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Aims: Exploring key genes and potential molecular pathways of ferroptosis in immunoglobulin A nephropathy (IgAN). Methods: The IgAN datasets and ferroptosis‐related genes (FRGs) were obtained in the Gene Expression Omnibus (GEO) and FerrDb database. Differentially expressed genes (DEGs) were identified using R software and intersected with FRGs to obtain differentially expressed FRGs (DE‐FRGs). After that, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis (PEA) and Gene Ontology (GO) functional annotation were performed on DE‐FRGs. In the Search Tool for the Retrieval of Interacting Genes (STRING) website, we construct a protein–protein interaction (PPI) network. The PPI network was further investigated with screening hub genes with Cytoscape software. The core genes were then subjected to gene set enrichment analysis (GSEA). Finally, the samples were analyzed for immune infiltration in R, and the correlation between hub genes and immune cells was analyzed. Results: A total of 347 DEGs were identified. CD44, CDO1, CYBB, IL1B, RRM2, AKR1C1, activated transcription factor‐3 (ATF3), CDKN1A, GDF15, JUN, MGST1, MIOX, MT1G, NR4A1, PDK4, TNFAIP3, and ZFP36 were determined as DE‐FRGs. JUN, IL1B, and ATF3 were then screened as hub genes. GSEA and immune infiltration analysis revealed that the hub genes were closely associated with immune inflammatory responses such as NOD‐like receptor signaling, IL‐17 signaling, and TNF signaling. Conclusions: Our results show that JUN and ATF3 are possibly critical genes in the process of IgAN ferroptosis and may be related with immune cell infiltration. [ABSTRACT FROM AUTHOR]

Objectives Febrile seizure is a neuroinflammatory disease involving feverinduced seizures affecting children in the early stages of life. TNFα is a pro-inflammatory cytokine reported to be elevated in FS. Specific promoter variants of TNFα could be associated with its elevated cytokine expression and susceptibility to FS. The present study analyzed the association of specific TNFα variants, including TNFα -238 G/A (a genetic variant; G: Guanine, A: Adenine) (rs361525), TNFα -308 G/A (rs1800629), and TNFα -376 G/A (rs1800750) promoter polymorphisms, with FS susceptibility, and TNFα serum levels in an Iranian population. Materials & Methods Sixty-eight FS patients and 136 controls were enrolled. The SSPPCR method was utilized to analyze TNFα promoter genotypes. This research also confirmed the genotyping results by sequencing samples of ten patients and normal controls. Results The GG (a genetic sequence; G: Guanine) genotype of -238 SNP was associated with the increased risk of FS [OR = 12.65, 95% CI (2.83-56.60), P-value = 0.0012]. The AA (a genetic sequence; A: Adenine) genotype in the-308 region was increased in patients with FS and associated with the disease [OR = 4.62, 95% CI (1.46-14.56), P-value = 0.028]. The increased occurrence of heterozygous AG in the -376 SNP among control groups has been linked to a decreased risk of FS [OR = 0.22, 95% CI (0.11-0.43), P-value = 0.0001]. This study revealed that AGA (a genetic sequence; G: Guanine, A: Adenine) (-238/ -308/ -376) haplotype with the highest frequency in controls was associated with a decreased risk of FS, while GAA (a genetic sequence; G: Guanine, A: Adenine) (-238/ -308/ -376) carriers were more susceptible to FS. Conclusion The current study suggested that TNFα gene promoter variants at rs361525, rs1800629, and rs1800750 could be associated with the susceptibility to FS and altered serum levels of TNFα. [ABSTRACT FROM AUTHOR]

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organs significantly impacts morbidity and mortality. The development of SLE is influenced by genetic predisposition and dysregulated immune response. Our objective was to investigate miR-21, IL-10, and PDCD4 expression in SLE patient plasma and analyze their correlations and potential diagnostic and prognostic values. Methods: The study included 100 healthy subjects, 50 newly diagnosed (ND), and 50 under-treatment (UT) SLE patients. The patients were observed for 24 weeks to track relapses. miR-21 and PDCD4 gene expression levels were measured using real-time RT-PCR, and IL-10 production was measured using ELISA. Results: miR-21 and IL-10 expression levels were significantly greater in SLE patients than in healthy subjects, with the highest levels observed in ND patients. PDCD4 expression was also significantly greater in SLE patients than in subjects, with the highest levels observed in UT patients. ROC curve analyses and Cox-Mantel Log-rank tests indicated miR-21, PDCD4, and IL-10 as proper diagnostic and prognostic biomarkers for SLE. The study also revealed a significant positive correlation between miR-21 and PDCD4 and IL-10 levels in SLE patients. Conclusions: The studies suggest that dysregulation of miR-21, PDCD4, and IL-10 in patients with SLE may contribute to disease development and provides new diagnostic and prognostic markers. Additionally, the observed correlation between miR-21, PDCD4, and IL-10 levels in SLE patients signifies a potential interplay between these molecules. [ABSTRACT FROM AUTHOR]

Psoriasis (PS) is characterized by hyperplasia of epidermis and infiltration of immune cells in the dermis. A negligible susceptibility of hypodermic permeation for local anti-inflammatory remedies is one of the major causes of medication failures. Although curcumin (CUR) has indicated effectiveness in treatment of inflammation, its successful permeation through the stratum corneum is yet a challenging issue. Therefore, niosome (NIO) nanoparticles were used as curcumin carriers to enhance its delivery and anti-inflammatory effects. Curcumin-niosome (CUR-NIO) formulations were constructed by the thin-film-hydration (TFH) technique and were added to hyaluronic acid and Marine-collagen gel-based formulation. Five mild-to-moderate PS patients (18–60 years) with PASI scores < 30 with symmetrical and similar lesions were included in the study. The prepared formulation (CUR 15 µM) was topically administered for 4 weeks on the skin lesions, in comparison to the placebo. Clinical skin manifestations were monitored and skin punches were obtained for further gene expression analyses. There was a significant reduction in redness, scaling, and an apparent improvement in CUR-NIO-treated group in comparison to the placebo-treated counterpart. The gene expression analyses resulted in significantly downregulation of IL17, IL23, IL22, and TNFα, S100A7, S100A12, and Ki67 in CUR-NIO-treated lesions. Consequently, CUR-NIO could provide therapeutic approaches for the patients with mild-to-moderate PS by suppressing the IL17/IL23 immunopathogenic axis. [ABSTRACT FROM AUTHOR]

Purpose: 1,25-dihydroxyvitamin D3 may regulate adipogenesis in adipocytes in-vitro, but little is known about possible molecular mechanisms related to the inhibitory effect of 1,25-dihydroxyvitamin D3 on adipogenesis in humans҆ adipose tissue. Methodology: In this study, human adipose-derived mesenchymal stem cells (hASCs) were cultured for 14 days in adipogenic differentiation media containing concentrations of 1,25-dihydroxyvitamin D3 (10−10–10−8 M). The extent of adipogenic differentiation in ASCs was assessed by Oil Red O staining and quantitative polymerase chain reaction (PCR) to determine expression levels of key adipogenic markers. Results: Our results showed that vitamin D receptor (VDR), as a mediator of most actions of 1,25-dihydroxyvitamin D3, glucose trasporter-4 (GLUT4),and fatty acid binding protein-4 (FABP4) was expressed in vitamin D-treated hASCs. However, the protein level of these markers was lower than the control group. Treatment of human preadipocytes with 1,25-dihydroxyvitamin D3 significantly altered expression of adipogenic markers and triglyceride accumulation in a dose-dependent manner. 1,25-dihydroxyvitamin D3 at concentration of 10−8 M enhanced expression of sterol regulatory element-binding protein-1c (SREBP1c), CCAAT-enhancer-binding protein-β (C/EBPβ), a mitotic clonal expansion, peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FASN), a marker of de novo lipogenesis,and lipoprotein lipase (LPL). Conclusion: Our findings revealed that 1,25-dihydroxyvitamin D3 may provoke adipocyte development in critical periods of adipogenesis at concentration of 10−8 M, thereby leading to a greater risk of obesity in adulthood and an augmented risk of obesity-related diseases including diabetes, cardiovascular diseases, and some cancers. [ABSTRACT FROM AUTHOR]

Background: Relapses and flares with delayed wound healing are among the main symptoms of systemic lupus erythematosus (SLE), a rheumatic autoimmune disease. The orientation of immune responses in SLE disease depends on the function of the population of macrophages. This study investigated the effect of indole-3-carbinol (I3C) on transcriptional profiling of macrophage-derived monocytes (MDMs) in four stages of the wound-healing process. Methods: In the first phase of study, MDMs were generated from peripheral blood mononuclear cells of three new SLE cases (unmedicated) and two healthy controls. The cases and controls were then divided into I3C treated and untreated groups after 24 hours of exposure to I3C. Single-end RNA sequencing was performed using an Illumina NextSeq 500 platform. After comprehensive analysis among differentially expressed genes, CDKN1A, FN1 and MMP15 were validated by quantitative real-time polymerase chain reaction as upregulated ranked genes involved in wound-healing stages. Results: The RNA sequencing analysis of treated cases and treated controls versus untreated cases and untreated controls (group 3 vs. group 4) revealed upregulation of various genes, for example: C1S, C1R, IGKV1-5, IGKV4-1, SERPING1, IGLC1 and IGLC2 in coagulation; ADAM19, CEACAM1 and CEACAM8 in M2 reprogramming; IRS1, FN1, THBS1 and LIMS2 in extracellular matrix organization; and STAT1, THBS1 and ATP2A3 in the proliferation stage of wound healing. Conclusions: The results showed that treatment with I3C could modulate the gene expression involved in wound healing in SLE cases and healthy controls. [ABSTRACT FROM AUTHOR]

Background: Daunorubicin (DNR) is capable of killing the human acute myeloid leukemia cells through apoptosis or necrosis with arresting cell cycle and various mechanisms. The response of AML cells to DNR associated with defect and or defiance in survival has been a consideration subject. Objectives: We have represented the transcription gene profile of some critical prosurvival proteins by qRT - PCR, including osteopontin (OPN), AKT1, mTOR, β - catenin, and NF - kB/RelB. Methods: The U937 cells were treated with DNR with clinically achievable concentrations for MTT assay, annexin V (AV) /Propidium iodide (PI), and cell cycle analysis. QRT - PCR was performed, using primers of OPN, NF - kB/RelB, AKT1, mTOR, PTEN, and β - catenin. Results: The AV/PI assay displayed that DNR - induced death in cells was a dose - dependent and necrotic manner. Cell cycle distribution following treatment with DNR exhibited a relatively lower chromatin of S phase than untreated cells. OPN gene expression was significantly attenuated. NF - kB/RelB, mTOR, β - catenin, as well as PTENgenes showed unchanged or non - significant increase in expression. However, AKT1increased significantly. Conclusions: U937 sensitivity to DNR could be due to the targeting of anti-apoptotic proteins in the transcriptional stages. The decrease in OPNlevels appears to play a significant role in the death of the observed by DNR. [ABSTRACT FROM AUTHOR]

Objective(s): Current acute myeloid leukemia (AML) therapeutic strategies have irreversible sideeffects. Berberine (BBR) is an isoquinoline alkaloid, which has been known as an aryl hydrocarbon receptor (AhR) ligand. AhR is a cytoplasmic receptor, which is involved in the regulation of cellular and immune responses. Here, we investigated the expression profile of genes involved in the cell cycle and different cytokines upon BBR-mediated AhR activation on AML THP-1 cell line. Materials and Methods: THP-1 cells and normal monocytes were treated with different concentrations of BBR (10 µM, 25 µM, 50 µM, and 100 µM) for 24 and 48 hr. The cell viability was measured by MTT assay. Real-time RT-PCR was conducted to evaluate the expression of AhR, cytochrome P450 1A1 (CYP1A1), interleukin 1 beta (IL1ß), p21, p27, cyclin-dependent kinase 2 (CDK2) and p53. Cellular expression of AhR was also assessed using immunofluorescence method. ELISA was used to determine the level of IL-10 and IL-12 cytokines. Results: BBR inhibits the proliferation of THP-1 cells in a dose- and time-dependent manner with minimal toxicity on normal monocytes. Phorbol 12-myristate 13-acetate (PMA) treatment increased the cellular expression of AhR. The AhR target genes (CYP1A1, IL1ß) were overexpressed upon BBR treatment. BBR downregulated Cdk2 and upregulated p21, p27 and p53 genes in THP-1 cells. IL-10 was significantly increased upon BBR treatment, while IL-12 was not significantly changed in all combinations. Conclusion: BBR could be introduced as an effective chemotherapeutic agent against AML by giving rise to the expression of CDK inhibitors and anti-inflammatory cytokines and downregulation of CDK2. [ABSTRACT FROM AUTHOR]

The article focuses on the use of the concentration of Indoleamine 2, 3-dioxygenase (IDO) and systemic lupus erythematosus (SLE) in determination of disease severity in SLE patients. Topics discussed include control of (1T helper) Th1-dependent immune responses by Interferon-γ (IFN-γ); use of peripheral blood mononuclear cells (PBMCs) for isolation of total RNA with Biozol; and use of IDO as suitable determinant and potential biomarker for the disease activity along with IFN-γ.

Background: Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood. Materials and Methods: In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis. Results: Our analysis revealed a gene signature with 406 genes that are up or down-regulated in APL. The pathway analysis determined that MAPK pathway and its involved elements such as JUN gene and AP-1 play important roles in APL pathogenesis along with insulin-like growth factor-binding protein-7. Conclusions: The results of this meta-analysis could be useful for developing more effective therapy strategies and new targets for diagnosis and drugs. [ABSTRACT FROM AUTHOR]

This study examined the influence of drought stress during the flowering stage of 2 canola cultivars on some physiological characteristics, antioxidant activities, and gene expression of antioxidant enzymes. Significant differences were observed among interactions of cultivars and levels of drought stress in total shoot dry material, relative water content percentage, proline, carbohydrates, gene expression, and activities of antioxidant enzymes. Moreover, a significant positive correlation was indicated between shoot dry materials with relative water content percentage, sucrose, catalase activity, ascorbate peroxidase activity, and cytosolic ascorbate peroxidase relative gene expression ratio. Antioxidant enzymatic activity and the association between gene transcript levels and activity seem to play roles in protecting plants from oxidative damage in drought stress. The lowest ascorbate peroxidase activity was measured under normal conditions in the cultivar Option (409 nmol ascorbate oxidation per min/g protein), and the highest ascorbate peroxidase was observed in RGS003 (600 nmol ascorbate oxidation per min/g protein) in high stress. Additionally, in the case of relative gene expression ratio the lowest cytosolic ascorbate peroxidase was observed under normal conditions in Option (1.05), and the highest cytosolic ascorbate peroxidase was seen in RGS003 (1.48) in high stress. According to the results of the current study, RGS003 seems to be more tolerant than Option. [ABSTRACT FROM AUTHOR]

Background: Recent evidence indicates that the PVT1, CCDC26, and CCAT1 long noncoding RNAs (lncRNAs) are involved in the leukemogenic process. This study quantified the expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs in patients with acute myeloid leukemia (AML) and also correlated their expression levels with the clinicopathological features of the patients. Materials and Methods: The expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs were analyzed using quantitative reverse transcription–polymerase chain reaction of bone marrow specimens obtained from 86 AML patients, 48 AML-M3 patients, and 40 normal controls. Results: No differences were found between the combined AML patient populations and the healthy controls with respect to the expression levels of PVT1, CCDC26, and CCAT1 (p = 0.35, p = 0.09, and p = 0.77, respectively). However, compared with the controls, the AML-M3 patients had higher PVT1 expression (p = 0.017). Furthermore, high-risk AML-M3 patients manifested higher expression levels of PVT1 than low- and intermediate-risk groups. In addition, distinctive CCDC26 and CCAT1 expression levels were observed among patients with different French–American–British subtypes (p = 0.001 for CCDC26 and p = 0.013 for CCAT1). Compared with the healthy controls, AML-M4 and M5 had higher CCAT1 expression (p = 0.04) and AML-M2 and AML-M4/M5 patients had higher CCDC26 expression (p < 0.001 and p = 0.02, respectively). In addition, different patterns of CCDC26 expression were found among the different cytogenetic risk subtypes (p = 0.005). Finally, patients with intermediate cytogenetic risk showed higher CCDC26 expression levels. Conclusion: The differential expression of the PVT1, CCDC26, and CCAT1 lncRNAs in different AML subtypes suggests that the deregulation of these transcripts may function in the multistep leukemogenic process and that they may serve as new therapeutic targets for this malignancy. [ABSTRACT FROM AUTHOR]

Predicting the performance of the semi-autogenous (SAG) mill is necessary for the best circuit design which is possible by suitable modeling and simulation. Numerous models of the SAG mill are studied in the literature, but the majority of them do not evaluate the predicted model for full-scale mill performance. Mill powers of the semi-autogenous mill have an effective influence on the mill performance. In this regard, a new predictive model based on gene expression programming (GEP) was developed to predict the mill power of the SAG mill. To achieve this purpose, a total number of 186 full-scale SAG mill works were investigated and the most effective parameters on SAG mill power, i.e., feed moisture, mass flowrate, mill load cell weight, SAG mill solid percentage, inlet and outlet water to the SAG mill and work index were measured and utilized to develop the GEP model. In order to determine the relationship between the input and output parameters, the GEP model was developed and the results were compared with non-linear multiple regression (NLMR) method. The results show the capability of the GEP model in predicting the mill power. It shows that the mill power is more sensitive to mass flowrate and work index than other input parameters. [ABSTRACT FROM AUTHOR]