Histone Methylation: Achilles Heel and Powerful Mediator of Periodontal Homeostasis.

The packaging of DNA around nucleosomes exerts dynamic control over eukaryotic gene expression either by granting access to the transcriptional machinery in an open chromatin state or by silencing transcription via chromatin compaction. Histone methylation modification affects chromatin through the addition of methyl groups to lysine or arginine residues of histones H3 and H4 by means of histone methyl transferases or histone demethylases. Changes in histone methylation state modulate periodontal gene expression and have profound effects on periodontal development, health, and therapy. At the onset of periodontal development, progenitor cell populations such as dental follicle cells are characterized by an open H3K4me3 chromatin mark on RUNX2, MSX2, and DLX5 gene promoters. During further development, periodontal progenitor differentiation undergoes a global switch from the H3K4me3 active methyl mark to the H3K27me3 repressive mark. When compared with dental pulp cells, periodontal neural crest lineage differentiation is characterized by repressive H3K9me3 and H3K27me3 marks on typical dentinogenesis-related genes. Inflammatory conditions as they occur during periodontal disease result in unique histone methylation signatures in affected cell populations, including repressive H3K9me3 and H3K27me3 histone marks on extracellular matrix gene promoters and active H3K4me3 marks on interleukin, defensin, and chemokine gene promoters, facilitating a rapid inflammatory response to microbial pathogens. The inflammation-induced repression of chromatin on extracellular matrix gene promoters presents a therapeutic opportunity for the application of histone methylation inhibitors capable of inhibiting suppressive trimethylation marks. Furthermore, inhibition of chromatin coregulators through interference with key inflammatory mediators such as NF-kB by means of methyltransferase inhibitors provides another avenue to halt the exacerbation of the inflammatory response in periodontal tissues. In conclusion, histone methylation dynamics play an intricate role in the fine-tuning of chromatin states during periodontal development and harbor yet-to-be-realized potential for the treatment of periodontal disease.

Effect of brain-derived neurotrophic factor on sperm function, oxidative stress and membrane integrity in human.

Oxidative stress has negative impacts on the clinical outcomes of assisted reproduction techniques. The brain-derived neurotrophic factor (BDNF) promotes the viability of nerve cells and is known to decrease oxidative stress and apoptosis in different cells. The aim of this study was to evaluate the effect of BDNF treatment on human sperm functions that are known to be essential for fertilisation. Our findings showed that treatment of human spermatozoa with 0.133 nM BDNF significantly increased the percentages of both total (P = 0.001) and progressive (P < 0.01) motile sperm cells compared to those observed in the nontreated (control) group. We also showed that the mean fluorescence intensity of DCFH-DA, as an indicator of intracellular reactive oxygen species, was significantly lower (P < 0.05) in spermatozoa treated with BDNF compared to the control group. Treatment of spermatozoa with BDNF significantly decreased the percentages of both dead (P = 0.001) and apoptotic-like sperm cells (P < 0.05) compared to the control group. On the other hand, BDNF treatment significantly increased the percentage of viable sperm cells compared to the control (P = 0.001). In conclusion, BDNF has protective effects against oxidative stress in spermatozoa and could improve sperm functions that are essential for sperm-egg fusion and subsequent fertilisation.

Expression pattern of key microRNAs in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

INTRODUCTION: Chronic myeloid leukemia (CML) is caused by reciprocal translocation in hematopoietic stem cells (HSCs). This translocation forms the BCR-ABL1 oncogene, which alters several signaling pathways that control malignancy. CML has three phases: chronic, accelerated, and blast crisis. The microRNAs (miRNAs or miRs) are noncoding RNAs that downregulate their target gene by targeting 3' UTR of mRNA or through translational inhibition. It has been shown that miRNAs regulate many biological processes, and dysregulation of these regulatory RNAs is involved in disease development, particularly in cancer. The important role of miRNAs as therapeutic agents and biomarkers has been demonstrated in CML patients at different phases of the disease. METHODS: Stem-loop reverse transcription polymerase chain reaction was used to characterize differentially expressed miRNAs of leukocytes in the peripheral blood of 50 newly diagnosed CML patients in chronic phase. RESULTS: Some onco-miRNAs were found to be downregulated (miR-155 and miR-106), and some tumor suppressor miRs (miR-16-1, miR-15a, miR-101, miR-568) were upregulated. CONCLUSION: These results show that very few miRNAs alone would be good candidates for CML diagnosis independently of conflicting results, but together could be an additional tool for CML diagnosis. Moreover, miRNAs might be good candidates for prognosis prediction and CML therapy.

A reassessment of two freshwater ascomycetes, Ceriospora caudae-suis and Submersisphaeria aquatica.

Ceriospora caudae-suis and Submersisphaeria aquatica, two freshwater pyrenomycetes reported infrequently since their original description, occur commonly on submerged woody debris in the USA. Based on analyses of 28S rDNA sequence data and morphology, both species belong in the Annulatascaceae. Ceriospora caudae-suis is transferred to Pseudoproboscispora, a genus in the Annulatascaceae with similar overall morphology and ecology. Submersisphaeria aquatica is redescribed and illustrated based on additional collections.