Histone deacetylases (HDACs) have been revealed to be involved in cerebrovascular diseases, while the role of HDAC9 in intracranial aneurysm (IA) remains seldom studied. We aim to explore the role of the HDAC9/microRNA-92a (miR-92a)/Bcl-2-like protein 11 (BCL2L11) axis in IA progression.

Expression of HDAC9, miR-92a and BCL2L11 in IA tissues was assessed. IA rat models were established by ligation of left renal artery and common carotid artery, and the rats were respectively injected with relative plasmid vectors and/or oligonucleotides. The blood pressure was measured to estimate the IA degree, and the pathological changes were observed. The expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) was detected, and the levels of inflammatory factors were evaluated. Expression of apoptosis-related proteins, HDAC9, miR-92a and BCL2L11 was assessed.

HDAC9 and BCL2L11 were upregulated while miR-92a was downregulated in IA clinical samples and rat models. HDAC9 inhibition or miR-92a elevation improved pathological changes and repressed apoptosis and expression of MMP-2, MMP-9, VEGF and inflammatory factors in vascular tissues from IA rats. Selleck ML792 Oppositely, HDAC9 overexpression or miR-92a reduction had contrary effects. miR-92a downregulation reversed the effect of silenced HDAC9 on IA rats.

HDAC9 inhibition upregulates miR-92a to repress the progression of IA

silencing BCL2L11.

HDAC9 inhibition upregulates miR-92a to repress the progression of IA via silencing BCL2L11.

To investigate the therapeutic effects of PERK activator CCT020312 (CCT) on inflammation-mediated osteoporosis (IMO) in ovariectomized rats.

Rats were divided into Sham, IMO, IMO + 1 mg/kg CCT and IMO + 2 mg/kg CCT groups. IMO models were constructed by bilateral ovariectomy (OVX) on 1st day followed by injection with magnesium silicate (Talc) on the 59th day. Sham rats did not undergo OVX surgery and were injected with saline instead of Talc. From 60th to 79th day, rats were treated with DMSO (vehicle control) in the Sham and IMO groups, and 1 or 2 mg/kg CCT020312 in treatment groups. Osteopontin (OPN), osteocalcin (OCN), tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type I collagen (CTX-I), and pro-inflammatory factors were measured on the 80th day. ProdigyDEXA was used to evaluate bone mineral density and content (BMD/BMC). Bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number (Tb.N), and trabecular separation (Tb.Sp) was assessed using 3D micro-CT scanner.

CCT up-regulated Conn.D, BV/TV, and Tb.N, but down-regulated Tb.Sp in IMO rats. Besides, the declined femoral BMD and BMC in IMO rats were elevated after CCT treatment. Besides, IMO rats represented declined OPN and OCN, as well as increased TRAP, CTX-I, and pro-inflammatory factors, whereas those in the treatment groups were ameliorated regarding these indexes, with 2 mg/kg CCT showing better effect.

PERK activator CCT020312 can be served as a new therapeutic option for the protection against bone loss in the OVX rat model associated with inflammation probably by manipulating inflammatory factors.

PERK activator CCT020312 can be served as a new therapeutic option for the protection against bone loss in the OVX rat model associated with inflammation probably by manipulating inflammatory factors.We aimed to analyze sex-related differences in clinical outcomes among patients with diabetic foot disease (DFD) managed in a third-level referral center. We retrospectively analyzed data of admissions performed in our department between 2011 and 2015 for DFD. We collected demographic and clinical data, procedures performed during the admission, and short- and long-term outcomes in terms of healing rate and healing time, major amputation, and mortality rates during the follow-up. We focused on differences between genders and tried to figure out if sex could be considered a predictive factor. We collected data from 1237 admission performed in 842 patients (615 men [73%] and 227 women [27%]; age 68.6 ± 27.9 years; diabetes duration 16.4 ± 13.4 years; body mass index 28.2 ± 6.4 kg/m2; hemoglobin A1c 7.9 ± 1.9%). Men showed a higher prevalence of comorbidities and previous ulcers or revascularization procedures. Men had a significantly higher healing rate compared with women (85.4% vs 63.2%, P less then .001), but a longer healing time (124 ± 27 days vs 87 ± 14 days, P = .02). Major amputation did not differ between groups, while mortality rate was significantly higher in men (24.5% vs 16.1%, P = .02). In Cox’s regression analysis, male sex was a positive predictive factor for healing and a negative one for time to heal and mortality. The difference in mortality was confirmed by a Kaplan-Meier analysis (log rank test P = .03). DFD represents a severe disease and a strong marker of mortality affecting more severely on clinical outcomes and survival on men.Cancer-related fatigue has been related to circadian disruptions and lower levels of sleep quality. However, it is unknown whether the circadian phase, which is associated with chronotype and timing of sleep, is related to fatigue after cancer. The aims of this study were to investigate the associations between (1) chronotype and cancer-related fatigue and (2) sleep quality and cancer-related fatigue. In this cross-sectional questionnaire study, 458 (non-)Hodgkin lymphoma survivors (n = 231 female, mean age 49.7 years) completed a Visual Analogue Scale for fatigue (VAS-fatigue) from 0 (no fatigue) to 10 (worst imaginable fatigue), the Munich Chronotype Questionnaire (MCTQ), and the Pittsburgh Sleep Quality Index (PSQI) between October 2018 and July 2019. A hierarchical linear regression analysis was used to evaluate the associations between the dependent variable fatigue and chronotype (based on early, intermediate, or late average midsleep) in Model 1, and fatigue and sleep quality in Model 2. The results showed no indications for an association between chronotype and fatigue (all p values ≥ 0.50). There were associations between two (out of seven) aspects of sleep quality and fatigue subjective sleep quality (p less then 0.001) and daily dysfunctioning (p less then 0.001). Therefore, it is more likely that fatigue is associated with self-reported sleep quality rather than with chronotype. However, experimental studies with objective, physiological data on circadian phase and sleep quality are necessary to confirm the conclusions of this cross-sectional study.