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.

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.

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.

Impact of miR-155 (rs767649 A>T) and miR-146a (rs57095329 A>G) polymorphisms in System Lupus Erythematosus susceptibility in an Egyptian cohort.

OBJECTIVE: Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disease. miR-155 and miR-146a were expressed in many autoimmune diseases such as rheumatoid arthritis. The aim of this study was to examine miR-155 rs767649 and miR-146a rs57095329 polymorphisms in SLE susceptibility in an Egyptian cohort and to investigate the correlation between them and clinical data and disease activity. PATIENTS AND METHODS: The two SNPs were analyzed in 120 patients with SLE and 100 healthy controls using RT-PCR. RESULTS: The TT genotype and T allele of miR-155 rs767649 were associated with a significant increase in the risk of SLE, particularly in females. On the other hand, miR-146a (rs57095329) polymorphism was not associated with SLE risk. The AT/TT genotypes of miR-155 rs767649 showed higher distributions among patients with higher SLEDAI and nephritis. CONCLUSIONS: This study had demonstrated for the first time the association between miR-155 rs767649 and the risk of development of SLE in an Egyptian cohort, mostly in females.

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.

Serum long noncoding RNAs FAS-AS1 & PVT1 are novel biomarkers for systemic lupus erythematous.

Background: Systemic Lupus Erythematous (SLE) is a chronic systemic autoimmune disorder whose diagnosis depends on combination of multiple factors. Circulating lncRNAs could serve as diagnostic non-invasive biomarkers for SLE. We hypothesised that serum FAS-AS1 and PVT1 are new biomarkers for SLE that relate to clinical features and laboratory markers. Materials and Method: Measurement of serum FAS-AS1 & PVT1 by qRT-PCR, analysis of the association between two RNAs and the clinical data, activity index and laboratory markers by standard routine methods. Results: There was a significant relative increased serum FAS-AS1 (median (IQR) 2.19 (0.13-8.62) and a significant reduced PVT1 (median (IQR) 0.52 (0.01-7.55) in SLE patients compared to controls (P < 0.0001 for FAS-AS1 and = 0.007 for PVT1). Serum FAS-AS1 and PVT1 were positively correlated (r= 0.37, P = 0.001). Higher FAS-AS1 was significantly linked with nephritis (P = 0.011), positive anti-dsDNA (P= 0.01) and lower serum PVT1 was significantly associated with oral ulcers (P= 0.023), photosensitivity (P= 0.017), and neurological manifestations (P= 0.041). Serum PVT1 negatively correlated with age (r= -0.52, P< 0.0001) and ESR level (r= -0.29, P= 0.011) in SLE patients. No correlation between disease activity and serum FAS-AS1 or PVT1 was detected. Conclusions: Our study provides evidence that serum FAS-AS1 and PVT1 are new biomarkers for SLE.

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.

Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that is deregulated in obesity. PPARγ exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPARγ and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPARγ. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPARγ promoter methylation was evaluated in peripheral blood mononuclear cells (PBMC). PPARγ level was evaluated by measuring mRNA level in PBMC and protein level in serum. The tested microRNAs (miR-27b, 130b and 138) were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPARγ. A significant negative correlation was found between PPARγ levels and the studied microRNAs. There was a significant PPARγ promoter hypermethylation in CRC patients that correlated to low PPARγ levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPARγ downregulation. Hypermethylation of PPARγ gene promoter is associated with CRC through suppression of PPARγ regardless of BMI.

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.

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.

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.

Expression of sirtuins 1, 6, tumor necrosis factor, and interferon-γ in psoriatic patients.

Sirtuins (SIRT) have been regarded as culprits in the pathogenesis of various diseases. Their exact role has not been explained. This study aimed to assess the expression of SIRT1, SIRT6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in psoriatic patients. Thirty psoriatic patients and 22 controls were enrolled. Clinical examination and Psoriasis Area and Severity Index (PASI) were obtained. Two skin biopsies (lesional, peri-lesional) and one from controls were obtained. Tissue levels of SIRT1, SIRT6, TNF-α, and IFN-γ were measured using ELISA. SIRT1 was significantly lower in lesional skin with gradual increase in perilesional followed by control skin (P <0.001). SIRT6, TNF-α, and IFN-γ were significantly higher in lesional than perilesional and control skin (P <0.001). Significant positive correlations were found between SIRT1 and TNF-α, IFN-γ and between SIRT6 and TNF-α in peri-lesional skin. SIRT1 and SIRT6 are potentially involved in the pathogenesis of psoriasis. Modulating their action could offer a novel therapy for such disease.

Malondialdehyde, superoxide dismutase and melatonin levels in gingival crevicular fluid of aggressive and chronic periodontitis patients.

BACKGROUND: The aim of this study was to investigate malondialdehyde (MDA), superoxide dismutase (SOD) and melatonin levels in the gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) and generalized aggressive periodontitis (GAgP) as biomarkers for oxidative stress. METHODS: The study comprised 65 subjects: 15 healthy individuals, 25 CP patients and 25 GAgP patients. Plaque index, gingival index, pocket depth, clinical attachment level measurements and GCF samples were obtained from all subjects. MDA, SOD and melatonin levels were determined utilizing enzyme-linked immunosorbent assay. RESULTS: GCF-MDA levels were significantly higher in the GAgP group compared to the CP and control groups (p < 0.001) and significantly higher in the CP group than the C group (p < 0.001). SOD and melatonin GCF levels were significantly higher in the control than the GAgP and CP groups (p < 0.05), and significantly lower in the GAgP than the CP group (p < 0.05). The CP group demonstrated a significant negative correlation between GCF-MDA and melatonin concentrations. A positive correlation was observed between SOD and CAL in the CP group and PD in the GAgP group. CONCLUSIONS: MDA, melatonin and SOD could be considered as biomarkers for oxidative stress in periodontal diseases and might be useful diagnostic aids in distinguishing CP and GAgP patients.

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.

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.

Estimation of tissue and serum lipocalin-2 in psoriasis vulgaris and its relation to metabolic syndrome.

Adipose tissue is now considered an endocrine organ secreting different cytokines known as adipocytokines. Lipocalin-2 has been recently identified as an adipokine present in the circulation, it is related to insulin resistance, obesity, atherosclerotic diseases and type 2 diabetes. Lipocalin-2 and psoriasis are assumed to be closely associated with the metabolic syndrome. The aim of the present study is to estimate the level of lipocalin-2 in the serum and tissue of psoriatic patients and to correlate these levels with markers of metabolic syndrome, CRP and disease severity. This study was done on 30 patients of psoriasis and 30 healthy controls. All patients and controls were subjected to clinical examination. Serum, tissue levels of lipocalin-2 and C-reactive protein (CRP) were measured by enzyme linked immunosorbent assay technique. Metabolic syndrome parameters including anthropometric measures, lipid profiles, blood sugar and blood pressure were studied. Patients with psoriasis showed significant association with metabolic syndrome parameters than controls. Tissue lipocalin-2 was significantly higher than serum levels in psoriasis patients. A significant difference was detected in tissue levels of lipocalin-2 and not in the serum between patients and controls. Both tissue and serum lipocalin-2 correlated with CRP. Although there was a correlation between tissue and serum levels of lipocalin-2 in patients, there was no correlation between both of them with metabolic syndrome and related disorders. Our results revealed that patients with psoriasis are at increased risk of metabolic and cardiovascular complications, tissue lipocalin-2 is more specific to psoriasis than serum lipocalin-2. Lipocalin-2 has no role in determining severity of the disease. Neither tissue nor serum lipocalin-2 conveys cardiovascular risk in psoriasis patients.

Transforming growth factor beta 1 and monocyte chemoattractant protein-1 as prognostic markers of diabetic nephropathy.

We aimed to find the relationship between serum transforming growth factor beta 1(TGF-ß(1)) and urinary monocyte chemoattractant protein-1 (MCP-1) throughout the course of diabetic nephropathy (DN) and to assess the relationship between both levels and other parameters of renal injury such as albumin/creatinine ratio and estimated glomerular filtration rate (eGFR). Serum TGF-ß(1), urinary MCP-1, eGFR, and glycosylated hemoglobin (HbA1c) were measured in 60 patients with type II diabetes mellitus with different degrees of nephropathy (20 patients with normoalbuminuria, 20 patients with microalbuminuria, and 20 patients with macroalbuminuria) and compared with 20 matched healthy control subjects. Both the levels of serum TGF-ß(1) and urinary MCP-1 were significantly higher in patients with micro- and macroalbuminuria (137.8 ± 69.5 and 329.25 ± 41.46 ng/dl, respectively, for TGF-ß(1) and 167.41 ± 50.23 and 630.87 ± 318.10 ng/g creatinine, respectively, for MCP-1) compared with normoalbuminuric patients and healthy controls (33.25 ± 17.5 and 29.64 ± 10.57 ng/dl, respectively, for TGF-ß(1) and 63.85 ± 21.15 and 61.50 ± 24.81 ng/g creatinine, respectively, for MCP-1; p < 0.001). There was a positive significant correlation between the levels of serum TGF-ß(1) and those of urinary MCP-1 (r = 0.73, p < 0.001). Also, serum TGF-ß(1) and urinary MCP-1 correlated positively with HbA1c (r = 0.49 and 0.55, respectively, p < 0.05 for both) and inversely with eGFR (r = -0.69 and -0.60, respectively, p < 0.001 for both). We can conclude that serum TGF-ß(1) and urinary MCP-1 can be used as the markers for detection of progression of DN. Antagonizing TGF-ß(1) and MCP-1 might be helpful in attenuating the progression of nephropathy in diabetic patients.

Pathogenesis of preeclampsia: Implications of apoptotic markers and oxidative stress.

This study aimed to investigate the implication of some apoptotic and lipid peroxidation markers in preeclampsia (PE). A total of 25 women with PE and 25 age- and parity-matched normal pregnant women were enrolled in this study. The malondialdehyde (MDA) level, caspase-9 activity and the percentage of DNA fragmentation were significantly higher in placental tissue of PE than in control women. The serum level of MDA was significantly elevated in women with PE having delivery by cesarean section (CS) than in women with PE having vaginal delivery. In vitro study demonstrated that the addition of 0.5 mM Fe(2+) and 0.1 mM ascorbate caused increase in the production of MDA level in placental tissue with PE than normal placentas, and vitamin E (100 µM) caused lower inhibition of in vitro lipid peroxidation in placental tissue with PE when compared with normal tissue. The activity of caspase-9 and percentage of DNA fragmentation were associated with the severity of the PE and both could differentiate between PE and control women with 88% and 100% sensitivity and 96% and 100% specificity, respectively. The activities of caspase-8 and/or -9 were positively correlated with the maternal age but only caspase-8 was negatively correlated with neonatal birth weight and placental weight. In conclusion, the elevations of MDA, caspase-9 activity and the percentage of DNA fragmentation in the placentas of women with PE implicate the involvement of lipid peroxidation and apoptosis in PE. The placenta represents a considerable source of the elevated circulating MDA in PE.

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.

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.