Salt-inducible kinase 2 (SIK2) has been established as a regulator of diverse biological processes including cell metabolism. A recent study has reported that SIK2 is required for adipocyte-induced ovarian cancer (OC) survival through facilitating fatty acid oxidation. However, whether SIK2 also plays a role in the lipid synthesis in OC cells remains elusive. Here, we showed that SIK2 significantly promoted the lipid synthesis in OC cells. On the one hand, SIK2 enhanced fatty acid synthesis through upregulating the expression of sterol regulatory element binding protein 1c (SREBP1c) and thus the transcription of major lipogenic enzyme FASN. On the other hand, SIK2 promoted cholesterol synthesis through upregulating the expression of sterol regulatory element binding protein 2 (SREBP2) and thus the transcription of major cholesterol synthesis enzymes HMGCR. Moreover, PI3K/Akt signaling pathway was found to be involved in the upregulation of SREBP1c and SREBP2 in OC cells. Moreover, in vitro and in vivo assays indicated that the SIK2-regulated fatty acid and cholesterol synthesis played a critical role in the growth of OC cells. Our findings demonstrate that SIK2 is a critical regulator of lipid synthesis in OC cells and thus promotes OC growth, which provides a strong line of evidence for this molecule to be used as a therapeutic target in the treatment of this malignancy.

Introduction: Neurocritical care patients are at high risk for stress-related upper gastrointestinal (UGI) bleeding. The aim of this meta-analysis was to evaluate the risks and benefits of stress ulcer prophylaxis (SUP) in this patient group. Methods: A systematic search of major electronic literature databases was conducted. Eligible studies were randomized controlled trials (RCTs) in which researchers compared the effects of SUP (with proton pump inhibitors or histamine 2 receptor antagonists) with placebo or no prophylaxis in neurocritical care patients. The primary outcome was UGI bleeding, and secondary outcomes were all-cause mortality and nosocomial pneumonia. Study heterogeneity was sought and quantified. The results were reported as risk ratios/relative risks (RRs) with 95 % confidence intervals (CIs). Results: We included 8 RCTs comprising an aggregate of 829 neurocritical care patients. Among these trials, one study conducted in a non–intensive care unit setting that did not meet our inclusion criteria was ultimately included based on further evaluation. All studies were judged as having a high or unclear risk of bias. SUP was more effective than placebo or no prophylaxis at reducing UGI bleeding (random effects: RR 0.31; 95 % CI 0.20–0.47; P < 0.00001; I² = 45 %) and all-cause mortality (fixed effects: RR 0.70; 95 % CI 0.50–0.98; P = 0.04; I² = 0 %). There was no difference between SUP and placebo or no prophylaxis regarding nosocomial pneumonia (random effects: RR 1.14; 95 % CI 0.67–1.94; P = 0.62; I² = 42 %). The slight asymmetry of the funnel plots raised the concern of small trial bias, and apparent heterogeneity existed in participants, interventions, control treatments, and outcome measures. Conclusions: In neurocritical care patients, SUP seems to be more effective than placebo or no prophylaxis in preventing UGI bleeding and reducing all-cause mortality while not increasing the risk of nosocomial pneumonia. The robustness of this conclusion is limited by a lack of trials with a low risk of bias, sparse data, heterogeneity among trials, and a concern regarding small trial bias. Trial registration: International Prospective Register of Systematic Reviews (PROSPERO) identifier: CRD42015015802. Date of registration: 6 Jan 2015.

Ovarian cancer (OC) is prone to adipose tissue metastasis. However, the underlying molecular mechanisms remain elusive. Here, we observed that omental adipocytes were induced into cancer-associated adipocytes (CAAs) by OC-derived TGF-β1 to establish a pre-metastatic niche (PMN) through collagen and fibronectin secretion. Mechanistically, OC-derived TGF-β1 binds to adipocyte membrane receptors and thus activates intracellular signaling by SMAD3 phosphorylation. The activation of TGF-β1/SMAD3 signaling pathway dedifferentiates adipocytes into CAAs by upregulating Tribbles homolog 3 (TRIB3), which suppresses the phosphorylation of CEBPβ. Additionally, CAAs secrete collagen I, collagen VI, and fibronectin to remodel the extracellular matrix and promote the adhesion of OC cells. Pharmacological inhibition of the TGF-β1/SMAD3 pathway significantly inhibits CAAs and PMN formation, thereby reducing the OC metastatic burden. Our findings indicate that the formation of CAAs and PMN in adipose tissues facilitates OC cell implantation and blocking the TGF-β1/SMAD3 signaling pathway could prevent OC omental metastasis.

Population aging is an unprecedented, multifactorial, and global process that poses significant challenges to healthcare systems. Enhanced recovery after surgery (ERAS) protocols aim to optimize perioperative care. The first neurosurgical ERAS protocol for elective craniotomy has contributed to a shortened postoperative hospital stay, accelerated functional recovery, improved patient satisfaction, and reduced medical care cost in adult patients aged 18 to 65 years compared with conventional perioperative care. However, ERAS protocols for geriatric patients over 65 years of age undergoing cranial surgery are lacking. In this paper, we propose a novel ERAS protocol for such patients by reviewing and summarizing the key elements of successful ERAS protocols/guidelines and optimal perioperative care for geriatric patients described in the literature, as well as our experience in applying the first neurosurgical ERAS protocol for a quality improvement initiative. This proposal aimed to establish an applicable protocol for geriatric patients undergoing elective craniotomy, with evidence addressing its feasibility, safety, and potential efficacy. This multimodal, multidisciplinary, and evidence-based ERAS protocol includes preoperative, intraoperative, and postoperative assessment and management as well as outcome measures. The implementation of the current protocol may hold promise in reducing perioperative morbidity, enhancing functional recovery, improving postoperative outcomes in geriatric patients scheduled for elective craniotomy, and serving as a stepping stone to promote further research into the advancement of geriatric patient care.