a negative regulatory factor, was also overexpressed after hypoxia and its expression was decreased when the pathway blocked. However, fluoxetine had no effect on the expression of Lingo1. Then, we demonstrated that demyelination was associated with failures of oligodendrocyte precursor cell proliferation and differentiation and increased apoptosis of oligodendrocytes. Collectively, our data indicate that the RhoA/ROCK pathway plays a vital role in the initial depression during hypoxia. Blocking this pathway in the early stage of hypoxia can enhance the effectiveness of antidepressants, rescue myelin damage, and reduce the expression of the negative regulatory protein of myelination. The findings provide new insight into the prophylaxis and treatment of depression. Show less