Potential Value of miR-23a for Discriminating Neuromyelitis Optica Spectrum Disorder from Multiple Sclerosis.

BACKGROUND: Until now, no laboratory test or test set can guarantee the diagnosis of multiple sclerosis (MS) at early disease stages, and the disease symptoms may interfere with many other disease conditions. Analyzing the expression of circulating miRNAs may provide a useful approach for early and differential MS diagnosis. The main objective is assessment of the potential of serum miR-23a, miR-155, and miR-572 to differentiate between MS and other neuroinflammatory diseases. METHODS: Serum miRNAs were obtained from 37 MS patients and 25 healthy age-matched controls, along with patients with neuromyelitis optica spectrum disorder (NMOSD) [n = 13] and neuropsychiatric systemic lupus erythematosus (NPSLE) [n = 10]. miRNA expression levels were analyzed using real-time polymerase chain reaction (PCR) and pairwise comparisons were made to reveal the diagnostic/distinguishing potential of the analyzed miRNAs. RESULTS: In the study cohort, the three investigated miRNAs failed to display significant dysregulation in MS patients. However, they could significantly discriminate patients with NMOSD and NPSLE [median (IQR): 8.1 (6.1-9.2) and 8.8 (7.9-9.7) for miR-23a, 7.5 (5.3-8.3) and 8.0 (7.5-9.5) for miR-155 and 6.9 (5.0-8.8) and 6.4 (5.3-8.8) for miR-572 in NMOSD and NPSLE, respectively] from healthy subjects [median (IQR): 3.4 (1.5-4.3), 3.1 (1.1-5.6) and 3.5 (1.7-5.6) for miR-23a, miR-155 and miR-572, respectively], with area under the curve (AUC) ≤0.8. Remarkably, miR-23a has been emerging as a prospective biomarker for differentiation of MS from NMOSD as well as NPSLE (AUC<0.9). The miRNA combined use contributed to enhanced diagnostic and discriminatory performance in the study groups. CONCLUSION: Certain miRNA expression levels would contribute to discriminating MS from other neuroinflammatory diseases.

Comparison of the percentages of CD4+ CD25high FOXP3+ , CD4+ CD25low FOXP3+ , and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia.

PROBLEM: Little is known about how preeclampsia affects regulatory T-cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4+  CD25high  FOXP3+ , CD4+  CD25low  FOXP3+ , and CD4+  FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia. METHOD OF STUDY: The percentage of umbilical cord blood CD4+  CD25high  FOXP3+ , CD4+  CD25low  FOXP3+ , and CD4+  FOXP3+ Tregs were analyzed by flow cytometry. RESULTS: CD4+  CD25high  FOXP3+ Treg (%) and CD4+  FOXP3+ Treg (%) were significantly lower, while CD4+  CD25low (%) was significantly higher in umbilical cord blood of babies born to preeclamptic mothers. CONCLUSION: Preeclampsia is associated with immune dysregulation which leads to a deficiency in Treg (CD4+  CD25high  FOXP3+ ) in the umbilical cord blood of babies born to preeclamptic mothers.

Assessment of Left Ventricular Diastolic Function in Egyptian Patients With Behçet's Disease.

OBJECTIVES: This study aims to evaluate left ventricular diastolic function in Egyptian patients with Behçet's disease using variable echocardiographic parameters by combining both transmitral and tissue Doppler velocities to overcome the occasional false interpretation of preload dependent transmitral parameters and to detect the correlation between various left ventricular diastolic parameters and different disease manifestations. PATIENTS AND METHODS: Forty patients (35 males, 5 females; mean age 31±8 years; range 19 to 52 years) with Behçet's disease and 32 age- and sex- matched healthy controls (26 males, 6 females; mean age 28±6 years; range 19 to 60 years) were enrolled. Left ventricular diastolic function was assessed using an algorithm that combined transmitral and tissue Doppler derived parameters. RESULTS: Mean disease duration of the patients was 7.4±6 years. Left and right ventricular systolic function was normal in both groups. The transmitral E/A was<1 in six patients (15%). There was no difference between patients and controls regarding the other left ventricular diastolic parameters. Compared to patients with an E/A ratio >1, patients with E/A<1 were significantly older and had a longer disease duration (p=0.001 and p<0.001, respectively). All the other echocardiographic parameters in both groups were comparable. CONCLUSION: Egyptian patients with Behçet's disease have normal left ventricular diastolic function regardless of disease duration and activity.

Aldose reductase inhibition of a saponin-rich fraction and new furostanol saponin derivatives from Balanites aegyptiaca.

BACKGROUND: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are used to treat hyperglycemia in Egyptian folk medicine and are sold by herbalists in the Egyptian open market for this purpose. Nevertheless, the fruits have not yet been incorporated into pharmaceutical dosage forms. The identity of the bioactive compounds and their possible mechanisms of action were not well understood until now. PURPOSE: Aldose reductase inhibitors are considered vital therapeutic and preventive agents to address complications caused by hyperglycemia. The present study was carried out to identify the primary compounds responsible for the aldose reductase inhibitory activity of Balanites aegyptiaca fruits. STUDY DESIGN: The 70% ethanolic extract of Balanites aegyptiaca fruit mesocarp and its fractions were screened for inhibition of the aldose reductase enzyme. Bio-guided fractionation of the active butanol fraction was performed and the primary compounds present in the saponin-rich fraction (D), which were responsible for the inhibitory activity, were characterized. HPLC chromatographic profiles were established for the different fractions, using the isolated compounds as biomarkers. METHODS: Aldose reductase inhibition was tested in vitro on rat liver homogenate. The butanol fraction of the 70% ethanolic extract was fractionated using vacuum liquid chromatography (VLC, RP-18 column). The most active sub-fraction D, which was eluted with 75% methanol, was subjected to preparative HPLC to isolate the bioactive compounds. RESULTS: The butanol fraction displayed inhibitory activity against the aldose reductase enzyme (IC50 = 55.0 ± 6 µg/ml). Sub-fraction D exhibited the highest inhibitory activity (IC50 = 12.8 ± 1 µg/ml). Five new steroidal saponin derivatives were isolated from this fraction. The isolated compounds were identified as compound 1a/b, a 7:3 mixture of the 25R:25S epimers of 26-O-ß-D-glucopyranosyl-furost-5-ene-3,22,26-triol 3-O-[α-L-rhamnopyranosyl-(1→3)- ß-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranoside; compound 2, 26-O-ß-D-glucopyranosyl-(25R)-furost-5-ene-3,22,26-triol 3-O-[ ß-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranoside; compound 3, 26-O-ß-D-glucopyranosyl-(25R)-furost-5,20-diene-3,26-diol 3-O-[α-L-rhamnopyranosyl-(1→3)- ß-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranoside; compound 4, 26-O-ß-D-glucopyranosyl-(25R)-furost-5,20-diene-3,26-diol 3-O-[ ß-D-glucopyranosyl-(1→2)]- α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranoside; and compound 5, which is the 25S epimer of compound 4, by using various spectroscopic methods [MS,1D and 2D NMR (HSQC, HMBC, DQF-COSY, HSQC-TOCSY)]. Compounds 1a/b, 2, 3, 4, 5 exhibited highly significant aldose reductase inhibitory activities (IC50 values were 1.9 ± 0.2, 1.3 ± 0.5, 5.6 ± 0.2, 5.1 ± 0.4, 5.1 ± 0.6 µM, respectively) as compared to the activity of the reference standard quercetin (IC50 = 6.6 ± 0.3 µM). CONCLUSION: The aldose reductase inhibitory activity of Balanites fruits is due to the steroidal saponins present. HPLC chromatographic profiles of the crude butanol fraction and its 4 sub-fractions showed that the most highly bioactive fraction D contained the highest amount of steroidal saponins (75%) as compared to the 21% present in the original butanol fraction. The isolated furostanol saponins proved to be highly active in an in vitro assay.

Value of certain echocardiographic findings in the initial suspicion of Behçet's disease.

PURPOSE: To describe the echocardiographic findings detected as first manifestations of Behçet's disease (BD) and compare these findings with those detected in established cases of BD receiving regular medical treatment. METHODS: Two groups of patients were studied. Group 1 comprised 41 patients with BD on regular medical treatment. Group 2 comprised 5 previously healthy patients who presented to the cardiology department because of cardiac symptoms and were diagnosed in retrospect during hospitalization as BD. Thirty-two age- and sex-matched individuals served as control subjects (control group). All patients and controls underwent complete M-mode, two-dimensional, and Doppler transthoracic echocardiographic examinations. RESULTS: Of the 41 treated patients with BD (mean age: 32 ± 8 years, 90% males, mean duration since diagnosis: 14.5 years), only 1 patient was found to have severe aortic regurgitation secondary to aortic root dilation. On the other hand, the 5 previously healthy patients who presented with cardiac symptoms (mean age: 24 ± 6 years, all males) had significant cardiac involvement and evident echocardiographic findings (P < 0.001). Four cases had intracardiac masses: 3 in the right atrium (RA), 1 in the right ventricle (RV), while the last patient had pericardial effusion (PE). All these patients were diagnosed in retrospect as BD. The RA masses disappeared on medical therapy, while the RV mass was surgically excised and proved to be multiple thrombi histopathologically. The patient with PE had recurrent attacks of massive effusion so a pericardial window was performed surgically. CONCLUSION: Diagnosis of BD might be initially suspected by the cardiologists based on certain echocardiographic findings, namely the presence of right-sided masses. Diagnosis of BD in such patients has important therapeutic implications and accordingly prognostic value.