Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder.

STUDY OBJECTIVES: The aims of this study were to explore changes in the telomere length (relative telomere repeat copy/single-copy gene [T/S ratio]) and serum neurofilament light chain (sNfL) levels in female patients with chronic insomnia disorder (CID), examine their relationships with emotional abnormalities and cognitive impairment, and determine whether these 2 indicators were independently associated with sleep quality. METHODS: The CID group contained 80 patients diagnosed with CID, and 51 individuals constituted a healthy control group. Participants completed sleep, emotion, and cognition assessments. Telomere length was detected through quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to determine sNfL concentrations. RESULTS: Relative to the healthy control group, the CID group had elevated Pittsburgh Sleep Quality Index, Hamilton Anxiety Scale-14, and Hamilton Depression Rating Scale-17 scores and reduced Montreal Cognitive Assessment scale scores, a decreased T/S ratio, and an increased sNfL concentration. Subgroup analysis according to various CID-associated sleep factors showed that poor sleep performance corresponded to a lower T/S ratio. Higher anxiety levels and more cognitive dysfunction correlated with shorter telomere lengths. The T/S ratio negatively correlated with age, whereas the sNfL concentration positively correlated with age in the CID group. The Pittsburgh Sleep Quality Index score negatively correlated with the T/S ratio but did not correlate with sNfL levels. Multiple linear regression analysis showed that the T/S ratio had a negative and independent effect on Pittsburgh Sleep Quality Index scores. CONCLUSIONS: The CID group had shorter telomeres and higher sNfL concentrations, and reduced telomere length independently affected sleep quality. CITATION: Ren C-Y, Liu P-P, Li J, et al. Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder. J Clin Sleep Med. 2022;18(2):383-392.

Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias.

Chromosomal translocations generating fusion proteins are frequently found in human leukemias. The fusion proteins play an important role in leukemogenesis by subverting the function of one or both partner proteins. The leukemogenic CALM-AF10 fusion protein is capable of interacting with the histone H3 lysine 79 (H3K79)-specific methyltransferase hDOT1L through the fused AF10 moiety. This interaction leads to local H3K79 hypermethylation on Hoxa5 loci, which up-regulates the expression of Hoxa5 and contributes to leukemogenesis. However, the long latency of leukemogenesis of CALM-AF10 transgenic mice suggests that the direct effects of fusion oncogene are not sufficient for the induction of leukemia. In this study, we show that the CALM-AF10 fusion protein can also greatly reduce global H3K79 methylation in both human and murine leukemic cells by disrupting the AF10-mediated association of hDOT1L with chromatin. Cells with reduced H3K79 methylation are more sensitive to gamma-irradiation and display increased chromosomal instability. Consistently, leukemia patients harboring CALM-AF10 fusion have more secondary chromosomal aberrations. These findings suggest that chromosomal instability associated with global epigenetic alteration contributes to malignant transformation in certain leukemias, and that leukemias with this type of epigenetic alteration might benefit from treatment regimens containing DNA-damaging agents. This study is registered with www.clinicaltrials.gov as NCT00266136.

Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair.

While methylcytosines serve as the fifth base encoding epigenetic information, they are also a dangerous endogenous mutagen due to their intrinsic instability. Methylcytosine undergoes spontaneous deamination, at a rate much higher than cytosine, to generate thymine. In mammals, two repair enzymes, thymine DNA glycosylase (TDG) and methyl-CpG binding domain 4 (MBD4), have evolved to counteract the mutagenic effect of methylcytosines. Both recognize G/T mismatches arising from methylcytosine deamination and initiate base-excision repair that corrects them to G/C pairs. However, the mechanism by which the methylation status of the repaired cytosines is restored has remained unknown. We show here that the DNA methyltransferase Dnmt3a interacts with TDG. Both the PWWP domain and the catalytic domain of Dnmt3a are able to mediate the interaction with TDG at its N-terminus. The interaction affects the enzymatic activity of both proteins: Dnmt3a positively regulates the glycosylase activity of TDG, while TDG inhibits the methylation activity of Dnmt3a in vitro. These data suggest a mechanistic link between DNA repair and remethylation at sites affected by methylcytosine deamination.

[Causes of benign central airway stenoses and the efficacy of interventional treatments through flexible bronchoscopy].

OBJECTIVE: To analyze the causes of benign central airway stenoses and to evaluate the efficacy of interventional treatments through flexible bronchoscopy. METHODS: Three hundred and eighty-six outpatients and inpatients with benign central airway stenoses in our hospital from January 1999 to December 2006 were retrospectively analyzed. Interventional treatments through flexible bronchoscopy were used to treat the benign central airway stenoses. The endoscopic interventional treatments included laser, electrocautery, argon plasma coagulation, cryotherapy, balloon dilation and stent insertion. Airway diameters, FEV1 and dyspnea index of patients were evaluated before and immediately after the last treatment procedure. RESULTS: The main causes of benign central airway stenoses were as follows: tuberculosis in 64.25% (248/386), secondary to prolonged orotracheal intubation or tracheotomy in 15.03% (58/386), injury in 3.63% (14/ 386) and inhalation burns in 3.11% (12/386), others were 54 cases. All the 386 patients received endoscopic interventional treatments. 89.89% (347/386) of the patients experienced improvement in dyspnea and cough. The average airway diameter increased from (2.49 +/- 1.57) mm to (6.41 +/- 1.70) mm (t = 47.427, P < 0.01). Dyspnea index decreased from 2.40 +/- 0.79 to 0.64 +/- 0.50 (t = 44.226, P < 0.01). The average value of FEV1 evaluated in 115 inpatients increased from (2.11 +/- 0.60) L to (3.46 +/- 0.75) L (t = 20.128, P < 0.01). Most patients needed multiple interventional treatments except 26 patients who received a single endoscopic treatment. Stable control of the diseases was achieved in 65.54% (253/ 386) patients 3 months after the last operation. CONCLUSION: Tuberculosis is the most common cause of benign central airway stenoses in this series. Utilization of interventional methods through flexible bronchoscopy is effective in treating benign central airway stenoses.

[Preparation of a composite coagulant from fly ash and its application in domestic wastewater treatment].

Fly ash was investigated as a raw material for the preparation of a composite coagulant with sulfuric acid. Types of acid solution, H2SO4 concentration, ratio of H2SO4 to fly ash and stirring time were respectively examined as factors that influenced the efficiency of converting the iron and aluminum components into a composite coagulant and coagulation performance on domestic wastewater. The coagulant was attained at the condition of H2SO4-fly ash ratio of 5 mL/g, H2SO4 of 2 mol/L, stirring time of 4h and stabling time of 30 min, and contained Fe3+ of 0.010 8 mol/L with conversion efficiency of 11.4% and Al3+ of 0.035 4 mol/L with conversion efficiency of 4.3%. Removal efficiencies of COD and SS by this type of coagulant reached 70.4% and 91.9% respectively when treating domestic wastewater. This study provides a promising means to utilize fly ash for coagulation, which possibly makes wastewater treatment more economical and more sustainable.