Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2^−/− and Ampkα2^−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2^−/− and Ampkα2^−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2^−/− and Ampkα2^−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser⁴⁸⁵), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser⁴⁸⁵), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.

Background: Two prevailing, totally implantable venous access ports are routinely utilized in oncology: chest port or arm port. This systematic review with meta-analysis was conducted to compare safety and efficiency of the two techniques. Methods: We performed evidence acquisition intensively from PubMed, Embase, and Cochrane Library. Available comparative studies that evaluated both techniques were identified. The outcomes of interest included total complication events, procedure-related infections, thrombosis, intra-operative complications, mechanical complications, conversion rate, early port removal, and operating time. Results: Thirteen comparative studies including 3,896 patients (2,176 for chest ports, and 1,720 for arm ports) were identified. The present study showed that arm port was associated with higher procedure conversion rate (2.51% in chest port group and 8.32% in arm port group; odd ratios [OR] 0.27, 95% confidence interval [CI] 0.15-0.46; p<0.001), but lower incidence of intra-operative complications (1.38% in chest port group and 0.41% in arm port group; OR 2.38, 95% CI 1.07–5.29; p=0.03). There were no between-group differences with respect to total complication events, procedure-related infections, thrombosis, mechanical complications, early port removal, and operating time. Subgroup analysis of patients under 60 years revealed that no significant difference was detected in intra-operative events (1.19% in chest port group and 0.02% in arm port group, OR 2.59, 95% CI 0.74–9.08; p<0.14), indicating that age may be a risk factor for intra-operative events. Sensitivity analysis did not change conclusions of all endpoints of interest. Conclusion: Arm port is associated with higher procedure conversion rate, but lower incidence of intra-operative complications, and age may be a risk factor for intra-operative events.

A meta-analysis was performed to compare the differences in outcomes between sutureless technique and conventional surgery for primary repair of Total Anomalous Pulmonary Venous Connection(TAPVC). Electronic databases, including PubMed, EMbase, Medline, CNKI, Wanfang Data and Weipu Data were searched systematically for the literature aimed mainly at comparing the therapeutic effects for primary repair of TAPVC administered by sutureless technique and conventional surgery. Corresponding data sets were extracted and two reviewers independently assessed the methodological quality. Seven studies meeting the inclusion criteria were included, involving a total of 1293 subjects. It was observed that sutureless technique entailed a lower occurrence rate of post-operative Pulmonary Veins Obstruction (PVO) (OR, 0.52 95%CI, 0.32–0.86; P = 0.01) and re-operation due to PVO (OR, 0.28;95%CI, 0.09–0.87; P = 0.03). However, meta-analyses of hospitalization time (WMD, 5.92; 95%CI, − 7.97-19.80; P = 0.40) and post-operative mortality (OR, 0.65; 95%CI, 0.41–1.04; P = 0.07) showed no significant differences between sutureless technique and conventional surgery. Meta-analysis of Cardiopulmonary Bypass (CPB) time and aortic cross-clamp time also showed no significant differences between the two surgical approaches (WMD, 5.07; 95%CI, − 9.29-19.42; P = 0.49); (WMD, 5.73; 95%CI, − 7.76-19.23; P = 0.40), but the result remained inconclusive due to pooling result changes after sensitivity analysis. Compared with conventional surgery, a lower occurrence rate of post-operative PVO and re-operation due to PVO were associated with sutureless technique. Meanwhile, hospitalization time and post-operative mortality were not statistically different between the two surgical approaches. Pooling result of CPB and aortic cross-clamp time between the two groups remained inconclusive.

BACKGROUND: Polyamidoamine (PAMAM) dendrimers have been investigated for decades and currently applied in various areas throughout nanomedicine, including gene therapy, drug delivery, anti-bacteria and imaging. It is therefore necessary to assess cyt

A complete and prompt cardiac arrest using a cold cardioplegic solution is routinely used in heart transplantation to protect the graft function. However, warm ischemic time is still inevitable during the procedure to isolate donor hearts in the clinical setting. Our knowledge of the mechanism changes prevented by cold storage, and how warm ischemia damages donor hearts, is extremely poor. The potential consequences of this inevitable warm ischemic time to grafts, and the underlying potential protective mechanism of prompt graft cooling, have been studied in order to explore an advanced graft protection strategy. To this end, a surgical procedure, including 10–15 min warm ischemic time during procurement, was performed in mouse models to mimic the clinical situation (Group I), and compared to a group of mice that had the procurement performed with prompt cooling procedures (Group II). The myocardial morphologic changes (including ultrastructure) were then assessed by electron and optical microscopy after 6 h of cold preservation. Furthermore, syngeneic heart transplantation was performed after 6 h of cold preservation to measure the graft heart function. An electron microscopy showed extensive damage, including hypercontracted myofibers with contraction bands, and damaged mitochondria that released mitochondrial contents in Group I mice, while similar patterns of damage were not observed in the mice from Group II. The results from both the electron microscopy and immunoblotting verified that cardiac mitophagy (protective mitochondrial autophagy) was present in the mice from Group II, but was absent in the mice from Group I. Moreover, the mice from Group II demonstrated faster rebeating times and higher beating scores, as compared to the mice from Group I. The pressure catheter system results indicated that the graft heart function was significantly more improved in the mice from Group II than in those from Group I, as demonstrated by the left ventricle systolic pressure (31.96 ± 6.54 vs. 26.12 ± 8.87 mmHg), the +dp/dt (815.6 ± 215.4 vs. 693.9 ± 153.8 mmHg/s), and the -dp/dt: (492.4 ± 92.98 vs. 418.5 ± 118.9 mmHg/s). In conclusion, the warm ischemic time during the procedure impaired the graft function and destroyed the activation of mitophagy. Thus, appropriate mitophagy activation has emerged as a promising therapeutic target that may be essential for graft protection and functional improvement during heart transplantation.