Expression of IL-1 Family Cytokines in Patients Before and After Cutaneous Leishmaniasis Cure

Cutaneous leishmaniasis is an infectious disease that presents an immune response marked by the activation of lymphocytes and production of cytokines, including those of the IL-1 family, which act as an important trigger for the activation of an effector immune response. Despite this, inflammation exacerbation is sometimes also attributed to IL-1 cytokines, although some others down-regulate inflammation or produce Th2 responses, which need to be further clarified in the CL. Assessing the gene and protein expression of IL-1 cytokines associated with different immune response profiles in PBMCs from patients with active and healed lesions, this study demonstrated that stimulation by L. braziliensis positively regulates inflammatory and anti-inflammatory IL-1 cytokines, as IL-1α/β and IL-37, while there was a marked inhibition of IL-1Ra and IL-18 genes in patients treated with antimony, which perhaps contributes to the mechanisms of resistance that control Leishmania infection.

ZNF354C is a transcriptional repressor that inhibits endothelial angiogenic sprouting

Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C has so far only been studied in bone and tumour, its function was determined in endothelial cells. ZNF354C is expressed in vascular cells and localises to the nucleus and cytoplasm. Overexpression of ZNF354C in human endothelial cells results in a marked inhibition of endothelial sprouting. RNA-sequencing of human microvascular endothelial cells with and without overexpression of ZNF354C revealed that the protein is a potent transcriptional repressor. ZNF354C contains an active KRAB domain which mediates this suppression as shown by mutagenesis analysis. ZNF354C interacts with dsDNA, TRIM28 and histones, as observed by proximity ligation and immunoprecipitation. Moreover, chromatin immunoprecipitation revealed that the ZNF binds to specific endothelial-relevant target-gene promoters. ZNF354C suppresses these genes as shown by CRISPR/Cas knockout and RNAi. Inhibition of endothelial sprouting by ZNF354C is dependent on the amino acids DV and MLE of the KRAB domain. These results demonstrate that ZNF354C is a repressive transcription factor which acts through a KRAB domain to inhibit endothelial angiogenic sprouting.

Efficacy of partial purified bacteriocin of Pseudomonas aeruginosa on Methicillin-resistant Staphylococcus aureus biofilm

Biofilms are microbial communities that cause serious chronic infections in the environment by enhancing antimicrobial resistance. Bacteria in the biofilm can be up to a thousand times more resistant to antibiotics than the same bacteria circulating in a planktonic state. The emergence of antibiotic-resistant microorganism has led to the exploration of different therapeutic agents like ribosomally synthesized microorganism peptides referred to as bacteriocins. In this study, bacteriocin producing bacteria Pseudomonas aeruginosa isolated from a soil sample. It was found to be effective against Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore the bacteriocin was partial purified by ammonium sulfate, the precipitate has highly effective against MRSA (400AU/mL). MRSA cells were treated with precipitated culture supernatant of P. aeruginosa TA6 was analyzed by FT-IR. The treated and untreated MRSA showed band variations at 682.59 and 3442.15cm-1 corresponding to the alkyl and amide group respectively. Bacteriocin showed marked inhibition activity against the biofilm of MRSA. About 0.05% and 0.02% attachment of biofilm was observed in the presence of 1X MIC (10 μg/mL) and 2X MIC (20 g/mL) respectively. Our results recommend that bacteriocins that make stable pores on biofilm cells are extremely potent for the treatment of MRSA biofilm infections.

The Effect and Mechanism of Apoptosis on Hela Cells Induced by Bufotalin

Cytotoxic activity of Bufotalin was determined by MTT assay at various concentrations ranging from 0.002 to 0.008 μmol/ml on Hela cells. The Apoptosis and its mechanism induced by Bufotalin was also studied. The results showed Bufotalin displayed the marked inhibition effect to Hela cells and the IC50 value is 0.0045 μmol/ml for 24 hour. The procaspase-3,-8 and-9 decreased and their active cleaved forms increased treated with Bufotalin at concentrations from 0.002 to 0.006 μmol/ml. These data suggest that the pro-apoptotic effect of Bufotalin is mediated through activation of caspases and mitochondria in Hela cells.