Implications of the cGAS-STING pathway in diabetes: Risk factors and therapeutic strategies.

Diabetes mellitus is an increasingly prevalent metabolic disorder characterized by chronic hyperglycemia and impaired insulin action. Although the pathogenesis of diabetes is multifactorial, emerging evidence suggests that chronic low-grade inflammation plays a significant role in the development and progression of the disease. The cyclic GMP-AMP synthase (cGAS) and its downstream signaling pathway, the stimulator of interferon genes (STING), have recently gained attention in the field of diabetes research. This article aims to provide an overview of the role of cGAS-STING in diabetes, focusing on its involvement in the regulation of immune responses, inflammation, insulin resistance, and ß-cell dysfunction. Understanding the contribution of cGAS-STING signaling in diabetes may lead to the development of targeted therapeutic strategies for this prevalent metabolic disorder. The results section presents key findings from multiple studies on the impact of STING in diabetes. It discusses the influence of STING on inflammation levels within a diabetic environment, its effect on insulin resistance, and its implications for the development and progression of diabetes. The cGAS-STING signaling pathway plays a crucial role in the development and progression of diabetes.

Angiotensin-converting enzyme I/D gene polymorphism and risk of type 2 diabetes mellitus in Iranian individuals.

This study aimed to examine the relationship between type 2 diabetes mellitus (T2DM) and renin-angiotensin system gene polymorphisms in the Iranian population. Additionally, we performed a straightforward meta-analysis of the present articles to better understand this role. A total of 100 Iranian individuals, 50 patients with T2DM, and 50 age-matched healthy individuals were included in this study. DNA was extracted using the salting-out approach, polymerase chain reaction was used to amplify the angiotensin-converting enzyme (ACE) gene, electrophoresis techniques were used, and genotyping was performed. We also searched PubMed, Web of Science, Scopus, and Google Scholar databases for papers published in 2023. We found a significantly higher frequency of I/D genotype in the patient group than in the control group, and the risk of T2DM was 10 times higher in individuals with the I/D genotype (OR, 10 [95% CI, 3.7 to 27]; p < 0.0001) and also 2.85 time higher in individuals with the D allele OR, 2.85 [95% CI, 1.55 to 5.24]; p < 0.001). The ACE polymorphism alleles D and I/D genotypes may increase the risk of developing T2DM in an Iranian population.

cGAS-STING and PD1/PDL-1 pathway in breast cancer: a window to new therapies.

Breast cancer is a complex malignancy with diverse molecular and cellular subtypes and clinical outcomes. Despite advances in treatment, breast cancer remains a significant health challenge. However, recent advances in cancer immunotherapy have shown promising results in the treatment of breast cancer, particularly the use of inhibitors that target the immune checkpoint PD1/PDL1. Also, the cGAS-STING pathway, an important part of the innate immune response, has been considered as a major potential therapeutic target for breast cancer. In this narrative review, we provide an overview of the cGAS-STING and PD1/PDL-1 pathway in breast cancer, including their role in tumor development, progression, and response to treatment. We also discuss potential future directions for research.

Role of cGAS-STING in colorectal cancer: A new window for treatment strategies.

Colorectal cancer (CRC) is a common and deadly form of cancer, leading to the need for new therapeutic targets and strategies for treatment. Recent studies have shown the cGAS-STING pathway to be a promising target for cancer therapy. The cGAS-STING pathway is a part of the innate immune system and serves to identify DNA damage and viral infection, promoting an immune response. Activation of this pathway leads to the production of immune mediators, such as type I interferons, that activate immune cells to attack cancer cells. Research has identified the cGAS-STING pathway as a frequently dysregulated component in CRC, promoting tumor growth and metastasis, or leading to chronic inflammation and tissue damage. The modulation of this pathway presents a potential therapeutic approach, either activating or inhibiting the pathway to enhance the immune response and prevent inflammation, respectively. Developing drugs that can modulate the cGAS-STING pathway offers promise for improving treatment outcomes for CRC patients. The present review explores recent research on the role of cGAS-STING in CRC and highlights the potential therapeutic benefits of targeting this pathway.

Molecular Function of cGAS-STING in SARS-CoV-2: A Novel Approach to COVID-19 Treatment.

Coronavirus illness 2019 is a significant worldwide health danger that began with severe acute respiratory syndrome coronavirus two infections. It is the largest pandemic of our lifetime to date, affecting millions of people and crippling economies globally. There is currently no viable therapy for this devastating condition. The fast spread of SARS-CoV-2 underlines the critical need for favorable treatments to prevent SARS-CoV-2 infection and dissemination. Regulating the upstream cytokine release might be a possible method for COVID-19 therapy. We propose that more consideration be paid to the dysregulated IFN-I release in COVID-19 and that cGAS and STING be considered therapeutic targets for avoiding cytokine storms and as critical components in host antiviral defense mechanisms.

Association between interleukin-1 receptor antagonist (IL-1ra) VNTR, gene polymorphism and breast cancer susceptibility in Iranian population: Experimental and web-based analysis.

Breast cancer is one of the leading causes of cancer mortality. Growing evidence indicates that interleukins and its polymorphisms are involved in the pathogenesis of breast cancer. Variable number of tandem repeat (VNTR) polymorphism can affect transcription rate, mRNA stability and also the resulting protein expression and activity. Hence, present study aimed to assess the possible association between interleukin-1 receptor antagonist (IL-1Ra) VNTR polymorphism, and breast cancer susceptibility in Iranian population. A total of 300 Iranian individuals, 150 breast cancer patients and 150 age-matched healthy women, were included in this study. DNA extracted by salting out method and genotyping was done using the polymerase chain reaction. The frequency of the allele 2(5% vs. 22%) and the 2/2 genotype (22% vs. 46%) of IL-1Ra VNTR polymorphism was significantly higher in healthy control compared to breast cancer patient: therefore, A2 allele may play a protective role against breast cancer and its progression (p = .0001 and OR = 0.105, 95% CI: [0.044-0.248]). The allele 2 and 2/2 genotype of the IL-Ra VNTR polymorphism can be a protective factor against breast cancer susceptibility.

PPARγ activation by pioglitazone enhances the anti-proliferative effects of doxorubicin on pro-monocytic THP-1 leukemia cells via inducing apoptosis and G2/M cell cycle arrest.

PURPOSE: Doxorubicin (DOX) is a common chemotherapeutic agent, with toxic side effects, and chemoresistance. Combination chemotherapy is a successful approach to overcome these limitations. Here, we investigated the effects of pioglitazone (PGZ), a PPARγ agonist, and/or DOX on the viability, cell cycle, apoptosis on THP-1 cells and normal human monocytes (NHMs). METHODS: MTT assay was used to evaluate the cytotoxicity of DOX and/or PGZ. Cell cycle progression and apoptosis induction were examined by PI or Annexin V-PI double staining, and analyzed by flow cytometry. Quantitative RT-PCR was used to evaluate the changes in the mRNA expression of cell cycle progression or apoptosis-associated genes including P27, P21, CDK2, P53, BCL2 and FasR. RESULTS: DOX, PGZ and DOX + PGZ exerted their cytotoxic effects in a dose- and time-dependent manner with low toxicity on NHMs. The cell growth inhibitory effects of DOX were in association with G2/M arrest, while PGZ executed S phase arrest. PGZ treatment enhanced G2/M among DOX-treated combinations with moderate elevation in the S phase. DOX, PGZ and combined treatments induced apoptosis (mostly late phase) in a dose-dependent manner. All treatments resulted in the significant overexpression of p21, p27, p53 and FasR genes and downregulation of CDK2. DOX + PGZ combined treatments exhibited the most significant changes in mRNA expression. CONCLUSION: We demonstrated that the antiproliferative, cell cycle regulation and apoptosis-inducing capacity of DOX was enhanced by PGZ in THP-1 leukemia cells in a dose-dependent manner. Therefore, the combination of DOX + PGZ could be used as a novel combination to target AML.

Evaluating the HLA-G (rs1063320) genetic variant and risk of human papillomavirus infection: a meta-analysis of 953 cases and 877 controls.

Human leukocyte antigen-G (HLA-G) has immune-modulatory functions. Although the role of genetic variant HLA-G (rs1063320) in susceptibility to human papillomavirus (HPV) infection has been widely considered, it is still a matter of discussion. In order to shed light on the issue, we, therefore, conducted a meta-analysis to evaluate the common impact of the HLA-G (rs1063320) variant on susceptibility to HPV infection. Subsequently, the distribution of genotypes, genotyping techniques and ethnicity groups was collected, and general analyses were performed. A total number of five studies with 953 cases and 877 controls were found to meet our criteria. The polymorphism of HLA-G (rs1063320) was evaluated. This is the first meta-analysis to explore the connection between the HLA-G 3' UTR + 3142C/G (rs1063320) genetic variant and the risk of HPV infection. Our results showed no association between the variant of HLA-G 3' UTR + 3142C/G (rs1063320) and susceptibility to HPV infection in studied target populations.Impact StatementWhat is already known on this subject? Human papillomavirus (HPV) is the most widespread sexually transmitted infection in both men and women all over the world. It is correlated with prominent load of diseases and malignancies, including anogenital warts and anogenital and oropharyngeal cancers. In recent years, several studies manifested that different SNPs located on special genes seems to influence HPV infection risk.What the results of this study add? Our findings disclosed no relation between the variant of HLA-G 3' UTR + 3142C/G (rs1063320) and vulnerability to HPV infection in the target individuals.What are the implications of these findings for clinical practice and/or further research? The findings in current survey may offer a basis for further study on HLA-G variant in future investigation.

IL1A and IL1B gene polymorphisms and keratoconus susceptibility: evidence from an updated meta-analysis.

Background: Several single-nucleotide polymorphisms (SNPs) in IL1B genes have been associated with KTCN. However, the results of these studies were not conclusive. This meta-analysis association study is aimed to quantitatively estimate the association of IL1B rs16944 (g.4490T>C) and rs1143627 (g.4970C>T), and IL1A rs2071376 (c.615 + 169C>A) polymorphisms with KTCN susceptibility.Materials and Methods: Systematic literature search was performed in Web of Science, MEDLINE, PubMed, Scopus, and Google Scholar databases. The odds ratios (ORs) and 95% confidence intervals (CI) were calculated assuming different contrasted genetic models.Results: The reference T allele of IL1B (g.4490T>C) polymorphism was significantly associated with decreased KTCN risk under all assessed genetic models. Regarding the reference C allele of IL1B (g.4970C>T) polymorphism, decreased risk of KTCN was found. The reference C allele of IL1A (c.615 + 169C>A) polymorphism conferred a decreased risk of KTCN under heterozygous codominant (AC vs. AA), homozygous codominant (CC vs. AA), and dominant (AC+CC vs. AA) genetic models. The pooling estimates showed that the T C haplotype was associated with a significant increase in KTCN risk. In contrast, the T T haplotype was correlated with a decreased risk of KTCN. With the assumption of a prior probability of 0.25, the false-positive report probability (FPRP) values were less than 0.2, indicating the observed significant associations were notable.Conclusion: These findings propose that the studied IL1B polymorphisms and the IL1A variation have opposite effects on KTCN susceptibility. More large-scale replication studies are warranted to illuminate the precise role of these SNPs on the etiology of eye disorders.

Quantitative Assessment of the Effects of IL-1ß -511 C>T Variant on Breast Cancer Risk: An Updated Meta-Analysis of 3331 Cases and 3609 Controls.

OBJECTIVE: Growing evidence suggests that IL-1ß -511C>T, as a functional variant, affects the risk of developing breast cancer (BC); however, the results have not been conclusive. This meta-analysis was conducted to estimate the link between this variant and BC risk. METHODS: We retrieved available publications on IL-1ß -511C>T polymorphism by conducting a comprehensive literature search on the Web of Science, MEDLINE, PubMed, Scopus, and Google scholar databases (last search on February 25, 2020). RESULTS: The overall analysis indicates that IL-1ß -511C>T polymorphism conferred an increased risk of BC under a recessive TT vs CT+CC model by 1.14-fold and showed protection against BC under an overdominant CT vs TT+CC genetic contrast model (odds ratio = 0.84). Stratified analysis based on ethnicity revealed the protective effect of this single-nucleotide polymorphism against BC risk in Caucasian patients. CONCLUSION: Our data results provide a proof of concept for the association of IL-1ß -511C>T with BC risk. Larger, well-designed population-based studies are needed to confirm these findings.

The Polymorphism of miR-146a (rs2910164) and Breast Cancer Risk: A Meta-Analysis of 17 Studies.

BACKGROUND: Single-Nucleotide Polymorphisms (SNPs) in genes responsible for coding microRNAs (miRNAs) are shown to be crucial in progression of Breast Cancer (BC). OBJECTIVE: The purpose of this meta-analysis is to obtain more definitive and reliable results due to the ambiguity and inconsistency of the previous findings in this regard. This study aimed at clarifying the association of mir14a polymorphisms with breast cancer. METHODS: We searched PubMed, EMBASE, Web of Science and Google Scholar databases for papers published before August 10, 2019. Afterward, genotypes' distribution, genotyping methods and ethnicity groups were extracted and Overall analyses were conducted. A total number of seventeen researches on 7676 subjects and 7476 controls were found to meet our criteria in this meta-analysis. RESULTS: Our observations confirmed the increased risk in breast cancer with rs 2910164 polymorphism in three genetic models: allele contrast fixed genetic model, Recessive fixed genetic model and CC vs. GG genetic model (P value 0.0109, 0.0404 and 0.0019, respectively). CONCLUSION: The rs2910164 polymorphism is associated with increased breast cancer risk. We suggest that more multicenter studies with larger samples investigate this matter to further clarify the association and verify our findings.

Nitric oxide, 8-hydroxydeoxyguanosine, and total antioxidant capacity in human seminal plasma of infertile men and their relationship with sperm parameters.

OBJECTIVE: Oxidative stress plays a key role in the pathogenesis of male infertility. But, the adverse effects of oxidative biomarkers on sperm quality remain unclear. This study aimed to investigate the levels of nitric oxide (NO), 8-hydroxydesoxyguanosine (8-OHdG), and total antioxidant capacity (TAC) oxidative biomarkers in seminal plasma and their relationship with sperm parameters. METHODS: A total of 77 volunteers participated in the study, including fertile (n=40) and infertile men (n=37). NO, 8-OHdG, and TAC levels were measured using the ferric reducing ability of plasma, Griess reagent method and an enzyme-linked immunosorbent assay kit, respectively. RESULTS: The mean values of sperm parameters in the infertile group were significantly lower than those in the fertile group (p<0.001). The mean 8-OHdG in the seminal plasma of infertile men was significantly higher (p=0.013) than those of controls, while the mean TAC was significantly lower (p=0.046). There was no significant difference in NO level between the two groups. The elevated seminal 8-OHdG levels were negatively correlated with semen volume, total sperm counts and morphology (p<0.001, p=0.001 and p=0.052, respectively). NO levels were negatively correlated with semen volume, total sperm counts and morphology (p=0.014, p=0.020 and p=0.060, respectively). Positive correlations between TAC and both sperm count and morphology (p=0.043 and p=0.025, respectively) were also found. CONCLUSION: These results suggested that increased levels of NO and 8-OHdG in seminal plasma could have a negative effect on sperm function by inducing damage to the sperm DNA hence their fertility potentials. Therefore, these biomarkers can be useful in the diagnosis and treatment of male infertility.

Association between vitamin D receptor gene FokI and TaqI variants with autism spectrum disorder predisposition in Iranian population.

BACKGROUND AND AIM: Autism spectrum disorder (ASD) is one of the neurodevelopmental and cognitive conditions that involves 1 in 160 children around the world. Several studies showed that there is a relationship between vitamin D receptor (VDR) gene polymorphisms with the neurodevelopmental behavioral disorders. In the current study, we aimed to highlight the association of VDR gene polymorphisms (FokI and TaqI) with the risk of autism in Birjand population. MATERIAL AND METHODS: In this case-control study eighty-one patients recognized with ASD and one hundred-eight healthy controls were recruited to the study from 2017 to 2018. Genotyping was carried out by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technique for all subjects. RESULTS: Calculated odds ratio and P-value for the alleles of VDR gene FokI and TaqI variants between autistic patients and controls did not show a significant difference (P > 0.05). However, calculated homozygous recessive (tt) for TaqI polymorphism was statistically significant (P = 0.015) in control group and there was also statistically meaningful difference in both case and control groups in ft haplotype (P = 0.04). CONCLUSION: These results provide preliminary evidence that genetic variants of the VDR gene (FokI and TaqI) might have a possible reduced risk of ASD occurrence in children. The additional examination is needed to acquire more decisive and precise results in this area.

Soluble guanylate cyclase isoenzymes: The expression of α1, α2, ß1, and ß2 subunits in the benign and malignant breast tumors.

Soluble guanylate cyclase (sGC) encompasses α and ß subunits. This study examined the expression of α1, α2, ß1, and ß2 subunits in the malignant and benign breast tumors using the Western blot analysis. Both benign and malignant tumors showed a significantly higher expression of the α1 subunit in comparison with normal tissues (p < 0.0001). In contrast, the expression of α2 and ß2 sGC were significantly lower in these tumors than normal tissues (p < .0015 and p < .001, p < .007 and p < .0001, respectively). The expression level of α1 sGC was significantly correlated with ER + PR+ (p < .0001). A significant correlation was also detected for sGC-α1 and -α2 expression with c-erbB2-negative status (p < .01). However, the expression level of sGC was not associated with tumor stage, tumor grade, or other clinicopathological features. In conclusion, as the expression of α1 sGC is upregulated and α2 and ß2 sGC are downregulated in malignant breast tumors. Variations in the expression of sGC isoenzymes may be suggested as an indicator to confirm the enzyme antitumor activity.

Differential expression of alternative transcripts of soluble guanylyl cyclase, GYCY1a3 and GUCY1b3 genes, in the malignant and benign breast tumors.

Extensive alterations in splicing is one of the molecular indicator for human cancers. Soluble guanylyl cyclase (sGC), an obligatory heterodimer, is composed of α1 and ß1 subunits. Each subunit is encoded by a separate gene, GUCY1a3 and GUCY1b3, correspondingly. sGC activity has been regulated by an alternative splicing and it has an important effect on the breast cancer. sGC alternative splicing has been evaluated in the 55 malignant, 25 benign and 30 normal breast tissues using qRT-PCR and RT-PCR. The differences between groups were analyzed by Mann-Whitney U. The expression of six different splice forms have been detected, three for α1 and three for ß1 sGC. Expressions of Tr1, Tr2 ß1 sGC and Tr7, Tr6 α1 sGC mRNA in the malignant breast tumors were significantly lower than those of benign and normal breast tissues. However, the expression of Tr3 α1 sGC mRNA was significantly higher than that of benign and normal tissues. Present data have provided some evidences for an alteration in the expression of α1 and ß1 sGC alternative splicing forms which may contribute to the loss of sGC functions in the breast cancer. The observed information might be discussed by the cGMP status.

Positive correlation between interleukin-1 receptor antagonist gene 86bp VNTR polymorphism and colorectal cancer susceptibility: a case-control study.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Genetic variations in cytokine genes and their receptors lead to the severity of the disease. The interleukin-1 receptor antagonist (IL1RN) is a cytokine that inhibits interleukin-1 (IL-1) activity by binding to IL-1 receptors. Also, interleukin-4 (IL-4) is an anti-inflammatory cytokine that can play an important role in several cancers. The present case-control study was aimed to evaluate the association of IL-4 and IL1RN VNTR polymorphisms with the susceptibility to CRC in a sample of Iranian population provided by the Research Center for Gastroenterology and Liver Disease at Taleghani Hospital, Tehran. A total of 123 patients diagnosed with CRC and 152 healthy controls were recruited in the present study. Genomic DNA was extracted by salting out method from whole blood and genotyping of IL1RN and IL-4 VNTR polymorphisms were determined by PCR-based technology. Our study manifested the frequency of 1/2 and 2/4 genotypes of IL1RN 68bp VNTR polymorphism are significantly different between both groups (p = 0.0001 and p = 0.01 respectively). However, we could not find any correlation between IL-4 VNTR polymorphism and CRC cancer. It seems that 1/2 and 2/4 genotypes of IL1RN are correlated with CRC susceptibility in our population, although, more studies are needed to confirm our results.

Comparison of large-scale deletions of the sperm mitochondrial DNA in normozoospermic and asthenoteratozoospermic men.

BACKGROUND AND OBJECTIVE: Mitochondria play a crucial role in energy metabolism for the survival and motility of sperm during fertilization. The aim of this study was to determine the association of large-scale mitochondrial DNA deletions with abnormal sperm motility and morphology in asthenoteratozoospermic patients. MATERIALS AND METHODS: In this case-control study, 41 semen samples were collected from 18 normozoospermic healthy men and 23 asthenoteratozoospermic patients, according to the WHO guidelines. The swim-up technique was used for separation of spermatozoa on the basis of their motility. Long-range polymerase chain reaction (PCR) was used for screening of mitochondrial DNA (mtDNA) large-scale deletions, and primer shift PCR was used for confirmation of deletions. RESULTS: The mean sperm motility, normal morphology, and progressive motility in asthenoteratozoospermic patients were significantly lower than in the normozoospermic group (P < 0.0001). There was a positive significant correlation between motility and normal sperm morphology ( P < 0.0001, r = 0.741). The results of long-range PCR revealed the existence of 4866-bp deletion along with the two common 4977-bp and 7436-bp deleted mtDNA in both groups. However, the frequency of multiple mtDNA deletions in the asthenoteratozoospermic group (15/23, 65.22%) was significantly higher than that in the normozoospermic group (7/18, 38.89%). Direct sequencing of the 534-bp PCR product revealed that it was amplified from the mtDNA with a 4866-bp deletion flanked by a seven-nucleotide direct repeat (5'-ACCCCCT-3'). CONCLUSIONS: Our findings suggested that these large-scale deletions of mtDNA may be genetic risk factors for poor sperm quality in asthenoteratozoospermia-induced male infertility. Thus, it is necessary to understand the mechanisms behind the generation of these deletions.

Positive correlation between vitamin D receptor gene FokI polymorphism and colorectal cancer susceptibility in South-Khorasan of Iran.

Colorectal cancer (CRC) is a global public health problem. Despite the major milestone in early diagnosis and treatment of colorectal cancer, the prevalence of CRC rates is still rising. The etiology of CRC is still unknown but we know CRC is influenced by both of environment and genetic factors. In this study, we aimed to elucidate the role of vitamin D receptor gene polymorphic regions; FokI and TaqI single nucleotide polymorphisms, in increasing the risk of colorectal cancer in Birjand population. One hundred patients with CRC and 100 healthy controls recruited to the study. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) method technique for all individuals. There were statistically significant differences between ff genotype and f allele of FokI SNP in case and control groups. Our results manifested positive correlation between ff genotype and f allele of FokI SNP with colorectal cancer predisposition (P = 0.035, P = 0.0001 respectively) in South Khorasan population. The present study showed that FokI polymorphism but not TaqI polymorphism may contribute to CRC susceptibility. In addition, ff genotype of FokI polymorphism was associated with CRC risk.

Near-infrared chemical imaging (NIR-CI) of 3D printed pharmaceuticals.

Hot-melt extrusion and 3D printing are enabling manufacturing approaches for patient-centred medicinal products. Hot-melt extrusion is a flexible and continuously operating technique which is a crucial part of a typical processing cycle of printed medicines. In this work we use hot-melt extrusion for manufacturing of medicinal films containing indomethacin (IND) and polycaprolactone (PCL), extruded strands with nitrofurantoin monohydrate (NFMH) and poly (ethylene oxide) (PEO), and feedstocks for 3D printed dosage forms with nitrofurantoin anhydrate (NFAH), hydroxyapatite (HA) and poly (lactic acid) (PLA). These feedstocks were printed into a prototype solid dosage form using a desktop 3D printer. These model formulations were characterized using near-infrared chemical imaging (NIR-CI) and, more specifically, the image analytical data were analysed using multivariate curve resolution-alternating least squares (MCR-ALS). The MCR-ALS algorithm predicted the spatial distribution of IND and PCL in the films with reasonable accuracy. In the extruded strands both the chemical mapping of the components in the formulation as well as the solid form of the active compound could be visualized. Based on the image information the total nitrofurantoin and PEO contents could be estimated., The dehydration of NFMH to NFAH, a process-induced solid form change, could be visualized as well. It was observed that the level of dehydration increased with increasing processing time (recirculation during the mixing phase of molten PEO and nitrofurantoin). Similar results were achieved in the 3D printed solid dosage forms produced from the extruded feedstocks. The results presented in this work clearly demonstrate that NIR-CI in combination with MCR-ALS can be used for chemical mapping of both active compound and excipients, as well as for visualization of solid form variation in the final product. The suggested NIR-CI approach is a promising process control tool for characterization of innovative patient-centred medicinal products.

Interleukin-1ß (IL-1ß) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE.

BACKGROUND & OBJECTIVES: Interleukin-1 (IL-1) is one of the pro-inflammatory cytokines that plays a main role in the regulation of immune and inflammatory responses. Interleukin 4 (IL-4) as an anti-inflammatory cytokine regulates balance between Th1 and Th2 immune responses. this study was undertaken to investigate the IL-1ß and IL-4 genes polymorphisms in patients with systemic lupus erythematosus (SLE) and also association between the polymorphisms and susceptibility to SLE. METHODS: One hundred and sixty three SLE patients and 180 healthy controls were genotyped for the IL-4 VNTR (variable number tandem repeat), IL-1ß C-511T and IL-1ß T-31C polymorphisms by polymerase chain reaction (PCR) or PCR-RFLP (restriction fragment length polymorphism) method. RESULTS: The frequencies of CC genotype and C allele of the IL-1ß T-31C polymorphism were significantly (P<0.01) lower in SLE patients than controls. Moreover, the frequencies of RP1/RP2 genotype and RP2 allele of IL-4 VNTR polymorphism were significantly (P<0.05) higher in the SLE patients. No association was observed between IL-1ß C-511T polymorphism and increased risk of SLE. We observed increased frequency of CT and TT genotypes of IL-1ß C-511T polymorphism in SLE patients with malar rash compared to SLE patients without this manifestation. INTERPRETATION & CONCLUSIONS: The present findings suggest that IL-1ß T-31C and IL-4 VNTR polymorphisms but not IL-1ß C-511T polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes of IL-1ß C-511T polymorphism were associated with SLE.