Mitochondrial function impairment due to abnormal opening of the mitochondrial permeability transition pore (MPTP) is considered the central event in acute pancreatitis; however, therapeutic choices for this condition remain controversial. Mesenchymal stem cells (MSCs) are a family member of stem cells with immunomodulatory and anti‐inflammatory capabilities that can mitigate damage in experimental pancreatitis. Here, it is shown that MSCs deliver hypoxia‐treated functional mitochondria to damaged pancreatic acinar cells (PACs) via extracellular vesicles (EVs), which reverse the metabolic function of PACs, maintain ATP supply, and exhibit an excellent injury‐inhibiting effect. Mechanistically, hypoxia inhibits superoxide accumulation in the mitochondria of MSCs and upregulates the membrane potential, which is internalized into PACs via EVs, thus, remodeling the metabolic state. In addition, cargocytes constructed via stem cell denucleation as mitochondrial vectors are shown to exert similar therapeutic effects to MSCs. These findings reveal an important mechanism underlying the role of mitochondria in MSC therapy and offer the possibility of applying mitochondrial therapy to patients with severe acute pancreatitis.

We aimed to investigate the effect of blood glucose levels on length of stay (LOS) in patients hospitalized with acute pancreatitis (AP). We retrospectively collected clinical data of patients diagnosed with AP from the Medical Information Mart for Intensive Care III (MIMIC‐III) database. Dose–response analysis curves of restricted cubic spline (RCS) function and multivariate logistic regression models were used to confirm the relationship between blood glucose levels and LOS. A total of 3656 patients with AP were included according to the inclusion and exclusion criteria. According to RCS, all patients were divided into three groups, namely the less than 68 mg/dl group, the 68‐104 mg/dl group, and the >104 mg/dl group. RCS showed a significant nonlinear correlation between blood glucose levels and LOS (p < 0.001). Multivariate logistic regression revealed a 53% higher risk of LOS greater than or equal to 2 days (adjusted odds ratio [aOR] = 1.53, 95% confidence interval [CI] 1.24–1.89, p < 0.001), a 114% higher risk of LOS greater than or equal to 5 days (aOR = 2.14, 95% CI 1.86–2.47, p < 0.001), and a 130% higher risk of LOS greater than or equal to 7 days (aOR = 2.30, 95% CI 1.97–2.69, p < 0.001) in patients with glucose levels greater than 104 mg/dl than patients with glucose levels 68–104 mg/dl. The risk of LOS greater than or equal to 7 days was higher in patients with blood glucose less than 68 mg/dl than patients with glucose levels 68–104 mg/dl (aOR = 1.45, 95% CI 1.02–2.05, p = 0.040). In addition, we observed similar results in many subgroups. Our findings suggest that either hyperglycemia or hypoglycemia increase LOS in patients hospitalized with AP. For hospitalized patients with AP, blood glucose control in a reasonable range of 68–104 mg/dl is required.

Backgrounds: Abnormal metabolism is the hallmark of hepatocellular carcinoma. Targeting energy metabolism has become the major focus of cancer therapy. The natural product, sanguinarine, displays remarkable anti-tumor properties by disturbing energy homeostasis; however, the underlying mechanism has not yet been elucidated. Methods: The anticancer activity of sanguinarine was determined using CCK-8 and colony formation assay. Morphological changes of induced cell death were observed under electron microscopy. Necroptosis and apoptosis related markers were detected using western blotting. PKM2 was identified as the target by transcriptome sequencing. Molecular docking assay was used to evaluate the binding affinity of sanguinarine to the PKM2 molecule. Furthermore, Alb-Cre^ERT2; PKM2^loxp/loxp; Rosa26^RFP mice was used to construct the model of HCC—through the intervention of sanguinarine in vitro and in vivo—to accurately explore the regulation effect of sanguinarine on cancer energy metabolism. Results: Sanguinarine inhibited tumor proliferation, metastasis and induced two modes of cell death. Molecular docking of sanguinarine with PKM2 showed appreciable binding affinity. PKM2 kinase activity and aerobic glycolysis rate declined, and mitochondrial oxidative phosphorylation was inhibited by sanguinarine application; these changes result in energy deficits and lead to necroptosis. Additionally, sanguinarine treatment prevents the translocation of PKM2 into the nucleus and suppresses the interaction of PKM2 with β-catenin; the transcriptional activity of PKM2/β-catenin signaling and its downstream genes were decreased. Conclusions: Sanguinarine showed remarkable anti-HCC activity via regulating energy metabolism by PKM2/β-catenin signaling. On the basis of these investigations, we propose that sanguinarine might be considered as a promising compound for discovery of anti-HCC drugs.

To examine the association between sleep duration with chronic constipation and diarrhea, we collected demographic and questionnaire data of participants from The National Health and Nutrition Examination Survey in the period 2005 to 2010. A restricted cubic spline curve function was used to determine the association between sleep duration and chronic constipation or diarrhea. Multivariate logistic regression models were used to estimate the association between sleep duration groups and chronic constipation or diarrhea. 14,054 eligible participants were included in this study. Among all sleep durations, 7 hours sleep per day had the highest percentage of normal stool forms (86.3%, P < .001), while people with ≤4 hours sleep had a higher number of bowel movements per week (P < .001). RCS models demonstrated a significant nonlinear association between sleep duration and risk of chronic constipation (P < .001). The inflection points of the U-shaped association curve corresponded to 7 hours of sleep per day. Multivariate logistic regression indicated that compared to participants with 7 hours daily sleep duration, participants with ≤4 hours and ≥10 hours sleep duration had a 54% (95%CI: (1.16–2.04), P = .002) and 90% (95%CI: (1.33–2.72), P < .001) higher risk of constipation, respectively. There is a non-linear association between sleep duration and the risk of chronic constipation. Our findings indicate that both shorter and longer sleep duration are associated with an increased risk of constipation.