ABSTRACT
X chromosome inactivation can balance the effects of the two X chromosomes in females, and emerging evidence indicates that numerous genes on the inactivated X chromosome have the potential to evade inactivation. The mechanisms of escape include modification of DNA, RNA, histone, epitope, and various regulatory proteins, as well as the spatial structure of chromatin. The study of X chromosome inactivation escape has paved the way for investigating sex dimorphism in human diseases, particularly autoimmune diseases. It has been demonstrated that the presence of TLR7, CD40L, IRAK-1, CXCR3, and CXorf21 significantly contributes to the prevalence of SLE (systemic lupus erythematosus) in females. This article mainly reviews the molecular mechanisms underlying these genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus. Therefore, elucidating the molecular mechanisms underlying sexual dimorphism in SLE is not only crucial for diagnosing and treating the disease, but also holds theoretical significance in comprehensively understanding the development and regulatory mechanisms of the human immune system.
Subject(s)
Lupus Erythematosus, Systemic , X Chromosome Inactivation , Female , Humans , X Chromosome Inactivation/genetics , Sex Characteristics , Lupus Erythematosus, Systemic/genetics , Chromosomes, Human, X/genetics , Immune SystemABSTRACT
To investigate the effect of chromium and iron on glucose metabolism via the PI3K/Akt/GLUT4 signaling pathway. Skeletal muscle gene microarray data in T2DM (GSE7014) was selected using Gene Expression Omnibus database. Element-gene interaction datasets of chromium and iron were extracted from comparative toxicogenomics database (CTD). Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVID online tool. Cell viability, insulin-stimulated glucose uptake, intracellular reactive oxygen species (ROS) level, and protein expression level were measured in C2C12 cells. The bioinformatics research indicated that PI3K/Akt signaling pathway participated in the effects of chromium and iron associated with T2DM. Insulin-stimulated glucose uptake level was significantly higher in chromium picolinate (Cr group) and lower in ammonium iron citrate (FA group) than that for the control group (P < 0.05); chromium picolinate + ammonium iron citrate (Cr + FA group) glucose uptake level was higher than that for the FA group (P < 0.05). Intracellular ROS level was significantly higher in the FAC group than that for the control group (P < 0.05), and that for the Cr + FA group was lower than that for the FA group (P < 0.05). p-PI3K/PI3K, p-Akt/Akt, and GLUT4 levels were significantly lower in the FA group than that for the control group (P < 0.05), and the Cr + FA group had higher levels than the FA group (P < 0.05). Chromium might have a protective effect on iron-induced glucose metabolism abnormalities through the ROS-mediated PI3K/Akt/GLUT4 signaling pathway.
Subject(s)
Ammonium Compounds , Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Reactive Oxygen Species/metabolism , Glucose/metabolism , Chromium/pharmacology , Signal Transduction , Insulin/metabolism , Diabetes Mellitus, Type 2/metabolism , Ammonium Compounds/pharmacology , Citrates/pharmacologyABSTRACT
Purpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause systemic damage to multiple organs. This study aims to analyze the value and function of IFI44 in the diagnosis and pathology of SLE by bioinformatics and immune infiltration analysis. Patients and Methods: GSE49454 and GSE65391 of SLE were obtained from the GEO dataset, and R software was employed to identify DEGs and investigate their functions. The PPI network was utilized to identify hub genes associated with SLE. CIBERSORT was used to assess differences in immune cell infiltration in SLE patients and controls. ROC curve analysis was performed to evaluate the diagnostic value of IFI44 in SLE. The expression of IFI44 in PBMCs was detected by RT-qPCR, and the correlation between IFI44 expression and SLE-related clinical indicators was analyzed. Results: A total of 65 DEGs were identified from the GSE49454 and GSE65391 databases. Through PPI analysis, IFI44 and RSAD2 were identified as significantly aberrantly expressed in SLE patients. SLE patients and controls showed a significant difference in the proportion of immune cell infiltration. IFI44 expression was positively correlated with activated DCs, monocytes, PCs, neutrophils, and activated memory CD4+T cells, while negatively correlated with M0 and CD8+T cells. The expression of IFI44 was significantly higher in SLE patients (P<0.01), especially in male patients (P=0.0376). ROC curve analysis demonstrated that IFI44 had a high diagnostic value for SLE. Correlation analysis indicated that IFI44 expression was correlated with levels of RBC, HGB, HCT, IgA, ESR, UPRO, C3, C4, and ENA in SLE patients. Conclusion: IFI44 may play a role in the pathogenesis of SLE by influencing the immune microenvironment of SLE patients, and thus has the potential to serve as a diagnostic marker and therapeutic target for SLE.
ABSTRACT
BACKGROUND: Digit ratio, especially 2D:4D, is hypothesised as a potential biological marker of exposure to intrauterine sex hormones. The aim of this study was to investigate the association between 10 SNPs of sex steroid hormone receptor (SSHR) related genes and 2D:4D. SUBJECTS AND METHODS: 814 college students were randomly selected as research participants. After taking pictures of both hands of the participants, Image Pro Plus (IPP) software was used to measure 2D:4D. ESR1 (rs2228480 and rs3798758), ESR2 (rs944459, rs8006145, rs928554, and rs8018687), GPER1 (rs10269151 and rs12702047), and PGR (rs1042839 and rs500760) were genotyped using multiplex PCR. RESULTS: Females had significantly higher 2D:4D in both hands than male students (p < 0.05), and the R2D:4D of the Han population was significantly higher than that of the Hui population (p < 0.05). The number of females carrying the GPER1 G allele of rs12702047 was significantly higher than that of males (p < 0.05). The L2D:4D in males was significantly different in rs1042839, and the R2D:4D in the Han ethnicity was significantly different in rs3798758. Logistic regression analysis showed that rs12702047 was significantly associated with 2D:4D in both hands (p < 0.05). CONCLUSIONS: GPER1 rs12702047 may be involved in the formation of digit ratio by affecting phalanx development in the Chinese population.
Subject(s)
Digit Ratios , Polymorphism, Single Nucleotide , Female , Humans , Male , Fingers/anatomy & histology , Gonadal Steroid Hormones , China , Steroids , Sex CharacteristicsABSTRACT
[This corrects the article DOI: 10.1155/2021/5547635.].
ABSTRACT
OBJECTIVE: To investigate microRNA (miRNA) expression profiles in individuals with systemic lupus erythematosus (SLE) and identify the valuable miRNA biomarkers in diagnosing and monitoring SLE. METHODS: Next-generation sequencing (NGS) was performed to assess miRNA amounts in peripheral blood mononuclear cells (PBMCs) from four SLE cases and four healthy controls. Quantitative polymerase chain reaction (qPCR) was carried out for validating candidate miRNAs in 32 SLE cases and 32 healthy controls. In addition, receiver operating characteristic (ROC) curve analysis was completed to evaluate diagnostic performance. Finally, the associations of candidate miRNAs with various characteristics of SLE were analyzed. RESULTS: A total of 157 miRNAs were upregulated, and 110 miRNAs were downregulated in PBMCs from SLE cases in comparison to healthy controls, of which the increase of miR-183-5p and decrease of miR-374b-3p were validated by qPCR and both showed good diagnostic performance for SLE diagnosis. Besides, miR-183-5p expression levels displayed a positive association with SLE disease activity index (SLEDAI) and anti-dsDNA antibody amounts. CONCLUSION: Our data indicated that miR-183-5p is a promising biomarker of SLE.
Subject(s)
Leukocytes, Mononuclear/immunology , Lupus Erythematosus, Systemic/diagnosis , MicroRNAs/blood , Adult , Antibodies, Antinuclear/blood , Biomarkers/blood , Biomarkers/metabolism , Case-Control Studies , Female , Gene Expression Profiling , Healthy Volunteers , Humans , Leukocytes, Mononuclear/metabolism , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Male , MicroRNAs/metabolism , ROC Curve , Up-Regulation/immunology , Young AdultABSTRACT
BACKGROUND Cytochrome P450 (CYP) genes are necessary for the production or metabolism of fetal sex hormones during pregnancy. The second-to-fourth digit ratio (2D: 4D) is formed in the early stage of human fetal development and considered an indicator reflecting prenatal sex steroids levels. We explored the association between 2D: 4D and single-nucleotide polymorphisms (SNPs) of CYP. MATERIAL AND METHODS Correlation analysis between 2D: 4D and 8 SNPs, rs2687133 (CPY3A7), rs7173655 (CYP11A1), rs1004467, rs17115149, and rs2486758 (CYP17A1), and rs4646, rs2255192, rs4275794 (CYP19A1), was performed using data from 426 female and 412 male Chinese university students. SNP genotyping was conducted using PCR. Digit lengths were photographed and measured by image processing software. RESULTS rs2486758 (CYP17A1) correlated with left hand 2D: 4D in men (P=0.026), and rs1004467 (CYP17A1) correlated with right hand 2D: 4D in men (P=0.008) and the whole population (P=0.032). In men, allele G rs1004467 decreased right hand 2D: 4D, while allele C of rs2486758 increased left hand 2D: 4D. In women, left hand 2D: 4D was higher in genotypes with allele A of SNP rs4646 (CYP19A1) under the dominant genetic model; female DR-L was higher in genotypes with allele T of rs17115149 (CYP11A1). SNPs rs2687133 (CYP3A7) and rs1004467 (CYP17A1) were significantly correlated with right hand 2D: 4D (P=0.0107). CONCLUSIONS SNPs rs1004467 and rs2486758 of CYP17A1 are significant in the relationship between 2D: 4D and CYP gene polymorphisms under different conditions. SNP interactions between CYP genes probably impact 2D: 4D. The correlation between 2D: 4D and some sex hormone-related diseases may be due to the effect of CYP variants on the 2 phenotypes.
Subject(s)
Cytochrome P-450 Enzyme System , Fingers , Female , Humans , Male , Young Adult , Alleles , Aromatase/genetics , Asian People/genetics , Case-Control Studies , China , Cholesterol Side-Chain Cleavage Enzyme/genetics , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 Enzyme System/genetics , Fingers/anatomy & histology , Gene Frequency/genetics , Genetic Association Studies/methods , Genotype , Polymorphism, Single Nucleotide/genetics , Steroid 17-alpha-Hydroxylase/genetics , Students , UniversitiesABSTRACT
Background: The role of T cell Ig and ITIM domain (TIGIT) and programmed cell death-1 (PD-1) in colorectal cancer (CRC) with mismatch repair deficiency is unknown.Methods: This was a study of 60 CRC patients with mismatch repair deficiency and 30 healthy controls between June 2015 and October 2015.Results: The expression of Foxp3, PD-1, and TIGIT was higher in cancer tissues compared with adjacent mucosa (all P < .05). Patients with advanced TNM stage had a significantly higher expression of TIGIT (P = .025) and PD-1 (P = .020) than patients with early-stage CRC. The disease-free survival (DFS) of patients with high TIGIT (HR = 3.96, 95%CI: 1.34-11.69, P = .013) or PD-1 (HR = 214.8, 95%CI: 49.88-925.2, P < .001) expression were better. The overall survival (OS) of the patients with CRC and high expression of PD-1 was worse than those with low expression (HR = 4.01, 95%CI:1.26-12.69, P = .019).Conclusion: TIGIT and PD-1 are upregulated in CRC with mismatch repair deficiency and associated with TNM stage and DFS.
Subject(s)
Brain Neoplasms/immunology , Colorectal Neoplasms/immunology , Neoplastic Syndromes, Hereditary/immunology , Programmed Cell Death 1 Receptor/immunology , Receptors, Immunologic/immunology , Brain Neoplasms/blood , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Case-Control Studies , Colorectal Neoplasms/blood , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Cytokines/blood , Forkhead Transcription Factors/genetics , Humans , Kaplan-Meier Estimate , Neoplastic Syndromes, Hereditary/blood , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/mortality , Programmed Cell Death 1 Receptor/genetics , Receptors, Immunologic/genetics , T-Lymphocytes/immunology , Up-RegulationABSTRACT
Treatment of human estrogen receptor (ER)positive breast cancer (ER+ BC) using conventional chemotherapy remains a challenge and is often ineffective as a result of tumor metastasis. The present study aimed to investigate the ability of narasin, an ionophore antibiotic, to potentially inhibit tumor metastasis and growth in human ER+ BC. Narasin was found to have significant inhibitory abilities on cell proliferation, migration and invasion in ER+ BC cell lines MCF7 and T47D compared with the triplenegative BC cell MDAMB231. For the in vivo studies, narasin effectively decreased the number of tumor metastasis nodules, tumor volume and weight without apparent toxicity in human MCF7 nude mouse left ventricle injection tumor metastasis and xenograft models. Mechanistically, it demonstrated that exposure to TGFß or IL6 induced the expression of epithelialmesenchymal transition (EMT) markers in ER+ BC cell lines. On the contrary, narasin dosedependently reversed EMT by increasing the expression of Ecadherin and decreasing the expression of Ncadherin, vimentin, ßcatenin and zinc finger Eboxbinding homeobox 1 at the protein and gene expression levels. Gene microarray, molecular docking and western blotting were performed to demonstrate that those protein and gene expression levels are regulated by the inactivation of the TGFß/phosphorylated (p)SMAD3 and IL6/pSTAT3 signaling pathways. Taken together, these findings indicated that narasin may be a promising candidate that can be further optimized for the treatment of human ER+ BC.
Subject(s)
Breast Neoplasms/drug therapy , Estrogen Receptor alpha/metabolism , Pyrans/pharmacology , Animals , Breast Neoplasms/metabolism , Cadherins/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , China , Epithelial-Mesenchymal Transition/drug effects , Estrogen Receptor alpha/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Interleukin-6/metabolism , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Docking Simulation , Neoplasm Metastasis/drug therapy , Pyrans/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Smad3 Protein/metabolism , Transforming Growth Factor beta/metabolism , Xenograft Model Antitumor AssaysABSTRACT
Long noncoding RNAs (lncRNAs) are a class of functional non-coding transcripts that are longer than 200 nt and regulate gene expression via diverse mechanisms in eukaryotes. In fact, they have emerged as critical epigenetic and transcriptional regulators of autophagy in mammals in response to various stressors. Autophagy not only plays a crucial role in maintaining cellular homeostasis, but it is also essential to immunity, targets intracellular pathogens for degradation, modulates inflammation, and participates in adaptive immune responses. However, the expression profile of lncRNA and its role in regulating autophagy in macrophages have been poorly defined. Here, we used transcriptomic and bioinformatics to analysis LncRNA expression profile during autophagy and functional studies to evaluate the function of the metastasis-associated lung adenocarcinoma transcript-1 (Malat1) lncRNA in macrophages. A total of 1112 putative lncRNAs (240 novel lncRNAs) were identified, including 831 large intergenic, 129 intronic, and 152 anti-sense lncRNA, of which 59 differentially expressed transcripts exhibited a greater than 1.5-fold change under different conditions. The interaction of Malat1 lncRNA with microRNA (mir)-23-3p and lysosomal-associated membrane protein 1 (Lamp1) was found, Malat1 releases inhibition of Lamp1 expression in macrophages through competitive adsorption of mir-23-3p. The results of this study provide a better understanding of lncRNA function in macrophages and a basis for further investigation into the roles and mechanisms of ncRNA in immunology, particularly the functions of Malat1 and mir-23-3p in the pathogenesis of macrophages.
Subject(s)
Autophagy/genetics , Lysosomal Membrane Proteins/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Animals , Computational Biology , Mice , MicroRNAs/genetics , RAW 264.7 Cells , RNA-SeqABSTRACT
Autophagy plays an important role in the fight against Mycobacterium tuberculosis infection. Massive researches proved that miRNAs could be the regulators of autophagy, which implied miRNAs could favor MTB invasion or latent infection. In our study, multiple bioinformatics databases and software were used to seek and lock the miRNAs associating with regulation of autophagy. Notably, a novel miR-129-3p was found and its target gene Atg4b showed grand potential in mediation of autophagy. Moreover, BCG infection triggered miR-129-3p overexpression in RAW264.7 cells. Up-regulation of miR-129-3p decreased mRNA or protein level of Atg4b and resulted in the inhibition of autophagy. The antagomir of miR-129-3p had the opposite impact. The LC3 puncta formation in RAW264.7 cells were also affected after transfection of miR-129-3p mimic or antagomir. The mRFP-GFP-LC3 analysis indicated that mimic of miR-129-3p impaired autophagic flux while antagomir improved autophagy. The CFU assay results showed that miR-129-3p promoted the intracellular survival of BCG in macrophages. Consequently, these data suggested that miR-129-3p could favor MTB survival by inhibiting autophagy via Atg4b.
Subject(s)
Autophagy-Related Proteins/metabolism , Autophagy/genetics , Cysteine Endopeptidases/metabolism , MicroRNAs/genetics , 3' Untranslated Regions/genetics , Animals , Autophagy-Related Proteins/genetics , BCG Vaccine/therapeutic use , Computational Biology/methods , Cysteine Endopeptidases/genetics , Gene Expression Regulation/genetics , HEK293 Cells , Humans , Mice , MicroRNAs/metabolism , Mycobacterium tuberculosis/pathogenicity , Phagosomes/metabolism , RAW 264.7 Cells , RNA, Messenger/metabolism , Tuberculosis/drug therapy , Tuberculosis/genetics , Tuberculosis/prevention & controlABSTRACT
Mice immunized with recombinant Echinococcus granulosus antigens Eg10 and Eg mMDH do not show elevated resistance to E. granulosus infection but show aggravated infection instead. To gain a deeper insight in the immune tolerance mechanisms in mice immunized with Eg10 and Eg mMDH, this study simulated the immune tolerance process in vitro by culturing bone marrow-derived dendritic cells (BMDCs) in the presence of Eg10 or Eg mMDH. Scanning electron microscopy revealed that Eg10- and Eg mMDH-treated DCs exhibited immature cell morphology, while addition of LPS to the cells induced changes in cell morphology and an increase in the number of cell-surface protrusions. This observation was consistent with the increased expression of the cell-surface molecules MHCII and CD80 in Eg10- and Eg mMDH-treated DCs pretreated with LPS. DCs exposed to the two antigens had a very weak ability to induce T-cell proliferation, but could promote the formation of Treg cells. Introduction of the indoleamine 2,3-dioxygenase (IDO) inhibitor, 1-methyl tryptopha (1-MT) enhanced the ability of the antigens to induce T cells and inhibited the induction of Treg cells. Eg mMDH-treated DCs showed a strong response to 1-MT: the DCs had high mRNA levels of IDO, IL-6, and IL-10, while 1-MT decreased the expression. In contrast, DCs treated with Eg10 did not show significant changes after 1-MT treatment. Eg mMDH inhibited DC maturation and promoted IDO expression, which, on the one hand, decreased the ability of DCs to induce T-cell proliferation, resulting in T-cell anergy, and on the other hand, induced the formation of Tregs, resulting in an immunosuppressive effect. In contrast, the escape mechanisms induced by Eg10 did not primarily depend on the IDO pathway and might involve other mechanisms that need to be further explored.
Subject(s)
Antigens, Helminth/immunology , Bone Marrow Cells/immunology , Dendritic Cells/immunology , Echinococcosis/immunology , Immune Tolerance , T-Lymphocytes, Regulatory/immunology , Animals , Antigens, Helminth/genetics , Antigens, Helminth/pharmacology , Bone Marrow Cells/pathology , Cell Proliferation/drug effects , Dendritic Cells/pathology , Echinococcosis/pathology , Echinococcus granulosus , Male , Mice , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/pharmacology , T-Lymphocytes, Regulatory/pathologyABSTRACT
Background: Genome-wide association studies identified several genomic regions associated with the risk of chronic obstructive pulmonary disease (COPD), including the 4q22 and 15q25 regions. These regions contain the FAM13A and IREB2 genes, which have been associated with COPD but data are lacking for Chinese patients. The objective of the study was to identify new genetic variants in the FAM13A and IREB2 associated with COPD in Northwestern China. Methods: This was a case-control study performed in the Ningxia Hui Autonomous Region between January 2014 and December 2016. Patients were grouped as COPD and controls based on FEV1/FVC<70%. Seven tag single-nucleotide polymorphisms (SNPs) in the FAM13A and IREB2 genes were genotyped using the Agena MassARRAY platform. Logistic regression was used to determine the association between SNPs and COPD risk. Results: rs17014601 in FAM13A was significantly associated with COPD in the additive (odds ratio [OR]=1.36, 95% confidence interval [CI]: 1.11-1.67, P=0.003), heterozygote (OR=1.76, 95% CI: 1.33-2.32, P=0.0001), and dominant (OR=1.67, 95% CI: 1.28-2.18, P=0.0001) models. Stratified analyses indicated that the risk was higher in never smokers. rs16969858 in IREB2 was significantly associated with COPD but in the univariate analysis only, and the multivariate analysis did not show any association. Conclusion: The results suggest that the new variant rs17014601 in the FAM13A gene was significantly associated with COPD risk in a Chinese rural population. Additional studies are required to confirm the role of this variant in COPD development and progression.
Subject(s)
GTPase-Activating Proteins/genetics , Iron Regulatory Protein 2/genetics , Polymorphism, Single Nucleotide , Pulmonary Disease, Chronic Obstructive/genetics , Adult , Case-Control Studies , China , Female , Genetic Predisposition to Disease , Genetic Variation , Genome-Wide Association Study , Humans , Male , Middle Aged , Non-Smokers , Prospective Studies , Pulmonary Disease, Chronic Obstructive/physiopathology , Rural Population , SmokersABSTRACT
OBJECTIVES: Digit ratio, especially the second-to-fourth digit ratio (2D:4D), is a proxy indicator for prenatal exposure and sensitivity to sexual hormones which may influence the susceptibility to certain cancers. The aim of the present study was to investigate whether there is a possible association between 2D:4D and gastric cancer (GCA) in north Chinese women. METHODS: Photographs of the left and right hands of 167 women (controls: 113; patients: 54) were collected. Left hand, right hand, and right minus left hand (Dr-l) 2D:4D were analyzed and compared. RESULTS: The GCA group presented significantly lower 2D:4D than controls (left: P < .01; right: P < .05). No significant difference was observed in Dr-l between the two groups. In patients, there were no correlations between 2D:4D and age at GCA or tumor staging. CONCLUSIONS: Decreased 2D:4D (especially of the left hand) may suggest a higher prenatal testosterone (lower prenatal estrogen) exposure in north Chinese women with GCA.
Subject(s)
Fingers/anatomy & histology , Stomach Neoplasms/physiopathology , Adult , Aged , Asian People , Case-Control Studies , Female , Humans , Middle AgedABSTRACT
Heroin abuse is linked to a deleterious effect on cognitive functioning in the individual. Recent evidences suggest that the serotonin7 receptor (5-HT7R) is engaged in the regulation of cognitive control and the drug use-associated behaviors. However, the role of 5-HT7R in the cognitive control after acute heroin administration has not been studied. The present study aims to investigate whether the knockdown of the 5-HT7R by virus-mediated gene silencing in the medial prefrontal cortex (mPFC) could ameliorate the acute heroin-induced cognitive impairments. The attentional function, impulsivity and compulsivity were assessed by the 5-choice serial reaction time task (5-CSRTT) in mice. The memory ability and locomotor activity were examined by the novel objects recognition (NOR), Y-maze and open-field test (OFT). Acute heroin administration at 5â¯mg/kg produced robust disruptions in attention, impulsivity and motivation in mice. 5-HT7R knockdown in the mPFC did not affect the 5-CSRTT baseline performance, spatial working memory, visual episodic memory and locomotion. However, mPFC 5-HT7R knockdown selectively ameliorated acute heroin-induced increase in omissions and premature responses under conditions of increased perceptual load. In addition, mPFC 5-HT7R knockdown induced increases in perseverative responding observed across both saline and heroin-treated animals. Moreover, 5-HT7R knockdown prevented the heroin-induced decrease in NR1/CaMKII phosphorylation in mPFC, thus suggesting that 5-HT7R and N-methyl-d-aspartic acid (NMDA) receptor signaling may be involved in the cognitive outcomes of acute heroin administration. Altogether, these observations suggest modest and restricted effects of mPFC 5-HT7R knockdown on cognitive behaviors, both in the presence or absence of acute heroin treatment.
Subject(s)
Analgesics, Opioid/administration & dosage , Cognition/drug effects , Heroin/administration & dosage , Prefrontal Cortex/drug effects , Receptors, Serotonin/deficiency , Animals , Choice Behavior/drug effects , Choice Behavior/physiology , Exploratory Behavior/drug effects , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Locomotion/drug effects , Locomotion/genetics , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microinjections , RNA, Messenger/metabolism , RNA, Small Interfering/pharmacology , Reaction Time/drug effects , Receptors, Serotonin/geneticsABSTRACT
INTRODUCTION: Digit ratio, especially second-to-fourth digit ratio (2D:4D) is used as a biomarker of prenatal testosterone exposure and was found associated with physical ability, such as handgrip strength (HGS). Recently, this association has been discussed in several ethnic groups. AIMS: To investigate correlations between 2D:4D and HGS in Chinese population of Ningxia Hui ethnicity. METHODS: Here we firstly present the evidence on digit ratio and HGS of 346 college students (119 males and 227 females) by collecting photographs and HGS of both hands at Yinchuan city, in the Ningxia province of China. RESULTS: Females have higher mean values of digit ratio than males; significant variances of 3D:5D (left and right: P<0.05), 2D:3D, 3D:4D (left and right: P<0.01) and 2D:4D, 2D:5D (left and right: P<0.001) were found between different sex. Males showed significantly greater HGS than females on both hands. 2D:4D of both hands were significantly negative correlated with HGS in females (but not in males). CONCLUSIONS: 2D:4D ratio is negatively correlated with HGS in a Chinese population (especially in females) of Ningxia Hui ethnicity.
Subject(s)
Fingers/growth & development , Hand Strength , Adolescent , Asian People , Female , Fingers/anatomy & histology , Humans , Male , Sex Factors , Testosterone/blood , Young AdultABSTRACT
BACKGROUND: In humans, the relative lengths of the index finger to the ring finger (2D:4D) is a sexually dimorphic trait which correlated with prenatal sex steroids and has been increasingly used as a promising tool to evaluate the impact of prenatal hormone exposure in some traits, such as physical performance. Handgrip strength (HGS) is one potent index of physical ability and its relationship with 2D:4D ratio has been discussed in several ethnic groups. AIMS: To investigate whether there is a correlation between 2D:4D ratio and HGS in Chinese college students of Ningxia Han ethnicity. METHODS: 608 students (211 males and 397 females) of Han ethnicity were recruited from Ningxia medical university. Photocopies and HGS of both hands were collected at Yinchuan city, in the Ningxia province of China. RESULTS: Sexual dimorphism of 2D:4D and HGS were found, males had significantly lower 2D:4D and greater HGS than females. 2D:4D in both hands were significantly negative correlated with HGS in females and not in males. CONCLUSIONS: 2D:4D ratio is negative correlated with HGS in a Chinese population of Ningxia Han ethnicity and this association should be considered on the anthropological research within an evolutionary concept in the future.
Subject(s)
Fingers/anatomy & histology , Hand Strength , Sex Characteristics , Adolescent , China , Female , Fingers/growth & development , Fingers/physiology , Humans , Male , Young AdultABSTRACT
BACKGROUND: Prenatal gonadal hormones may play a major role in pathogenesis of schizophrenia. It has been reported that second to fourth digit ratio (2D:4D) was influenced by the levels of exposure to prenatal testosterone and estrogen. So, 2D:4D may help to predict the disease susceptibility to schizophrenia. AIMS: The aim of this study was to investigate the relationship between the digit ratio (2D:4D) and schizophrenia in Chinese population. METHODS: We recruited 178 schizophrenics (males: 76; females: 102) and 365 controls (males: 218; females: 147) in this study. Photocopies of both hands were collected and left hand, right hand, mean hand and left minus right hand (DL-R) 2D:4D were analyzed. RESULTS: The right and mean hand 2D:4D ratios were significantly higher in schizophrenics compared to that of controls in both males and females. The left hand 2D:4D ratio in female schizophrenics was also significantly higher than in controls. Compared to controls, the DL-R 2D:4D in male schizophrenics was obviously higher. There was a weakly (but not significantly) negative correlation between the mean hand 2D:4D ratio and the age of onset. CONCLUSIONS: The 2D:4D ratio may correlate with the schizophrenia in Chinese population, and it may be an indicator of schizophrenia.
Subject(s)
Fingers/growth & development , Schizophrenia/epidemiology , Adult , Case-Control Studies , China , Female , Fingers/anatomy & histology , Humans , Male , Middle Aged , Sex FactorsABSTRACT
INTRODUCTION: Sex steroid exposure during human development may influence disease susceptibility. Second to fourth digit ratio (2D:4D) is thought to be a putative biomarker for prenatal hormone level during foetal life. Recently there has been a great deal of interest in 2D:4D and risk of disease in adulthood. METHODS: We explored the relationship between 2D:4D ratio and coronary heart disease. Photocopies of the two hands of 310 males (controls: 155; patients: 155) were collected at Yin chuan city, in the Ningxia province of China. Left hand, right hand, mean hand and right minus left 2D:4D (Dr-l) were analysed. RESULTS: The mean values of 2D:4D ratio in patients were higher than those of CSIN controls. The patients showed significantly higher 2D:4D (left hand: P < 0.01; right hand, mean hand: P < 0.05) than controls. In patients, 2D:4D (especially left hand 2D:4D) were inversely associated with age at diagnosis (left hand: P < 0.001; right hand, mean hand: P < 0.05). No association between Dr-l and age or age at presentation of disease was observed in the groups. CONCLUSION: 2D:4D may correlate particularly with risk of coronary heart disease in Chinese men.
Subject(s)
Coronary Disease/etiology , Fingers , Sex Characteristics , Adult , Aged , China , Humans , Male , Middle Aged , Risk AssessmentABSTRACT
BACKGROUND: Coronary artery disease (CAD) is an enormous health problem in the world. Dermatoglyphs are cutaneous ridges on the fingers, palms, and soles, formed by genetic regulation and control during early intrauterine life. The Dermatoglyphic traits do not change significantly as the growth of the age. They may be the phenotypic characters of individual genes and represent the predisposition to certain diseases. AIMS AND OBJECTIVES: The study was carried out to document characteristic dermatoglyphic patterns in coronary artery disease which could be useful in early diagnosis of the disease. MATERIALS AND METHODS: Dermatoglyphic study of 258 male (129 coronary artery disease cases and 129 normal subjects) of Ningxia China were studied in the present cross-sectional study. It involved the digital patterns, ATD angles, A-B ridge counts on the hands. Chi-square test, t-test were used for the statistical analysis in this study. RESULTS: The overall frequency of whorls was higher followed by loop and arch in both two groups. It was observed that there was significant difference of digital frequency of whorls and ulnar loops in patients in both hands as compared to controls (p≤0.01). The mean value of finger ridge counts, total ridge counts were similar between two groups. The A-B ridge counts were significantly higher in coronary artery disease compared with controls on the right palm (p≤0.01). However, the mean ATD angle values were significantly higher in cases than those of in normal on both hands (p<0.05). CONCLUSION: Abnormally high A-B ridge count, ATD angles and the frequency of whorls are characteristic dermatoglyphic patterns of coronary artery disease. Dermatoglyphics may have an important role in early diagnosis of coronary artery disease in future.