In previous studies involving the following heteroleptic Ru complexes, [Ru(pic)(dppb)(bipy)]PF<sub>6</sub> (SCAR1), [Ru(pic)(dppb)(Me-bipy)]PF<sub>6</sub> (SCAR2), [Ru(pic)(dppb)(phen)]PF<sub>6</sub> (SCAR4), <i>cis</i>-[Ru(pic)(dppe)<sub>2</sub>]PF<sub>6</sub> (SCAR5), and [Ru(pic)(dppe)(phen)]PF<sub>6</sub> (SCAR7), we observed excellent anti-TB activity, moderate cell-toxicity, and a lack of oral bioavailability in an <i>in vivo</i> model of these complexes.
Since both P. aeruginosa DsbB1 and M. tuberculosisVKOR complement an E. coli dsbB knockout, we screened simultaneously for inhibitors of each complemented E. coli strain expressing a disulfide-bond sensitive β-galactosidase reported previously.
Increased cytokine secretion was subsequently observed with vimentin stimulation of sarcoidosis PBMCs vs. tuberculosis PBMCs (IFN-γ: 396.6 pg/mL vs 0.1 pg/mL, p = 0.0009; TNF-α: 1139 pg/mL vs 0.1 pg/mL, p<0.0001).
Besides, the expression of vimentin in avirulent strain, Mycobacterium tuberculosis H37Ra- infected macrophages was similar to the expression in heat-killed H37Rv- infected macrophages.
Pleural effusion VEGF levels were significantly higher in the malignant group than in the tuberculosis group (2,091.47 ± 1,624.80 pg/mL vs. 1,291.05 ± 1,100.53 pg/mL, P < 0.05), whereas pleural effusion endocan levels were similar between the two groups (1.22 ± 0.74 ng/mL vs. 0.87 ± 0.53 ng/mL).
In accordance with our in vitro and in vivo results, we show that the level of VEGF in TB patients is elevated and that endothelial progenitor cells are mobilized from the bone marrow.
A biosignature comprising unstimulated IFN-γ, MIP-1β, TGF-α and antigen-specific levels of TGF-α and VEGF, identified on a training sample set (n = 311), validated by diagnosing TB disease in the test set (n = 134) with an AUC of 0.81(95% CI, 0.76-0.86), corresponding to a sensitivity of 64.2%(95% CI, 49.7-76.5%) and specificity of 82.7%(95% CI, 72.4-89.9%).
Polymorphisms in genes encoding natural-resistance-associated macrophage protein, vitamin D receptor and mannose-binding lectin were associated with tuberculosis.
A quantitative synthesis was performed for the published studies based on the association between the VDR ApaI gene polymorphism and the risk of TB retrieved from PubMed (Medline) and EMBASE web databases.
Polymorphisms in human leukocyte antigen (HLA), MBL2, CD209, vitamin D receptor, cytokine, chemokine and chemokine receptor genes have been shown to be associated with development of TB in HIV patients.
Plasma levels of vitamin D and polymorphisms in the vitamin D receptor may affect tuberculosis, and HIV infection associates with vitamin D deficiency.
We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis.
Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB.
Studies have reported genetic markers to predict TB development in human leukocyte antigen (HLA) and non-HLA genes like killer immunoglobulin-like receptor (KIR), toll-like receptors (TLRs), cytokine/chemokines and their receptors, vitamin D receptor (VDR) and SLC11A1 etc.
Many genes involved in tuberculosis susceptibility (e.g., NRAMP1 (SLC11A1), IFNG, NOS2A, VDR, ISG15, TACO, TLR1, TLR, IL18R1, chemokines, PADI, DUSP14, MBL, and MASP-2) have been subjected to epigenetic modification.
A cohort of pulmonary tuberculosis (TB) patients in a South African admixed population was investigated to determine if the vitamin D receptor gene (VDR) polymorphisms FokI, ApaI, and TaqI are associated with TB susceptibility or time to sputum conversion, and to investigate other clinical and demographic factors affecting the rate of response to treatment.
When Monocytes Derived Macrophages (MDM) from DM2 patients with low VDR expression were supplemented with vitamin D, MDMs eliminate efficiently M. tuberculosis.