ABSTRACT
Understanding the impact of environmental pollution on organismal energy budgets is crucial for predicting adaptive responses and potential maladaptation to stressors. However, the regulatory mechanism governing the trade-off between energy intake and consumption remains largely unknown, particularly considering the diverse adaptations influenced by exposure history in realistic field conditions. In the present study, we conducted a simulated field reciprocal transplant experiment to compare the energy budget strategies of Strauchbufo raddei tadpoles exposed to heavy metal. The simulated heavy metal concentrations (0.29 mg/L Cu, 1.17 mg/L Zn, 0.47 mg/L Pb, 0.16 mg/L Cd) mirrored the actual environmental exposure concentrations observed in the field habitat. This allowed for a comparison between tadpoles with parental chronic exposure to heavy metal pollutants in their habitat and those without such exposure. Results revealed that under heavy metal exposure, tadpoles originating from unpolluted areas exhibited heightened vulnerability, characterized by reduced food intake, diminished nutrient absorption, increased metabolism cost, reduced energy reserves, and increased mortality rates. In contrast, tadpoles originating from areas with long-term heavy metal pollution demonstrated adaptive strategies, manifested through adjustments in liver and small intestine phenotypes, optimizing energy allocation, and reducing energy consumption to preserve energy, thus sustaining survival. However, tadpoles from polluted areas exhibited certain maladaptive such as growth inhibition, metabolic suppression, and immune compromise due to heavy metal exposure. In conclusion, while conserving energy consumption has proven to be an effective way to deal with long-term heavy metal stress, it poses a threat to individual survival and population development in the long run.
Subject(s)
Anura , Larva , Metals, Heavy , Animals , Larva/growth & development , Larva/drug effects , Metals, Heavy/toxicity , Anura/physiology , Energy Metabolism/drug effects , Adaptation, Physiological , Environmental Pollution , Water Pollutants, Chemical/toxicity , Environmental ExposureABSTRACT
This study delves into the clinical implications of cyclin-dependent kinase inhibitor 2 (CDKN2) deletion in adult T-lineage acute lymphoblastic leukemia (T-ALL). Among 241 patients included in this study, 57 had CDKN2 deletion and 184 had CDKN2 wild-type (WT), and 165 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 76 did not undergo allo-HSCT. CDKN2 deletion correlated with higher white blood cell count, more high-risk diseases, and complex karyotype. The 5-year overall survival (OS) was 36.8% and 58.2% (P < 0.001), 5-year disease-free survival (DFS) was 47.1% and 59.3% (P = 0.018), and 5-year cumulative incidence of relapse (CIR) was 33.7% and 22.3% (P = 0.019) in patients with CDKN2 deletion and WT, respectively. Multivariate analysis identified CDKN2 deletion as an independent adverse prognostic factor for OS (HR 2.11, P = 0.003). In the CDKN2 deletion subgroup, landmark analysis showed that the 5-year OS was 56.7% and 19% (P = 0.002) for patients who underwent allo-HSCT and those who did not, respectively. And multivariate analysis confirmed the beneficial role of allo-HSCT in OS (HR 0.23, P < 0.001). In conclusion, CDKN2 deletion was associated with a poor prognosis in adult T-ALL, and allo-HSCT might be beneficial for this population.
Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Adult , Hematopoietic Stem Cell Transplantation/methods , Male , Female , Adolescent , Middle Aged , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Gene Deletion , Young Adult , Disease-Free Survival , Allografts , Survival Rate , Transplantation, HomologousABSTRACT
PURPOSE OF REVIEW: This review aims to provide an overview of the genes and molecular pathways involved in monogenic lupus, the implications for genome diagnosis, and the potential therapies targeting these molecular mechanisms. RECENT FINDINGS: To date, more than 30 genes have been identified as contributors to monogenic lupus. These genes are primarily related to complement deficiency, activation of the type I interferon (IFN) pathway, disruption of B-cell and T-cell tolerance and metabolic pathways, which reveal the multifaceted nature of systemic lupus erythematosus (SLE) pathogenesis. SUMMARY: In-depth study of the causes of monogenic lupus can provide valuable insights into of pathogenic mechanisms of SLE, facilitate the identification of effective biomarkers, and aid in developing therapeutic strategies.
Subject(s)
Interferon Type I , Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/therapy , Lupus Erythematosus, Systemic/drug therapy , Complement System Proteins , Interferon Type I/metabolism , BiomarkersABSTRACT
Albumin is derived from human or animal blood, and its ability to bind to a large number of endogenous or exogenous biomolecules makes it an ideal drug carrier. As a result, albumin-based drug delivery systems are increasingly being studied. With these in mind, detailed studies of the transport mechanism of albumin-based drug carriers are particularly important. As albumin receptors, glycoprotein 60 (GP60) and secreted protein acidic and rich in cysteine (SPARC) play a crucial role in the delivery of albumin-based drug carriers. GP60 is expressed on vascular endothelial cells and enables albumin to cross the vascular endothelial cell layer, and SPARC is overexpressed in many types of tumor cells, while it is minimally expressed in normal tissue cells. Thus, this review supplements existing articles by detailing the research history and specific biological functions of GP60 or SPARC and research advances in the delivery of antitumor drugs using albumin as a carrier. Meanwhile, the deficiencies and future perspectives in the study of the interaction of albumin with GP60 and SPARC are also pointed out.
ABSTRACT
Metastasis, the major cause of cancer mortality, requires cancer cells to reprogram their metabolism to adapt to and thrive in different environments, thereby leaving metastatic cells metabolic characteristics different from their parental cells. Mounting research has revealed that the de novo serine synthesis pathway (SSP), a glycolytic branching pathway that consumes glucose carbons for serine makeup and α-ketoglutarate generation and thus supports the proliferation, survival, and motility of cancer cells, is one such reprogrammed metabolic pathway. During different metastatic cascades, the SSP enzyme proteins or their enzymatic activity are both dynamically altered; manipulating their expression or catalytic activity could effectively prevent the progression of cancer metastasis; and the SSP enzymatic proteins could even conduce to metastasis via their nonenzymatic functions. In this article we overview the SSP dynamics during cancer metastasis and put the focuses on the regulatory role of the SSP in metastasis and the underlying mechanisms that mainly involve cellular anabolism/catabolism, redox balance, and epigenetics, aiming to provide a theoretical basis for the development of therapeutic strategies for targeting metastatic lesions.
Subject(s)
Neoplasms , Serine , Serine/metabolism , Oxidation-Reduction , Metabolic Networks and Pathways , Neoplasms/genetics , Neoplasms/metabolismABSTRACT
Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with toll-like receptor 7 (TLR7)-driven lupus, ZEB2 is essential for ABC formation and autoimmune pathology. ZEB2 binds to +20-kb myocyte enhancer factor 2b (Mef2b)'s intronic enhancer, repressing MEF2B-mediated germinal center B cell differentiation and promoting ABC formation. ZEB2 also targets genes important for ABC specification and function, including Itgax. ZEB2-driven ABC differentiation requires JAK-STAT (Janus kinase-signal transducer and activator of transcription), and treatment with JAK1/3 inhibitor reduces ABC accumulation in autoimmune mice and patients. Thus, ZEB2 emerges as a driver of B cell autoimmunity.
Subject(s)
Autoimmunity , B-Lymphocytes , Cell Differentiation , Gene Expression Regulation , Lupus Erythematosus, Systemic , Zinc Finger E-box Binding Homeobox 2 , Animals , Humans , Mice , Autoimmunity/genetics , B-Lymphocytes/cytology , B-Lymphocytes/metabolism , Cell Differentiation/genetics , Cell Lineage/genetics , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , MEF2 Transcription Factors/genetics , MEF2 Transcription Factors/metabolism , Zinc Finger E-box Binding Homeobox 2/genetics , Zinc Finger E-box Binding Homeobox 2/metabolism , Haploinsufficiency , Aging/immunology , Disease Models, Animal , FemaleABSTRACT
Caddisworms (Trichoptera) spin adhesive silks to construct a variety of underwater composite structures. Many studies have focused on the fibroin heavy chain of caddisworm silk and found that it contains heavy phosphorylation to maintain a stable secondary structure. Besides fibroins, recent studies have also identified some new silk proteins within caddisworm silk. To better understand the silk composition and its secretion process, this study reports the silk gland proteome of a retreat-building caddisworm, Stenopsyche angustata Martynov (Trichoptera, Stenopsychidae). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), 2389 proteins were identified in the silk gland of S. angustata, among which 192 were predicted as secreted silk proteins. Twenty-nine proteins were found to be enriched in the front silk gland, whereas 109 proteins were enriched in the caudal silk gland. The fibroin heavy chain and nine uncharacterized silk proteins were identified as phosphorylated proteins. By analysing the sequence of the fibroin heavy chain, we found that it contains 13 Gly/Thr/Pro-rich regions, 12 Val/Ser/Arg-rich regions and a Gly/Arg/Thr-rich region. Three uncharacterized proteins were identified as sericin-like proteins due to their larger molecular weights, signal peptides and repetitive motifs rich in serine. This study provides valuable information for further clarifying the secretion and adhesion of underwater caddisworm silk.
Subject(s)
Bombyx , Fibroins , Animals , Silk/chemistry , Fibroins/genetics , Fibroins/chemistry , Insecta/metabolism , Larva/metabolism , Proteome/metabolism , Chromatography, Liquid , Tandem Mass Spectrometry , Bombyx/metabolism , Insect Proteins/metabolismABSTRACT
OBJECTIVE: The diminished expression of microRNA-146a (miR-146a) in systemic lupus erythematosus (SLE) contributes to the aberrant activation of the interferon pathway. Despite its significance, the underlying mechanism driving this reduced expression remains elusive. Considering the integral role of enhancers in steering gene expression, our study seeks to pinpoint the SLE-affected enhancers responsible for modulating miR-146a expression. Additionally, we aim to elucidate the mechanisms by which these enhancers influence the contribution of miR-146a to the activation of the interferon pathway. METHODS: Circular chromosome conformation capture sequencing and epigenomic profiles were applied to identify candidate enhancers of miR-146a. CRISPR activation was performed to screen functional enhancers. Differential analysis of chromatin accessibility was used to identify SLE-dysregulated enhancers, and the mechanism underlying enhancer dysfunction was investigated by analyzing transcription factor binding. The therapeutic value of a lupus-related enhancer was further evaluated by targeting it in the peripheral blood mononuclear cells (PBMCs) of patients with SLE through a CRISPR activation approach. RESULTS: We identified shared and cell-specific enhancers of miR-146a in distinct immune cells. An enhancer 32.5 kb downstream of miR-146a possesses less accessibility in SLE, and its chromatin openness was negatively correlated with SLE disease activity. Moreover, CCAAT/enhancer binding protein α, a down-regulated transcription factor in patients with SLE, binds to the 32.5-kb enhancer and induces the epigenomic change of this locus. Furthermore, CRISPR-based activation of this enhancer in SLE PBMCs could inhibit the activity of interferon pathway. CONCLUSION: Our work defines a promising target for SLE intervention. We adopted integrative approaches to define cell-specific and functional enhancers of the SLE critical gene and investigated the mechanism underlying its dysregulation mediated by a lupus-related enhancer.
Subject(s)
Lupus Erythematosus, Systemic , MicroRNAs , Humans , Chromatin , Chromosomes/metabolism , Interferons/genetics , Leukocytes, Mononuclear/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Transcription Factors/geneticsABSTRACT
BACKGROUND: Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis. METHODS: This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques. RESULTS: The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis. CONCLUSIONS: This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.
Subject(s)
Multiomics , Skin , Animals , Skin/metabolism , Goats/geneticsABSTRACT
Southeast Asia plays a crucial role in global food production and trade, yet it grapples with challenges related to food security, regional stability, and security. Cultivated land is the material foundation for ensuring food production. With the development of society and the economy, people's food consumption has undergone significant changes. This paper employs a comprehensive approach to analyze trends in food consumption, the cultivated land footprint, and associated land pressures in Southeast Asia over the period 1961-2019. The main findings are as follows: (1) Between 1961 and 2019, the total food consumption in Southeast Asia surged by 3.1 times. Notably, the proportion of livestock-based foods increased steadily from 6.62% in 1961 to 16.82% in 2019. (2) Due to advancements in agricultural productivity across Southeast Asia, the cultivated land footprint for food consumption only increased by 0.7 times, showcasing a diminishing demand for grain-cultivated land. (3) On the whole, the pressure of food consumption on cultivated land in Southeast Asia is on the decline, albeit with considerable variations among different countries. The Philippines is facing a relative undersupply, whereas Thailand has experienced the lowest cultivated land pressure. (4) Encouraging a shift towards a Mediterranean-style diet, aligned with existing dietary patterns, holds promise for reducing future pressures on cultivated land and promoting better health outcomes for the populace in Southeast Asia.
ABSTRACT
Kelch-like ECH-associated protein 1 (Keap1) is a drug target for diseases involving oxidative stress and inflammation. There are three covalent Keap1-binding drugs on the market, but noncovalent compounds that inhibit the interaction between Keap1 and nuclear factor erythroid 2-related factor 2 (Nrf2) represent an attractive alternative. Both compound types prevent degradation of Nrf2, leading to the expression of antioxidant and antiinflammatory proteins. However, their off-target profiles differ as do their exact pharmacodynamic effects. Here, we discuss the opportunities and challenges of targeting Keap1 with covalent versus noncovalent inhibitors. We then provide a comprehensive overview of current noncovalent Keap1-Nrf2 inhibitors, with a focus on their pharmacological effects, to examine the therapeutic potential for this compound class.
Subject(s)
NF-E2-Related Factor 2 , Oxidative Stress , Kelch-Like ECH-Associated Protein 1/chemistry , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/chemistry , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/pharmacology , Protein Binding , Antioxidants/pharmacologyABSTRACT
An acidic deep eutectic solvent (DES, choline chloride/citric acid) was used to efficiently extract edible pectin from Premna microphylla Turcz (PMTP) and further prepare the film sensor with the purpose of "four birds with one stone" with the roles of extractant, coalescent, conductivity promoter and bacteriostatic agent. The optimized extraction process accorded with pseudo second-order kinetics, which was carried out at 78.2 °C for 1.29 h with the solid-liquid ratio of 1:34.66 g/mL with the yield up to 0.8210 g/g. After comprehensive characterizations of pectin product, a simple casting method was used to prepare the PMTP-DES based composite film. It showed that the composite film has promising compatibility, smooth surface, good breathability and ideal homogeneity. After 30 power on/power off cycles at 10 V, it exhibited satisfied conductivity stability. Moreover, the PMTP-DES film could be simply assembled as the flexible visual temperature sensor, with sensitive response at breathing or finger touch; it exhibited the highest sensitivity of 134 %/°C when the external temperature changed from 15 to 55 °C. Besides, the composite film also has preferable antimicrobial activity. The whole results and findings were aimed to contribute for the raw material, composition, preparation, and functions of the existing flexible functional materials.
Subject(s)
Deep Eutectic Solvents , Pectins , Solvents , TemperatureABSTRACT
Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.
Subject(s)
Hyperthermia, Induced , Metal Nanoparticles , Neoplasms , Female , Animals , Mice , Gold , Metal Nanoparticles/therapeutic use , Hyperthermia , Toll-Like Receptors , Neoplasms/therapy , Cytokines , ImmunityABSTRACT
BACKGROUND: Nurses suffer a certain degree of work alienation (a psychological state in which employees feel separated from their jobs because the jobs do not meet the needs of employees or do not match their expectations). It is necessary to identify predictors of work alienation and find effective interventions. OBJECTIVE: To explore the influence of organizational climate and job stress on work alienation among nurses in emergency departments. METHODS: This was a cross-sectional study conducted from June to August 2022. A convenience sampling method was adopted to invite 342 nurses from emergency departments in 12 tertiary public hospitals in 4 cities in China. Data were collected using self-reported questionnaires on organizational climate, job stress, and work alienation. Path analysis implemented by IBM AMOS 21.0 was used to explore the associations among organizational climate, job stress, and work alienation. RESULTS: Job stress can positively affect work alienation among nurses in emergency departments (ß = 0.44, P < .01). Organizational climate can directly and negatively affect work alienation (ß = -0.33, P < .01); it can also negatively and indirectly affect work alienation through job stress (ß = -0.20, 95% confidence interval: -0.252 to -0.146). CONCLUSIONS: Job stress partially mediated the effect of organizational climate on work alienation among nurses in emergency departments. The findings provided a valuable perspective on predictors of work alienation among emergency department nurses.
Subject(s)
Nurses , Occupational Stress , Humans , Cross-Sectional Studies , Emotions , Emergency Service, HospitalABSTRACT
Liaoning cashmere goat (LCG) is one of the excellent cashmere goat breeds in China. Because of its larger size, better cashmere, and better cashmere production performance, people pay special attention to it. This article mainly studied the relationship between SNP loci of LIPE gene and ITGB4 gene and milk production, cashmere production and body measurement traits of LCGs. We further identified potential SNP loci by PCR-Seq polymorphism detection and gene sequence comparison of LIPE and ITGB4 genes. Further, we use SPSS and SHEsis software to analyze their relationship to production performance. The consequence indicated that CC genotype of LIPE gene T16409C locus was dominant genotype in milk production and cashmere production, while CT genotype of LIPE gene T16409C locus was dominant in body size. The CT genotype of C168T locus of ITGB4 gene is the dominant genotype of body type and cashmere production, while the dominant genotype of milk production is TT genotype. Through joint analysis, in haploid combinations, H1H2:CCCT is the dominant haplotype combination in cashmere fineness. H3H4:TTCT is a dominant haplotype combination of milk production traits and body measurement traits. These dominant genotypes can provide a reliable basis for the study of production performance of LCG.
Subject(s)
Goats , Polymorphism, Single Nucleotide , Animals , Polymorphism, Single Nucleotide/genetics , Goats/genetics , Milk , Phenotype , GenotypeABSTRACT
Cancer vaccines are designed to motivate antigen-specific immune responses and facilitate tumor regression with minimal side effects. To fully exert the potential of vaccines, rationally designed formulations that effectively deliver antigens and trigger potent immune reactions are urgently needed. This study demonstrates a simple and controllable vaccine-developing strategy that assembles tumor antigens into bacterial outer membrane vesicles (OMVs), natural delivery vehicles with intrinsic immune adjuvant properties, via electrostatic interaction. This OMV-delivered vaccine (OMVax) stimulated both innate and adaptive immune responses, leading to enhanced metastasis inhibition and prolonged survival of tumor-bearing mice. Moreover, the influence of different surface charged OMVax on antitumor immunity activation is investigated and declined immune response activation occurred with increased positive surface charge. Together, these findings suggest a simple vaccine formulation that can be enhanced by optimizing the surface charges of vaccine formulations.
Subject(s)
Cancer Vaccines , Neoplasms , Animals , Mice , Antigens , Adjuvants, Immunologic , Neoplasms/therapyABSTRACT
Mature milk, as a nutrient-rich endogenous metabolite, has various beneficial effects on the human body. In order to investigate the specific nutrients provided by different dairy products to humans, we used UHPLC-Q-TOF MS to analyze the highly significantly differentially expressed metabolites in 13 species of mammalian mature milk, which were grouped into 17 major metabolite classes with 1992 metabolites based on chemical classification. KEGG shows that 5 pathways in which differentially significant metabolites are actively involved are ABC transporters, Purine metabolism, Pyrimidine metabolism, Phosphotransferase system, Galactose metabolism. The study found that pig milk and goat milk are closer to human milk and contain more nutrients that are beneficial to human health, followed by camel milk and cow milk. In the context of dairy production, the development of goat milk is more likely to meet human needs and health.
ABSTRACT
OBJECTIVE: Increased Toll-like receptor 7 (TLR-7) signaling leading to the production of type I interferon (IFN) is an important contributor to human systemic lupus erythematosus (SLE). Protein kinase C and casein kinase substrate in neurons 1 (PACSIN1), a molecule that regulates synaptic vesicle recycling, has been linked to TLR-7/TLR-9-mediated type I IFN production in humans and mice, but the underlying mechanism is unknown. We undertook this study to explore the pathogenicity and underlying mechanism of a de novo PACSIN1 missense variant identified in a child with SLE. METHODS: PACSIN1 Q59K de novo and null variants were introduced into a human plasmacytoid dendritic cell line and into mice using CRISPR/Cas9 editing. The effects of the variants on TLR-7/TLR-9 signaling in human and mouse cells, as well as PACSIN1 messenger RNA and IFN signature in SLE patients, were assessed using real-time polymerase chain reaction and flow cytometry. Mechanisms were investigated using luciferase reporter assays, RNA interference, coimmunoprecipitation, and immunofluorescence. RESULTS: We established that PACSIN1 forms a trimolecular complex with tumor necrosis factor receptor-associated factor 4 (TRAF4) and TRAF6 that is important for the regulation of type I IFN. The Q59K mutation in PACSIN1 augments binding to neural Wiskott-Aldrich syndrome protein while it decreases binding to TRAF4, leading to unrestrained TRAF6-mediated activation of type I IFN. Intriguingly, PACSIN1 Q59K increased TLR-7 but not TLR-9 signaling in human cells, leading to elevated expression of IFNß and IFN-inducible genes. Untreated SLE patients had high PACSIN1 expression in peripheral blood cells that correlated positively with IFN-related genes. Introduction of the Pacsin1 Q59K mutation into mice caused increased surface TLR-7 and TRAIL expression in B cells. CONCLUSION: PACSIN1 Q59K increases IFNß activity through the impairment of TRAF4-mediated inhibition of TLR-7 signaling, possibly contributing to SLE risk.
Subject(s)
Interferon Type I , Lupus Erythematosus, Systemic , Child , Humans , Mice , Animals , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/metabolism , Interferon-alpha , Protein Kinase C/metabolism , TNF Receptor-Associated Factor 4/metabolism , TNF Receptor-Associated Factor 6/genetics , TNF Receptor-Associated Factor 6/metabolism , Lupus Erythematosus, Systemic/metabolism , Interferon Type I/metabolism , Neurons/metabolism , Toll-Like Receptor 9 , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
Liaoning cashmere goat (LCG) is a famous cashmere goat breed in China. Cashmere fineness, as an important index to evaluate cashmere quality, is also one of the problems to be improved for Liaoning cashmere goats. Transcriptome studies all mRNA transcribed by a specific tissue or cell in a certain period. It is a key link in the study of gene expression regulation. It plays an important role in the analysis of biological growth and disease. Transcriptome is spatio-temporal specific, that is, gene expression varies in different tissues or at different times. Three coarser and three fine LCG skin samples were sequenced by RNA-seq technology, and a total of 427 differentially expressed genes were obtained, including 291 up-regulated genes and 136 down-regulated genes. In the experiment, we screened out 16 genes that had significant differences in the expression of coarse and fine cashmere of Liaoning cashmere goats, so it was inferred that these 16 genes might have regulatory effects on cashmere fineness. Moreover, GO gene set enrichment analysis revealed that differential genes mainly consist of immune response, MHC protein complex, Heme binding and other pathways. KEGG analysis showed that transplant-versus-host disease and allograft rejection were the main pathways of differential genes.
Subject(s)
Gene Expression Regulation , Transcriptome , Animals , Gene Expression Profiling/veterinary , Base Sequence , Goats/genetics , Hair Follicle/metabolismABSTRACT
Liaoning cashmere goat (LCG) have tall bones, high cashmere production and outstanding meat production performance. In recent years, good breeding progress has not been made in terms of body size, meat yield, milk yield and other properties in terms of production. The study focused on the correlation between the SNPs of MSTN and IGFBP-3 genes with the body size performance, cashmere production and milk performance. The MSTN and IGFBP-3 gene sequence alignment and PCR-Seq polymorphism were used to detect the potential SNPs, and the correlation with production performance was analyzed by SPSS and SHEsis software. The results showed that the TT genotype at the T1662G locus of the MSTN gene is dominant and has significant advantages in body measurements such as sacrum height, chest width, and waist height. The C allele at the C4021T locus of IGFBP-3 gene shows an advantage in the body measurement performance. Among the haplotype combinations, H2H2:TGTC is preponderant combination for body size performance, H2H2:TGTC and H1H2:TGCC are preponderant combinations for cashmere production performance, H1H3:GGCC is preponderant combination for milk production performance. It may be a molecular marker for future selection and breeding.