Restoring SRSF3 in Kupffer cells attenuates obesity-related insulin resistance.

Background And Aims: In obesity, depletion of KCs expressing CRIg (complement receptor of the Ig superfamily) leads to microbial DNA accumulation, which subsequently triggers tissue inflammation and insulin resistance. However, the mechanism underlying obesity-mediated changes in KC complement immune functions is largely unknown.

Approach And Results: Using KC-specific deactivated Cas9 transgenic mice treated with guide RNA, we assessed the effects of restoring CRIg or the serine/arginine-rich splicing factor 3 (SRSF3) abundance on KC functions and metabolic phenotypes in obese mice.

Gut lumen-leaked microbial DNA causes myocardial inflammation and impairs cardiac contractility in ageing mouse heart.

Emerging evidence indicates the critical roles of microbiota in mediating host cardiac functions in ageing, however, the mechanisms underlying the communications between microbiota and cardiac cells during the ageing process have not been fully elucidated. Bacterial DNA was enriched in the cardiomyocytes of both ageing humans and mice. Antibiotic treatment remarkably reduced bacterial DNA abundance in ageing mice.

Loss-of-function mutations in the histone methyltransferase EZH2 promote chemotherapy resistance in AML.

Chemotherapy resistance is the main impediment in the treatment of acute myeloid leukaemia (AML). Despite rapid advances, the various mechanisms inducing resistance development remain to be defined in detail. Here we report that loss-of-function mutations (LOF) in the histone methyltransferase EZH2 have the potential to confer resistance against the chemotherapeutic agent cytarabine.

Loss of KDM6A confers drug resistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm resulting from the malignant transformation of myeloid progenitors. Despite intensive chemotherapy leading to initial treatment responses, relapse caused by intrinsic or acquired drug resistance represents a major challenge. Here, we report that histone 3 lysine 27 demethylase KDM6A (UTX) is targeted by inactivating mutations and mutation-independent regulation in relapsed AML.

Adenoma size and postoperative IGF-1 levels predict surgical outcomes in acromegaly patients: results of the Swiss Pituitary Registry (SwissPit).

Aims Of The Study: Acromegaly due to a growth hormone-secreting pituitary adenoma is a rare disease with high morbidity if not treated adequately. Using data of the Swiss Pituitary Registry (SwissPit), we studied initial presentation and predictors for adverse clinical outcomes in acromegalic patients treated during the last 10 years in our institution.

Methods: We evaluated 21 patients from the SwissPit registry with a final diagnosis of acromegaly confirmed by laboratory results (insulin-like growth factor-1 [IGF-1] and growth hormone suppression tests) and magnetic resonance imaging.

Sleep-wake disturbances 3 years after traumatic brain injury.

Background: 6 months after traumatic brain injury (TBI), almost three out of four patients suffer from sleep-wake disturbances (SWD) such as post-traumatic hypersomnia (increased sleep need of ≥2 h compared with before injury), excessive daytime sleepiness (EDS), fatigue and insomnia. The long-term course of post-traumatic SWD, however, is unknown.

Objectives: To assess the prevalence and characteristics of post-traumatic SWD 3 years after trauma.