Potential mitigating impact of a dipeptidyl peptidase-IV inhibitor, vildagliptin, on oxazolone-induced ulcerative colitis: Targeting the role of PI3K/AKT/mTOR and AMPK/Nrf2 signaling pathways.

Growing evidence suggests that phosphoinositide 3-kinase (PI3K) and adenosine monophosphate-activated protein kinase (AMPK) signaling cascades are critical in ulcerative colitis (UC) pathophysiology by influencing gut mucosal inflammation. Recently, the coloprotective properties of dipeptidyl peptidase-IV (DPP-IV) inhibitors have emerged. Thus, this study assessed for the first time the potential mitigating impact of a DPP-IV inhibitor, vildagliptin (Vilda), on oxazolone (OXZ)-induced colitis in rats, targeting the role of PI3K/AKT/mTOR and AMPK/Nrf2 pathways. Thirty-two adult Albino rats were divided into four groups: control, Vilda (10 mg/kg/day orally), OXZ (300 µL of 5 % OXZ in 50 % aqueous ethanol solution introduced once into the colon via catheter), and Vilda+OXZ. Inflammatory cytokines (interleukin 13, tumor necrosis factor-α, interleukin 10), oxidative/endoplasmic reticulum stress markers (myeloperoxidase, reduced glutathione, catalase, CHOP), mitochondrial reactive oxygen species, adenosine triphosphate levels, and mitochondrial transmembrane potential were estimated. p-AMPK, p-AKT, beclin-1, and SQSTM1 levels were immunoassayed. Nrf2, PI3K, and mTOR expression levels were quantified using the real-time polymerase chain reaction. Furthermore, p-NF-ĸBp65 and LC3II immunoreactivity were evaluated. Vilda administration effectively ameliorated OXZ-induced colitis, as evidenced by the reduced Disease Activity Index, macroscopic colon damage score, colon weight/length ratio, ulcer index, and histopathological and electron microscopic changes in the colon tissues. Vilda treatment also counteracted OXZ-triggered inflammation, oxidative/endoplasmic reticulum stress, mitochondrial dysfunction, and enhanced autophagy in the colon. Vilda substantially suppressed PI3K/AKT/mTOR and activated the AMPK/Nrf2 pathway. Vilda has potent coloprotective and anti-ulcerogenic properties, primarily attributed to its antiinflammatory, antioxidant, and modulatory impact on mitochondrial dysfunction and autophagy activity. These effects were mostly mediated by suppressing PI3K/AKT/mTOR and activating AMPK/Nrf2 signaling cascades, suggesting a potential role of Vilda in UC therapy.

Stimulator of interferon genes/Interferon regulatory factor 3 (STING-IRF3) and inflammasome-activation mediated pyroptosis biomarkers: a network of integrated pathways in diabetic nephropathy.

Background: Diabetic Nephropathy (DN) is serious diabetic complication affecting the structure and function of the kidney. This study assessed the stimulator of interferon genes/ Interferon regulatory factor 3 (STING/IRF3) signaling pathway roles and inflammasome-activation mediated pyroptosis, being imperative pathways of inordinate importance in disease progression, in DN throughout its different stages. Methods: 45 Diabetic cases were categorized into three groups based on their albuminuric status as follow: Normoalbuminuric, Microalbuminuric and Macroalbuminuric diabetic groups and 15 healthy subjects as controls were included. We evaluated STING and absent in melanoma 2 (AIM2) messenger RNA (mRNA) expressions from whole blood using quantitative RT-PCR. Additionally, Serum levels of STING, AIM2, IRF3, Nod like receptor pyrins-3 (NLRP3), interleukin-1ß (IL-1ß) and caspase-1 were assessed by ELISA technique. Results: The study documented that STING and AIM2 mRNA expressions had significantly increased in DN cases with highest value in macroalbuminuric diabetic groups (p < 0.001*). Parallel results were observed concerning serum STING, AIM2, IRF3, NLRP3, Caspase-1 in addition to IL-1ß levels (p < 0.001*). Conclusion: The study documented the forthcoming role of STING in DN progression and its positive correlation with inflammasome-activation mediated pyroptosis biomarkers throughout its three different stages; launching new horizons in DN pathogenesis by highlighting its role as a reliable prognostic biomarker.

Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy.

Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure and death. It has no definite treatment. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has protective potential in PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate the ameliorative effect of EMPA against bleomycin (BLM)-induced PF and the potential mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA treated, and EMPA+BLM treated. EMPA significantly improved the histopathological injuries illustrated by both hematoxylin and eosin and Masson's trichrome-stained lung tissue sections, as confirmed by electron microscopic examination. It significantly reduced the lung index, hydroxyproline content, and transforming growth factor ß1 levels in the BLM rat model. It had an anti-inflammatory effect, as evidenced by a decrease in the inflammatory cytokines' tumor necrosis factor alpha and high mobility group box 1, inflammatory cell infiltration into the bronchoalveolar lavage fluid, and the CD68 immunoreaction. Furthermore, EMPA mitigated oxidative stress, DNA fragmentation, ferroptosis, and endoplasmic reticulum stress, as evidenced by the up-regulation of nuclear factor erythroid 2-related factor expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, and a decrease in C/EBP homologous protein levels. This protective potential could be explained on the basis of autophagy induction via up-regulating lung sestrin2 expression and the LC3 II immunoreaction observed in this study. Our findings indicated that EMPA protected against BLM-induced PF-associated cellular stress by enhancing autophagy and modulating sestrin2/adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling.

Coagulation Profile in COVID-19 Patients and its Relation to Disease Severity and Overall Survival: A Single-Center Study.

Objectives: This study aims to investigate hemostatic changes in patients with coronavirus disease (COVID-19) and their relationship to disease severity and survival. Methods: This study included 284 patients with COVID-19 who attended the Security Forces Hospital, Makkah, Saudi Arabia between October 2020 and March 2021, and retrospectively reviewed their demographic, radiological, and laboratory findings. The coagulation profile was assayed at the time of diagnosis for platelet counts using an automated hematology analyzer; Sysmex XN2000 while international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, factor VIII, ristocetin cofactor (RiCoF), and von Willebrand factor antigen (VWF-Ag) were measured by Stago kits on a Stago automated coagulation analyzer (STA Compact Max®). Results: In this study, 32.3% of the cases had severe disease, while 8.8% of the cases died. D-dimer, factor VIII, and RiCoF were the only independent predictors of disease severity, with factor VIII and RiCoF having significantly higher areas under the curve (AUCs) than D-dimer (all p < 0.001). Furthermore, age, aPTT, and factor VIII were associated with an increased risk of mortality in multivariate Cox regression analysis, with factor VIII having a higher AUC of 0.98 than aPTT with an optimal cut-off value of >314 IU/dl in predicting mortality. Cases with factor VIII levels >314 IU/dl, compared to those with factor VIII levels <314 IU/dl, were associated with a significantly shorter mean overall survival time (20.08 vs. 31.35 days, p < 0.001), a lower survival rate (30.3% vs. 99.2%, p < 0.001), and a 16.62-fold increased mortality risk. Conclusion: RiCoF is a novel predictor of disease severity in COVID-19, while factor VIII is confirmed as a predictor of severity and mortality in COVID-19 patients and is associated with lower overall survival and increased mortality risk.

Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by silent information regulator 1.

BACKGROUND AND PURPOSE: Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and the involved molecular mechanisms. EXPERIMENTAL APPROACH: Fifty-two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 ß-hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8-hydroxy-2'-deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors-class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl-2 and its associated X protein and nuclear factor kappa-light-chain-enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR-34a expression was quantified by quantitative reverse transcription-polymerase chain reaction. KEY RESULTS: The varicocele induced testicular histological injury, enhanced oxidative stress, P53-mediated apoptosis, DNA damage and increased testicular miR-34a expression paralleled with down-regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti-apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR-34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele. CONCLUSION AND IMPLICATIONS: Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.

Impact of XRCC1 genetic variants on its tissue expression and breast cancer risk: A case-control study.

X-ray repair cross-complementing group 1 (XRCC1), a coordinator protein of the DNA repair complex, is thought to be involved in cancer progression. This case-control study aimed to investigate the association of two biallelic single-nucleotide polymorphisms (SNPs; Arg399Gln, Arg194Trp) of the XRCC1 gene with its tissue expression level and breast cancer (BC) risk in Egyptian women. This study included 100 BC female patients (case group 1) and 100 healthy females (control group 2). The XRCC1 tissue expression was assessed by immunohistochemistry (IHC). Genotyping of the two XRCC1 SNPs (Arg399Gln, Arg194Trp) using real-time polymerase chain reaction (PCR) was also conducted. The XRCC1 expression level was significantly lower in cancerous tissues than adjacent non-cancerous tissues (p < .001). The XRCC1 399Gln/Gln genotype, 399Gln allele, the dominant, and recessive models were significantly associated with lower XRCC1 expression in breast cancerous tissues and increased risk for BC (3.390-, 1.965-, 2.241-, and 2.429-folds, respectively). The XRCC1 399Gln/Gln genotype was associated with lower incidence of advanced tumor grade (OR: 0.06; 95%CI: 0.01-0.74; p = .028). Conversely, the XRCC1 Arg194Trp polymorphism did not show any significant association with either XRCC1 expression in breast cancer tissues or BC risk in all genetic models. The XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with 1.800- and 1.675-folds risk for BC, respectively. The XRCC1 gene polymorphism (Arg399Gln) is associated with reduced XRCC1 tissue expression and enhanced BC risk with a well-differentiated nature in Egyptian women. Moreover, XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with increased BC risk.

Utility of serum neuropilin-1 and angiopoietin-2 as markers of hepatocellular carcinoma.

This study aimed to assess the diagnostic value of two serum angiogenetic markers neuropilin-1 (NRP-1) and angiopoietin-2 (ANG-2) in patients with hepatocellular carcinoma (HCC) and their relation to tumor characteristics. 149 subjects were recruited and divided into 50 patients with recently diagnosed HCC, 49 patients with cirrhosis on top of hepatitis C virus infection, and 50 healthy subjects. Serum NRP-1 and ANG-2 were estimated by ELISA. Alpha-fetoprotein (AFP) levels were measured using fluorescence immunoassay. Serum NRP-1 and ANG-2 levels were significantly higher in patients with HCC (2221.8±1056.6 pg/mL and 3018.5±841.4 pg/mL) than healthy subjects (219.3±61.8 pg/mL and 2007.7±904.8 pg/mL) and patients with cirrhosis (1108.9±526.6 pg/mL and 2179.1±599.2 pg/mL), respectively. In multivariate logistic regression analysis, NRP-1 and AFP were the only independent factors of HCC development and correlated positively with each other (r=0.781, p<0.001). Receiver operating characteristic curve analysis showed that the area under the curve (AUC) of NRP-1 was higher than that of ANG-2 in discriminating HCC from patients with cirrhosis (0.801 vs 0.748, p=0.250) and healthy subjects (0.992 vs 0.809, p<0.001). The AUC of NRP-1 was detected to be increased (0.994) when combined estimation with AFP was performed. Elevated serum NRP-1 and ANG-2 levels were detected in patients with HCC with tumor numbers >3, tumor size ≥5 cm, tumor stages B/C according to the Barcelona Clinic Liver Cancer staging system, vascular invasion, and distant metastasis. In conclusion, NRP-1 is a potential serological marker for HCC diagnosis and is better than ANG-2. It is feasible to be estimated in combination with AFP to enhance its diagnostic power. High serum NRP-1 and ANG-2 levels are associated with advanced HCC tumor characteristics.

Diagnosis of acute appendicitis in children using urinary 5-hydroxy indol acetic acid and pediatric appendicitis score: A randomized control trial.

PURPOSE: Acute appendicitis in children represents a common problem. Diagnosis may be difficult due to lack of clinical data. Several scoring systems and laboratory investigations are used for diagnosis. This study aimed to build a model for diagnosis of acute appendicitis in children using urinary 5-hydroxyindoleacetic acid (5-HIAA) and pediatric appendicitis score. METHODS: This study was conducted on 191 children with suspicion of acute appendicitis. They were divided into two groups A and B. Children were evaluated in group A with pediatric appendicitis score, ultrasound, and CRP. In group B children were evaluated in the same manner of group A plus measuring of 5-HIAA. RESULTS: mean age was 13.3 ± 5.2 years. The mean duration of symptoms was 2.2 ± 1.4 days. The mean level of urinary 5-HIAA was 43.53 ± 24.05 in appendicitis patients in group B. In group A there were 65 cases who had appendectomy. Seventy-five children were operated in group B. Negative appendectomies were found in 13 and 7 cases in groups A and B respectively. Thirteen cases were readmitted in group A with diagnosis of acute appendicitis while seven cases were readmitted in group B. CONCLUSION: This combination of urinary 5-HIAA and pediatric appendicitis score builds a model for diagnosis of acute appendicitis in children. This model improves the accuracy of diagnosis of acute appendicitis, reduces both the incidence of negative appendectomies and the incidence of readmission or missed cases in children.

Diagnostic efficacy of serum and urinary netrin-1 in the early detection of diabetic nephropathy.

This study aimed to assess the diagnostic value of serum and urinary netrin-1 in patients with type 2 diabetes mellitus (T2DM) at different stages of diabetic nephropathy (DN) and to compare its efficacy of estimation in serum with that in the urine. This study was carried out on 135 patients with T2DM and 45 healthy subjects. The patients with diabetes were divided according to urinary albumin creatinine ratio (UACR) into: T2DM with normoalbuminuria, incipient DN with microalbuminuria, and overt DN with macroalbuminuria groups. Serum and urinary levels of netrin-1 were measured by ELISA. The mean levels of serum and urinary netrin-1 were significantly higher in the microalbuminuric and macroalbuminuric patients with DN than those in the normoalbuminuric patients with T2DM, with the highest values detected in macroalbuminuric patients with DN. Urinary netrin-1 level was significantly higher in the normoalbuminuric T2DM group than control group, whereas no significant difference existed regarding serum netrin-1 level. In T2DM groups, the urinary and serum netrin-1 correlated with each other and were independently related to fasting blood glucose, UACR, and estimated glomerular filtration rate. Receiver operating characteristic curve analysis showed that the area under the curve of urinary netrin-1 was 0.916 which is significantly higher than that of serum netrin-1 (0.812) for the detection of incipient DN and reached 0.938 on coestimation of both urinary and serum netrin-1. In conclusion, netrin-1 is a potential diagnostic marker for early detection of DN with its estimation in urine has higher accuracy than that of serum.

Circulating miR-146a expression predicts early treatment response to imatinib in adult chronic myeloid leukemia.

This study aimed to investigate the prognostic role of circulating miR-146a in the prediction of early response to imatinib treatment in patients with chronic myeloid leukemia (CML). Sixty patients with CML and 20 healthy controls were recruited in this study. BCR-ABL was assessed by quantitative rt-PCR at days 0 and 90 of imatinib therapy. Circulating miR-146a levels were assessed by quantitative rt-PCR at days 0, 14 and 90 of imatinib therapy for patients and once for controls. At day 90 of treatment, treatment response was achieved in 48 patients (80.0%). Responders had significantly lower baseline Sokal score when compared with non-responders. They also had significantly lower BCR-ABL expression at day 90 of treatment. The circulating miR-146a level was significantly lower in patients with CML than in healthy subjects and showed a significant rise after 14 days of imatinib treatment and an inverse correlation with BCR-ABL expression levels at 90 days. Using multivariate logistic regression analysis, baseline BCR-ABL (%) (OR (95% CI) 1.09 (1.03 to 1.016), p=0.006) and miR-146a at 14 days (OR (95% CI) 0.002 (0.0 to 0.09), p=0.001) were significant predictors of treatment response. Using ROC curve analysis, it was found that miR-146a expression at 14 and 90 days could distinguish responders from non-responders (AUC (95% CI) 0.849 (0.733 to 0.928) and 0.867 (0.755 to 0.941), respectively). This study reported for the first time that measurement of the circulating miR-146a expression at 14 days can predict the early response to imatinib treatment in patients with CML. Thus, this work indicates that miR-146a should be investigated in the setting of treatment response to other tyrosine kinase inhibitors.

An overview of the classical and tissue-derived renin-angiotensin-aldosterone system and its genetic polymorphisms in essential hypertension.

The renin-angiotensin-aldosterone system (RAAS) is a specific hormonal cascade implicated in the blood pressure control and sodium balance regulation. Several components of this pathway have been identified including renin, angiotensinogen, angiotensin-converting enzyme, angiotensins with a wide range of distinct subtypes and receptors, and aldosterone. The RAAS is not only confined to the systemic circulation but also exists locally in specific tissues such as the heart, brain, and blood vessels with a particular paracrine action. Alteration of RAAS function can contribute to the development of hypertension and the emergence of its associated end-organ damage. Genotypic variations of the different genes of RAAS cascade have been linked to the susceptibility to essential hypertension. Accordingly, to understand the pathogenesis of essential hypertension and its related complications, deep insight into the physiological and genetic aspects of RAAS with its different components and pathways is necessary. In this review, we aimed to illustrate the physiological and genetic aspects of RAAS and the underlying mechanisms which link this system to the predisposition to essential hypertension.

Cross talk between Hsp72, HMGB1 and RAGE/ERK1/2 signaling in the pathogenesis of bronchial asthma in obese patients.

BACKGROUND: The incidence of obesity-related asthma has shown a remarkable increase. OBJECTIVES: We aimed to explore the role of heat shock protein 72 (Hsp72) and receptor for advanced glycation end products (RAGE) axis with its downstream signaling in the pathogenesis of obesity-related asthma. METHODS: We enrolled a total of 55 subjects and divided them into three groups. Groups I and II included healthy, normal weight (n = 15) and obese (n = 15) subjects, respectively. Twenty-five obese asthmatics (group III) were subdivided into group IIIa (10 patients with mild to moderate asthma) and group IIIb (15 patients with severe asthma). High mobility group box 1 (HMGB1), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and urinary Hsp72 were immunoassayed. Hydrogen peroxide (H2O2) and free fatty acids (FFAs) levels were photometrically measured. RAGE mRNA expression was relatively quantified by real-time PCR. RESULTS: We found significant elevations of serum HMGB1, IL-8, MCP1, ERK1/2, FFAs, and H2O2 levels as well as urinary Hsp72 levels in obese subjects compared to healthy control. These were more evident in patients with severe asthma (group IIIb). Multivariate regression analysis identified Hsp72 and ERK1/2 as independent predictors of bronchial asthma severity. Receiver operating characteristic (ROC) curve analysis revealed that areas under the curve (AUC) for Hsp72 and ERK1/2 were 0.991 and 0.981, respectively, which denotes a strong predictive value for identifying the severity of bronchial asthma in obese patients. CONCLUSION: The current study highlights the role of Hsp72 and HMGB1/RAGE/ERK1/2 signaling cascade in the pathogenesis of bronchial asthma and its link to obesity, which could be reflected on monitoring, severity grading, and management of this disease.

Autologous dendritic cells pulsed with lysate from an allogeneic hepatic cancer cell line as a treatment for patients with advanced hepatocellular carcinoma: A pilot study.

OBJECTIVES: This is a randomized trial adopted to evaluate the safety and efficacy of immunization with specific anti-hepatocellular carcinoma dendritic cells (DCs) in Egyptian patients with advanced hepatocellular carcinoma (HCC) as a treatment or adjuvant therapy in comparison with the traditional therapy. METHODS: This study was conducted on 20 HCC patients who were assigned to four groups according to BCLC staging; group I: HCC patients (stage B) received trans-arterial chemoembolization (TACE) and DCs as an adjuvant therapy; group II: HCC patients (stage B) received TACE only; group III: advanced HCC patients (stage D) received DCs vaccine; group IV: advanced HCC patients (stage D) received supportive treatment. DCs were generated from peripheral blood monocytes and pulsed with a lysate of an allogeneic hepatic cancer cell line (HepG2). Toxicity and immunological response were reported as primary outcomes whereas clinical biochemical and radiological responses were reported as secondary outcomes. RESULTS: Our study detected that patients who received DCs vaccine (group III) showed mild decrease in Child-Pugh score as well as AFP and PIVKA II levels and developed 20% partial response [PR] 40% stable disease [SD] and 40% progressive disease [PD] compared to the patients of group IV on supportive treatment who developed 100% PD. Although group I patients developed PR (60%) SD (20%) and PD (20%) no significant difference was detected in the clinical biochemical or radiological response between group I and group II patients. DCs vaccine had minimal adverse effects with no autoimmunity and elicited a better immunological response such as increased CD8 cells percentage and number as well as decreased TGFß levels in the vaccinated patients. CONCLUSION: DCs vaccine is safe as it is not associated with significant toxicity. However due to the small number of included patients the efficacy and immune response of using DCs vaccine in the treatment of advanced HCC patients need to be justified by testing of a large cohort.

Role of serum Metadherin mRNA expression in the diagnosis and prediction of survival in patients with colorectal cancer.

Early diagnosis and treatment of colorectal cancer (CRC) are important for improving patients' survival. Metadherin is an oncogene that plays a pivotal role in carcinogenesis and can be suggested as a cancer biomarker. This study aimed to elucidate the efficacy of serum Metadherin mRNA expression as a potential non-invasive biomarker for early diagnosis of CRC in relation to other screening markers as carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9) and Fecal occult blood (FOB) and also to assess its relationship with the tumor stage and survival rate. A convenience series of 86 CRC cases (group I) were recruited with 78 subjects as controls (group II). Serum Metadherin mRNA expression level was determined using reverse transcription polymerase chain reaction (RT-PCR). Serum Metadherin mRNA expression level was significantly elevated in CRC cases when compared with controls (P < 0.001). For CRC diagnosis; Receiver operator characteristic (ROC) analyses revealed that the diagnostic accuracy of serum Metadherin mRNA (AUC = 0.976) was significantly higher than other routine CRC screening markers as CEA, CA19.9 and FOB. The combined accuracy of these markers (AUC = 0.741) was increased when used with serum Metadherin mRNA (AUC = 0.820). High serum Metadherin mRNA expression was associated with poorly differentiated histological grade, advanced tumor stage and lower survival rate. AUC of Metadherin was 0.820 for differentiating advanced versus early tumor stages. Serum Metadherin mRNA expression is a useful non-invasive biomarker for CRC. It can be used for screening and early diagnosis of CRC and can increase the efficacy of other routine CRC screening markers when it is estimated in CRC patients with them. It is also associated with advanced tumor stage and a lower survival rate.

Diagnostic value of the serum Midkine in patients with rheumatoid arthritis.

Early diagnosis and detection of rheumatoid arthritis (RA) activity which is a potential therapeutic target, depends mainly on clinical presentation. However, laboratory tests may contribute to diagnosis and disease activity assessment of RA. This study aims to evaluate the accuracy of serum Midkine as serological marker for RA diagnosis and its activity detection. All patients with RA were recruited during the period from January 2016 to August 2018 in addition to healthy subjects as control. Serum Midkine level was estimated using enzyme immunoassay. The accuracy was determined for serum Midkine against the used American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA diagnosis and disease activity score derivative for 28 joints-erythrocyte sedimentation rate (ESR) score for assessment of RA disease activity. A total of 211 of patients with RA (group I) were enrolled in this study with 112 healthy subjects (group II). Patients with RA were divided into two subgroups according to the disease activity; patients with active RA (group IA) and RA in remission (group IB). We detected that the area under curve (AUC) of serum Midkine level (AUC=0.851) was significantly lower than that of rheumatoid factor IgM and anti-cyclic citrullinated peptide IgG for RA diagnosis. However, Midkine presents a significantly higher diagnostic accuracy (AUC=0.939) in detecting RA activity than that offered by C reactive protein (CRP) or ESR. Our study suggested that serum Midkine is a potential serological marker for detection of active inflammatory state with higher diagnostic accuracy than other inflammatory markers as CRP or ESR. Therefore, it can be used as an inflammatory marker for detection of disease activity rather than diagnosis of RA.

Assessment of two novel renal tubular proteins in type 2 diabetic patients with nephropathy.

Nephropathy is a common health issue associated with type 2 diabetes mellitus (T2DM). Treatment of diabetic nephropathy (DN) in an early stage can effectively inhibit its progression. Albuminuria is the currently accepted marker for detection of DN.This study aims to evaluate the urinary level of two novel renal tubular proteins (cyclophilin A and periostin) in patients with T2DM and among different nephropathy stages and also to validate the diagnostic accuracy of both cyclophilin A and periostin as potential markers for early prediction of DN relative to albuminuria.This cross-sectional study recruited 137 patients with T2DM, and they were divided based on their urinary albumin:creatinine ratio into T2DM with normoalbuminuria (group II), incipient T2DN with microalbuminuria (group III) and overt T2DN with macroalbuminuria (groupIV) beside 41 healthy subjects as group I Cyclophilin A and periostin were measured in the urine using ELISA. Diagnostic accuracy of both markers was determined for prediction of DN via receiver operating characteristic curve analyses.Urinary cyclophilin A and periostin levels were significantly higher in DN groups when compared with T2DM with normoalbuminuria group. For prediction of incipient and overt DN, areas under the curve (AUCs) of periostin were 0.954, 0.997 and cyclophilin A were 0.914, 0.937, respectively. AUCs of periostin were higher than that for cyclophilin A with a significant AUC difference (p=0.022) in overt DN stage.Periostin and cyclophilin A could be regarded as a potential urinary biomarker for early prediction of DN. Periostin exhibits a higher diagnostic accuracy than urinary cyclophilin A specifically in overt DN stage.

Association of aldosterone synthase CYP11B2 (-344C/T) gene polymorphism with essential hypertension and left ventricular hypertrophy in the Egyptian population.

Background and Objectives: Essential hypertension is a complex progressive cardiovascular disorder. Renin-angiotensin aldosterone system (RAAS) plays a major role in blood pressure regulation. Aldosterone, synthesized in the adrenal cortex by aldosterone synthase is encoded by the CYP11B2 gene. This case-control study was aiming to investigate the relationship between the aldosterone synthase gene (CYP11B2) biallelic polymorphism in the promoter at position -344 (-344C/T) with essential hypertension and left ventricular hypertrophy in the Egyptian population.Methods: This study was conducted on 100 hypertensive patients (group I) and 50 healthy control subjects (group II). Serum aldosterone, plasma renin, ARR levels were investigated. Echocardiography was done to evaluate LV dimensions. Genotyping of the CYP11B2 gene was performed by PCR/RFLP confirmed by direct sequencing.Results: Our study revealed that CYP11B2 (-344T) allele was significantly higher than (-344C) allele in hypertensive patients as compared to healthy control (OR-2.51; 95% CI:1.3-3.5; P = 0.002) and -344TT genotype was associated with increased LVMI as compared with -344CC genotype (P = 0.001).Conclusion: A Significant association was observed between the CYP11B2 (-344C/T) polymorphism and -344T allele and essential hypertension in the Egyptian population. Also, we found that the CYP11B2 -344C/T polymorphism and -344T allele are associated with left ventricular hypertrophy which may predispose to cardiovascular complications of hypertension.

Vildagliptin Recruits Regulatory T Cells in Patients Undergoing Primary Percutaneous Coronary Intervention.

Regulatory T cells (Treg) has been documented to be protective against myocardial ischemia-reperfusion injury (MIRI). The administration of drugs which recruit Treg cells may participate in the cardioprotection of MIRI. The purpose of the present study was to investigate whether the add-on vildagliptin (vild) to standard treatment of MIRI prior to reperfusion could increase Treg recruitment, anti-inflammatory, and antioxidant effects of the standard treatment or not. Sixty diabetic patients with ST-segment elevation myocardial infarction were randomly divided into two equal groups: control group was given the standard medical treatment and vild group was given the standard medical treatment plus vild. There were no statistical differences between the mean of percentage of changes in nitric oxide, ischemia modified albumin, highly sensitive C reactive protein, and interferon-gamma levels in the studied groups. While, the percentages of changes of myeloperoxidase level, CD4+CD25+ Treg cells count, and transforming growth factor-beta1 level were significantly higher in vild group compared with control group. We concluded that addition of vild to standard medical treatment of MIRI could increase its effectiveness through recruitment of CD4+CD25+ Treg cells.