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Background: Type 2 diabetes mellitus (T2DM) has emerged as a global epidemic issue, with high rates of disability and fatality. Traditional diagnostic biomarkers are typically detected once a metabolic imbalance has already occurred, thus the development of early diagnostic biomarkers is crucial for T2DM. Metabolomics studies have identified several predictive biomarkers for T2DM, including miR‐320. Our previous research found that miR‐320b was significantly downregulated in T2DM patients, but the underlying mechanism remains unclear. Therefore, this study was designed to investigate the significance of miR‐320b for T2DM diagnosis and to explore the involved molecular mechanism. Methods: A total of 50 patients with T2DM and 80 sex‐ and age‐matched healthy subjects were selected. The plasma miR‐320b of all participations was detected by qRT‐PCR and its correlations with other biomarkers of T2DM were analyzed. Besides, the expression of miR‐320b in HepG2 cells was suppressed by miRNA inhibitors. Then the glucose consumption of HepG2 cells was measured. The target gene of miR‐320b was predicted by four bioinformatics tools and intersected these prediction results by Venny method. The T2DM relevant target genes were identified by the GeneCards database. To ensure disease relevance, these T2DM relevant target genes were subsequently intersected with the target genes of miR‐320b. Protein–protein analysis (PPI) was used to screening the gene with the most connections in these target genes. Finally, the target gene of miR‐320b specific to T2DM was confirmed directly by luciferase reporter assay. The expression of target gene in HepG2 cell culture supernatant and plasma of all participations was detected. Results: Our results showed that the expression level of miR‐320b was significantly lower in T2DM patients compared to the healthy controls. It was negatively correlated with fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and homeostasis model assessment of insulin resistance (HOMA‐IR), but positively with HOMA‐β. The glucose consumption of HepG2 cells in the miR‐320b inhibitor group was significantly lower compared to inhibitor‐NC and blank control group. We predicted and confirmed that phosphatase and tensin homolog (PTEN) was the direct target gene of miR‐320b using Bioinformation tools and luciferase reporter assay. Moreover, the concentration of PTEN was significantly higher in the HepG2 cell culture supernatant and plasma of T2DM patients. Conclusions: Our research demonstrated a negative correlation between miR‐320b and FPG, HbA1C, and HOMA‐IR, while exhibiting a positive correlation with HOMA‐β. Suppressing miR‐320b expression would impair glucose consumption of HepG2 cells through PI3K pathway by targeting PTEN. These results suggest that miR‐320b may be a potential biomarker for diagnosing T2DM and a promising target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound‐healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin‐resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)‐treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n‐dotriacontanol (1), shikimic acid (2), 1‐O‐caffeoylquinic acid methyl ester (3), 5‐O‐caffeoylquinic acid methyl ester (4), 5‐O‐coumaroylquinic acid methyl ester (5), 5‐O‐caffeoylquinic acid butyl ester (6), quercetin‐3‐O‐α‐L‐rhamnoside (7), quercetin (8), quercetin‐3‐O‐(4״‐methoxy)‐α‐L‐rahmnopyranosyl (9), hyperoside (10), and rutin (11). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin‐resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 μM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 μM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA‐treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. Practical applications: Hypericum patulum is a well‐known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin‐resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA‐treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1, 2, 3, 5, 6, 9, 10, and 11 were isolated from the plant for the first time. Quercetin‐3‐O‐(4"‐methoxy)‐α‐L‐rahmnopyranosyl (9) and hyperoside (10) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum. [ABSTRACT FROM AUTHOR]

In vitro embryo production (IVP) efficiency is reduced when compared to in vivo. The basic knowledge of bovine in vitro oocyte maturation (IVM) mechanisms provides support to improve in vitro embryo production yields. The present study assessed the effects of bone morphogenetic protein 15 (BMP15), fibroblast growth factor 16 (FGF16) and their combined action on cumulus cells (CC) expansion, oocyte and CC DNA fragmentation, oocyte nuclear maturation, energetic metabolism and progesterone production in bovine IVM. Cumulus‐oocyte complexes (COC) were matured in control or supplemented media containing BMP15 (100 ng/ml), FGF16 (10 ng/ml) or BMP15 combined with FGF16; and assessed at 0 and 22 hr of IVM. BMP15 alone or its association with FGF16 enhanced cumulus expansion. BMP15 decreased DNA fragmentation in both CC and oocytes, and improved oocyte nuclear maturation rate. In addition, BMP15 increased CC progesterone production, an effect not previously reported. The present study reinforces previous data pointing to a beneficial influence of BMP15 during IVM, while providing novel evidence that the underlying mechanisms involve increased progesterone production. [ABSTRACT FROM AUTHOR]

The fruits of Swietenia macrophylla King have been processed commercially to a variety of health foods and healthcare products and exhibited antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. This study was aimed to examine the glucose consumption in human hepatoma HepG2 cells and the expression of PPARγ of limonoids isolated from the fruits of S. macrophylla. The phytochemical investigation of the fruits led to the isolation of ten limonoids which structures were elucidated by spectroscopic analysis as swietenine (1), khayasin T (2), 6-deoxyswietenine (3), 3-O- tigloylswietenolide (4), swietenolide (5), 3,6-O, O-diacetylswietenolide (6), 7-deacetoxy- 7- oxogedunin (7), fissinolide (8), proceranolide (9), 7-deacetoxy- 7a- hydroxygedunin (10), and compound 10 was isolated from this plant for the first time. The glucose consumption assay revealed that compounds 1, 2, 3, 5, and 9 could promote glucose consumption significantly in normal hyperglycemia-induced HepG2 cells, furthermore, compounds 1, 5, and 9 had a better effect on promoting glucose consumption in insulin-resistant HepG2 cells. In addition, compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells according to the western blotting analysis result. Practical applications: Swietenia macrophylla King belongs to the family Meliaceae and the fruits have been exhibited a wide range of biological activities, such as antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. Phytochemical investigations of S. macrophylla have revealed that limonoids and triterpenoids were effective antidiabetic agents. However, the mechanism of these limonoids to antidiabetic activity is unclear. In this study, limonoids were isolated from the fruit of S. macrophylla and their effects on the glucose consumption of insulin-resistant HepG2 cells were studied. The results showed that compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells, which will give aid to explore the mechanism of these limonoids in the treatment of type 2 diabetes. Therefore, this research might facilitate further research and development of S. macrophylla. [ABSTRACT FROM AUTHOR]

Diabetes is a chronic metabolic disease characterized by insulin resistance (IR). SHP2 has previously been identified as a potential target to reduce IR in diabetes. Here, we examined the effects of SHP2 on glucose consumption (GC), IR level and the expression of insulin receptor substrate (IRS), AKT and extracellular signal‐regulated kinase (ERK)1/2 proteins in a cellular and animal model of diabetes. IR was induced in hepatocellular carcinoma (HCC) cells, and SHP2 was up‐regulated or down‐regulated in cells. Diabetic rats were treated with SHP2 inhibitor. GC of cells, and the weight, total cholesterol, triglycerides, fasting blood glucose, fasting insulin, homeostasis model assessment‐IR index and insulin sensitivity (ISI) of the rats were analyzed. The levels of SHP2 and the activation of IRS‐2, AKT and ERK1/2 in cells and rats were measured by quantitative real‐time PCR (qRT‐PCR) or western blot. GC was reduced, but expression of SHP2 was enhanced in IR HCC cells. Phosphorylation of IRS‐2 and AKT in IR HCC cells and diabetic rats was decreased, whereas phosphorylation of ERK1/2 was enhanced. In both the cell and animal models, SHP2 knockdown enhanced GC, ameliorated IR, activated IRS‐2 and AKT, and inhibited ERK1/2 phosphorylation, in contrast with the effects of SHP2 overexpression. SHP2 knockdown may enhance GC and ameliorate IR through phosphorylation of IRS‐2 via regulating AKT and ERK1/2 in liver. [ABSTRACT FROM AUTHOR]

The demand for plant‐derived antidiabetic nutraceuticals is increasing. In this study, the effects of three common caffeoylquinic acids (CQAs) (chlorogenic acid, isochlorogenic acid A, and cynarin) on α‐glucosidase activity and glucose consumption in HepG2 cells were systematically compared. Their α‐glucosidase inhibitory activities followed the order of isochlorogenic acid A > chlorogenic acid > cynarin. The fluorescence analysis indicated that they exerted the inhibitory role by forming the complex with α‐glucosidase at the molar ratio of 1:1. Isochlorogenic acid A possessed the highest binding capacity, followed by chlorogenic acid and cynarin. The effect of caffeoyl group distribution on the α‐glucosidase inhibitory activity was clarified by the molecular docking results. In the HepG2 cells, isochlorogenic acid A also showed the best glucose consumption with negligible cytotoxicity, which might be related to its reactive oxygen species scavenging capacity in cells. Our results confirm its potential application as the antidiabetic nutraceutical. Practical applications: The hypoglycemic activities of three common CQAs (chlorogenic acid, isochlorogenic acid A, and cynarin) were systemically evaluated in this study. Isochlorogenic acid A exhibited the strongest α‐glucosidase inhibitory activity and highest glucose consumption in HepG2 cells with low cytotoxicity. The results suggest that isochlorogenic acid A can be used as the potential hypoglycemic nutraceutical in functional foods. [ABSTRACT FROM AUTHOR]

piRNA‐823 as a member of the piRNA family is reported to promote tumour cell proliferation in multiple myeloma and hepatocellular cancer. However, few studies on the function of piRNA‐823 in colorectal cancer (CRC). Our present study data showed that piRNA‐823 plays an oncogene role in CRC cells. Inhibition of piRNA‐823 can significantly inhibit the proliferation, invasion and apoptosis resistance of CRC cells. Mechanism studies have shown that piRNA‐823 inhibits the ubiquitination of hypoxia‐inducible factor‐1 alpha (HIF‐1α) by up‐regulating the expression of Glucose‐6‐phosphate dehydrogenase (G6PD) and ultimately up‐regulates the glucose consumption of carcinoma cells and inhibits the content of intracellular reactive oxygen species (ROS). Therefore, we speculate piRNA‐823 promotes the proliferation, invasion and apoptosis resistance of CRC cells by regulating G6PD/HIF‐1α pathway. In this study, we set up the cancer‐promoting function recovery experiment of piRNA‐823 by silencing G6PD gene to confirm the dominance of the above‐mentioned pathways. Using clinical samples, we found that overexpression of piRNA‐823 correlated with poor overall survival and predicted a poor response to adjuvant chemotherapy of patients with CRC. In a word, our research has further enriched the theory of piRNA‐823 promoting the progression of CRC, and laid a solid foundation for the development of piRNA‐823‐based gene therapy for CRC and its use as a promising prognostic biomarker in CRC patients. [ABSTRACT FROM AUTHOR]

Background and Objectives Partially replacing plasma with additive solutions in platelet ( PLT) concentrates ( PCs) may help to reduce transfusion reactions. Constituents of PLT additive solutions ( PASs) have been revealed to affect the quality of PCs. Previous studies involved pairwise comparison of identical PLTs with two different PASs or multicomparison using random PLTs with three or more PASs. In this study, we performed parallel comparison using PCs from identical donors with four PASs. In addition to traditional parameters, the release of bioactive substances and plasma proteins was assessed. Materials and Methods Platelets collected four times by apheresis from three donors were suspended in Intersol, SSP+, Composol or M-sol with 35% autologous plasma. The PC parameters, including PLT activation markers, glucose consumption, chemokines and plasma proteins, were assessed during 5-day storage. Results Mean PLT volumes were decreased in SSP+, Composol and M-sol after 5-day storage, with significant differences, whereas the hypertonic shock response ( HSR) was decreased only in Intersol. Glucose consumption was faster in Intersol and M-sol than in SSP+ or Composol. PLT activation, determined as CD62 P, s CD62 P, s CD40 L and RANTES, was significantly higher in Intersol than the other three PASs. No marked change was observed in fibrinopeptide A and C3a in any PASs. Conclusions M-sol, SSP+ and Composol effectively preserved the quality of PCs. PLT activation was significantly enhanced in Intersol compared with the other three PASs. These effects seem to depend on magnesium and potassium as a constituent. Parallel comparison further verified that the PC quality largely depended on PASs but not donors. [ABSTRACT FROM AUTHOR]