Genetic variation in CYP1A1 and AHRR genes increase the risk of systemic lupus erythematosus and exacerbate disease severity in smoker patients.

BACKGROUND: Genetic variations of aryl hydrocarbon receptor (AHR) pathway genes could influence the imbalanced immune response to xenobiotics. Therefore, we aimed to investigate the polymorphism of AHR pathway genes in systemic lupus erythematosus (SLE) patients in association with smoking. METHODS: Genomic DNA from patients (N = 107) and controls (N = 105) of a population from northeast of Iran was used for genotyping of CYP1A1 T>C (rs4646903) and AHRR C>G (rs2292596) variants. The SLEDAI score and smoking status of the patients were registered. The AHR activity was estimated by CYP1A1 and CYP1B1 gene expression in peripheral blood mononuclear cells (PBMC). RESULTS: The C allele in rs4646903 (odds ratio [OR] = 2.67) and G allele in rs2292596 (OR = 1.79) SNPs were significantly associated with the increased risk of SLE. The AHR pathway was more active in high-risk CYP1A1/AHRR: C/G haplotype. The most severe disease was observed in smoker patients with high-risk haplotype and both smoking (Exp (ß) = 9.5) and high-risk CYP1A1/AHRR (C/G) haplotype (Exp (ß) = 3.7) can significantly increase the likelihood of having severe (SLEDAI ≥ 20) SLE disease activity. CONCLUSION: Our findings indicated the association of xenobiotic-metabolizing genes (CYP1A1, AHRR) polymorphisms with the susceptibility to SLE and disease severity regarding the smoking background, suggesting the interaction of gene and environmental risk factors in SLE pathogenesis.

The expansion of CD14+ CD163+ subpopulation of monocytes and myeloid cells-associated cytokine imbalance; candidate diagnostic biomarkers for celiac disease (CD).

Celiac disease (CD) is a chronic autoimmune disorder of small intestine against dietary gluten, among genetically predisposed individuals. Monocytes are versatile innate immune cells involved in the regulation of inflammation, and strongly involved in the intestinal immunity. However, the role of monocytes and their subtypes in CD is not well demonstrated. METHODS: Here, we assessed the polarization of CD14+ monocytes by evaluating the M1 (CD16) and M2 (CD163) markers by flowcytometry, their soluble forms (sCD16 and sCD163), and the serum levels of IL-10, IL-12, TGF-ß, and TNF-α cytokines using ELISA method, among 30 CD patients and 30 sex- and age-matched healthy subjects (HS). We also analyzed the diagnostic values of all variables with significant differences. RESULTS: CD14+CD163+ monocytes were more frequent in CD patients than HS, while CD14+CD16+ monocytes were higher in HS. IL-10and TNF-α increased, and TGF-ß expression was decreased among CD patients. The sCD16 serum levels were elevated in patients, while sCD163 was higher but not significant among CD patients. CD163+/CD16+ and IL-10/IL-12 ratios were higher in CD patients, and TGFß/TNFα ratio was higher in HS group. IL-10, CD14+CD163+, TNF-α, and IL-10/IL-12 ratios with the AUC over 0.7 were introduced as fair diagnostic markers. Our findings revealed that the M2 (CD14+CD163+) monocytes were more frequent among CD patients, and the cytokine balance was disturbed. CONCLUSION: According to the significant functional diversities of monocyte subtypes between CD patients and HS group, these immunologic markers could be introduced as specific diagnostic biomarkers for CD.

The Agglutinin of Common Nettle (Urtica dioica L.) Plant Effects on Gene Expression Related to Apoptosis of Human Acute Myeloid Leukemia Cell Line.

Treatment of acute myeloid leukemia (AML) requires new drugs as result of a rise in new cases and high disease relapse. Plant lectins with the ability to bind carbohydrates on the cell surface have the potential to treat cancer. Urtica dioica L. agglutinin (UDA) is a low weight lectin with anti-benign prostatic hyperplasia (BPH) impact. Here, we examine the impact of UDA on HL-60 cell line. Cytotoxicity and cytostatic effects were assessed in HL-60 cells treated with UDA and vincristine (positive control). The effects of the lectin on cell cycle phases and cell death mechanism were surveyed by propidium iodide (PI) staining and annexin V/PI, respectively. The activation status of the apoptosis pathway was determined by western blotting. Finally, the expression levels of 84 genes were examined by the Human cancer drug target gene PCR array kit. The results indicated that the increase in UDA concentration inhibited the proliferation of HL-60 cells as well as apoptosis induction. Cell cycle analysis showed that the number of sub G1 cells increased essentially. Experimental observations showed that UDA can induce cell apoptosis through a caspase 9-dependent pathway. The expression changes of 21 genes confirmed the apoptotic events in HL-60 cells treated with UDA. In this, we have presented the first investigation on the cytotoxic and apoptotic effects of a lectin isolated from rhizomes and roots of Urtica dioica L. on human AML cells. Generally, the results suggest that UDA may have therapeutic value for leukemia and would be studied further as a new drug for AML later on.

Effect of indole-3-carbinol on transcriptional profiling of wound-healing genes in macrophages of systemic lupus erythematosus patients: an RNA sequencing assay.

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.

Urtica dioica agglutinin (a plant lectin) has a caspase-dependent apoptosis induction effect on the acute lymphoblastic leukemia cell line.

Urtica dioica agglutinin (UDA) is a very small plant lectin with anti-prostatic activity. In this study, we investigated the effect of UDA on proliferation and apoptosis induction in human acute lymphoid leukemia (ALL) cell lines. The effect of UDA on Jurkat and Raji cell proliferation was examined by MTS assay. Distribution of cell cycle phases was determined by PI staining and apoptosis was examined with annexin V/PI and western blot. Results showed UDA treatment reduced cell proliferation in cells by inducing apoptosis. PI staining was associated with a higher percentage of the cell population in sub G1. Caspase-8 and caspase-9 dependent apoptosis occurred in Jurkat cells. Generally, UDA treatment resulted in cell death in ALL cell lines and induced apoptosis in the T-ALL cell line, Jurkat, through extrinsic and intrinsic pathways. These results may be considered as a guide to working on UDA as an anti-leukemic drug in the future.

Enhanced nuclear translocation and activation of aryl hydrocarbon receptor (AhR) in THP-1 monocytic cell line by a novel niosomal formulation of indole-3-carbinol.

Although niosomes structurally resemble liposomes, they are composed of nonionic surfactants which result in less toxicity and more stability. Here, we developed a novel niosomal formulation of I3C and investigated the nuclear translocation and activation of AhR among human acute myeloid leukaemia (AML) monocytic THP-1 cell line. Niosomal vesicles comprised of nonionic surfactants, cholesterol and I3C were prepared using thin film hydration (TFH) method and characterized according to the entrapment efficiency (EE %), size and zeta potential, by Dynamic light scattering method (DLS), and the surface morphology visualized by Transmission electron microscopy (TEM). In vitro release of I3C was evaluated and MTS assay was used to evaluate the viability of THP-1 cells. The nuclear translocation of AhR was assessed by immunocytochemistry (ICC) and Real-time RT-PCR was conducted using AhR target genes. The ratio of Cholesterol:Span 60 (1:1) niosomal formulations with the highest significant EE% were selected. I3C exerted cytotoxic effects on THP-1 cells in a dose- and time-dependent manner, while administration of niosomal I3C reduced these effects. Both niosomal and free I3C formulations facilitated the nuclear translocation of AhR. CYP1A1 was overexpressed in response to both free and niosomal I3C treatments, while IL1ß was overexpressed merely in niosomal I3C-treated THP-1 cells. Niosomal formulation of I3C resulted in reduced cytotoxicity effects by enhancing the functional effects of I3C on AhR in THP-1 cells, including its nuclear translocation and overexpression of the target genes.

Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR-RFLP technique was used to detect IL10 promoter genotypes at the positions of -1082 (G/A), -819 (C/T) and -592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of -1082 polymorphism was associated with the increased risk of SLE [OR = 2.65, 95% CI (1.21-5.82), p-value = 0.046]. The CC genotype in -819 region was associated with SLE susceptibility [OR = 3.38, 95% CI (1.26-9.07), p-value = 0.034] and C allele was introduced as risk allele [OR = 1.86, 95% CI (1.15-3.01), p-value = 0.009] in this region. IL10 plasma levels were overexpressed in CC genotype carriers of -592 SNP and decreased in AA genotype carriers of -1082. IL10 was also increased in SLE patients with CGT (-592/-1082/-819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of -592 and TT genotype carriers at the region of -819. SLEDAI was also elevated among patients with CGC (-592/-1082/-819) and CAC (p = 0.011) haplotypes. The present study suggests that the IL10 -819(C/T), -1082(G/A) and -592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings.

Indole-3-carbinol induces G1 cell cycle arrest and apoptosis through aryl hydrocarbon receptor in THP-1 monocytic cell line.

OBJECTIVES: The role of aryl hydrocarbon receptor (AhR) in carcinogenesis has been studied recently. Indole-3-carbinol (I3C) is an AhR agonist and a potential anticancer agent. Here, we investigated the effects of I3C on cell cycle progression and apoptosis through activation of AhR on THP-1 acute myeloid leukemia (AML) cell line. METHODS: MTT viability assay was used to measure the cytotoxic effects of I3C on THP-1 cells. Apoptosis and cell cycle assays were investigated using flow cytometry. Real time RT-PCR was conducted to measure the alterations in the expression of AhR gene, key genes associated with AhR activation (IL1ß and CYP1A1) and major genes involved in cell cycle regulation and apoptosis including P27, P21, CDK2, P53, BCL2 and FasR. RESULTS: Our findings revealed that I3C inhibits the proliferation of THP-1 cells in a dose- and time-dependent manner with minimal toxicity over normal monocytes. The AhR target genes (CYP1A1, IL1ß) were overexpressed upon I3C treatment (p < .05 to p < .001). The antiproliferative effects of I3C were in association with programed cell death. I3C downregulated BCL2 and upregulated FasR in THP-1 cells (p < .05 to p < .001). G1 cell cycle arrest was also observed using flow cytometry. G1-acting cell cycle genes (P21, P27 and P53) were overexpressed (p < .05 to p < .001), while CDK2 was downregulated upon I3C treatment (p < .01 to p < .001). CONCLUSIONS: I3C could exert its antileukemic effects through AhR activation which is associated with programed cell death and G1 cell cycle arrest in a dose- and time-dependent manner. Therefore, AhR could be targeted as a novel treatment possibility in AML.

The prognostic effect of PTEN expression status in colorectal cancer development and evaluation of factors affecting it: miR-21 and promoter methylation.

BACKGROUND: PTEN is a tumor suppressor gene which is involved in cellular proliferation, differentiation, and apoptosis. Loss or down-regulation of PTEN plays an important role in human cancers development. In this study, we investigated the effect of miR-21 and promoter methylation on the PTEN expression status in CRC tissues and analyzed association of the PTEN expression status with clinicopathological features in patients with CRC. RESULTS: The PTEN expression was positively detected in 67.2 % CRC tissues and all adjacent non-cancerous samples. PTEN mRNA level was negatively correlated with miR-21 level (r = -0.595, P < 0.001). PTEN expression was also correlated directly with the PTEN mRNA level (r = 0.583, P < 0.001) and conversely with miR-21 level (r = -0.632, P < 0.001). PTEN Promoter methylation was significantly associated with PTEN expression status (p = 0.013). PTEN expression was negatively associated with tumor size (p = 0.007) and advanced tumor stage (P = 0.011). Multivariate analysis indicated that tumor stage, tumor differentiation and PTEN expression status were independent prognostic factors for overall carcinoma in CRC patients (P < 0.05). The Kaplan-Meier curve indicated a negative correlation between PTEN expression levels and survival of CRC patients (P = 0.013). CONCLUSIONS: This study suggests a high frequency of miR-21 overexpression and aberrant promoter methylation in down-regulation of PTEN expression in colorectal carcinoma. Loss of PTEN may be a prognostic factor for patients with CRC.

Myeloid-derived suppressor cells in B cell malignancies.

Tumor cells use several mechanisms such as soluble immune modulators or suppressive immune cells to evade from anti-tumor responses. Immunomodulatory cytokines, such as transforming growth factor-ß, interleukin (IL)-10, and IL-35, soluble factors, such as adenosine, immunosuppressive cells, such as regulatory T cells, NKT cells and myeloid-derived suppressor cells (MDSCs), are the main orchestra leaders involved in immune suppression in cancer by which tumor cells can freely expand without immune cell-mediated interference. Among them, MDSCs have attracted much attention as they represent a heterogenous population derived from myeloid progenitors that are expanded in tumor condition and can also shift toward other myeloid cells, such as macrophages and dendritic cells, after tumor clearing. MDSCs exert their immunosuppressive effects through various immune and non-immune mechanisms which make them as potent tumor-promoting cells. Although, there are several studies regarding the immunobiology of MDSCs in different solid tumors, little is known about the precise characteristics of these cells in hematological malignancies, particularly B cell malignancies. In this review, we tried to clarify the precise role of MDSCs in B cell-derived malignancies.

Folate-conjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy.

The selective and efficient drug delivery to tumor cells can remarkably improve different cancer therapeutic approaches. There are several nanoparticles (NPs) which can act as a potent drug carrier for cancer therapy. However, the specific drug delivery to cancer cells is an important issue which should be considered before designing new NPs for in vivo application. It has been shown that cancer cells over-express folate receptor (FR) in order to improve their growth. As normal cells express a significantly lower levels of FR compared to tumor cells, it seems that folate molecules can be used as potent targeting moieties in different nanocarrier-based therapeutic approaches. Moreover, there is evidence which implies folate-conjugated NPs can selectively deliver anti-tumor drugs into cancer cells both in vitro and in vivo. In this review, we will discuss about the efficiency of different folate-conjugated NPs in cancer therapy.

Natural inhibitors of PI3K/AKT signaling in breast cancer: emphasis on newly-discovered molecular mechanisms of action.

Epidermal growth factor receptor (EGFR) plays a critical role in the initiation and progression of a variety of human cancers, including breast cancer. An important signaling pathway downstream of EGFR is the PI3K/AKt pathway, which regulates cellular processes as diverse as cell growth, survival, proliferation and migration. Deregulated activity of this pathway may lead to uncontrolled cell growth, survival, migration and invasion, contributing to tumor formation. In this review, we evaluate natural compounds that, in vitro (breast cancer cell lines) and/or in vivo (animal model, clinical) studies, suppress breast cancer cells or tumors mainly by suppressing the PI3K/AKT signaling pathway. The effect of these compounds on cell cycle arrest, inhibition of cell migration and invasion, tumor angiogenesis and metastasis in breast cancer are discussed.

Promoter methylation analysis of WNT/ß-catenin pathway regulators and its association with expression of DNMT1 enzyme in colorectal cancer.

BACKGROUND: Aberrant DNA methylation as the most important reason making epigenetic silencing of genes is a main mechanism of gene inactivation in patients with colorectal cancer. In this study, we decided to identify promoter methylation status of ten genes encoding WNT negative regulators, and measure the expression of DNMT1 enzyme in colorectal cancer samples. RESULTS: Aberrant methylation of APC gene was statistically significant associated with age over 50 (p = 0.017), DDK3 with male (p < 0.0001), SFRP4, WIF1, and WNT5a with increasing tumor stage (p = 0.004, p = 0.029, and p = 0.004), SFRP4 and WIF1 with tumor differentiation (p = 0.009 and p = 0.031) and SFRP2 and SFRP5 with histological type (p = 0.001 and p = 0.025). The increasing number of methylated genes correlated with the expression levels of the DNMT1 mRNA. CONCLUSIONS: The rate of gene promoter methylation of WNT pathway regulators is high in colorectal cancer cells. Hyper-methylation is associated with increased expression of the DNMT1 enzyme.

Impact of hepcidin antimicrobial peptide on iron overload in tuberculosis patients.

BACKGROUND: Iron acquisition is essential for the growth of Mycobacterium tuberculosis. Hepcidin is known as an antimicrobial peptide and a component of the innate immune response. Hepcidin inhibits M. tuberculosis growth in vitro. In this study, we decided to identify -582A> G variants of the HAMP promoter in patients with tuberculosis (TB) and investigate its effect on serum iron, ferritin, and hepcidin levels. METHODS: The sample population consisted of 105 patients with TB and 104 healthy individuals. The -582A> G polymorphism was genotyped using a tetra-primers PCR set. Serum levels of hepcidin were determined using an ELISA kit. Statistical analysis was performed using SPSS software. RESULTS: The G allele is meaningfully associated with TB disease (95% confidence interval = 2-4.8, p < 0.000). Significant differences were seen in the levels of serum iron and hepcidin but not ferritin between the -582A>G polymorphism genotypes. There was significant reverse correlation between hepcidin and iron (r = -0.849, p = 0.006). CONCLUSION: A high association was found between serum hepcidin levels and the HAMP -582A> G variants in patients with TB. These observations indicate a hypothetical role of this polymorphism in iron metabolism. Hepcidin could perhaps be an option for the treatment of TB.

Functional analyses of recombinant mouse hepcidin-1 in cell culture and animal model.

Hepcidin is a peptide hormone that plays an important role in iron metabolism. We have produced a recombinant mouse hepcidin-1 by using baculovirus expression system. Its expression yield was 25 µg/ml when cell culture media were supplemented with a protease inhibitor cocktail. The recombinant mouse hepcidin-1 and synthetic human hepcidin-25 had similar effects on reducing ferroportin expression in J774A cell line and in peritoneal macrophages. However, synthetic human hepcidin-25 was more efficient than recombinant mouse hepcidin-1 in reducing iron concentration in blood circulation (p < 0.01).

Altered expression of miR-125a and dysregulated cytokines in systemic lupus erythematosus: Unveiling diagnostic and prognostic markers.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder impacting multiple organs, influenced by genetic factors, especially those related to the immune system. However, there is a need for new biomarkers in SLE. MicroRNA-125a (miR-125a) levels are decreased in T cells, B cells, and dendritic cells of SLE patients. MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12), which are crucial pro-inflammatory cytokines in SLE pathogenesis. AIM: To assess the levels of miR-125a, IL-12, and TNF-α in SLE patients' plasma, evaluating their diagnostic and prognostic value. METHODS: The study included 100 healthy individuals, 50 newly diagnosed (ND), and 50 SLE patients undergoing treatment. The patients were monitored for a duration of 24 wk to observe and record instances of relapses. MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction, while ELISA kits were used to assess IL-12 and TNF-α production. RESULTS: The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals, with the lowest levels in ND patients. TNF-α and IL-12 expression levels were significantly elevated in SLE patients, especially in the early stages of the disease. Receiver operating characteristic curve analyses, and Cox-Mantel Log-rank tests indicated miR-125a, TNF-α, and IL-12 as proper diagnostic biomarkers for SLE. A negative correlation was found between plasma miR-125a expression and IL-12/TNF-α levels in SLE patients. CONCLUSION: Decreased miR-125a levels may be involved in the development of SLE, while elevated levels of IL-12 and TNF-α contribute to immune dysregulation. These findings offer new diagnostic and prognostic markers for SLE. Moreover, the negative correlation observed suggests an interaction between miR-125a, TNF-α, and IL-12. Further research is necessary to uncover the underlying mechanisms that govern these relationships.

Circulating miR-21 Overexpression Correlates with PDCD4 and IL-10 in Systemic Lupus Erythematosus (SLE): A Promising Diagnostic and Prognostic Biomarker.

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.

More Related Gene Pathways to Vincristine-Induced Death Events in a Human T-Acute Lymphoblastic Leukemia Cell Line.

Background: Acute lymphoblastic leukemia (ALL) is common in children but rare in adults. Vincristine (VCR) is one of the drugs used at the beginning of treatment. Some genes are resistant to VCR in B-ALL. Methods: Here, we examined the effect of VCR on gene expression changes in a T-ALL cell line, Jurkat. The MTT method was used to determine the IC50 in Jurkat cells treated with different concentrations of VCR for 48 and 72 hours. Total RNA was isolated from the cells and cDNA was prepared. The Human Cancer Drug Target PCR Array kit was used to evaluate the 84 gene expression changes in Jurkat cells. Protein-protein interaction was analyzed by STRING software. Results: We identified 66 differentially expressed genes as comparison to untreated cells. The response to VCR-induced apoptotic events was remarkable in the pathways of heat shock protein, topoisomerases, protein kinases, cathepsins and cell cycle. In other pathways, there were resistant genes as well as sensitive genes to VCR treatment. Some proteins like HSP90AA1 and ESR1 had determining associations with other proteins. Conclusion: The results suggest VCR target genes in T-ALL cells may be beneficial biomarkers for ALL treatment and can be used to select appropriate synergistic drugs for VCR.

Association of salivary physicochemical characteristics and peptide levels with dental caries in children.

AIM: The purpose of this investigation was to evaluate the association of physicochemical properties and antimicrobial peptide levels of saliva with caries activity in children. MATERIALS AND METHODS: The required volume of unstimulated saliva was collected from 41 children aged 3-12 years with no systemic diseases. Caries activity was calculated using DMFS and dmfs records for each participating child. Collected saliva samples were then examined for their flow rate, pH, and buffering capacity. The concentration of three peptides was assessed including LL-37, human neutrophil peptide (HNP) 1-3, and human beta-defensin (HBD)-3 through an enzyme-linked immunosorbent assay. The correlation between caries activity score (CAS) and salivary variables was looked using the linear regression and Spearman's correlation method. The comparison of CAS means between high- and low-value groups of salivary items was performed using independent sample t-test while the association of CAS and salivary parameters in categorical scale was tested by Chi-square test. RESULTS: No statistically significant differences were found between the CAS means at low and high categories of each salivary physicochemical parameter and those of antimicrobial peptides. There was a negative correlation between HNP1-3 and CAS and also between HBD-3 and CAS, but these results were not statistically meaningful. High HNP1-3 concentration was noted in 67% of the low caries rate group and 29% of the high caries rate group, with a statistically significant difference between the low and high caries rate groups (P = 0.019). CONCLUSION: Salivary inherent factors are not dominant determinants in caries activity. The current results may suggest that α-defensins (HNP1-3) have a protective role against dental caries.

Association of serum levels and receptor genes BsmI, TaqI and FokI polymorphisms of vitamin D with the severity of multiple sclerosis.

PURPOSE: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Vitamin D has a major role in preventing inflammatory disorders. Therefore, any alteration in vitamin D receptor (VDR) might be a genetic risk factor for MS development. This study aimed to evaluate the effect of serum levels and VDR FokI, BsmI, and TaqI gene polymorphisms on the severity of MS. METHODS: This case-control study recruited 160 MS patients (71.9% females, mean age of 34.3 ± 8.3 years) and 162 (66.7% females, mean age 35.4 ± 7.9 year) age, sex, and ethnicity matched healthy controls. FokI (rs2228570), BsmI (rs1544410), and TaqI (rs731236) polymorphisms were carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Demographic, clinical parameters, and the levels of vitamin D were compared between groups. RESULTS: We found that the frequency of FokI and TaqI polymorphisms significantly differed between the patients and the controls (p = 0.0127 and p = 0.0236, respectively). The MS patients had low levels of vitamin D compared to the controls (p = 0.011). In addition, TaqI T/C polymorphism significantly decreased the levels of vitamin D in the MS patients (p = 0.002). However, there was no significant association between FokI or BsmI SNPs and the levels of vitamin D in MS patients (p > 0.5). CONCLUSION: Our results suggest that FokI and TaqI polymorphisms of VDR are associated with MS risk and TaqI polymorphism is associated with Vitamin D levels in MS patients. Meanwhile, no difference was observed between VDR gene polymorphisms and any types of MS.