Evaluation of circulating zonulin as a potential marker in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested. Liver function tests, serum glucose, fasting insulin, C peptide, lipid profile, homeostasis model assessment of insulin resistance (HOMA‐IR), IL‐6, and circulating zonulin were performed to all subjects. Aspartate transaminase (AST), alanine transaminase (ALT), gamma‐glutamyl transferase (GGT), triglycerides, HDL‐c, fasting insulin, C peptide, HOMA‐IR, IL‐6, and serum zonulin were higher in NAFLD group than in controls (p < 0.05), and in NASH patients than those with simple steatosis (p < 0.05). Zonulin was positively correlated with body mass index (BMI), ALT, triglycerides, fasting insulin, HOMA‐IR, liver histopathology, and serum IL‐6 (p < 0.05), with inverse correlation to HDL‐C (p < 0.05). At cut off 8.3 pc/mL, serum zonulin was found to be of diagnostic value of NASH occurrence with 100% sensitivity and specificity (AUR = 1.000, p‐value = <0.001). The increasing zonulin levels in NAFLD patients with steep rise in NASH group denotes a possible role in pathogenesis of NAFLD occurrence and progression. This could open a new avenue of implicating zonulin antagonists as targeted therapies in NAFLD prevention.     

Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers,tumor characteristics,and disease outcome

Toll‐like receptors (TLRs) are involved in colorectal cancer (CRC) pathogenesis. However, the significance of serum TLR concentrations in CRC is unknown. We analyzed serum TLR2 and TLR4 concentrations with ELISA in preoperative samples from 118 patients with CRC and 88 matched controls. We also assessed tissue TLR expression with immunohistochemistry and by detecting serum determinants of systemic inflammation. Most participants (>70%) had undetectable serum TLR2. The mean serum TLR4 levels were lower in patients than in controls (1.1 vs 1.8 ng/mL; p = 0.015). Undetectable TLR4 was more common in stage I (39%) than in stages II–IV (11%, p < 0.001). TLR2 or TLR4 expression in tumor cells did not correlate with serum levels, but abundant TLR2 expression in normal colon epithelium was associated with detectable serum TLR2 (p = 0.034). Undetectable serum TLR2 was linked to high modified Glasgow prognostic scores (p = 0.010), high CRP levels (p = 0.013), blood vessel invasion (p = 0.013), and tended to be associated with worse 5‐year survival (p = 0.052). In conclusion, serum TLR2 levels were inversely associated with systemic inflammation in patients with CRC. Moreover, serum TLR2 levels might depend more on normal colorectal mucosa contributions than on tumor tissue contributions. Further studies are required to assess the prognostic value of serum TLR2.     

Effect of Interleukin-2 Level and Genetic Variants on Coronary Artery Disease

Inflammation plays important roles in the development of atherosclerosis and coronary artery disease (CAD). Interleukin-2 (IL-2) is a proinflammatory cytokine and induces proliferation of T cells. The aim of the study was to understand the effect of IL-2 on the development of CAD from genetic polymorphism perspective and serum level perspective. IL-2 ?330T/G and +114T/G polymorphisms were tested in 692 CAD cases and 723 healthy controls. IL-2 expression of these two polymorphisms was compared. Serum level of IL-2 in CAD patients and controls was analyzed. Data showed that prevalence of IL-2 ?330GG genotype was significantly increased in CAD than in controls (p?=?5.1?×?10^?6). Function analysis revealed that subjects carrying IL-2 ?330GG genotype had higher serum level of IL-2 than those with TG or TT genotypes (p?<?0.01). Serum level of IL-2 in the study subjects was further analyzed, and results showed that CAD patients had significantly increased IL-2 level than healthy controls (p?<?0.01). Also, cases with three vessels affected were observed to have higher IL-2 level than cases with one vessel affected (p?<?0.05). These data suggested IL-2 polymorphism could affect the susceptibility to CAD by elevating protein expression, and serum level of IL-2 may be closed correlated with the development and progression of this disease.     

Levels of Interleukin‐(IL)‐12p40 are Markedly Increased in Brucellosis Among Patients with Specific IL‐12B Genotypes

Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T‐helper 1 (Th1) cytokines such as interleukin‐12 (IL‐12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL‐12p40 cytokine (IL‐12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL‐12p40. We genotyped IL‐12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case‐control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL‐12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429–0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218–0.900 for the CC genotype). Comparison of IL‐12B genotypes and serum levels of the IL‐12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL‐12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL‐12p40 and could possibly contribute to an inherited predisposition to brucellosis.     

IL‐17A[G197G]—Association between NOx and gestational age in a South African birth cohort

Interleukin (IL‐)17A, plays a role in pathogenic defence, but is implicated in chronic inflammatory diseases, and has recently been associated with variable pregnancy outcomes. We investigated the role of maternal IL‐17‐[G197A]‐specific effects of third‐trimester IL‐17 mRNA expression, NO_x exposure levels and other variables on gestational age, in the Mother and Child in the Environment (MACE) birth cohort in South Africa. A total of 327 participants were genotyped for IL‐17‐[G197A] by polymerase chain reaction restriction‐fragment length polymorphism (PCR‐RFLP). Quantitative real‐time PCR was used to quantitate IL‐17‐mRNA expression in whole blood. Multivariate linear regression analysis, stratified by IL‐17‐[G197A] genotype, was used to test for effects of NO_x, IL17A/GAPDH, haemoglobin, body mass index, HIV‐1 positivity, maternal education and income level on gestational age. Lower expression was associated with the IL‐17‐GG versus GA in the cohort and HIV‐1‐negative group (p = .0007, p = .0058), while no difference was observed in the HIV‐1 positives. Elevated IL‐17A expression was observed in the high NO_x exposure groups, within IL‐17[G197G] (p = .0004). IL‐17[G197G] was associated with PTB (p < .0001), and the PTB group had lower IL‐17A expression compared to the full‐term group (p = .0002). IL‐17 expression was associated with an increase in gestational age (p = .038), and NO_x was associated with a decrease in gestational age in the IL‐17[G197G] model (p = .046).     

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human leucocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14‐bp insertion/deletion (InDel) polymorphism in the 3′ untranslated region (3′‐UTR) of HLA‐G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA‐G (sHLA‐G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57–0.99; p = 0.040). Distribution of the 14‐bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33–0.99; p = 0.044) and the log‐additive model (OR = 0.76; 95% CI: 0.58–0.99; p = 0.044). The serum sHLA‐G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA‐G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856–0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA‐G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA‐G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA‐G 14‐bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA‐G may act as a promising biomarker for noninvasive diagnosis of OSCC.     

Increased risk of pertussis in adult patients with mannose‐binding lectin deficiency

Mannose‐binding lectin (MBL) is an important molecule of the innate immunity. The low level of MBL in the serum is associated with increased susceptibility to respiratory infections. In this study, MBL concentrations were determined from the sera of 125 Finnish pertussis patients and from 430 control subjects. Severe MBL deficiency (<50 ng/mL) was found more often in the patients than in the controls (11.2% vs 5.8%, p = 0.038). Moreover, the deficiency was detected more frequently in the adult patients than in the controls [20.4% vs 8.6%, p = 0.021; odds ratio 2.7 (95% confidence interval 1.1–6.5)]. Our findings suggest, for the first time, that MBL deficiency predisposes to pertussis infection, at least in adults.     

IL‐12B Gene Polymorphisms and IL‐12 p70 Serum Levels Among Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. IL‐12 is now recognized as a critical cytokine in terms of regulating the balance between Th1 and Th2 cells. We investigated the role of single nucleotide polymorphisms (SNPs) (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL‐12B gene in the genetic susceptibility to RA and in the severity of the disease. Six hundred and thirty‐four Caucasian RA patients and 341 healthy matched controls were studied using PCR‐RFLP method and high‐resolution melting analysis. Concentration of IL‐12 cytokine level in serum was evaluated using ELISA. The genotype frequency did not deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype were statistically higher in patients with RA compared with the healthy control group in both codominant and recessive models (P = 0.037; P = 0.04, respectively). The frequency of rs3212227 C allele also showed similar tendency (P = 0.07). IL‐12 level in serum was significantly higher in RA group compared with control (P < 0.0001). We observed that increased IL‐12 serum level was correlated with higher number of tender and swollen joints, ExRA presence and higher levels of haemoglobin, CRP and PLT. Also higher IL‐12 level in serum was observed within RA patients with hypertension. Present findings indicated that IL‐12p40 + 1188A/C polymorphism as well as IL‐12p70 protein levels may be associated with RA in the Polish population.     

Association between interleukin‐21 gene polymorphisms (rs12508721) and HBV‐related hepatocellular carcinoma

Interleukin‐21 (IL‐21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL‐21 gene and susceptibility of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV‐related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction–ligase detection reaction (PCR‐LDR) method was used to genotype the SNPs (rs2221903, rs907715 and rs12508721) within IL‐21 gene. Our results showed that IL‐21 polymorphisms were associated with the risk of HCC and chronic HBV infection when compared with healthy controls. The rs2221903A/G AG genotype was associated with a higher risk of chronic HBV infection when compared with healthy controls [AG versus AA + GG, P = 0.036, OR = 1.898, 95%CI = 1.038–3.471]. The rs12508721C/T TT genotype was related with a lower risk of chronic HBV infection and HBV‐related HCC than in healthy controls [TT versus CT + CC, P = 0.026, OR = 0.451, 95%CI = 0.221–0.920; P = 0.049, OR = 0.482, 95%CI = 0.231–1.005]. No significant difference in the genotype and allele distrubutions of rs907715G/A SNP was observed in the HBV‐related HCC group, chronic HBV‐infected group and the healthy control group when compared to each other. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL‐21 gene are associated with the susceptibility of HBV‐related HCC and chronic HBV infection. The genetic variant may in fact cause protection against the HBV‐related HCC. However, the function in these SNPs of IL‐21 gene needs to clarify the mechanisms involved in the pathogenesis of HBV‐related HCC further.     

Changes in hemostasis parameters in nonfatal methicillin‐sensitive Staphylococcus aureus bacteremia complicated by endocarditis or thromboembolic events: a prospective gender‐age adjusted cohort study

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin‐sensitive Staphylococcus aureus bacteremia (MS‐SAB) – a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender‐age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p < 0.05), elevated antithrombin III at day 90 (p < 0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p < 0.05), and enhanced thrombin–antithrombin complex at day 4 (p < 0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin–antithrombin complex at day 4 (p < 0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p < 0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D‐dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS‐SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.     

Dysregulation of toll‐like receptor (TLR) 2 expression on monocytes and upregulation of the frequency of T cells expressing TLR2 in patients with chronic hepatitis C virus infection

Toll‐like receptors (TLRs) initiate inflammatory responses that may play a role in disease progression in patients infected with hepatitis C virus (HCV). TLR2 and TLR4 surface expression were assessed on CD14⁺ monocytes, CD4⁺ and CD8⁺ T cells in treatment naïve patients with chronic HCV infection with fibrosis, without fibrosis, co‐infected with human immunodeficiency virus (HIV), and in healthy controls. Increased expression of TLR2 was found on monocytes in HCV‐infected patients with fibrosis (p < 0.01), co‐infected with HIV (p = 0.03), and possibly in patients without fibrosis (p = 0.07) when compared to controls. TLR2 positive CD4⁺ and CD8⁺ T cells were upregulated in patients with fibrosis only (p < 0.01). However, expression of TLR2 was not associated with T cell activation. TLR4 expression was similar in patients and healthy controls. In conclusion, TLR2 expression on monocytes and the frequency of T cells expressing TLR2 may contribute to disease progression in chronic HCV infection.     

Site‐specific absence of microfibrillar‐associated protein 4 (MFAP4) from the internal elastic membrane of arterioles in the rheumatoid arthritis synovial membrane: an immunohistochemical study in patients with advanced rheumatoid arthritis versus osteoarthritis

Microfibrillar‐associated protein 4 (MFAP4) is a non‐structural matrix protein with cell regulatory activities and a potential as seromarker for fibrosis. We aimed to study the occurrence of MFAP4 in the synovial membrane from patients with rheumatoid arthritis (RA) vs osteoarthritis (OA). Formaldehyde‐fixed synovial tissue sections, from patients with RA (N = 6) and OA (N = 6) undergoing total hip arthroplasty, were deparaffinized and immunostained with monoclonal antibodies against MFAP4. Elastin was detected using ElastiKit. MFAP4 in serum (sMFAP4) and synovial fluid was measured by an immunoassay. MFAP4 was present in synovial biopsies from both RA and OA patients, particularly prominent in deep arterioles where it colocalized with elastin. Notably however, MFAP4 was absent from the internal elastic lamina in RA arterioles irrespective of disease duration and synovitis activity, while present although with irregular staining patterns in OA specimens. sMFAP4 was increased in RA and OA serum vs healthy controls: median (interquartile range) 29.8 (25.3–39.1) and 25.5 U/L (18.1–43.3) vs 17.7 U/L (13.7–21.2), p = 0.006 and p = 0.02, respectively The concentration of synovial fluid was lower than in serum in both RA and OA. These findings may suggest that MFAP4 is involved in adaptive vessel wall remodeling associated with chronic joint disease.     

Comprehensive coronary plaque assessment in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non‐calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty‐one adult subjects (59 ± 9 years, 15 men) underwent a 256‐slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty‐two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea‐hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.     

Differential serum cytokine profile in patients with systemic lupus erythematosus and posterior reversible encephalopathy syndrome

Systemic lupus erythematosus (SLE) patients are susceptible to the development of posterior reversible encephalopathy syndrome (PRES). The main theory concerning the physiopathology of PRES suggests that there is brain–blood barrier damage, which is associated with endothelial dysfunction, and characterized by vasogenic oedema. However, current evidence regarding its physiopathogenic mechanisms is quite scant. The aim of this study was to analyse the expression of different serum cytokines, as well as vascular endothelial growth factor (VEGF) and soluble CD40 ligand (sCD40L), in patients with PRES/systemic lupus erythematosus (SLE) and to compare them with levels in SLE patients without PRES and in healthy controls. We performed a transversal study in a tertiary care centre in México City. We included 32 subjects (healthy controls, n = 6; remission SLE, n = 6; active SLE, n = 6 and PRES/SLE patients, n = 14). PRES was defined as reversible neurological manifestations (seizures, visual abnormalities, acute confusional state), associated with compatible changes by magnetic resonance imaging (MRI). Serum samples were obtained during the first 36 h after the PRES episode and were analysed by cytometric bead array, Luminex multiplex assay or enzyme‐linked immunosorbent assay (ELISA). Interleukin (IL)‐6 and IL‐10 levels were significantly higher in PRES/SLE patients (P = 0·013 and 0·025, respectively) when compared to the other groups. Furthermore, IL‐6 and IL‐10 levels displayed a positive correlation (r = 0·686, P = 0·007). There were no differences among groups regarding other cytokines, sCD40L or VEGF levels. A differential serum cytokine profile was found in PRES/SLE patients, with increased IL‐6 and IL‐10 levels. Our findings, which are similar to those described in other neurological manifestations of SLE, support the fact that PRES should be considered among the SLE‐associated neuropsychiatric syndromes.     

Analysis of the association between IL‐23R rs11209026 polymorphism and incidence of atherosclerosis

Th17/IL‐23 axis is an important pro‐inflammatory pathway in atherosclerosis. IL‐23 receptor (IL‐23R) pathway has an important role in T‐helper cells 17 (Th17) differentiation and survival. We compared normal subjects and patients with atherosclerosis in terms of the R381Q variant of the IL‐23R gene as a functional single‐nucleotide polymorphism (SNP). This case–control study recruited 200 patients who presented with cardiovascular symptoms to Afshar Hospital, Yazd, Iran. The participants were allocated to five groups based on angiographic results. The severity of the disease was determined according to the numbers of involved vessels. Patients with normal coronary arteries, minimal coronary artery involvement, one involved vessel, two involved vessels and three‐vessel disease were allocated to groups I–V, respectively. DNA was extracted from whole blood samples by the salting‐out method. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism assay and multinomial logistic regression for analyses The presence of SNP A>G rs11209026 of IL‐23 receptor gene was significantly associated with disease severity (P = 0.008). The frequencies of the heterozygous (AG) genotype in the control group and subjects with minimal involvement, and patients with one‐, two‐, and three‐vessel disease were 22.5%, 12.5%, 10%, 10.24% and 4.8%, respectively. Our results indicated an association between the rs11209026 G>A polymorphism of the IL‐23 receptor gene and the risk of atherosclerosis. This genetic variant may in fact cause protection against atherosclerosis progression. However, further studies on gene polymorphism and cell expression are required to clarify the mechanisms involved in the pathogenesis of atherosclerosis.     

Defective immunoglobulin A (IgA) glycosylation and IgA deposits in patients with IgA nephropathy

Defective glycosylation and immune complex (IC) formation may be of primary importance in immunoglobulin A nephropathy (IgAN) pathogenesis. The aim of this study was to determine whether defective IgA1 glycosylation might support renal deposition of IgA and disease activity. IgA was isolated from the serum of 44 IgAN patients and 46 controls and glycosylation analysed by ELISA using glycan‐specific lectins. IgA was measured by immunodiffusion and immune complexes by ELISA. IgA subclasses in IC deposits in kidney glomeruli were identified by immunohistochemical methods. A significant increase in N‐acetylgalactosamine (GalNAc) in terminal position (p = 0.02) observed in some of the IgAN patients, became more pronounced when sialic acid was removed from IgA1, indicating enhanced expression of α‐2,6‐sialyltransferase in patients compared with controls (p < 0.0001). Patients with defective galactosylation had lower serum IgA than other IgAN patients (p = 0.003). IgAN patients with both IgA1 and IgA2 glomerular deposits (21.7%) had increased GalNAc in terminal position (p = 0.003). Taken together, our results show that increased IgA glycosylation in IgAN associates with low levels of IgA, concomitant IgA1 and IgA2 glomerular deposits and poor clinical outcome.     

The association between immunoexpression levels of oxidant and antioxidant enzymes and lip squamous cell carcinoma

The aim of this study was to investigate the associations among the immunoexpression levels of manganese superoxide dismutase (Mn‐SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) in lip squamous cell carcinoma (LSCC) tissues and the clinicopathological characteristics, and prognostic factors in patients with LSCC. The immunoexpression levels of Mn‐SOD, GPx, and MPO were examined in 76 LSCC tissue samples using immunohistochemical staining on tissue microarray slides, and compared to those in normal lip mucosa adjacent to venous lakes (normal controls), normal tissue adjacent to corresponding tumors (NTACT), and recurrent tumors. Associations between immunoexpression levels and clinicopathological characteristics were analyzed using the Student's t‐test. The prognostic factors were analyzed using Cox regression. The immunoexpression levels of Mn‐SOD, GPx, and MPO were significantly different among the normal controls, NTACTs, tumors, and recurrent tumors (Mn‐SOD: p = 0.001, GPx: p < 0.001, MPO: p < 0.001). Lower lip cancer was associated with higher Mn‐SOD immunoexpression levels (p = 0.04) and probably indicated higher oxidative stress. Lymph node involvement with a lower immunoexpression level of MPO (p = 0.007) indicated compensatory mechanism to attenuate oxidative damage. A low Mn‐SOD immunoexpression level was borderline significantly associated with a worse prognosis for disease‐specific survival, and it was probably related to a lower capacity for coping with oxidative stress.     

Interleukin‐ 28B: a prognostic marker in interferon based therapy of chronic HCV patients of the Pakistan with variable treatment response

Unfortunately Pakistan carries one of the world's highest burdens of chronic hepatitis along with mortality due to liver failure and hepatocellular carcinoma. Scientists after extensive research have come up with this outcome that host genetics play a vital role in dictating the type of treatment response produced by the patients. In 2009, a genome wide association study (GWAS) revealed that genetic variants in close proximity to the IL28B (IFNL3) gene predicted greater likelihood of achieving sustained virological response (SVR) following treatment with pegylated IFN‐alpha (peg INF‐α) and ribavirin. IL28B (rs12979860 and rs8099917) single nucleotide polymorphisms (SNPs) have been recently found among the Pakistani population associated with response to chronic HCV infection INF‐α + ribavirin therapy. Therefore, this study was aimed to investigate the IL‐28B protein levels in the HCV infected patients. The findings showed that the serum IL28B protein level was higher in HCV infected patients as compared to healthy controls (7.743 ± 1.519 pg/mL versus 1.600 ± 0.06054 [mean ± SEM], p < 0.05). When the chronic hepatitis C (CHC) patients were further categorized into SVR and NR (non‐responders) on the basis of treatment outcomes, the mean IL28B protein level was higher in NRs (15.54 ± 3.609) than SVRs (4.259 ± 0.3405). Thus, there was a significant correlation between IL28B protein level in varied treatment response (p < 0.05). However, the findings can lead us to propose that IL28B could be used as a prognostic marker. It can help the clinicians to take better pre‐informed decisions whether to take combinational therapy of peg IFN ± ribavirin or not. This will in turn prove beneficial for the patient by saving patients’ health, treatment cost and undesirable treatment side effects.     

Evaluation of the serum levels of soluble IL‐2 receptor and endothelin‐1 in children with Crimean‐Congo hemorrhagic fever

We aimed to assess the association between serum levels of soluble IL‐2 receptor (sIL‐2r) and endothelin‐1 and severe infection in children with Crimean‐Congo hemorrhagic fever (CCHF). Fifty‐two patients under 18 years of age with a laboratory‐ confirmed diagnosis of CCHF and 38 healthy controls were enrolled in the study. Patients were classified into two groups based on disease severity (severe group and non‐severe group). The sIL‐2r and endothelin‐1 levels were observed to be significantly higher in patients with severe CCHF compared with those with non‐severe CCHF and the control group (p < 0.05). In addition, those with non‐severe CCHF were also found to have a significantly higher sIL‐2r level relative to the control group (p < 0.001). Although there was a positive correlation between sIL‐2r and endothelin‐1 levels, serum levels of both sIL‐2r and endothelin‐1 were negatively correlated with the platelets count. In children with CCHF, serum levels of sIL‐2r and endothelin‐1 were increased, and this increase is related to the severity of the disease. In this study, we concluded through prognosis that serum levels of sIL‐2r and endothelin‐1 might be related, and that hemophagocytic lymphohistiocytosis and endothelial injury might contribute to a pathogenesis of the disease.