Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products.

Retinal pericyte migration occurs in the early stage of diabetic retinopathy (DR), which is one of the important causes of pericyte loss. Autophagy has been found to play essential roles in the regulation of many types of cell migration. In this study, we explored the relationship between autophagy and retinal pericyte migration. In diabetic rats, the retinas became thinner, and the level of autophagy in each cell layer increased. In the primary culture of bovine retinal pericytes, we found that advanced glycation end products (AGEs) increased the migratory cell ability without influencing cell viability, which also increased the phosphorylation of focal adhesion kinase (FAK) and the expression of matrix metalloproteinase (MMP)-2 and decreased the expression of vinculin. AGEs-induced retinal pericyte autophagy and the inhibition of autophagy with chloroquine significantly inhibited cell migration, reversed AGEs-induced FAK phosphorylation, and changed vinculin and MMP-2 protein expression. These results provide a new insight into the migration mechanism of retinal pericytes. The early control of autophagy has a potential effect on regulating pericyte migration, which may contribute to keeping the integrity of retinal vessels in DR.

Neuroprotective Role of GLP-1 Analog for Retinal Ganglion Cells via PINK1/Parkin-Mediated Mitophagy in Diabetic Retinopathy.

GLP-1 analogs have been widely used to treat patients with type 2 diabetes in recent years and studies have found that GLP-1 analogs have multiple organ benefits. However, the role of GLP-1 analogs in diabetic retinopathy (DR), a common complication of diabetes mellitus (DM), remains controversial. Retinal ganglion cells (RGCs) are the only afferent neurons responsible for transmitting visual information to the visual center and are vulnerable in the early stage of DR. Protection of RGC is vital for visual function. The incretin glucagon-like peptide-1 (GLP-1), which is secreted by L-cells after food ingestion, could lower blood glucose level through stimulating the release of insulin. In the present study, we evaluated the effects of GLP-1 analog on RGCs both in vitro and in vivo. We established diabetic rat models in vivo and applied an RGC-5 cell line in vitro. The results showed that in high glucose conditions, GLP-1 analog alleviated the damage of RGCs. In addition, GLP-1 analog prevented mitophagy through the PINK1/Parkin pathway. Here we demonstrated the neuroprotective effect of GLP-1 analog, which may be beneficial for retinal function, and we further elucidated a novel mechanism in GLP-1 analog-regulated protection of the retina. These findings may expand the multi-organ benefits of GLP-1 analogs and provide new insights for the prevention of DR.

Preoperative color Doppler ultrasonography predicts early recurrence in AFP-positive hepatocellular carcinoma.

The present study aimed to evaluate the hepatic hemodynamics of patients with α-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) and early recurrence (ER), as determined by color Doppler ultrasound. Screening with color Doppler ultrasound was performed in 150 patients with AFP-positive HCC, yielding 43 cases with postoperative ER. In addition, 35 healthy controls were enrolled in the study for comparison of the blood flow parameters between the healthy control and the HCC groups. Receiver operating characteristic curve analysis was performed to evaluate the predicted effect of Doppler for the ER of HCC. The average mean flow velocity of portal vein in patients with HCC (14.686±5.873 cm/s) was significantly lower in the HCC group compared with the healthy control group (17.631±3.569 cm/s; P=0.005). Additionally, the preoperative portal vein diameter in the HCC group was significantly higher compared with that in the healthy control group (P=0.001). Regarding the effect of surgery, the portal vein diameter was significantly increased in the patients postoperatively compared with preoperatively (P=0.003), while the pulsation and resistance indexes exhibited a decreasing trend in the postoperative group (P=0.001 and P=0.003, respectively). Notably, patients with HCC and ER presented with a higher resistance index (1.163±0.342) compared with the ER-free group (1.023±0.176; P=0.004). Furthermore, a significant difference in hepatic artery pulsation index was also observed between the ER group (0.673±0.075) and the ER-free group (0.624±0.056; P=0.018), indicating that an increased hepatic artery pulsation index may significantly predict the ER of HCC. In addition, areas under the curve of 0.683 and 0.700, respectively, suggested that the hepatic artery resistance and pulsation indexes may be used to diagnose ER in HCC (P=0.009 and P=0.004, respectively). Taken together, Doppler ultrasound provides a reliable and accurate quantification of hepatic hemodynamics for detecting ER in HCC with a good diagnostic accuracy.

Contrast-Enhanced Ultrasound to Monitor Early Recurrence of Primary Hepatocellular Carcinoma after Curative Treatment.

OBJECTIVE: To evaluate contrast-enhanced ultrasound (CEUS) for monitoring early intrahepatic recurrence of primary hepatocellular carcinoma (HCC) after curative treatment. METHODS: We prospectively analyzed 97 patients (124 nodules) with primary HCC who underwent hepatic resection or radiofrequency ablation and subsequently experienced intrahepatic recurrence. Patients were assessed with conventional ultrasound and CEUS. They were also assessed with contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI). The image characteristics of CEUS of recurrent hepatocellular carcinoma and high-grade dysplastic nodules (HGDNs) were analyzed. In addition, the ability of CEUS and CECT/MRI to assess internal artery vascularization in recurrent disease was compared. RESULTS: CEUS of recurrent hepatocellular carcinoma showed hyperenhancement in the arterial phase in 96 of 99 nodules, and it showed hypo- or isoenhancement for portal venous and delayed phases. The most common enhancement patterns were "fast-in and slow-out" and "fast-in and fast-out". Based on the arterial hyperenhancement of lesions and with clinical data such as patient history of HCC and increased level of serum alpha-fetoprotein, the diagnostic accuracy of CEUS for recurrent HCC was significantly higher than that based on the enhancement pattern of "fast-in and fast-out". CEUS of HGDNs showed local or global hyperenhancement during the arterial phase, isoenhancement during the portal venous phase, and isoenhancement or slight hypoenhancement during the delayed phase. The enhancement pattern was "fast-in and slow-out". In some cases, it was difficult to differentiate HGDNs from recurrent disease using CEUS. Vascularization in recurrent disease was significantly higher when assessed by CEUS than when assessed with CECT/MRI (P < 0.05). For detecting recurrent disease, CEUS showed sensitivity of 97.0%, specificity of 68.0%, positive predictive value of 92.3%, and negative predictive value of 85.0%. The corresponding parameters for CECT/MRI were 71.7%, 72.0%, 88.8%, and 39.1%. CONCLUSION: Intrahepatic recurrent HCC and HGDNs with diameter ≤ 3.0 cm have a characteristic appearance on CEUS. This imaging modality may be effective for monitoring early intrahepatic recurrence after curative treatment of primary HCC.

Consistency analysis of contrast-enhanced ultrasound and contrast-enhanced CT in diagnosis of small hepatocellular carcinoma.

UNLABELLED: To compare the consistency of contrast-enhanced ultrasound (CEUS) and contrast-enhance CT (CECT) in diagnosis of 1~2 cm and 2.1~3 cm small hepatocellular carcinoma (HCC) and evaluate the value of CEUS in diagnosis of HCC. METHODS: A total of 74 patients (89 lesions) with small HCC and cirrhosis background were retrospectively analyzed. All of the eighty-nine lesions were confirmed by histopathological examination of surgical samples or needle biopsy. All the cases were divided into 1~2 cm group and 2.1~3 cm group. The CEUS and CECT enhanced pattern and diagnosis results of the two groups were compared and the consistency between the two imaging methods were statistically analyzed. RESULTS: In the diagnosis of 1.0-2.0 cm HCC, CEUS and CECT had a moderate consistency in arterial phase, CEUS showed a tolerable consistency with CECT in portal venous and delayphase. The two imaging methods have a better consistency for the diagnosis in 2.1-3.0 cm HCC. CONCLUSION: CEUS can be used as a supplement to provide important diagnostic information in clinical practice when positive results or definite diagnoses cannot obtain.