Effect of vitamin D supplementation on management of anemia in hemodialysis patients with vitamin D deficiency: A double-blind, randomized, controlled trial.

INTRODUCTION: Anemia and vitamin D deficiency are common problems among hemodialysis (HD) patients. This study aimed to assess the impact of correction of vitamin D deficiency with vitamin D supplementation on the improvement of anemia in patients with end-stage renal disease (ESRD) on maintenance HD. METHODS: This double-blind, randomized, controlled study included 100 anemic HD patients with vitamin D deficiency who were randomly divided using the closed envelop method into two groups (1:1). The first group received vitamin D (50,000 IU) monthly for 6 months, and the other group received a placebo for the same period. 25-Hydroxyvitamin D (25(OH)D) levels were measured for both groups at the beginning of the study and after 6 months at the end of the study. Hemoglobin (Hb) concentrations were recorded monthly. FINDINGS: Vitamin D supplementation during the period of the study increased 25(OH)D levels in the vitamin D group more than the placebo group (p > 0.001). Serum ferritin, serum iron, and transferrin saturation did not differ significantly between both groups during the period of the study. Hb concentration in the vitamin D group increased more than that in the other group over the period of the study, and there was a statistically significant difference between the two groups in all durations of follow-up. Erythropoietin (EPO) dosage requirements were found to be lower in the vitamin D group than in the placebo group, and this was statistically significant (p > 0.001). DISCUSSION: Vitamin D supplementation in anemic ESRD patients on HD with vitamin D deficiency or insufficiency is safe and effective in improving anemia and decreasing EPO dosage.

Ammonia scavenger and glutamine synthetase inhibitors cocktail in targeting mTOR/ß-catenin and MMP-14 for nitrogen homeostasis and liver cancer.

The glutamine synthetase (GS) facilitates cancer cell growth by catalyzing de novo glutamine synthesis. This enzyme removes ammonia waste from the liver following the urea cycle. Since cancer development is associated with dysregulated urea cycles, there has been no investigation of GS's role in ammonia clearance. Here, we demonstrate that, although GS expression is increased in the setting of ß-catenin oncogenic activation, it is insufficient to clear the ammonia waste burden due to the dysregulated urea cycle and may thus be unable to prevent cancer formation. In vivo study, a total of 165 male Swiss albino mice allocated in 11 groups were used, and liver cancer was induced by p-DAB. The activity of GS was evaluated along with the relative expression of mTOR, ß-catenin, MMP-14, and GS genes in liver samples and HepG2 cells using qRT-PCR. Moreover, the cytotoxicity of the NH3 scavenger phenyl acetate (PA) and/or GS-inhibitor L-methionine sulfoximine (MSO) and the migratory potential of cells was assessed by MTT and wound healing assays, respectively. The Swiss target prediction algorithm was used to screen the mentioned compounds for probable targets. The treatment of the HepG2 cell line with PA plus MSO demonstrated strong cytotoxicity. The post-scratch remaining wound area (%) in the untreated HepG2 cells was 2.0%. In contrast, the remaining wound area (%) in the cells treated with PA, MSO, and PA + MSO for 48 h was 61.1, 55.8, and 78.5%, respectively. The combination of the two drugs had the greatest effect, resulting in the greatest decrease in the GS activity, ß-catenin, and mTOR expression. MSO and PA are both capable of suppressing mTOR, a key player in the development of HCC, and MMP-14, a key player in the development of HCC. PA inhibited the MMP-14 enzyme more effectively than MSO, implying that PA might be a better way to target HCC as it inhibited MMP-14 more effectively than MSO. A large number of abnormal hepatocytes (5%) were found to be present in the HCC mice compared to mice in the control group as determined by the histopathological lesions scores. In contrast, PA, MSO, and PA + MSO showed a significant reduction in the hepatic lesions score either when protecting the liver or when treating the liver. The molecular docking study indicated that PA and MSO form a three-dimensional structure with NF-κB and COX-II, blocking their ability to promote cancer and cause gene mutations. PA and MSO could be used to manipulate GS activities to modulate ammonia levels, thus providing a potential treatment for ammonia homeostasis.

Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases.

Despite all the advances in the management of breast cancer (BC), patients with distance metastasis are still considered incurable with poor prognosis. For that reason, early detection of the metastatic lesions is crucial to improve patients' life span as well as quality of life. Many markers were proposed to be used as biomarkers for metastatic BC lesions, however many of them lack organ specificity. This highlights the need for novel markers that are more specific in detecting disseminated BC lesions. Here, we investigated mammaglobin-1 expression as a potential and specific marker for metastatic BC lesions using our patient cohort consisting of 30 newly diagnosed BC patients. For all patients, bone marrow (BM) aspiration, BM biopsy stained by H&E and BM immunohistochemically stained for mammaglobin-1 were performed. In addition, the CA15-3 in both serum and bone marrow plasma was also evaluated for each patient. Indeed, mammaglobin-1 immuno-staining was able to detect BM micrometastases in 16/30 patients (53.3%) compared to only 5/30 patients (16.7%) in BM biopsy stained by H&E and no cases detected by BM aspirate (0%). In addition, our results showed a trend of association between mammaglobin-1 immunoreactivity and the serum and BM plasma CA15-3. Further validation was done using large publicly available databases. Our results showed that mammaglobin-1 gene expression to be specifically upregulated in BC patients' samples compared to normal tissue as well as samples from other cancers. Moreover, our findings also showed mammaglobin-1 expression to be a marker of tumour progression presented as lymph nodes involvement and distant metastasis. These results provide an initial evidence for the use of mammaglobin-1 (SCGB2A2) immunostaining in bone marrow as a tool to investigate early BM micrometastases in breast cancer.