👤 Tingting Feng

The poorly understood regulatory mechanisms impede gastric cancer therapy. Kruppel-like factors (KLFs) are associated with the development of various tumors, The studies on the role of the KLF transcription factor 13 (KLF13) in gastric cancer progression haven't been studied. The current study aimed to investigate the role of KLF13 in the migration and invasion of gastric cancer and the regulatory mechanism of KLF13 in gastric cancer progression. The research team performed a laboratory study. The study took place at the Zengcheng District People's Hospital of Guangzhou in Zengcheng, China. In addition to using normal gastric cells, GES1, and seven gastric cancer cell lines, the research team compared the fresh, gastric cancer tissues (T) and paired, adjacent, noncancerous gastric tissues (ANT) from eight patients undergoing surgical resection at the hospital. The research team also downloaded the data for 33 gastric cancer tissues and adjacent, normal gastric tissues from the Cancer Genome Atlas' TCGA database. The research team used: (1) short hairpin RNAs (shRNAs) to knock down KLF13, (2) wound healing and transwell invasion analyses to determine the effects of KLF13 on the migration and invasion of gastric cancer, and (3) a Luciferase reporter assay to determine the effects of KLF13 on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. KLF13 was upregulated in gastric cancer cells and tissues, and the patients with a high KLF13 expression had poor outcome. Downregulation of KLF13 significantly inhibited the migration and invasion of gastric cancer cells. Mechanistically, downregulation of KLF13 significantly inhibited NF-κB activity, and its targets such as: (1) snail family transcriptional repressor 1 (SNAI1 or Snail), (2) snail family transcriptional repressor 2 (SNAI2 or Slug), (3) zinc finger e-box binding homeobox 1 (ZEB1), (4) Smad interacting protein 1 (Sip1), (5) twist family basic helix-loop-helix (BHLH) transcription factor (Twist), (6) matrix metallopeptidase 2 (MMP2), and (7) MMP9. Tumor necrosis factor alpha (TNF-α) can activate NF-κB. Treating with TNF-α can reverse the effects of KLF13 downregulation on migration and invasion, confirming that KLF13 promotes the migration and invasion of gastric cancer cells through activating the NF-κB pathway. KLF13 promoted the migration and invasion of gastric cancer cells through activating the NF-κB pathway, providing a new target for gastric cancer therapy. Show less

Multiple myeloma (MM) is a fatal malignant tumor in hematology. Mitophagy plays vital roles in the pathogenesis and drug sensitivity of MM. We acquired transcriptomic expression data and clinical index of MM patients from NCI public database, and 36 genes involved in mitophagy from the gene set enrichment analysis (GSEA) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was conducted to construct a risk score prognostic model. Kaplan-Meier survival analysis and receiver operation characteristic curves (ROC) were conducted to identify the efficiency of prognosis and diagnosis. ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) was performed to uncover the level of immune infiltration. QRT-PCR was performed to verify gene expression in clinical samples of MM patients. The sensitivity to chemotherapy drugs was evaluated upon the database of the genomics of drug sensitivity in cancer (GDSC). Fifty mitophagy-related genes were differently expressed in two independent cohorts. Ten out of these genes were identified to be related to MM overall survival (OS) rate. A prognostic risk signature model was built upon on these genes: VDAC1, PINK1, VPS13C, ATG13, and HUWE1, which predicted the survival of MM accurately and stably both in training and validation cohorts. MM patients suffered more adverse prognosis showed more higher risk core. In addition, the risk score was considered as an independent prognostic element for OS of MM patients by multivariate cox regression analysis. Functional pathway enrichment analysis of differentially expressed genes (DEGs) based on risk score showed terms of cell cycle, immune response, mTOR pathway, and MYC targets were obviously enriched. Furthermore, MM patients with higher risk score were observed lower immune scores and lower immune infiltration levels. The results of qRT-PCR verified VDAC1, PINK1, and HUWE1 were dysregulated in new diagnosed MM patients. Finally, further analysis indicated MM patients showed more susceptive to bortezomib, lenalidomide and rapamycin in high-risk group. Our research provided a neoteric prognostic model of MM based on mitophagy genes. The immune infiltration level based on risk score paved a better understanding of the participation of mitophagy in MM. Show less

Chronic pain is defined as pain that persists typically for a period of over six months. Chronic pain is often accompanied by an anxiety disorder, and these two tend to exacerbate each other. This can make the treatment of these conditions more difficult. Glucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family and plays a critical role in glucose metabolism. Previous research has demonstrated the multiple roles of GIP in both physiological and pathological processes. In the central nervous system (CNS), studies of GIP are mainly focused on neurodegenerative diseases; hence, little is known about the functions of GIP in chronic pain and pain-related anxiety disorders. The chronic inflammatory pain model was established by hind paw injection with complete Freund's adjuvant (CFA) in C57BL/6 mice. GIP receptor (GIPR) agonist (D-Ala In the present study, we found that hind paw injection with CFA induced pain sensitization and anxiety-like behaviors in mice. The expression of GIPR in the ACC was significantly higher in CFA-injected mice. D-Ala GIPR activation was found to produce analgesic and anxiolytic effects, which were partially due to attenuation of neuroinflammation and inhibition of excitatory transmission in the ACC. GIPR may be a suitable target for treatment of chronic inflammatory pain and pain-related anxiety. Show less

Diabetes is a risk factor for Parkinson's disease (PD) and shares similar dysregulated insulin pathways. Glucagon-like peptide-1 (GLP-1) analogs originally designed to treat diabetes have shown potent neuroprotective activity in preclinical studies of PD. They are neuroprotective by inhibiting inflammation, improving neuronal survival, maintenance of synapses, and dopaminergic transmission in the brain. Building on this, three clinical studies have reported impressive effects in patients with PD, testing -4 (Exenatide, Bydureon) or liraglutide (Victoza, Saxenda). Glucose-dependent insulinotropic peptide (GIP) is another peptide hormone that has shown good effects in animal models of PD. Novel dual GLP-1/GIP agonists have been developed that can penetrate the blood-brain barrier (BBB) and show superior effects in animal models compared to GLP-1 drugs. The review summarizes preclinical and clinical studies testing GLP-1R agonists and dual GLP-1/GIPR agonists in PD and discusses possible mechanisms of action. Current strategies to treat PD by lowering the levels of alpha-synuclein have not shown effects in clinical trials. It is time to move on from the 'misfolding protein' hypothesis. Growth factors such as GLP-1 that can cross the BBB have already shown impressive effects in patients and are the future of drug discovery in PD. Show less

SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist. Show less

Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dual agonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their multiplexed pharmacological actions over monoagonists such as semaglutide, we determine cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR. The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the near-atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility of tirzepatide and peptide 20. Show less

We demonstrated previously that there is a correlation between glucagon-like peptide-1 (GLP-1) single-nucleotide polymorphism (SNP) and bone mineral density in postmenopausal women. Both GLP-1 and glucose-dependent insulinotropic peptide are incretins. The glucose-dependent insulinotropic peptide receptor (GIPR) SNP rs10423928 has been extensively studied. However, it is not clear whether GIPR gene mutations affect bone metabolism. The aim of this study was to investigate the association between rs10423928 and bone mineral density in postmenopausal women in Shanghai. rs10423928 was detected in 884 postmenopausal women in Shanghai, and the correlation between the GIPR SNP and bone mineral density was assessed. The dominant T/T genotype of rs10423928 was found to be related to the bone mineral density of the femoral neck (P = 0.035). Overall, our findings indicate that the dominant T/T genotype of rs10423928 in postmenopausal women is significantly associated with a higher bone mineral density and that the T/T genotype exerts a bone-protective effect. Show less

Secreted proteins are important proteins in the human proteome, accounting for approximately one-tenth of the proteome. However, the prognostic value of secreted protein-related genes has not been comprehensively explored in lung adenocarcinoma (LUAD). In this study, we screened 379 differentially expressed secretory protein genes (DESPRGs) by analyzing the expression profile in patients with LUAD from The Cancer Genome Atlas database. Following univariate Cox regression and least absolute shrinkage and selection operator method regression analysis, 9 prognostic SPRGs were selected to develop secreted protein-related risk score (SPRrisk), including CLEC3B, C1QTNF6, TCN1, F2, FETUB, IGFBP1, ANGPTL4, IFNE, and CCL20. The prediction accuracy of the prognostic models was determined by Kaplan-Meier survival curve analysis and receiver operating characteristic curve analysis. Moreover, a nomogram with improved accuracy for predicting overall survival was established based on independent prognostic factors (SPRrisk and clinical stage). The DESPRGs were validated by quantitative real-time PCR and enzyme-linked immunosorbent assay by using our clinical samples and datasets. Our results demonstrated that SPRrisk can accurately predict the prognosis of patients with LUAD. Patients with a higher risk had lower immune, stromal, and ESTIMATE scores and higher tumor purity. A higher SPRrisk was also negatively associated with the abundance of CD8 Show less

To investigate the aqueous levels of angiogenic factors in nonproliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and to ascertain their association with optical coherence tomography angiography (OCTA) metrics. This study enrolled 21 NPDR eyes with DME (NPDR/DME+), 17 NPDR eyes without DME (NPDR/DME-), and 16 diabetic eyes without retinopathy (DWR). Luminex bead-based multiplex array was used to measure the levels of 25 cytokines. OCTA system with a scan area of 3 × 3 mm was used to measure retinal thickness (RT), retinal volume (RV), superficial vessel density (SVD), deep vessel density (DVD), foveal avascular zone (FAZ) area, perimeter and acircularity index. The levels of ANGPTL4 were significantly different among the three groups ( The level of ANGPTL4 in aqueous humor of NPDR patients with DME was significantly increased and ANGPTL4 might predict RT, RV, and parafoveal DVD of DME in NPDR patients. Show less

Podocyte injury is an important cause of proteinuria. Angiopoietin-like protein 4 (Angptl4) is a secreted glycoprotein and has a role in proteinuria. However, the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified. In this study, we used lipopolysaccharide (LPS)-induced mice and cultured podocytes as podocyte injury models. Our results indicated that LPS increased the expression of podocyte Angptl4 Show less

Small bowel adenocarcinoma (SBA) is a gastrointestinal malignancy with low incidence but poor prognosis, and its pathogenesis is still unclear. This study aimed to explore potential disease-causing biomarkers of SBA. The gene expression datasets of SBA and normal samples were downloaded from the Gene Expression Omnibus database. First, differential gene expression analysis and weighted gene coexpression network analysis (WGCNA) were performed. Common genes (CGs) were obtained by intersection of differentially expressed genes (DEGs) and optimal modal genes of WGCNA. Subsequently, a protein‒protein interaction network was established to screen hub genes, and target genes were obtained by Lasso regression analysis of hub genes. An SBA risk prediction model was established based on target genes. The prediction accuracy of the model was evaluated by the area under the receiver operating characteristic curve (AUC). The levels of immune cell infiltration and activation of immune pathways were compared between SBA and normal samples using the "ggpubr" and "reshape2" packages. A total of 1058 DEGs were identified. WGCNA showed that the signature gene in the brown module was significantly associated with SBA (p = 7E-17), and 469 CGs were obtained. Four target genes (APOA4, APOB, COL1A2, FN1) were identified and showed excellent prediction of SBA risk (AUC = 0.965). In addition, active dendritic cells and macrophages showed higher infiltration levels in SBA. Meanwhile, the APC_co_stimulation pathway and parainflammation pathway were strongly active in SBA. Four target genes (APOA4, APOB, COL1A2, FN1) may be involved in the pathogenesis of small bowel adenocarcinoma. Show less

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, whose etiology is poorly understood. Accumulating evidence indicates that gut microbiota plays an important role in the occurrence and progression of various human diseases, including NAFLD. In this study, NAFLD mouse models were established by feeding a high-fat diet (HFD). Baicalein, a natural flavonoid with multiple biological activities, was administered by gavage, and its protective effect on NAFLD was analyzed by histopathological and blood factor analysis. Gut microbiota analysis demonstrated that baicalein could remodel the overall structure of the gut microbiota from NAFLD model mice, especially Show less

Arginyl-tRNA-protein transferase 1 (ATE1) catalyses N-terminal protein arginylation, a post-translational modification implicated in cell migration, invasion and the cellular stress response. Herein, we report that ATE1 is overexpressed in NRAS-mutant melanomas, while it is downregulated in BRAF-mutant melanomas. ATE1 expression was higher in metastatic tumours, compared with primary tumours. Consistent with these findings, ATE1 depletion reduced melanoma cell viability, migration and colony formation. Reduced ATE1 expression also affected cell responses to mTOR and MEK inhibitors and to serum deprivation. Among putative ATE1 substrates is the tumour suppressor AXIN1, pointing to the possibility that ATE1 may fine-tune AXIN1 function in melanoma. Our findings highlight an unexpected role for ATE1 in melanoma cell aggressiveness and suggest that ATE1 constitutes a potential new therapeutic target. Show less

Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Aβ and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Show less

Multi-targeted directed ligands (MTDLs) are emerging as promising Alzheimer's disease (AD) therapeutic possibilities. Coumarin is a multifunctional backbone with extensive bioactivity that has been utilized to develop innovative anti-neurodegenerative properties and is a desirable starting point for the construction of MTDLs. Herein, we explored and synthesized a series of novel coumarin derivatives and assessed their inhibitory effects on cholinesterase (AChE, BuChE), GSK-3β, and BACE1. Among these compounds, compound 30 displayed the multifunctional profile of targeting the AChE (IC Show less

We determined the effectiveness of absolute binding free energy (ABFE) calculations to refine the selection of active compounds in virtual compound screening, a setting where the more commonly used relative binding free energy approach is not readily applicable. To do this, we conducted baseline docking calculations of structurally diverse compounds in the DUD-E database for three targets, BACE1, CDK2 and thrombin, followed by ABFE calculations for compounds with high docking scores. The docking calculations alone achieved solid enrichment of active compounds over decoys. Encouragingly, the ABFE calculations then improved on this baseline. Analysis of the results emphasizes the importance of establishing high quality ligand poses as starting points for ABFE calculations, a nontrivial goal when processing a library of diverse compounds without informative co-crystal structures. Overall, our results suggest that ABFE calculations can play a valuable role in the drug discovery process. Show less

To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer's disease (AD). Sixty-six AD patients received by the Department of Neurology of our hospital from October 2019 to September 2021 were gathered, according to the Clinical Dementia Rating Scale (CDR) score, they were grouped into mild group (≤1 point, n = 41) and moderate-to-severe group (> 1 point, n = 25). Another 32 cases of serum and cerebrospinal fluid samples from outpatient physical examination personnel were regarded as the control group. The general materials on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), β-amyloid (Aβ) 40 and Aβ42 in cerebrospinal fluid;Spearman's method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with MMSE and MoCA scores;Pearson method was performed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio (SUVR) and cerebrospinal fluid miR-27a-3p, NEAT1, BACE1, Aβ42 and Aβ40 levels. The MMSE score, MoCA score, serum miR-27a-3p level, cerebrospinal fluid miR-27a-3p, Aβ42 levels and Aβ42/Aβ40 ratio of AD patients in mild group and moderate-to-severe group were all lower than those in the control group, and the moderate-to-severe group were lower than the mild group (all P < 0.05);the serum NEAT1 level, SUVR, and cerebrospinal fluid NEAT1 and BACE1 levels were higher than those in the control group, and the moderate-to-severe group were higher than the mild group (all P < 0.05). Serum NEAT1 level in AD patients was positively correlated with SUVR, cerebrospinal fluid NEAT1 and BACE1 (r = 0.350, 0.606, 0.341, all P < 0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level (r = 0.695, P < 0.05), and negatively correlated with SUVR and cerebrospinal fluid BACE1 level (r = - 0.521, - 0.447, both P < 0.05). The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are consistent, the level of NEAT1 is increased, and the level of miR-27a-3p is decreased. The levels of the two are negatively correlated, which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD. Show less

Obesity is a global epidemic elevating the risk of various metabolic disorders. As there is a lack of effective drugs to treat obesity, we combined bioinformatics and reverse network pharmacology in this study to identify effective herbs to treat obesity. We identified 1011 differentially expressed genes (DEGs) of adipose tissue after weight loss by analyzing five expression profiles (GSE103766, GSE35411, GSE112307, GSE43471, and GSE35710) from the Gene Expression Omnibus (GEO) database. We identified 27 hub genes from the protein-protein interaction (PPI) network by performing MCODE using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these hub genes have roles in the extracellular matrix-receptor interaction, cholesterol metabolism, PI3K-Akt signaling pathway, etc. Ten herbs (Aloe, Portulacae Herba, Mori Follum, Silybum Marianum, Phyllanthi Fructus, Pollen Typhae, Ginkgo Semen, Leonuri Herba, Eriobotryae Folium, and Litseae Fructus) targeting the nine hub genes (COL1A1, MMP2, MMP9, SPP1, DNMT3B, MMP7, CETP, COL1A2, and MUC1) using six ingredients were identified as the key herbs. Quercetin and (-)-epigallocatechin-3-gallate were determined to be the key ingredients. Lastly, Ingredients-Targets, Herbs-Ingredients-Targets, and Herbs-Taste-Meridian Tropism networks were constructed using Cytoscape to elucidate this complex relationship. This study could help identify promising therapeutic targets and drugs to treat obesity. Show less

To explore the correlation of cytochrome B-245 alpha chain ( The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups ( Show less

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)-GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p~1.45 × 10 Show less

Differentiation blockade is a hallmark of acute myeloid leukemia (AML). A strategy to overcome such a blockade is a promising approach against the disease. The lack of understanding of the underlying mechanisms hampers development of such strategies. Dysregulated ribonucleotide reductase (RNR) is considered a druggable target in proliferative cancers susceptible to deoxynucleoside triphosphate (dNTP) depletion. Herein, we report an unanticipated discovery that hyperactivating RNR enables differentiation and decreases leukemia cell growth. We integrate pharmacogenomics and metabolomics analyses to identify that pharmacologically (eg, nelarabine) or genetically upregulating RNR subunit M2 (RRM2) creates a dNTP pool imbalance and overcomes differentiation arrest. Moreover, R-loop-mediated DNA replication stress signaling is responsible for RRM2 activation by nelarabine treatment. Further aggravating dNTP imbalance by depleting the dNTP hydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) enhances ablation of leukemia stem cells by RRM2 hyperactivation. Mechanistically, excessive activation of extracellular signal-regulated kinase (ERK) signaling downstream of the imbalance contributes to cellular outcomes of RNR hyperactivation. A CRISPR screen identifies a synthetic lethal interaction between loss of DUSP6, an ERK-negative regulator, and nelarabine treatment. These data demonstrate that dNTP homeostasis governs leukemia maintenance, and a combination of DUSP inhibition and nelarabine represents a therapeutic strategy. Show less

Cell experiments were implemented in this research to investigate the molecular mechanism by which H19 affected senescence of human DFs (HDFs). By conducting luciferase assay, we analyzed the relations between H19 and miR-296-5p and between miR-296-5pand IGF2. Ectopic expression and silencing experiments were performed to assess their effects on the growth and senescence of HDFs. β-Gal, DUSP6, p21, and p16 were utilized as markers for evaluating cell senescence. H19 and IGF2 were downregulated but miR-296-5p was upregulated in the aging HDFs. Mechanistic analysis showed that H19 bound to miR-296-5p to upregulate the miR-296-5p target, IGF2, and that activating the PI3K/mTOR pathway and upregulating AQP3 expression in HDFs. H19 upregulation or miR-296-5p downregulation facilitated the viability but restrained the senescence of HDFs, accompanied with reductions in the expression of cell senescence markers. Knockdown of IGF2 expression counteracted the effects induced by miR-296-5p inhibition, while inhibited PI3K/mTOR pathway reversed the impacts of IGF2 overexpression on HDFs. In summary, our data provided a novel insight into the anti-senescent mechanism of H19 in HDFs, offers a better understanding of cellular mechanisms during the process of aging. Show less

The function of long non-coding RNA (lncRNA) can be achieved through the regulation of target genes, and the deposition of fat is regulated by lncRNA. Fat has an important effect on meat quality. However, there are relatively few studies on lncRNAs in the subcutaneous adipose tissue of Duolang sheep and Small Tail Han sheep. In this study, RNA-Seq technology and bioinformatics methods were used to identify and analyze the lncRNA and mRNA in the subcutaneous adipose tissue of the two breeds of sheep. The results showed that 107 lnRNAs and 1329 mRNAs were differentially expressed. The differentially expressed genes and lncRNA target genes were significantly enriched in the biosynthesis of unsaturated fatty acids signaling pathway, fatty acid metabolism, adipocyte differentiation and other processes related to fat deposition. Among them, LOC105616076, LOC114118103, LOC105607837, LOC101116622, and LOC105603235 target FADS1, SCD, ELOVL6, HSD17B12 and HACD2, respectively. They play a key regulatory role in the biosynthesis of unsaturated fatty acids. This study lays a foundation for the study of the molecular mechanism of lncRNA on fat development, and has reference value for studying the differences in fat deposition between Duolang sheep and Small Tail Han sheep. Show less

The aim of this study was to investigate the effects of different probiotic fermented feed (PFF) on ameliorating liver fat accumulation by modulating the gut microbiota. A total of 216, 120-day-old Shaoxing ducks were divided into three groups, including the control group (basal diet), or the basal diet supplemented with 25 or 35% PFF. The results of the animal experiment showed that supplementation with PFF markedly alleviated the formation of liver and abdominal lipid droplet and decreased the levels of serum triglyceride (TG) in Shaoxing ducks. 16s rDNA showed that PFF could modulate the composition of gut microbiota, in particular, modulating the ratio of Firmicutes to Bacteroidetes. Moreover, PFF restructures the gut microbiome by reducing the abundance of Ruminococcaceae, Lachnospiraceae, and Prevotellaceae in ducks. Additionally, liver transcriptome analysis indicated that the PFF supplementation significantly downregulated the mRNA expression of peroxisome proliferator-activated receptor gamma Show less

Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion. Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL-1β, IL-17, IL-27, and IFN-γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real-time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions. CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL-1β, IL-17, IL-27, and IFN-γ, in TPE were much higher than in other pleural effusions. Moreover, CD14 CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE. Show less

Liver sinusoidal endothelial cells (LSECs) serve as sentinel cells to detect microbial infection and actively contribute to regulating immune responses for surveillance against intrahepatic pathogens. We recently reported that hepatitis B e antigen (HBeAg) stimulation could induce LSEC maturation and abrogate LSEC-mediated T cell suppression in a TNF-α and IL27 dependent manner. However, it remains unclear how HBeAg deficiency during HBV infection influences LSEC immunoregulation function and intrahepatic HBV-specific CD8 T cell responses. The function of LSECs in regulating effector T cell response, intrahepatic HBV-specific CD8 T cell responses and HBV viremia were characterized in both HBeAg-deficient and -competent HBV hydrodynamic injection (HDI) mouse models. LSECs isolated from HBeAg-deficient HBV HDI mice showed a reduced capacity to promote T cell immunity Our study underlines that HBeAg is indispensable for HBV-induced LSEC maturation to trigger intrahepatic HBV-specific T cell activation, and provides a new mechanism to elucidate the intrahepatic immune microenvironment regulation upon HBV exposure. Show less