Urinary BLACAT1 as a non-invasive biomarker for bladder cancer.

BACKGROUND: Bladder cancer (BC) is recorded as the fifth most common cancer worldwide with high morbidity and mortality. The most urgent problem in BCs is the high recurrence rate as two-thirds of non-muscle-invasive bladder cancer (NMIBC) will develop into muscle-invasive bladder cancer (MIBC), which retains a feature of rapid progress and metastasis. In addition, only a limited number of biomarkers are available for diagnosing BC compared to other cancers. Hence, finding sensitive and specific biomarkers for predicting the diagnosis and prognosis of patients with BC is critically needed. Therefore, this study aimed to determine the expression and clinical significance of urinary lncRNA BLACAT1 as a non-invasively diagnostic and prognostic biomarker to detect and differentiate BCs stages. METHODS AND RESULTS: The expression levels of urinary BLACAT1 were detected by qRT-PCR assay in seventy (70) BC patients with different TNM grades (T0-T3) and twelve (12) healthy subjects as control. BLACAT1 was downregulated in superficial stages (T0 = 0.09 ± 0.02 and T1 = 0.5 ± 0.1) compared to healthy control. Furthermore, in the invasive stages, its levels started to elevate in the T2 stage (1.2 ± 0. 2), and higher levels were detected in the T3 stage with a mean value of (5.2 ± 0.6). This elevation was positively correlated with disease progression. Therefore, BLACAT1 can differentiate between metastatic and non-metastatic stages of BCs. Furthermore, its predictive values are not like to be influenced by schistosomal infection. CONCLUSIONS: Upregulation of BLACAT1 in invasive stages predicted an unfavorable prognosis for patients with BCs, as it contributes to the migration and metastasis of BCs. Therefore, we can conclude that urinary BLACAT1 may be considered a non-invasive promising metastatic biomarker for BCs.

Urinary Urea, Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple Sclerosis Patients.

Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). The objective was to investigate the level of some urinary metabolites (urea, uric acid and hippuric acid) in patients with MS and correlate their levels to the severity of the disease, MS subtypes and MS treatment. The urine samples were collected from 73 MS patients-48 with RRMS and 25 with SPMS- and age matched 75 healthy controls. The values of urinary urea, uric acid and hippuric acid in MS patients were significantly decreased, and these metabolites in SPMS pattern showed significantly decrease than RRMS pattern. Also showed significant inverse correlation with expanded disability status scale and number of relapses. Accordingly, they may act as a potential urinary biomarkers for MS, and correlate to disease progression.

The combined effect of IL-17F and CCL20 gene polymorphism in susceptibility to multiple sclerosis in Egypt.

BACKGROUND: Levels of CCL20 and its CCR6 receptor are elevated in many autoimmune diseases which help in the recruitment of T helper (Th17) cells to site of inflammation. OBJECTIVES: Determine the value of single nucleotide polymorphism of CCL20 (rs6749704) and IL-17F (rs763780) genes and their concomitant effect on the serum CCL20 level and susceptibility to MS in Egyptian patients. SUBJECTS AND METHODS: Blood samples were collected from 83 patients and 95 healthy subjects. Serum levels of CCL20 were measured by ELISA. The DNA was analyzed for rs6749704 and rs763780 using Genotyping Taqman assay. RESULTS: The mean serum levels of CCL20 in the MS group were significantly higher than healthy group (P < 0.001). Frequencies of CT genotype of rs6749704 in CCL20 gene and C allele in MS patients were significantly higher compared to controls. Also significant increase of rs763780 in IL-17F gene was detected in MS patients. Concomitant polymorphism in both genes in MS patients showed an increase risk to MS rather than individual locus. CONCLUSION: CCL20 may play an important role in the pathogenesis of MS. Both allelic variation of (rs6749704) within CCL20 gene and (rs763780) within IL-17F gene can be considered risk factor for development of MS in Egyptian patients.

Asc-dependent and independent mechanisms contribute to restriction of legionella pneumophila infection in murine macrophages.

The apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) is an adaptor molecule that mediates inflammatory and apoptotic signals. Legionella pneumophila is an intracellular bacterium and the causative agent of Legionnaire's pneumonia. L. pneumophila is able to cause pneumonia in immuno-compromised humans but not in most inbred mice. Murine macrophages that lack the ability to activate caspase-1, such as caspase(-1-/-) and Nlrc4(-/-) allow L. pneumophila infection. This permissiveness is attributed mainly to the lack of active caspase-1 and the absence of its down stream substrates such as caspase-7. However, the role of Asc in control of L. pneumophila infection in mice is unclear. Here we show that caspase-1 is moderately activated in Asc(-/-) macrophages and that this limited activation is required and sufficient to restrict L. pneumophila growth. Moreover, Asc-independent activation of caspase-1 requires bacterial flagellin and is mainly detected in cellular extracts but not in culture supernatants. We also demonstrate that the depletion of Asc from permissive macrophages enhances bacterial growth by promoting L. pneumophila-mediated activation of the NF-κB pathway and decreasing caspase-3 activation. Taken together, our data demonstrate that L. pneumophila infection in murine macrophages is controlled by several mechanisms: Asc-independent activation of caspase-1 and Asc-dependent regulation of NF-κB and caspase-3 activation.