Clinical features and bleeding risk factors of angiodysplasia lesions in a Tunisian population.

INTRODUCTION: Gastrointestinal angiodysplasia (GIAD) is the most common vascular anomaly in the gastrointestinal (GI) tract, yet little is known about the factors favoring their bleeding. Our study aim was to determine the characteristics of patients with GIAD lesions in a Tunisian population and identify the risk factors of bleeding. PATIENTS AND METHODS: A retrospective study was carried out from January 2010 to February 2020 at a tertiary care medical center in Tunisia. Clinical and endoscopic data were collected from each patient's medical reports. We divided the patients into two groups: group A, patients with symptomatic GIAD; and group B, patients with incidental lesions. Group A was subsequently divided into two subgroups, according to the presence or absence of recurrent bleeding. The groups were compared by clinical, laboratory, and endoscopic features. RESULTS: GIAD was diagnosed in 114 patients, with a mean age of 70 ±â€¯13.3 years. GIAD lesions were mainly located in the colon (n = 72, 63%). Fifty-four patients (47%) presented with GIAD-related bleeding. The bleeding diagnosis was made during endoscopic procedures by visualizing active bleeding and the stigmata of recent hemorrhage in 10 (18.5%) and 12 (22.2%) cases, respectively. Most of the patients were treated by argon plasma coagulation (93%). Predictive factors of bleeding were age > 75 years, number of lesions >10, chronic kidney disease, diabetes mellitus, and coronary artery disease (p: 0.008; 0.002; 0.016; 0.048; and 0.039, respectively). CONCLUSION: Knowledge of the predictive factors of bleeding aids endoscopists in the decision-making process in cases of angiodysplasia.

Comparison of clinicodemographic characteristics and pattern of vascular involvement in 126 patients with Takayasu arteritis: a report from Iran and Turkey.

Takayasu arteritis (TA) is an extremely uncommon vasculitis that primarily affects the aorta and its branches. Due to the genetic and ethnicity effect, a diverse array of TA clinical manifestations has been reported worldwide. The purpose of the present study was to compare the clinicodemographic characteristics and pattern of vascular involvement of Iranian and Turkish TA patients. This study was a retrospective, cross-sectional investigation of 126 TA patients in Iran and Turkey. All of the variables analyzed were extracted from historical medical records. In 126 TA patients, the ratio of females to males was 8.6:1, and the average age at onset of disease was 30.5±11.1 years. Fatigue (49.2%) and a weak or absent pulse (79.4%) were the most prevalent symptoms and signs, respectively. The most prevalent angiographic classifications were types V and I in Iranian patients (41.09%) and type I in the Turkish population (47.7%) The left subclavian artery was the vessel most frequently affected by TA (66.6%). Our findings indicated that there were no significant differences between the two countries in terms of clinicodemographic characteristics or vascular involvement. Some clinical manifestations, such as claudication, were more prevalent in the Turkish population due to a higher incidence of occlusive lesions in the right subclavian artery.

Identification of Acanthamoeba spp. from water and soil of public parks in the north of Iran.

Acanthamoeba, a free-living and opportunistic protozoan parasite, is a causative agent of severe human infections of the cornea and brain. The present study evaluated the distribution and genotyping of Acanthamoeba spp. in water and soil of recreational places in various areas in Guilan province in northern Iran. Eighty water and 20 soil samples were collected from the study area. Water samples were vacuum filtered through a 0.45 µm pore-size membrane filter. Soil samples were washed with sterile distilled water, and washings were similarly filtered, as mentioned for water samples. The filtered material was cultured on non-nutrient agar plates seeded with heat-killed Escherichia coli. Molecular analysis was performed by PCR and sequencing using specific primers for Acanthamoeba. Finally, 26 isolates were successfully sequenced. According to culture and PCR methods, 54% of water and 100% of soil samples were contaminated with Acanthamoeba. Based on the sequencing data, genotypes T4 (47%), T5 (35.29%), T3 (11.76%), and T11 (5.88%) were identified in water samples. Genotypes T4 (66.6%), T5 (22.2%) and T15 (11.1%) were identified in water samples. Most isolates might present a potential health hazard for humans in this region. To the best of our knowledge, this is the first comprehensive survey of water and soil of recreational areas in northern Iran and the first report on identifying genotype T15 from soil sources.

Predictive factors of difficult biliary cannulation: An experience of a tunisian tertiary center.

Introduction: Selective biliary cannulation is a prerequisite for a successful endoscopic retrograde cholangiopancreatography (ERCP). However, conventional biliary access can be difficult. The aims of our study were to determine the prevalence of difficult biliary cannulation (DBC) and its associated factors and to describe the efficiency and safety of used standard and advanced cannulation techniques. Methods: We conducted a single-center retrospective study including all patients with naïve papilla who had an ERCP procedure in Gastroenterology department of Mohamed Taher Maamouri Hospital from June 2019 to December 2021. Efficiency was defined as successful selective deep biliary cannulation. DBC was defined based on the presence of one or more of the European Society of Gastrointestinal Endoscopy (ESGE) criteria (5-5-1): more than five cannulation attempts, more than 5 min before cannulation and more than one accidental passage in the wirsung. Prevalence was measured using ESGE 5-5-1 cutoffs and chinese set cutoffs 15-10-2. Predictors of DBC were sought by univariate and multivariate analysis (SPSS software, p significant if < 0.05). Results: We included 664 patients (mean age 62 years and sex ratio M/W = 0.8). Main indication for ERCP was choledocholithiasis (67%, n = 442) followed by malignant biliary stenosis (21%, n = 138). Based on ESGE criteria, prevalence of DBC was 42.62% (n = 283). Prevalence was 21.15% when 15-10-2 cutoffs are applied in trainee-involved procedure. Cumulative biliary success rate was 96.46%. Standard cannulation method achieved access in 98.2% while advanced methods permitted success in 92.2% in fistulotomy, 94.1% in papillotomy and 77.3% in transpancreatic sphincterotomy. Independent predictive factors of DBC in multivariate analysis were: Trainee presence OR 1.80 [1.24-2.65], SOD OR 4.71 [1.11-19.88], biliary stenosis found on imaging examinations (OR 2.53 [1.63-3.92], small papilla OR 4.09 [1.82-9.17] and difficult orientation of the papilla OR 14.90 [3.28-67.62]. Conclusion: DBC is a frequent endoscopic situation. Predictors of DBC can be related to trainee involvement in the procedure, anatomical and clinical factors. A thorough understanding of these factors can actively contribute to ERCP management plans.

Pollen viability of Euro-Mediterranean orchids under different storage conditions: The possible effects of climate change.

The future impact of climate change and a warmer world is a matter of great concern. We therefore aimed to evaluate the effects of temperature on pollen viability and fruit set of Mediterranean orchids. The in vitro and controlled pollination experiments were performed to evaluate the ability of pollinia stored at lower and higher temperatures to germinate and produce fruits and seeds containing viable embryos. In all of the examined orchids, pollen stored at -20 °C remained fully viable for up to 3 years, reducing its percentage germination from year 4 onwards. Pollinia stored at higher temperatures had a drastic reduction in vitality after 2 days at 41-44 °C, while pollinia stored at 47-50 °C did not show any pollen tube growth. The different levels of pollen viability duration among the examined orchids can be related to their peculiar reproductive biology and pollination ecology. The germinability of pollinia stored at lower temperatures for long periods suggests that orchid pollinia can be conserved ex situ. In contrast, higher temperatures can have harmful effects on the vitality of pollen and consequently on reproductive success of the plants. To our knowledge, this is the first report demonstrating the effects of global change on orchid pollen, and on pollen ability to tolerate, or not, higher air temperatures. Although vegetative reproduction allows orchids to survive a few consecutive warm years, higher temperatures for several consecutive years can have dramatic effects on reproductive success of orchids.

The role of graphene oxide interlayer on corrosion barrier and bioactive properties of electrophoretically deposited ZrO2-10 at. % SiO2 composite coating on 316 L stainless steel.

In order to overcome the poor adhesion of zirconia-silica coating electrophoretically deposited on 316 L stainless steel, graphene oxide (GO) was used as an interlayer. The effect of this interlayer on morphological, microstructural, corrosion performance and bioactivity behavior of ZrO2-10 at. % SiO2 coating was studied. The zirconia-silica coating with the GO interlayer revealed a higher barrier performance as a more compact and a greater adhesive layer to the substrate was created. Indeed, the GO interlayer led to an improvement in apatite formation on zirconia-silica coating surface probably due to create higher roughness. Briefly, the GO interlayer was effective on enhancement of electrochemical performance and biological property of zirconia-silica composite coating, making it a suitable candidate for biomaterials applications.

Predictors of Favorable Outcome after Endovascular Thrombectomy in MRI: Selected Patients with Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Clinical outcomes after endovascular treatment for acute basilar artery occlusions need further investigation. Our aim was to analyze predictors of a 90-day good functional outcome defined as mRS 0-2 after endovascular treatment in MR imaging-selected patients with acute basilar artery occlusions. MATERIALS AND METHODS: We analyzed consecutive MR imaging-selected patients with acute basilar artery occlusions endovascularly treated within the first 24 hours after symptom onset. Successful and complete reperfusion was defined as modified TICI scores 2b-3 and 3, respectively. Outcome at 90 days was analyzed in univariate and multivariate analysis regarding baseline patient treatment characteristics and periprocedural outcomes. RESULTS: One hundred ten patients were included. In 10 patients, endovascular treatment was aborted for failed proximal/distal access. Overall, successful reperfusion was achieved in 81.8% of cases (n = 90; 95% CI, 73.3%-88.6%). At 90 days, favorable outcome was 31.8%, with a mortality rate of 40.9%; the prevalence of symptomatic intracranial hemorrhage within 24 hours was 2.7%. The median time from symptom onset to groin puncture was 410 minutes (interquartile range, 280-540 minutes). In multivariable analysis, complete reperfusion (OR = 6.59; 95% CI, 2.17-20.03), lower pretreatment NIHSS (OR = 0.77; 95% CI, 0.64-0.94), the presence of posterior communicating artery collateral flow (OR = 2.87; 95% CI, 1.05-7.84), the absence of atrial fibrillation (OR = 0.18; 95% CI, 0.03-0.99), and intravenous thrombolysis administration (OR = 2.75; 95% CI, 1.04-7.04) were associated with 90-day favorable outcome. CONCLUSIONS: In our series of MR imaging-selected patients with acute basilar artery occlusions, complete reperfusion was the strongest predictor of a good outcome. Lower pretreatment NIHSS, the presence of posterior communicating artery collateral flow, the absence of atrial fibrillation, and intravenous thrombolysis administration were associated with favorable outcome.

The clinical value of the delta finger to palm distance in systemic sclerosis.

Systemic sclerosis (SSc) is a collagen-vascular disorder characterized by fibrosis and vasculopathy. Delta finger to palm distance (delta FTP) is an index measuring the distance between the tip of the third finger to the distal palmar crease in the flexed and extended position. The present study aimed to evaluate the clinical value of delta FTP and to assess the correlation of delta FTP with modified Rodnan skin score (mRSS) and forced vital capacity (FVC) over the 12-month follow-up. This prospective longitudinal study began with 50 participants who were followed for twelve months. Lowess smoothing and linear regression were applied to detect and assess the relationship between delta FTP and mRSS. p-values were adjusted by the Benjamini-Hochberg method (BHM) as a control for false discovery rate. Delta FTP was lower among patients with higher disease duration (p-valueadj: 0.008), diffuse cutaneous SSc (p-valueadj: 0.006), digital ulcers (p-valueadj: 0.003), telangiectasia (p-valueadj: 0.006) and dysphagia (p-valueadj: 0.036). The mRSS has a significant negative linear effect on the delta FTP at the baseline and the end of the follow-up (r: -0.31 and -0.40, respectively). Moreover, changes of mRSS and delta FTP showed a negative linear association over time (r: -0.22). These linear effects remained significant after regrouping the patients based on their SSc subtype. Delta FTP and FVC were not correlated either at the baseline or at the end. It seems that the delta FTP can be a valuable clinical index, supported by its correlated changes with mRSS and other SSc clinical manifestations over the one-year follow-up.

Rapid and direct molecular detection of Streptococcus pneumoniae and Haemophilus influenzae isolated in oropharynx and nasal cavity of children.

There is a direct correlation between asymptomatic oropharyngeal colonization by pathogenic bacteria and the prevalence of paediatric respiratory infections. Streptococcus pneumoniae and Haemophilus influenzae are common cause of serious bacterial infections such as meningitis in children. This study aimed to monitor healthy children to detect asymptomatic carriers of S. pneumoniae and H. influenzae. In the present cross-sectional study, real-time PCR assay was developed and evaluated in comparison with culture for direct detection of S. pneumoniae and H. influenzae in 123 oropharynx and nasal cavity specimens from healthy children in Ilam, Iran. In addition, virulence factor (ply and hpd) and iron uptake (tbpA and piuA) genes were evaluated by PCR. Our results demonstrated that among all isolates only 14 S. pneumoniae and eight H. influenzae were identified by phenotypic methods, whereas 37 and 21 S. pneumoniae and H. influenzae were identified, respectively, by real-time PCR assay. All S. pneumoniae and H. influenzae isolates possessed tbpA and piuA genes. Also, 81% (30/37) of S. pneumoniae isolates were positive for ply gene, which encoded pneumolysin, as well as 90% (19/21) of H. influenzae isolates were positive for hpd gene. Simultaneous colonization of S. pneumoniae and H. influenzae could indicate the importance of monitoring of healthy children to identification of carriers.

Report of Giardia assemblages and giardiasis in residents of Guilan province-Iran.

Giardia duodenalis is considered a highly diverse organism that infects a variety of mammalian hosts. Giardiasis is a significant public health problem in Iran. The purpose of this study was to investigate the occurrence of Giardia duodenalis (G. lamblia, G. intestinalis) infections in humans residing in the Guilan province of Iran. Stool samples were collected during 12 months from 8356 individuals that had been referred to certain hospitals in the capital city of Rasht in the Guilan province, of which 4126 were males and 4230 were females. The samples were separated into three groups according to patient age: group A 1-9 years old (n = 483); group B 10-19 years old (n = 491); and group C greater than 20 years old (n = 7382). The wet mount technique was performed directly on 8356 fecal samples for microscopy. Samples were examined using a saline and iodine direct smear technique in order to confirm the presence of G. duodenalis. The results indicated that 2.5% (206/8356) of the samples were identified as positive for G. duodenalis. A total of 30% of the infected patients (n = 62) had no symptoms. In symptomatic cases, the most common symptoms (46%, n = 95) were abdominal cramps and bloating. Twenty-four percent of patients (n = 50) had cramps, bloating, nausea, and diarrhea. Sixty positive samples were sent for G. duodenalis genotyping based on the amplification of the gdh gene. Forty-one PCR products were successfully selected and sequenced, where 38 (92.6%) samples were identified as genotype A/subgenotype II and in three samples (7.4%) genotype B/subgenotype IV. Genotype A-II had a dominant prevalence as compared to the genotype B-IV samples that were identified in the study. Based on the samples provided by the regional teaching hospitals and subsequent sample analysis, the authors concluded that assemblage A-II is most likely the most common Giardia subgroup infection in the Guilan region. Assemblages have been reported in both humans and animals; however, further studies need to investigate the role of domestic animals and water reservoirs as potential sources of Giardia infection in the Guilan region.

Giant Goos-Hänchen shift in two different enantiomers' chiral molecules via quantum coherence.

The Goos and Hänchen (GH) shifts in reflected and transmitted probe light through a cavity mixture of left- and right-handed chiral molecules into two enantiomer states are investigated. Due to the broken mirror symmetry of the left- and right-handed chiral molecules in the presence of cyclic population transfer, such quantum systems can be selectively excited because of the coexistence of one- and two-photon transitions. With the help of coupling Rabi frequency and damping effects due to scattering processes, the generated GH shifts accompanied by simultaneously negative and positive lateral shifts in reflected and transmitted probe lights are greatly enhanced. It is found that the large negative and positive GH shifts are available in the presence of multiphoton resonance and off-resonance conditions for two different enantiomers' chiral molecules. Moreover, the switching between superluminal and subluminal light propagation is extremely dependent on choosing the left- and right-handed chiral molecules. Furthermore, the effects of pulse shape and mode of Laguerre-Gaussian probe light on the GH shifts that lead to a switch between negative and positive shift are also studied. The negative and positive GH shifts in a reflected and transmitted probe beam for an incident Gaussian and different mode of Laguerre-Gaussian shaped beam with various widths by the use of two different enantiomers' chiral molecules are also discussed.

Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-Beta1 in Iranian children with atopic dermatitis

Background: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. Objective: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-Beta1 gene polymorphisms. Methods: The allele and genotype frequencies of genes encoding for IL-10 and TGF-Beta1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. Results: A significant increase was found in the frequency of the TGF-Beta1 codon 10/C allele among patients (p < 0.001, OR = 6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p < 0.001, OR = 0.14). The frequency of the TGF-Beta1 codon 25/G allele in the control group was significantly higher than among patients (p < 0.001, OR = 0.08). A significant positive correlation was seen between CC (p < 0.001, OR = 15.10) and CG (p < 0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-Beta1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p = 0.042). A significant increase was found in the frequency of TGF-Beta CC (36% in patients vs. 7.6% in controls, p < 0.001) and TC (14% in patients vs. 0% in controls, p < 0.001) haplotypes among patients compared to controls. By contrast, the TGF-Beta1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p < 0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. Conclusions: We found a strong association between the polymorphisms of the TGF-Beta1 gene at codon 10 and codon 25 positions and atopic dermatitis (AU)

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Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-ß1 in Iranian children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. OBJECTIVE: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-ß1 gene polymorphisms. METHODS: The allele and genotype frequencies of genes encoding for IL-10 and TGF-ß1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. RESULTS: A significant increase was found in the frequency of the TGF-ß1 codon 10/C allele among patients (p<0.001, OR=6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p<0.001, OR=0.14). The frequency of the TGF-ß1 codon 25/G allele in the control group was significantly higher than among patients (p<0.001, OR=0.08). A significant positive correlation was seen between CC (p<0.001, OR=15.10) and CG (p<0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-ß1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p=0.042). A significant increase was found in the frequency of TGF-ß CC (36% in patients vs. 7.6% in controls, p<0.001) and TC (14% in patients vs. 0% in controls, p<0.001) haplotypes among patients compared to controls. By contrast, the TGF-ß1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p<0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. CONCLUSIONS: We found a strong association between the polymorphisms of the TGF-ß1 gene at codon 10 and codon 25 positions and atopic dermatitis.

Association of killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands with susceptibility to Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder with remissions and exacerbations. It is thought that defects in the natural killer (NK) cell repertoire may be involved in BD through killer cell immunoglobulin-like receptors (KIRs). This study aimed to evaluate KIR and HLA genes, their interactions in BD patients, and their associations with clinical manifestations. METHOD: The presence or absence of KIR and HLA alleles and genotypes was analysed by polymerase chain reaction sequence-specific primer on genomic DNA of 397 BD patients and 300 healthy controls. RESULTS: None of the KIR genes showed significant effects on BD susceptibility. HLA-C1Asn80 showed a protective effect against BD, whereas HLA-C2Lys80, HLA-B-Bw4Ile80, HLA-B5, and HLA-B51 were associated with a susceptibility risk for BD. In the combination of KIR and HLA genes, the frequencies of HLA genotypes no. 2, 3, 5, and 8, and inhibitory KIR no. 4 were significantly higher in patients than in controls. The frequencies of KIR genotype no. 3 and HLA genotypes no. 1, 4, 6, 7, and 9 were significantly lower in patients than in controls. There were many associations between KIR and HLA genes with clinical features of BD. CONCLUSION: Differences in the frequency of HLA genes, KIR-HLA interactions, and genotypes between BD and healthy controls and their associations with clinical manifestations indicate that NK cells are involved in BD pathogenesis. The observed differences indicated an NK cell activity imbalance in BD patients, and suggest a role of the KIR-HLA repertoire in the development of BD.

Gene expression and levels of IL-6 and TNFα in PBMCs correlate with severity and functional class in patients with chronic heart failure.

BACKGROUND: Evidence shows that proinflammatory cytokines are important determinants of assessment of severity and prognosis of chronic heart failure (CHF). AIMS: We investigated whether peripheral expression of the proinflammmatory factors, TNF-α and IL-6 can predict variable of clinical assessment of patients with CHF. METHODS: In this report, we used real-time PCR assay to compare relative gene expression of TNFα and IL-6 in PBMC from CHF patients with various heart diseases (n = 42, EF < 45%, NYHA I to IV) and matched healthy control subjects (n = 42).We also determined the TNFα and IL-6 concentrations of cell culture supernatant of PBMCs with ELISA. RESULTS: There was a significant negative correlation between gene expression of TNFα and LVEF(r = 0.4, p < 0.05). Patients with CHF had increased gene expression of TNFα and IL-6 in PBMCs (p < 0.05). They also had elevated the supernatant levels of these cytokines in cultured PBMCs (p < 0.001). Levels of TNFα and IL-6 were increased in ischemic heart disease compared to non-ischemic heart disease. There was a positive correlation between TNFα and IL-6 levels in CHF patients and severity of CHF in patients. Levels of these cytokines were higher in patients with NYHA III-IV than in NYHA I-II and normal subjects. CONCLUSIONS: Results of this study indicate that peripheral expression of proinflammatory cytokines, TNF-α and IL-6, is important indicators of severity and prognosis in patients with chronic heart disease.

FOXP3, RORγt and IL-10 cytokine profile in chronic heart failure.

BACKGROUND: Distinct subsets of T cells play crucial regulatory roles in inflammatory processes of chronic heart failure (CHF). Retinoic acid receptor-related orphan receptor-γt (Ror-γt) and Forkhead box P3 (Foxp3) have been defined as the "master regulators" of Th17 cells and Treg cells, respectively. At the same time, anti-inflammatory cytokines such as IL-10 may neutralize inflammation in CHF. The current study was designed to compare FOXP3, RORγt and IL-10 protein expression in the blood and IL-10 in supernatant PBMCs in CHF patients versus normal subjects. PATIENTS AND METHODS: Our study population consisted of 42 patients with CHF in four different function classes and 42 healthy subjects who served as controls. RNA extraction and cDNA synthesis was performed and mRNA expression for genes FOXP3, RORγt, IL-10 was determined by RT-PCR. The amount of IL-10 protein in supernatant of PBMCs was measured by ELISA technique. RESULTS: There was no significant difference in FOXP3, RORγt, IL-10 protein expression and supernatant PBMCs IL-10 in CHF patients as compared to control. The level of Foxp3 was significantly lower in CHF patients with ischemic vs non-ischemic cause (p = 0.04). DISCUSSION: Although inflammation plays a central role in the pathophysiology of CHF, the roles of FOXp3, RORγt, and IL-10 remain to be determined (Tab. 3, Ref. 33).

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles.

Following exposure to biological milieus (e.g. after systemic administration), nanoparticles (NPs) get covered by an outer biomolecular corona (BC) that defines many of their biological outcomes, such as the elicited immune response, biodistribution, and targeting abilities. In spite of this, the role of BC in regulating the cellular uptake and the subcellular trafficking properties of NPs has remained elusive. Here, we tackle this issue by employing multicomponent (MC) lipid NPs, human plasma (HP) and HeLa cells as models for nanoformulations, biological fluids, and target cells, respectively. By conducting confocal fluorescence microscopy experiments and image correlation analyses, we quantitatively demonstrate that the BC promotes a neat switch of the cell entry mechanism and subsequent intracellular trafficking, from macropinocytosis to clathrin-dependent endocytosis. Nano-liquid chromatography tandem mass spectrometry identifies apolipoproteins as the most abundant components of the BC tested here. Interestingly, this class of proteins target the LDL receptors, which are overexpressed in clathrin-enriched membrane domains. Our results highlight the crucial role of BC as an intrinsic trigger of specific NP-cell interactions and biological responses and set the basis for a rational exploitation of the BC for targeted delivery.

Promoter hypermethylation of BCL11B gene correlates with downregulation of gene transcription in ankylosing spondylitis patients.

Methylation of DNA is one of the important regulatory mechanisms of gene transcription. B-cell chronic lymphocytic leukemia/lymphoma 11B (BCL11B) plays a key role in the development, proliferation, differentiation, and survival of T cells. The aim of this study was to evaluate promoter methylation of BCL11B gene and its mRNA level in peripheral blood mononuclear cells (PBMCs) of ankylosing spondylitis (AS) patients in relation to healthy controls and evaluate their correlation with diseases clinical indices. Fifty AS patients and 50 healthy controls entered in this study. PBMCs were isolated from whole blood and RNA and DNA contents of leukocytes were extracted. The expression level of BCL11B gene was measured through real-time PCR assay using SYBR Green Master Mix, and PCR products of bisulfite-treated DNA were sequenced to determine the methylation level of promoter. Decreased transcript and increased promoter methylation levels of BCL11B gene were identified in AS patients compared with healthy controls. Hypermethylation of CpG3 and CpG5 was associated with increased AS risk. Promoter hypermethylation and mRNA overexpression correlated with each other but not with clinical manifestations. We identified aberrancies in expression and methylation of BCL11B gene in AS patients compared with healthy control group; however, they might not impress the clinical face of AS.

M2000 (ß-D-Mannuronic Acid) as a Novel Antagonist for Blocking the TLR2 and TLR4 Downstream Signalling Pathway.

To date, selective blockade of Toll-like receptor (TLR) signalling has been developed as a new approach for treatment for many inflammatory diseases. As ß-D-mannuronic acid (M2000) has been known as an anti-inflammatory molecule in several experimental models, we investigated the antagonistic effects of M2000 on TLR2 and TLR4 downstream signalling transduction pathway in human embryonic kidney (HEK) 293 cell lines overexpressing TLR2/CD14 and the TLR4/MD2/CD14 complex, respectively. M2000 effectively inhibited mRNA expression of MyD88 and p65, major subunit of nuclear factor-κB, in HEK293 cells stimulated by lipoteichoic acid (LTA, a TLR2 agonist) and lipopolysaccharide (LPS, a TLR4 agonist) with no evidence of cytotoxicity. In addition, M2000 also suppressed LTA and LPS-induced production of TNF-α and IL-6 inflammatory cytokines in these cells. Furthermore, the results revealed that M2000 had no significant effect on Tollip mRNA expression as a negative regulator of TLR signalling in aforesaid cells. Overall, these data point to M2000 inhibitory effect on Toll-like receptor (TLR) 2, 4 signalling in HEK293 cells. This information might provide new insights into the possible roles of this small drug in order to introduce it as a TLR signalling pathway inhibitor. However, more studies are needed to confirm ß-D-mannuronic acid antagonistic effects including the effects of M2000 on peritoneal isolated macrophages and also on blood cells in patients with inflammatory diseases such as ankylosing spondylitis.

Association of interleukin-2 and interferon-γ single nucleotide polymorphisms with Juvenile systemic lupus erythematosus

Purpose: Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes in a case control study. Materials and methods: The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at −330, rs2069762, and G/T at +166, rs2069763) and IFN-γ (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. Results: Results of the analysed data revealed a negative allelic association for JSLE in IL-2 −330/T (P=0.02), as well as a positive allelic association for IL-2 −330/G (P=0.02). IL-2 GG genotype (−330) in the patient group was also significantly overrepresented (P<0.001), while IL-2 GT genotype (−330) was notably decreased in the patients with JSLE (P<0.001). Additionally, the frequency of IL-2 (−330, +166) GT haplotype was significantly higher in the patient group (P<0.001). Conclusion: IL-2 cytokine gene polymorphisms could affect individual susceptibility to JSLE and can take on the role of possible genetic markers for vulnerability to JSLE

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