Effect of Neem (Azadirachta indica) versus 2.5% sodium hypochlorite as root canal irrigants on the intensity of post-operative pain and the amount of endotoxins in mandibular molars with necrotic pulps: a randomized controlled trial.

AIM: To assess the effect of Neem versus 2.5% NaOCl as root canal irrigants on the intensity of post-operative pain and amount of endotoxins following root canal treatment of mandibular molars with necrotic pulps. METHODOLOGY: This parallel, prospective, double-blinded, randomized controlled trial with allocation ratio 1:1 was conducted in the out-patient clinic of the Endodontic Department, Faculty of Dentistry, Cairo University, Egypt. Fifty healthy patients with mandibular molars with necrotic pulps were randomly assigned into two equal groups using computer software. In the intervention group, root canals were irrigated using Neem; whilst 2.5% NaOCl was used in the control group. A standard root canal treatment was performed in two visits using ProTaper Next rotary files, with no intracanal medication. Pain intensity was assessed using a numerical rating scale (NRS) 6, 12, 24 and 48 h following instrumentation and canal filling. Endotoxin samples were collected using three paper points before and after canal instrumentation and a sandwich ELISA method was used to quantify the level of endotoxins. Demographic, baseline, and outcome data were collected and analysed using chi-square tests (for the comparisons of categorical variables), Mann-Whitney tests (for non-normally distributed variables) and Student's t tests (for normally distributed variables), A P-value < 0.05 was considered to be statistically significant. RESULTS: The mean pain scores within the two groups decreased continually over time. The mean pain scores in the Neem group were lower than those in the 2.5% NaOCl group at 6, 12, 24 and 48 h following instrumentation and canal filling with no significant difference between them except at 24 h following instrumentation (P = 0.012). Both irrigants significantly reduced endotoxin levels compared to the pre-instrumentation samples (P < 0.001) by 8% for the NaOCL group and 18% for the Neem group. CONCLUSION: Neem and 2.5% NaOCl were not significantly different in terms of reducing the intensity of post-operative pain during all follow-up periods except at 24 h following instrumentation where Neem was associated with lower pain intensity. Both irrigants significantly reduced endotoxin levels but were not effective in eliminating endotoxins completely from root canals of mandibular molars with necrotic pulps.

The anti-aging protein alpha-Klotho in systemic sclerosis patients: does a relationship to telangiectasia exist?

OBJECTIVE: The anti-aging protein alpha-Klotho has been reported to have an emerging role in the pathogenesis of systemic sclerosis (SSc). More studies are needed to approach this issue. This study aimed to assess the serum levels of α­Klotho in SSc patients compared to healthy controls, and to correlate them with the disease parameters. METHODS: Forty-two SSc patients were included in this study. History taking, clinical examination, and related investigations were performed. The modified Rodnan skin score (mRss) was used to assess skin tightness in SSc patients. Twenty-seven age- and sex-matched healthy participants served as controls. Serum α­Klotho was assessed in the two groups. RESULTS: SSc patients comprised 39 females and 3 males; mean age was 42.2 ± 12.1 years and mean disease duration 8.5 ± 6.3 years. Serum α­Klotho levels were decreased in scleroderma patients in comparison to healthy controls (p < 0.001). Scleroderma patients who had higher frequencies of telangiectasias and digital ischemic lesions had higher serum α­Klotho levels (p = 0.01 and p = 0.04, respectively). By simple regression, only telangiectasias were significantly associated with higher α­Klotho levels (p = 0.01). No other significant relationships were found between serum α­Klotho and SSc disease parameters. CONCLUSION: Scleroderma patients had significantly lower serum α­Klotho levels than healthy controls. Higher α­Klotho levels were significantly associated with telangiectasias. An imbalance in serum α­Klotho levels may be involved in systemic sclerosis. Further longitudinal studies in a larger population of systemic sclerosis patients may provide a clearer clue for its role.

Measurement of serum interferon alpha in Egyptian patients with systemic lupus erythematosus and evaluation of its effect on disease activity: a case-control study.

Much evidence highlighted the role of interferon alpha (IFN-α) in systemic lupus erythematosus (SLE) and suggested its possible role in assessing disease activity. We measured serum IFN-α in Egyptian SLE patients in order to determine a cutoff value that can be used to distinguish patients from healthy controls and explored its clinical value in monitoring disease activity and different aspects of the disease, in particular lupus nephritis. This cross-sectional, case-control study was conducted on 59 SLE patients and 30 healthy controls. Serum IFN-α was measured in all participants using sensitive enzyme-linked immunosorbent assay (ELISA). SLE patients underwent assessment of disease activity using the SLE disease activity index-2000 (SLEDAI-2K) as well as an evaluation of proteinuria, complement C3 and C4, and serology. Patients with evidence of renal involvement underwent renal biopsy. The median serum IFN-α was 81.8 pg/mL (interquartile range [IQR] 63.4:102.4), which was significantly higher than in healthy controls (median 10.3 pg/mL [IQR 7.3:11.6]) (p<0.001). At serum level of 14.7 pg/mL, IFN-α has high sensitivity and specificity to discriminate SLE patients from controls, with high positive and negative predictive values. Serum IFN-α was not associated with markers of disease activity, clinical features and anti-double stranded DNA. Furthermore, it was not associated with markers of renal activity, including proteinuria, C3 and C4 complement factors and histopathology renal classes. Despite elevated levels of serum IFN-α in SLE patients, it is not possible to use it as a biomarker for disease activity.

Detection of antibiotic susceptibility by colorimetric minimum inhibitory concentration in staphylococcal isolates.

AIM: Assess performance of broth microdilution (BMD) as well as agar dilution methods for antimicrobial susceptibility testing of Staphylococci using tetrazolium salt. METHODS AND RESULTS: Minimum inhibitory concentration (MIC) of eight antimicrobials; vancomycin (VA), linezolid, oxacillin, gentamicin (CN), tetracycline, ciprofloxacin, erythromycin and clindamycin was investigated for 80 isolates of Staphylococci by BMD with the addition of dimethyl thiazole diphenyl tetrazolium bromide (MTT), agar dilution with the addition of MTT and triphenyl tetrazolium chloride at the standard bacterial concentration together with addition of MTT at an experimental bacterial concentration. BMD (MTT) showed the highest agreement in comparison with the standard BMD. CONCLUSIONS: Colorimetric BMD was rapid and easy to interpret. Colorimetric agar dilution (MTT) was less tedious than BMD. SIGNIFICANCE AND IMPACT OF THE STUDY: Colorimetric antibiotic susceptibility is a good option to provide rapid reliable results for critically ill patients. In addition, agar dilution (MTT) helps to investigate outbreaks of methicillin-resistant Staphylococcus aureus (MRSA), VISA or VRSA. BMD (MTT) can be performed routinely to detect VA MIC in MRSA blood stream infections and hospital acquired pneumonia, where, high VA MIC is associated with a higher mortality rate.

Serum microRNAs as predictors for liver fibrosis staging in hepatitis C virus-associated chronic liver disease patients.

Accurate staging of liver fibrosis is important for clinical decision making and personalized management. Liver fibrosis is influenced by patients' genomics, including IFNL3 genotype and microRNA expression. However, incorporating microRNAs into fibrosis prediction algorithms has not been investigated. We examined the potential of eight selected serum microRNAs; miR-122, miR-126, miR-129, miR-199a, miR-155, miR-203a, miR-221, and miR-223 as non-invasive biomarkers to stage liver fibrosis in HCV-associated chronic liver disease (HCV-CLD). 145 Egyptian HCV-CLD patients were divided according to Metavir fibrosis scores. MicroRNAs and IFNL3 rs12979860 genotype were assayed by RT-qPCR and allelic discrimination techniques, respectively. Serum miR-122 was downregulated, whereas miR-203a and miR-223 were upregulated in significant fibrosis (≥F2) compared with no/mild fibrosis (F0-F1). Serum miR-126, miR-129, miR-203a, and miR-223 were upregulated in severe fibrosis (≥F3) and cirrhosis (F4) compared with F0-F2 and F0-F3, respectively. miR-221 was upregulated in ≥F3, but unchanged in F4. miR-155, miR-199a, and IFNL3 rs12979860 genotype were not significantly different in all comparisons. Differentially expressed serum microRNAs discriminated ≥F2, ≥F3, and F4 by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a model combining miR-129, miR-223, AST, and platelet count with high diagnostic accuracy for ≥F3 (AUC=0.91). The model also discriminated F4 (AUC=0.96) and ≥F2 (AUC=0.783), and was superior to APRI and FIB-4 in discriminating ≥F3 and F4, but not ≥F2. In conclusion, combining serum microRNAs with baseline predictors could serve as a new non-invasive algorithm for staging HCV-associated liver fibrosis. Additional studies are required to confirm this model and test its significance in liver fibrosis of other etiologies.

Corticotropin-releasing hormone (CRH) and CRH receptor 1 gene expression in vitiligo.

BACKGROUND: Vitiligo is a disorder characterized by depigmented patches in the skin. Psychological stress can activate the hypothalamic-pituitary-adrenal axis in the brain as well as on the peripheral level and aggravate autoimmune skin diseases. Skin appendages have dual functions dually as prominent targets and sources of the peripheral corticotropin-releasing hormone (CRH)-proopiomelanocortin axis. AIM: To assess the role of CRH and CRHR-1 in vitiligo, and its possible association with psychological stress. METHODS: In total, 30 patients with vitiligo and 30 healthy controls were collected from the outpatient clinic. Expression of CRH and CRHR-1 was measured by real-time PCR in lesions and control skin. RESULTS: A significant increase in CRH and CRHR-1 expression was significantly correlated with psychological stress in vitiligo. CONCLUSION: We conclude that CRH and CRHR-1 are altered by psychological stress and play an important role in the pathogenesis of vitiligo.

Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection.

Hepatitis C virus (HCV) infection represents a serious health problem. The -174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is associated with developing liver diseases. Likewise, the S and Z mutations in the serine protease inhibitor α1-antitrypsin (A1AT) are associated with pulmonary emphysema and/or liver cirrhosis. We explored the distribution of the single nucleotide polymorphisms (SNPs) of IL-6 and A1AT genes in chronic HCV-infected patients and evaluated their impact on the progression of liver cirrhosis. One hundred and fifty Egyptian HCV-infected patients together with 100 healthy controls were enrolled in this study. The patient groups were subdivided into chronic hepatitis patients (n = 85) and cirrhotic patients (n = 65). The SNP of IL-6 (-174 G/C, rs1800795), A1AT Z mutation (342 Glu/Lys, rs28929474) and A1AT S mutation (264 Glu/Val, rs17580) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Cirrhotic patients exhibited significantly increased frequency of the A1AT S allele compared with the controls (34.6 vs. 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7 vs. 2.5%). Remarkably, IL-6 (CC genotype) was detected only in the chronic hepatitis patients. Multivariate regression analysis showed that aspartate transaminase (AST) and the S alleles of A1AT, represented as SS+MS genotypes, were significantly independent predictors for development of liver cirrhosis. We concluded that inheritance of deficient S and Z alleles of the A1AT gene but not IL-6 (-174 G/C), were associated with progressive liver diseases.

Human papillomavirus (HPV) in Egyptian females: study by cytology, histopathology, colposcopy and molecular diagnosis of high risk types.

OBJECTIVES: In Northern Africa, the region Egypt belongs to, about 10.7% of women are estimated to harbour cervical human papillomavirus (HPV) infection and 78.4% of invasive cancers are attributed to HPVs 16 or 18. We aimed at comparing HPV detection by ISH-PCR tissue with other conventional available cheaper techniques, finding which of them can be relied upon in a developing country like Egypt for HPV detection. METHODS: Sixty patients were included. For them colposcopy, PAP smear, histopathology and detection of HPV using ISH PCR tissue and PCR swab were achieved. RESULTS: PCR-ISH tissue was positive in 53.33%, 46.6% were negative. Pap smear was negative in 26 cases (43.33%) and 43 cases (56.67%) were positive. LSIL with perinuclear halo represented nearly half of the positive cases (16/34; 47.05%), 10 cases were diagnosed as HSIL, 4 cases as ASCUS and 4 as AGC. Histopathology was negative in 12 (20%) cases and 48 (80%) cases were positive. CIN I and CIN I+ koliocytosis represented half of the cases (30/60) and more than half of positive cases (30/48; 62.5%). Comparing the results of pap smear, histopathology, colposcopy and PCR swab with ISH PCR tissue, highly significant results were seen with sensitivity of 87.5%, 100%, 62.5% and 56.2% respectively but the specificity were 78.6%, 42.9%, 28.6% and 100% respectively. CONCLUSION: Conventional cytology and histopathology were sensitive tests for detection of HPV. This may help for early detection of cancer cervix in a developing country like Egypt. PCR swab showed the highest specificity and the lowest sensitivity.

Salivary microRNAs in oral cancer.

OBJECTIVE: This study investigated the use of three salivary microRNAs (miRNA-21, miRNA-184, and miRNA-145) as possible markers for malignant transformation in oral mucosal lesions. MATERIALS AND METHODS: Salivary whole unstimulated samples were collected from a study group of 100 subjects, consisting of 20 clinically healthy controls, 40 patients with oral potentially malignant disorders (PMDs) [20 with dysplastic lesions and 20 without dysplasia], 20 with biopsy-confirmed oral squamous cell carcinoma (OSCC), and 20 with recurrent aphthous stomatitis (RAS) as disease controls. Total RNA was isolated and purified from saliva samples using the microRNA Isolation Kit (Qiagen, UL). miRNA expression analysis was performed using qRT-PCR (Applied Biosystems). RESULTS: There was a highly significant increase in salivary miRNA-21 and miRNA-184 in OSCC and PMD (with and without dysplasia) when compared to healthy and disease controls (P < 0.001). Conversely, miRNA-145 levels showed a highly significant decrease in OSCC and PMD overall (P < 0.001). RAS cases showed no significant difference from normal controls in any measured miRNA (P > 0.05). The only microRNA to discriminate between OSCC and PMD with dysplasia was miRNA-184. When receiver operating characteristic curves were designed for the three miRNAs, cutoff points delineating the occurrence of malignant change were a fourfold increase in miRNA-21 with specificity 65% and sensitivity 65%, a 0.6 decrease in miRNA-145, with specificity 70% and sensitivity 60%, and a threefold increase of miRNA-184, with specificity 75% and sensitivity 80%. Calculating the area under the curve revealed that miRNA-184 was the only one among the studied miRNAs that provided good diagnostic value. CONCLUSION: Salivary determination of the miRNAs tested might furnish a noninvasive, rapid adjunctive aid for revealing malignant transformation in oral mucosal lesions, particularly miRNA-184.

Estimation of vitamin D levels in patients with pemphigus vulgaris.

BACKGROUND: Keratinocyte acantholysis as a result of pathogenic Dsg3-antibodies production by B cells leads to Pemphigus vulgaris (PV). Vitamin D, through its participation in several immune modulatory functions including B cells apoptosis, Th2 cell differentiation, apoptotic enzyme regulation and Tregs functions, may be actively involved in the immune regulation of PV. OBJECTIVE: To evaluate Vitamin D status in PV patients in comparison to controls in an attempt to determine its role in this autoimmune disease. METHODS: Using ELISA technique, 25-hydroxyvitamin D (25OHD) was determined for 34 pemphigus vulgaris patients and 20 healthy volunteers. Phosphorus and parathormone were also determined in the patient group. RESULTS: 25OHD was significantly lower in patients than controls (P = 0.008). There was a statistically significant difference between both groups regarding suboptimal Vit. D levels (P = 0.007). CONCLUSION: Patients with PV have significantly lower serum vitamin D levels in comparison to controls and that these low levels were not related to age, BMI or pattern of sun exposure. The associated Vitamin D insufficiency in patients with PV may possibly exacerbate their disease through various immune related mechanisms.

Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and other hypopigmented disorders: suggestive possible therapeutic targets.

BACKGROUND: In healthy skin, there is a molecular microenvironment that favours the survival of melanocytes and regulates their function. Keratinocytes synthesize and secrete several cytokines that have stimulatory and inhibitory effects on melanocytes. AIM OF THE WORK: This work was conducted to evaluate the expression of basic fibroblast growth factor (bFGF) and tumour necrosis factor alpha (TNF-α) mRNA levels in lesional skin of vitiligo, hypopigmented mycosis fungoides and hypopigmented tinea versicolor. PATIENTS AND METHODS: Forty eight patients (25 vitiligo, 14 hypopigmented mycosis fungoides, 9 hypopigmented tinea versicolor) and 10 healthy controls were included. A 4 mm punch skin biopsy was taken from lesional skin of patients, and the normal skin of controls for quantitative PCR examination of TNF-α and bFGF mRNA. RESULTS: The level of TNF-α mRNA in lesional skin of the three studied disorders was significantly higher than in the control group, while the level of bFGF mRNA was significantly lower in lesional skin of the three diseases than the control skin. A significant inverse correlation was demonstrated between the mRNA levels of the two studied cytokines in vitiligo and hypopigmented MF lesions. CONCLUSION: The study's findings demonstrate that the studied hypopigmented (vitiligo, hypopigmented MF, hypopigmented TV) disorders show similar changes in their cutaneous microenvironment with increased TNF-α and decreased bFGF mRNA expression. This cytokine microenvironment change may be implicated in the pigment loss and hence these cytokines may have future therapeutic implications.

Detection of IL-17A and IL-17F gene polymorphism in recurrent and disseminated pityriasis versicolor: a case-control study.

Recurrent and disseminated pityriasis versicolor (RDPV) is a common clinical entity, characterized by its recurrent and disfiguring nature. Studies demonstrated host genetic variations in the immune response, especially the role of IL-17 in antifungal immunity. This study aimed to detect whether IL-17A and F gene polymorphisms are found in cases of RDPV. It included 100 cases of RDPV and 100 age and sex matched controls, from which EDTA blood samples were taken for single-nucleotide polymorphism analysis. IL-17A (rs2275913) and F (rs763780) were associated with a significantly increased incidence of developing RDPV. IL-17A and F gene polymorphism could be implicated as a risk factor for the development of RDPV.

Peroxisome proliferator-activated receptor gamma, a possible culprit in mycosis fungoides: an immunohistochemical study.

BACKGROUND: It still remains debatable whether peroxisome proliferator-activated receptor gamma (PPARγ) is pro- or antineoplastic, and its exact role in mycosis fungoides (MF) remains unclear. OBJECTIVE: This prospective comparative study aimed to investigate the expression of PPARγ in MF and compare it with psoriatics and controls in a trial to deduce its possible role in MF. Also, we tried to clarify the relation between PPARγ and Bcl-2 in MF. METHODS: Twenty MF patients, 20 psoriatic patients and 20 controls were included. All participants underwent a skin biopsy, and immunohistochemical staining for both PPARγ and Bcl-2 were performed. Western blot analysis was performed for detection of both PPARγ and Bcl-2. RESULTS: The mean area per cent of PPARγ measured in the MF patients (57.1217±9.502417) was significantly higher (P<0.001) when compared with that of both the psoriatics (2.989±1.723) and controls (35.9357±8.1789). The mean area per cent of Bcl-2 in MF patients (9.3763±6.6328) was significantly higher (P<0.001) than that of both the psoriatics (2.35±1.35) and the controls (0.73105±0.5302)]. Our results were confirmed using the western blot analysis. We detected a highly significant positive correlation between the PPARγ and Bcl-2 mean area per cents in all patients. In our MF patients, both parameters were also positively correlated with the age of the patient, duration and stage of MF (P<0.05). CONCLUSION: Our data suggest a possible role for PPARγ in the pathogenesis of MF possibly through several mechanisms, one of which might be conferring upon the lymphoma cells, a survival advantage at least partially through up regulating Bcl-2.

Effect of some medicinal plant extracts on the oxidative stress status in Alzheimer's disease induced in rats.

BACKGROUND/AIM: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Increased oxidative stress has been shown to be a prominent and early feature in AD. Medicinal plants with antioxidant activities have been used traditionally in the treatment of several human diseases. The present study aims to investigate the effect of Salvia triloba and Piper nigrum plant extracts on the oxidative stress status in Alzheimer's disease induced in rats. MATERIALS AND METHODS: 70 male rats were enrolled in this study and were classified into 7 groups (ten each). Group 1: control group, group 2: AD-induced rats by aluminum chloride, and served as positive control; group 3: AD group treated with Rivastigmine in a dose of 0.3 mg/kg b. wt. daily for three months; group 4 & 5: AD group treated with total extract of Salvia triloba in a dose of 750 or 375 mg/kg b. wt. respectively, daily for three months; group 6 & 7: AD group treated with total extract Piper nigrum in a dose of 187.5 or 93.75 mg/kg b. wt. respectively, daily for three months. After three months of treatment animals' sera and brain samples were collected. Malondialdehyde (MDA), nitric oxide (NO) and total antioxidant capacity (TAC) were determined in serum while superoxide dismutase (SOD) in erythrocyte. Brain samples were divided sagitally into two portions, the first portion was separated for determination of acetylcholine (Ach) and acetycholinesterase (AchE). The second portion was used for histopathological investigation. RESULTS: The results indicated that extracts of Salvia triloba and Piper nigrum as well as Rivastigmine showed significant increase in brain Ach, serum TAC and SOD and significant decreases in brain AchE, MDA and NO in AD-induced rats. Moreover, histological investigation of brain sections showing nearly normal histological structure of hippocampus. Treatment with Salvia triloba in a dose of 750 mg/kg b. wt. was more powerful in protection from Alzheimer's disease than Piper nigrum, as indicated by both biochemical and histopathological findings. CONCLUSION: This study revealed that the treatment of AD-induced rats with Salvia triloba and Piper nigrum, total plant extracts significantly reduced the oxidative stress status and ameliorates the neurodegeneration characteristic of Alzheimer's diseases in rats. Noteworthy, Salvia triloba extract showed more interest in improvement Alzheimer's disease in rats.

Androgen receptor-CAG repeats in infertile Egyptian men.

This study aimed to assess the androgen receptor (AR) codon amino acids glutamine (CAG) repeats in 185 Egyptian men divided into fertile controls (n = 30), oligoasthenoteratozoospermic (OAT) men (n = 35), nonobstructive azoospermic (NOA) men (n = 120; 18 successful testicular sperm extraction (TESE) and 102 unsuccessful TESE cases). They were subjected to history taking, genital examination, semen analysis, testicular biopsies for NOA cases, serum hormones and CAG repeats by PCR. The mean AR-CAG repeats showed significant difference between NOA group compared with fertile controls or OAT groups. Nonsignificant difference was elicited between OAT group and fertile controls. In NOA cases, CAG repeats demonstrated nonsignificant difference between unsuccessful and successful TESE. AR-CAG repeats elicited significant negative correlation with sperm count, significant positive correlation with sperm normal forms percentage and nonsignificant correlations with sperm motility per cent, tested serum hormones or testicular volume. It is concluded that AR-CAG repeats in Egyptian infertile men are in the range of other international or regional studies. AR-CAG repeats have demonstrated nonsignificant difference regarding TESE outcome in NOA cases.

The emerging role of lncRNA MEG3 and MEG3 rs7158663 in hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in Egypt. Genetic and environmental factors play a role in its development. This study explored the association between the long non-coding RNA (lncRNA) MEG3 rs7158663 polymorphism, MEG3 expression, and the risk of HCC and other clinicopathologic characteristics in an Egyptian population. PATIENTS AND METHODS: This case-control study included 114 patients with HCC and 110 healthy controls. TaqMan Real-time PCR was used to analyze lncRNA MEG3 rs7158663. Serum MEG3 expression levels were measured using RT-PCR. RESULTS: The AA, GA+AA, and A alleles were associated with increased risk for HCC (adjusted odds ratio (OR) 11.84%, 95% CI 4.07-34.45, p < 0.0001; adjusted OR 3.18, 95% CI 1.79-5.67, p < 0.0001; and adjusted OR 2.87, 95% CI 1.91-4.34, p < 0.0001, respectively). The mutant genotype and allele were linked to an increased risk in male patients and patients ≥ 50 years old. MEG3 serum expression level was downregulated in HCC patients. The rs7158663 G > A polymorphism and downregulated MEG3 were significantly associated with larger tumor size and advanced disease stage. CONCLUSIONS: MEG3 rs7158663 single nucleotide polymorphisms and downregulated lncRNA MEG3 were associated with HCC risk and may represent diagnostic and bad prognostic factors for HCC patients.

Role of interleukin-17 in the pathogenesis of vitiligo.

BACKGROUND: Skewing of the immune response towards T helper (Th)1 or Th17 and away from regulatory T cells (Tregs) and Th2 cells may be responsible for the development and progression of autoimmune disease. An autoimmune theory has been proposed in the pathogenesis of vitiligo. No previous reports have investigated alterations in IL-17 produced by Th17 cells in lesional skin in vitiligo. AIM: To investigate the role of IL-17 in the pathogenesis of vitiligo by assessing its levels in lesional skin and serum of patients with vitiligo compared with controls. METHODS: In total, 30 patients with vitiligo and 20 controls matched for age and gender were enrolled in the study. Serum and tissue IL-17 levels were measured by ELISA and compared between both groups for correlations with age, gender, family history, disease duration, activity of vitiligo and percentage of involved body surface area. RESULTS: A significant difference between patients and healthy controls was found for both serum and tissue IL-17 levels (P<0.001 for both). Significant positive correlations were found between disease duration and IL-17 level in both serum (r=0.42, P=0.02) and lesional skin (r=0.45, P<0.015); between extent of vitiligo and IL-17 levels in both serum (r=0.65, P<0.001) and skin (r=0.48, P<0.05); and between the serum and the tissue IL-17 levels in patients with vitiligo (r=0.54, P=0.002). CONCLUSIONS: Multiple factors have been implicated in the pathogenesis of vitiligo. The increased levels of IL-17 we found in serum and lesional skin suggest an important role for this cytokine in the pathogenesis of vitiligo.

Insulin-like growth factor-1 in psoriatic plaques treated with PUVA and methotrexate.

BACKGROUND: The pathogenesis of psoriasis is thought to depend on the activation of immune cells and their secreted cytokines, chemokines and growth factors like IGF-1 which may contribute to the epidermal hyperplasia of psoriasis. Treatment of psoriasis with PUVA and methotrexate are associated with clinical improvement and decrease in epidermal hyperplasia. OBJECTIVE: To examine the effects of PUVA and methotrexate therapy on IGF-1 expression in psoriatic plaques and whether this change correlates with clinical response. METHODS: For 24 psoriatic patients, the PASI score and levels of lesional IGF-1 and its mRNA were determined by RT-PCR before and after treatment with either methotrexate or PUVA. Skin biopsies from 12 healthy volunteers served as control for IGF-1 levels in normal skin. RESULTS: Lesional skin of psoriatic patients showed a statistically significant elevation in IGF-1 and its mRNA levels in comparison to control (P = 0.0001). Both methotrexate and PUVA treatment were associated with a significant decrease in both PASI scores and lesional IGF-1 after 10 month treatment. CONCLUSION: Both methotrexate and PUVA therapy for psoriasis are associated with a decrease in PASI score and IGF-1. The IGF-1 down-regulation may possibly be a consequence of the decrease in cytokines and inflammatory cellular infiltrate that occur following treatment with either modalities or due to their effect on local fibroblast activity and proliferation.

Late-onset granular intra-amniotic infection following amniotic membrane transplantation.

BACKGROUND: The amniotic membrane (AM) is used in ocular surface reconstruction and is effective at promoting epithelialization and preventing corneal perforation in cases of acute microbial keratitis. Here, we report a case of isolated AM infection after AM transplantation for a persistent epithelial defect following tectonic penetrating keratoplasty. CASE PRESENTATION: A 47-year-old man with poorly controlled type 2 diabetes mellitus presented to the emergency department with a referral for perforated microbial keratitis. After ophthalmic examination, corneal scraping was performed, and corneal gluing was attempted and failed. Hence, the patient underwent tectonic penetrating keratoplasty. After keratoplasty, the patient developed a persistent epithelial defect that required AM transplantation as an overlay. Thirty days post-AM transplant, the patient presented with signs and symptoms resembling granular microbial infection of the cornea. After two days, the granular findings began dislodging from the corneal surface and were sent for culture, sensitivity, and histopathological identification. Histological analysis of the granular material indicated it to be a small piece of AM stroma infiltrated with mixed-type inflammatory cells. Corneal scraping cultures indicated Streptococcus mitis and Streptococcus oralis. CONCLUSION: The infiltrate was localized to the basement membrane of the AM as, despite the anti-inflammatory effects of AM, it can also act as a barrier against polymorphonuclear leukocyte infiltration from the tear film and microbial invasion into the cornea.

Association of miR-146a rs57095329 with Behçet's disease and its complications.

BACKGROUND: Behçet's disease is a chronic relapsing and remitting autoimmune multisystem inflammatory disease characterised by oral aphthae, genital ulcers, skin lesions, gastrointestinal involvement, arthritis, vascular lesions and neurological manifestations. We hypothesised a link between rs57095329 of miR-146a and Behçet's disease, with further links with common clinical features. METHODS: We tested our hypothesis in 130 Behçet's disease patients and 131 age and sex-matched healthy controls. Behcet's disease current activity index (BDCAI) was used to assess patients' disease activity status. MiR-146a (rs57095329) was genotyped in all participants using RT-PCR and results in patients analysed according to clinical features. RESULTS: The frequency of the GG and AG genotypes in rs57095329 were strongly associated with Behçet's disease (adjusted OR 8.05, 95% CI 3.63-17.82; P < 0.001 and OR 2.26, 95% CI 1.27-4.04; P = 0.006, respectively), and in dominant (GG+AG > AA) and recessive (GG > AA+AG) models (both P < 0.001). Additionally, G allele distribution was significantly greater in Behçet's disease compared with controls (OR 2.85, 95% CI 1.98-4.11, P < 0.001). The AA genotype and A allele were linked to oral ulcers, the GG genotype and G allele to neurological disease, and the GG genotype and G allele to ocular disease (all P < 0.01). There were no links with genital ulceration, skin lesions, vascular disease or the result of the pathergy test. CONCLUSION: The miR-146a (rs57095329) is associated with Behçet's disease and certain genotypes and alleles with oral ulcers, and with ocular and neurological manifestations.