Previous reports showed that recombinant fragments of adiponectin (adipo) displayed pharmacological effects when injected into rodents, but the relevance of these observations to the physiological function of adipo is unclear. We generated Adipo ؊/؊ mice by gene targeting. Adipo ؊/؊ mice are fertile with normal body and fat pad weights. Plasma glucose and insulin levels of Adipo ؊/؊ and Adipo ؉/؉ mice are similar under fasting conditions and during an intraperitoneal glucose tolerance test (GTT). Insulin tolerance test (ITT) also produces similar plasma glucose and insulin levels in the two groups of mice. Hyperinsulinemic-euglycemic clamp analysis showed that Adipo ؊/؊ and Adipo ؉/؉ mice have similar glucose infusion rates to maintain a similar serum glucose. High-fat diet feeding for 7 months led to similar weight gain and similar GTT and ITT responses. We next measured ␤-oxidation and found it to be significantly increased in muscle and liver of Adipo ؊/؊ mice. In conclusion, our study indicates that absence of adipo causes increased ␤-oxidation but does not cause glucose intolerance or insulin resistance in mice.

Background Magnifying endoscopy with narrow band imaging (M-NBI) has been applied to examine early gastric cancer by observing microvascular architecture and microsurface structure of gastric mucosal lesions. However, the diagnostic efficacy of non-experts in differentiating early gastric cancer from non-cancerous lesions by M-NBI remained far from satisfactory. In this study, we developed a new system based on convolutional neural network (CNN) to analyze gastric mucosal lesions observed by M-NBI. Methods A total of 386 images of non-cancerous lesions and 1702 images of early gastric cancer were collected to train and establish a CNN model (Inception-v3). Then a total of 341 endoscopic images (171 non-cancerous lesions and 170 early gastric cancer) were selected to evaluate the diagnostic capabilities of CNN and endoscopists. Primary outcome measures included diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results The sensitivity, specificity, and accuracy of CNN system in the diagnosis of early gastric cancer were 91.18%, 90.64%, and 90.91%, respectively. No significant difference was spotted in the specificity and accuracy of diagnosis between CNN and experts. However, the diagnostic sensitivity of CNN was significantly higher than that of the experts. Furthermore, the diagnostic sensitivity, specificity and accuracy of CNN were significantly higher than those of the non-experts. Conclusions Our CNN system showed high accuracy, sensitivity and specificity in the diagnosis of early gastric cancer. It is anticipated that more progress will be made in optimization of the CNN diagnostic system and further development of artificial intelligence in the medical field.

BackgroundAlthough Argonaute proteins are considered to play important roles in stem cell self-renewal, RNA interference (RNAi) and translational regulation, relatively little is known about their functions in human disease. In this study, we investigated the expression of eight members of human Argonaute family in colon cancer and identified their potential roles in tumor development and progression.MethodsAntibodies against human Argonaute proteins were prepared by immunizing rabbits with synthetic peptides derived from the sequences of Argonaute members. Then we constructed a tissue microarray containing 75 specimens from colon cancer and 75 specimens from adjacent non-cancer tissue, and assayed eight different proteins (EIF2C1, EIF2C2, EIF2C3, EIF2C4, PIWIL1, PIWIL2, PIWIL3 and PIWIL4) by immunohistochemistry on consecutive formalin-fixed tissue microarray sections.ResultsThe expression of EIF2C1-4 and PIWIL1-4 was significantly higher in tumorous tissue than in adjacent tissue. Notably, a significant correlation was observed between the positive expression of EIF2C2, EIF2C3, EIF2C4, PIWIL4 and the presence of distant metastasis. Logistic regression analysis revealed that an increased expression of EIF2C1 and PIWIL2 was significantly associated with occurrence of colon cancer tissue compared with non-cancer tissue.ConclusionsArgonaute proteins are overexpressed in colon cancer relative to adjacent non-cancer tissue. The expression of EIF2C2-4 and PIWIL4 appears increased in advanced tumors with distant metastasis, suggesting it may promote tumor invasion. Furthermore, EIF2C1 and PIWIL2 might represent novel colon cancer markers with early diagnostic significance.

Approximately 60% of individuals with schizophrenia do not take their antipsychotic medications as prescribed, and nonadherence is associated with exacerbation of psychotic symptoms, increased hospital and emergency room use, and increased healthcare costs. Behavioral-tailoring strategies that incorporate medication taking into the daily routine and use environmental supports have shown promise as adherence-enhancing interventions. Informed by the Information-Motivation-Behavioral (IMB) Skills Model and using the iterative process of user-centered design, we collaborated with individuals with schizophrenia and psychiatrists to develop an interactive smartphone application and web-based clinician interface, MedActive, for improving adherence to oral antipsychotic treatment. MedActive facilitates the active involvement of individuals with schizophrenia in managing their antipsychotic medication regimen by providing automated reminders for medication administration and tailored motivational feedback to encourage adherence, and by displaying user-friendly results of daily ecological momentary assessments (EMAs) of medication adherence, positive psychotic symptoms, and medication side effects for individuals and their psychiatrists. In a 2-week open trial completed by 7 individuals with schizophrenia and their psychiatrists, MedActive was determined to be both feasible and acceptable, with patient participants responding to 80% of all scheduled EMAs and providing positive evaluations of their use of the application. Psychiatrist participants were interested in viewing the information provided on the MedActive clinician interface, but cited practical barriers to regularly accessing it and integrating into their daily practice.

Both myocardial infarction (MI) and the follow-up reperfusion will lead to an inevitable injury to myocardial tissues, such as cardiac dysfunctions, fibrosis, and reduction of intercellular cell-to-cell interactions. Recently, exosomes (Exo) derived from stem cells have demonstrated a robust capability to promote angiogenesis and tissue repair. However, the short half-life of Exo and rapid clearance lead to insufficient therapeutic doses in the lesion area. Herein, an injectable conductive hydrogel is constructed to bind Exo derived from human umbilical cord mesenchymal stem cells to treat myocardial injuries after myocardial infarction–ischemia/reperfusion (MI-I/R). To this end, a hyperbranched epoxy macromer (EHBPE) grafted by an aniline tetramer (AT) was synthesized to cross-link thiolated hyaluronic acid (HA-SH) and thiolated Exo anchoring a CP05 peptide via an epoxy/thiol “click” reaction. The resulting Gel@Exo composite system possesses multiple features, such as controllable gelation kinetics, shear-thinning injectability, conductivity matching the native myocardium, soft and dynamic stability adapting to heartbeats, and excellent cytocompatibility. After being injected into injured hearts of rats, the hydrogel effectively prolongs the retention of Exo in the ischemic myocardium. The cardiac functions have been considerably improved by Gel@Exo administration, as indicated by the enhancing ejection fraction and fractional shortening, and reducing fibrosis area. Immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) results demonstrate that the expression of cardiac-related proteins (Cx43, Ki67, CD31, and α-SMA) and genes (VEGF-A, VEGF-B, vWF, TGF-β1, MMP-9, and Serca2a) are remarkably upregulated. The conductive Gel@Exo system can significantly improve cell-to-cell interactions, promote cell proliferation and angiogenesis, and result in a prominent therapeutic effect on MI-I/R, providing a promising therapeutic method for injured myocardial tissues.

Mesenchymal stem cells (MSCs) have fueled ample translation for treatment of immune-mediated diseases. Our previous study had demonstrated that MSCs could elicit macrophages (Mφ) into anti-inflammatory phenotypes, and alleviate kidney injury in diabetic nephropathy (DN) mice via improving mitochondrial function of Mφ, yet the specific mechanism was unclear. Recent evidence indicated that MSCs communicated with their microenvironment through exchanges of mitochondria. By a coculture system consisting of MSCs and Mφ, we showed that MSCs-derived mitochondria (MSCs-Mito) were transferred into Mφ, and the mitochondrial functions were improved, which contributed to M2 polarization. Furthermore, we found that MSCs-Mito transfer activated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis. In addition, PGC-1α interacted with TFEB in high glucose-induced Mφ, leading to the elevated lysosome-autophagy, which was essential to removal of damaged mitochondria. As a result, in Mφ, the mitochondrial bioenergy and capacity to combat inflammatory response were enhanced. Whereas, the immune-regulatory activity of MSCs-Mito was significantly blocked in PGC-1α knockdown Mφ. More importantly, MSCs-Mito transfer could be observed in DN mice, and the adoptive transfer of MSCs-Mito educated Mφ (MφMito) inhibited the inflammatory response and alleviated kidney injury. However, the kidney-protective effects of MφMito were abolished when the MSCs-Mito was impaired with rotenone, and the similar results were also observed when MφMito were transfected with sipgc-1α before administration. Collectively, these findings suggested that MSCs elicited Mφ into anti-inflammatory phenotype and ameliorated kidney injury through mitochondrial transfer in DN mice, and the effects were relied on PGC-1α-mediated mitochondrial biogenesis and PGC-1α/TFEB-mediated lysosome-autophagy.

The main function of the mammary gland is to secret milk for newborn growth. Milk production process is regulated by hormones, growth factors, noncoding RNAs and other factors locally. Long non-coding RNAs (lncRNAs), one type of recently discovered non-coding RNA, have been found in mammary gland and some studies suggested lncRNA may play important roles in mammary gland development. Competing endogenous RNAs (ceRNAs) are emerging to compete for miRNA binding and, in turn, regulate each other. In the current study, we sequenced mRNA, miRNA and lncRNA in goat mammary tissue at 2 points in lactation (early and mature). All data were co-expressed together from the same samples. Our data showed that the ceRNAs up-regulated during the mature lactation phase were associated with lipid, protein, carbon and amino acid synthesis and metabolism. This correlates with the function of the mature lactation phase: i.e. the continuous production of large amounts of milk, rich in proteins, lipids, amino acids and other nutrients. Alternately, the ceRNAs up-regulated during early lactation were associated with PI3K-AKT pathways and ECM-receptor interactions; these fulfil the functional role of preparing the mammary gland for full lactation. Therefore, the results suggest that ceRNAs work synergistically during different developmental stages to regulate specific functions associated with lactation control. This study suggests that ceRNAs (lncRNA-mRNA) may be involved in lactation process.

Introduction Our previous study suggested that NSC-CM (neural stem cell-conditioned medium) inhibited cell apoptosis in vitro. In addition, many studies have shown that neurotrophic factors and microparticles secreted into a conditioned medium by NSCs had neuroprotective effects. Thus, we hypothesized that NSC-CM had the capacity of protecting against cerebral I/R injury. Methods Adult male Sprague-Dawley rats receiving middle cerebral artery occlusion surgery as an animal model of cerebral I/R injury were randomly assigned to two groups: the control group and NSC-CM-treated group. 1.5 ml NSC-CM or PBS (phosphate buffer saline) was administrated slowly by tail vein at 3 h, 24 h, and 48 h after ischemia onset. Results NSC-CM significantly ameliorated neurological defects and reduced cerebral infarct volume, accompanied by preserved mitochondrial ultrastructure. In addition, we also found that NSC-CM significantly inhibited cell apoptosis in the ischemic hemisphere via improving the expression of Bcl-2 (B-cell lymphoma-2). Conclusion NSC-CM might be an alternative and effective therapeutic intervention for ischemic stroke.