Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via Inhibition of FoxO1 in Type I Diabetic Rats.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease which has been previously shown to be associated with type 2 diabetes mellitus (T2DM). Recent research has indicated that type 1 diabetes mellitus (T1DM) is also involved in the development of nonalcoholic fatty liver disease, whereas the underlying mechanisms are largely unknown. Forkhead box O1 (FoxO1) and adiponectin (APN) have been proposed to play an important role in the processes in NAFLD in T1DM. We herein investigated the effects of FoxO1 and APN on the development of NAFLD and the underlying mechanism in streptozotocin-induced T1DM. Serum liver enzymes AST, ALT, and triglyceride (TG) were determined by commercially available kits. Blood glucose levels were measured by the OneTouch Ultra glucose meter. Relevant protein expression was tested by Western blot analysis. Results showed that serum AST, ALT, and TG were all significantly increased in T1DM rats, which was ameliorated by application of APN or selective inhibition of FoxO1 with AS1842856. Moreover, APN and AS1842856 both decreased the expression of liver nuclear FoxO1 which was significantly increased in diabetic rats. However, the inhibition of FoxO1 did not alter the expression of APN and its receptors. We also found that Akt1 expression was significantly declined in diabetic rat which was restored by APN and moderately and significantly increased by FoxO1 inhibition. It is concluded that APN ameliorates NAFLD via inhibition of FoxO1 through Akt1/FoxO1 signaling pathway.

Risk factors for osteoporosis in liver cirrhosis patients measured by transient elastography.

Osteoporosis or osteopenia is a common complication in patients with cirrhosis, but little is known about the risk factors for the occurrence of osteoporosis.Patients with liver cirrhosis due to chronic virus infection and alcoholic abuse were enrolled. Bone mineral density (BMD) was determined using dual-energy x-ray absorptiometry (DXA). Osteoporosis was diagnosed according to WHO criteria. The severity of liver stiffness was measured by Fibroscan. Demographic data, such as age, gender, weight, height, and body mass index (BMI), were collected. Logistic regression analysis was used to recognize the risk factors of osteoporosis in patients with cirrhosis.A total of 446 patients were included in this study: 217 had liver cirrhosis (male, 74.2%; mean age, 57.2 ±â€Š10.27) and 229 were matched controls (male, 69%, mean age, 56.69 ±â€Š9.37). Osteoporosis was found in 44 patients (44/217, 20.3%). The spine and hip BMD in cirrhotic patients were significantly lower than that in controls. When the cirrhotic and control subjects were stratified by age, gender, and BMI, the significant difference was also observed in women patients, patients older than 60, and patients with BMI < 18. Multivariate analysis showed that the older age [odds ratio (OR) = 1.78, P = .046], lower BMI (OR = 0.63, P = .049), greater fibroscan score (OR = 1.15, P = .009), and liver cirrhosis induced by alcohol liver disease (OR = 3.42, P < .001) were independently associated with osteoporosis in cirrhotic patients.Osteoporosis occurred in about one-fifth of patients with liver cirrhosis, which was associated with age, BMI, Fibroscan score, and alcohol liver disease related liver cirrhosis.

Upregulation of miR­598 promotes cell proliferation and cell cycle progression in human colorectal carcinoma by suppressing INPP5E expression.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Recently, microRNAs (miRs) have been considered as novel therapeutic targets for the treatment of cancer. miR­598 is a poorly investigated miR. The underlying mechanism of miR­598 in CRC cells remains to be elucidated. In the present study, miR­598 was demonstrated to be significantly upregulated in CRC tissue by analyzing data from The Cancer Genome Atlas and the Gene Expression Omnibus. The results of a polymerase chain reaction demonstrated that miR­598 expression was significantly upregulated in CRC tissues and cells. Gain of function and loss of function assays demonstrated that miR­598 significantly promoted cell proliferation and cell cycle progression. miR­598 was demonstrated to modulate cell functions by regulating 72 kDa inositol polyphosphate­5­phosphatase (INPP5E). In addition, knockdown of INPP5E counteracted the growth arrest caused by an miR­598­inhibitor. In conclusion, the present study demonstrated that miR­598 contributed to cell proliferation and cell cycle progression in CRC by targeting INPP5E.

Long non-coding RNA SPRY4-IT1 pormotes colorectal cancer metastasis by regulate epithelial-mesenchymal transition.

Colorectal cancer (CRC) remains one of the most common cancers worldwide. Increasing evidence indicates that SPRY4 intronic transcript 1 (SPRY4-IT1) regulate cell growth, differentiation, apoptosis, and cancer progression. However, the expression and function of SPRY4-IT1 in the progression of CRC remains largely unknown. Here, we reported that SPRY4-IT1 was upregulated in CRC. Increased SPRY4-IT1 expression in CRC was associated with larger tumor size and higher clinical stage. In vitro experiments revealed that SPRY4-IT1 knockdown significantly inhibited CRC cell proliferation by causing G1 arrest and promoting apoptosis, whereas SPRY4-IT1 overexpression promoted cell proliferation. Further functional assays indicated that SPRY4-IT1 overexpression significantly promoted cell migration and invasion by regulate the epithelial-mesenchymal transition (EMT). Taken together, our study demonstrates that SPRY4-IT1 could act as a functional oncogene in CRC, as well as a potential therapeutic target to inhibit CRC metastasis.