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Aberrant activation of hedgehog (Hh) signaling has been implicated in various cancers. Current FDA-approved inhibitors target the seven-transmembrane receptor Smoothened, but resistance to these drugs has been observed. It has been proposed that a more promising strategy to target this pathway is at the GLI1 transcription factor level. GANT61 was the first small molecule identified to directly suppress GLI-mediated activity; however, its development as a potential anti-cancer agent has been hindered by its modest activity and aqueous chemical instability. Our study aimed to identify novel GLI1 inhibitors. JChem searches identified fifty-two compounds similar to GANT61 and its active metabolite, GANT61-D. We combined high-throughput cell-based assays and molecular docking to evaluate these analogs. Five of the fifty-two GANT61 analogs inhibited activity in Hh-responsive C3H10T1/2 and Gli-reporter NIH3T3 cellular assays without cytotoxicity. Two of the GANT61 analogs, BAS 07019774 and Z27610715, reduced Gli1 mRNA expression in C3H10T1/2 cells. Treatment with BAS 07019774 significantly reduced cell viability in Hh-dependent glioblastoma and lung cancer cell lines. Molecular docking indicated that BAS 07019774 is predicted to bind to the ZF4 region of GLI1, potentially interfering with its ability to bind DNA. Our findings show promise in developing more effective and potent GLI inhibitors.

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OBJECTIVES: To investigate whether magnetic resonance imaging (MRI) best detects early malignancy in high-risk women. METHODS: A retrospective, cross-sectional study, carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, included 419 female breast cancer patients aged 16-84 years (mean age of 49). Data were collected from the radiological department's database to compare the MRI, ultrasound (US), and mammography results, with or without tissue biopsy. RESULTS: In diagnosing benign versus malignant lesions, MRI showed significant agreement with tissue biopsy, with high sensitivity (70%) and specificity (87%); its positive predictive value (PPV) was 92% and negative predictive value (NPV) was 56%. While US has a PPV of 84% and NPV of 63%; with a sensitivity (79%) and specificity (71%). In patients without tissue biopsy, there was little difference between mammography and US compared with MRI results. CONCLUSION: Magnetic resonance imaging is more effective than US and mammography for early detection of BC. It showed high sensitivity in detecting breast lesions and high specificity in characterizing their nature when correlated with pathological results. Ultrasound screening followed by MRI is suggested for undetected or suspected lesions. This will increase the breast lesion detection rate, reduce unneeded tissue biopsies, and enhance the disease's survival rate.

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Introduction Multiple sclerosis (MS) is one of the most prevalent disorders of the central nervous system (CNS), and it can be observed in the field of radiological cross-sectional magnetic resonance imaging (MRI). The prevalence of MS in Saudi Arabia has increased as compared to the past few years. MRI is the gold standard non-invasive modality of choice in MS diagnosis according to the National Multiple Sclerosis Society (NMSS), New York City. This study aimed to highlight the significance of using diffusion-weighted images (DWIs) and the use of contrast media in the MS protocol, as well as the importance of identifying the suitable time of imaging after contrast enhancement to detect active lesions. Methods A retrospective cross-sectional study was conducted of 100 MS patients with an age range of 17 to 56 years. The data set included 41 active cases and 59 inactive cases. All patients had an MRI standard protocol of both the brain and spine in addition to DWI sequence and contrast agent (CA) injection, with images taken in early and delayed time. Results Of the patients, 71% were female and 29% were male. Active MS disease was more significant at younger ages than at older ages. Active lesions were significantly enhanced in delayed contrast images and showed high signal intensity in both the DWI and apparent diffusion coefficient (ADC) map, while inactive lesions showed no enhancement after contrast injection and showed an iso-signal intensity in both the DWI and ADC map. Conclusion The use of CA has developed over the years in the diagnosis of MS patients. In this study, the relationship between active lesions, DWI, and delayed contrast enhancement is very strong. In future research, we recommend adding a DWI sequence for the suspected active MS spine lesions in addition to delayed enhancement time in active MS after contrast injection to increase MRI sensitivity toward active MS lesions of the brain and spinal cord as well.

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Diabetic nephropathy (DN) is a major leading cause of kidney failure. So, early detection of DN by assessing urinary microRNAs (miRNAs) expression may be of clinical value. In this study, the diagnostic value of two urinary miRNAs (miR-210 & miR-34a) as biomarkers for diagnosis of DN was assessed using a simple colorimetric gold nanoparticle (AuNP) assay and real-time PCR. MiR-(210 & 34a) were markedly up-regulated in DN groups (micro-albuminuric and macro-albuminuric groups) compared to the non-albuminuric group and healthy controls. The sensitivity and specificity for the qualitative detection of urinary miR-(210 & 34a) using the AuNP assay were (78% and 72%) & (81% and 69%), respectively, which were consistent with the results of real-time PCR. There was a highly significant correlation between urinary miR-(210 & 34a) detected by either qRT-PCR or qualitative AuNP assay. Accordingly, this simple AuNP assay may be considered a valid test for the detection of these two urinary miRNAs as potential biomarkers that can aid in the noninvasive diagnosis of DN.

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PURPOSE: The current study aimed at assessing vitamin D level and vitamin D receptor polymorphism in hypothyroid Egyptian patients and its effect on hypothyroidism and thyroid morphology, also to find a causal relation between vitamin D and hypothyroidism. METHODS: This case-control study was conducted on 35 hypothyroid patients and 35 matched unrelated healthy controls. Total serum 25-hydroxyvitamin D3 and thyroid antibodies were measured using a human ELISA kit. Genotyping was performed by using real-time PCR. HOMA-IR was also calculated (fasting insulin in mIU/L × fasting glucose in mg/dL/405). All subjects were assessed for thyroid morphology by thyroid ultrasonography. RESULTS: Vitamin D level was lower in hypothyroid patients than in control subjects. Vitamin D was also inversely related to TSH, HOMA-IR, and levels of anti-TG and anti-TPO. VDR polymorphism (Fok1 and Apa1) had no relation to TSH or vitamin D levels in both patients and control groups. Low vitamin D levels were associated with increased thyroid vascularity and nodularity; furthermore, vitamin D was inversely proportional to thyroid gland volume. Correlation of HOMA-IR with the levels of both anti-TG and anti-TPO in the 70 subjects proved that HOMA-IR was positively correlated to both antibodies. CONCLUSION: This study confirmed the association of vitamin D deficiency with hypothyroidism, thyroid autoimmunity, increased volume, nodularity, and vascularity of thyroid gland in hypothyroid patients as well as increased HOMA-IR. It proved the association between HOMA-IR and thyroid autoimmunity. The study proved no association between VDR polymorphisms (Fok1 and Apa1) with either vitamin D levels or TSH levels.

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INTRODUCTION: Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We aimed to study the expression of podocyte-associated genes in urinary sediment and their relation to disease severity in type 2 diabetic Egyptian patients with diabetic nephropathy. METHOD: ology: Sixty patients with type 2 diabetes mellitus were recruited in addition to twenty non diabetic healthy volunteers. Relative mRNA abundance of nephrin, podocalyxin, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined. RESULTS: The urinary mRNA levels of all genes studied were significantly higher in diabetics compared with controls (p < 0.001), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and HbA1c. The expression of nephrin, podocalyxin, and podocin mRNA correlated with serum creatinine {(r = 0.397, p value = 0.002), (r = 0.431, p value = 0.001), (r = 0.433, p value = 0.001) respectively}. CONCLUSION: The urinary mRNA profiles of nephrin, podocalyxin, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

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BACKGROUND AND OBJECTIVE: Type 2 DM and obesity are the coming epidemics and their association with NAFLD is well established; essential fatty acids are vital for body health yet the body cannot make them; 2 essential fatty acids are especially important: linoleic (omega-6) and alpha-linoleic (omega-3) acids; they can be considered as "bioactive lipids" and serve as functional foods. METHODS: 50 type 2 Egyptian diabetic patients controlled on oral hypoglycemic drugs together with 20 age- and sex-matched healthy participants were enrolled in the study; all were subjected to complete history taking, BMI, fasting plasma glucose, HOMA-IR, ALT, AST, GGT, urea and creatinine, total lipid profile, hepatitis markers including hepatitis B surface antigen and hepatitis C virus antibodies, conjugated linoleic fatty acid "CLA," and abdominal ultrasound for grading of NAFLD. RESULTS: Our study in Egyptian diabetics with NAFLD revealed a low level of serum CLA compared to healthy control; such deficiency was more marked with advanced grades of NAFLD; lowest levels were observed in those with severe steatosis (NASH) with definite association between CLA and obesity. CONCLUSION: Insulin resistance is the main link between NAFLD, diabetes, and obesity. Conjugated linoleic acid (CLA) has a role in fat deposition in the liver and in development and improvement of insulin resistance. Fatty food had a documented role in the pathogenesis of obesity and diabetes but it can also be the cure.

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There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.

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Thyroid nodules are a common medical and surgical concern. Thyroid ultrasound (US) is the primary imaging modality used for initial evaluation and assortment of nodules for fine needle aspiration (FNA) cytology/biopsy. Ultrasound elastography (USE) is believed to improve the diagnostic accuracy of US in distinguishing benign from malignant nodules. The aim of the work described here is to evaluate the diagnostic criteria and accuracy of US and USE in the diagnosis of malignant thyroid nodules. A prospective study of 88 patients who have thyroid nodules was performed. US, color Doppler, and USE were evaluated using a Philips iU22 equipped with a 5 to 12 MHz, linear transducer, followed by FNA of the each scanned nodule. The most sensitive US criteria for malignant nodules were a height-to-width ratio greater than one and the absence of a halo sign (sensitivity 0.875% and 1.000%, respectively). The most specific criteria for malignancy were a spiculated/blurred margin and the presence of microcalcifications (specificity 0.968% and 0.888%, respectively). The receiver operating characteristic curve showed that the cutoff diagnostic criteria of malignancy are two US characteristics and an elastography score of 4. The diagnostic accuracy of US for malignant thyroid nodules increases by combining US and USE.

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OBJECTIVE: To clarify the role of ghrelin in malnutrition in uremia and its relationship to fat composition using dual x-ray absorptiometry (DXA). METHODS: This is a cohort study including Group I: 60 patients with end stage renal disease 30 on hemodialysis [group IA] and 30 pre-dialysis [group IB] and Group II: 20 controls. This study was carried out in Cairo University Hospital, Kasr Al-Aini, Cairo, Egypt in 2007. Body fat composition (total, differential, and lean body mass) was assessed using DXA, and plasma ghrelin was measured. RESULTS: Ghrelin was significantly higher in hemodialysis and pre-dialysis groups compared to the control group, and higher in hemodialysis group compared to the pre-dialysis group. In hemodialysis, ghrelin was negatively correlated with weight, body mass index (BMI), and truncal fat mass, and positively correlated with serum creatinine. In pre-dialysis, ghrelin inversely correlated with weight, BMI, and truncal fat mass, and positively correlated with serum creatinine, lean body mass. In control, plasma ghrelin showed negative correlation with weight, BMI, truncal fat mass, and body fat mass, and positive correlation with lean body mass. CONCLUSION: Ghrelin was markedly elevated in renal failure due to its decrease in excretion. Negative correlation between ghrelin and fat composition was detected in dialysis patients. Serial evaluation of body fat composition using DXA is recommended for assessment of nutritional status of those patients.

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