An SGLT2 inhibitor modulates SHH expression by activating AMPK to inhibit the migration and induce the apoptosis of cervical carcinoma cells.

In addition to their hypoglycemic effect, sodium-glucose cotransporter 2 (SGLT2) inhibitors have many other benefits. In the present study, we examine the anticancer effect of the SGLT2 inhibitor empagliflozin using cervical carcinoma models. In vivo antitumor activities of empagliflozin were observed in a nude mouse model. Empagliflozin intervention and downregulation of Sonic Hedgehog Signaling Molecule (Shh) inhibited the migration and promoted the apoptosis of cervical cancer cells in nude mice. Compared with the control group, the empagliflozin treatment group had an increased level of AMP-activated protein kinase (AMPK) and decreased levels of Forkhead Box A1 (FOXA1) and SHH in tumor tissue. In vitro experiments also showed that empagliflozin (50 µM) inhibited the migration of cervical cancer cells and induced their apoptosis by activating the AMPK/FOXA1 pathway and inhibiting the expression of SHH. Kaplan-Meier survival analysis was used to determine the relationship between SHH expression and total survival time. The results showed that in cervical cancer patients, high SHH expression resulted in unfavorable overall survival. The downregulation of SHH with small interfering RNA (siRNA) inhibited the migration and invasion and promoted the apoptosis of HeLa cells. These findings show that empagliflozin has a potential therapeutic effect on cervical cancer. This effect was related to the activation of the AMPK pathway and the inhibition of SHH expression.

A Simple High-resolution Near-field Probe for Microwave Non-Destructive Test and Imaging.

Non-destructive tests working at lower microwave frequencies have large advantages of dielectric material penetrability, lower equipment cost, and lower implementation complexity. However, the resolution will become worse as the work frequencies become lower. Relying on designing the structure of high field confinement, this study realizes a simple complementary spiral resonators (CSRs)-based near-field probe for microwave non-destructive testing (NDT) and imaging around 390 MHz (λ = 769 mm) whereby very high resolution (λ/308, 2.5 mm) is achieved. By applying an ingenious structure where a short microstrip is connected to a microstrip ring to feed the CSR, the probe, that is a single-port microwave planar circuit, does not need any extra matching circuits, which has more application potential in sensor arraying compared with other microwave probes. The variation of the electric field distribution with the standoff distance (SOD) between the material under test and the probe are analyzed to reveal the operation mechanisms behind the improved sensitivity and resolution of the proposed probe. Besides, the detection abilities of the tiny defects in metal and non-metal materials are demonstrated by the related experiments. The smallest detectable crack and via in the non-metal materials and the metal materials are of a λ/1538 (0.5 mm) width, a λ/513 (1.5 mm) diameter, a λ/3846 (0.2 mm) width and a λ/513 (1.5 mm) diameter, respectively. Moreover, to further evaluate the performance of the proposed probe, the defects under skin layer in the multilayer composite materials and the defects under corrosion in the carbon steel are inspected and imaged. Due to lower work frequency, high resolution, outstanding detection abilities of tiny defects, and large potentials in sensor arraying, the proposed probe would be a good candidate for microwave NDT and imaging.

MiR-155-5p inhibits PDK1 and promotes autophagy via the mTOR pathway in cervical cancer.

Cervical cancer is one of the most common malignant tumors and the leading cause of cancer-related mortality in women. Persistent cervical infection by high-risk human papillomavirus (hrHPV) is related to cervical cancer. MicroRNAs could regulate autophagy caused by viral infection. The aim of the present study was to investigate the regulation of autophagy by miR-155-5p in cervical cancer. In HPV+ human cervical lesion tissues, miR-155-5p expression was found to be markedly decreased. Compared to C33A cancer cells (HPV-), the miR-155-5p expression was significantly lower in Siha and HeLa cells (HPV+), which are both hrHPV positive. The level of autophagy was higher in C33A cells than in Siha and HeLa cells. In addition, in C33A, Siha and HeLa cervical cancer cells, miR-155-5p overexpression promoted autophagy, whereas miR-155-5p downregulation had the opposite effects. Furthermore, miR-155-5p downregulation suppressed LC3 and promoted P62 protein expression in C33A cells through promoting the PDK1/mTOR pathway, whereas miR-155-5p overexpression recovered LC3 and suppressed P62 protein expression by suppressing PDK1/mTOR signaling. Taken together, our results indicate the importance of miR-155-5p in cervical cancer cells and suggest a novel mechanism of hrHPV in promoting cervical lesions.

Plasma metabolic profile reveals PGF2α protecting against non-proliferative diabetic retinopathy in patients with type 2 diabetes.

Diabetic retinopathy (DR) is the most frequent microvascular complications of diabetes and the leading cause of blindness in adults worldwide. Non-proliferative DR (NPDR) is the first stage of DR but currently has few recommended intervention. Eicosanoids play important roles in maintaining vessel homeostasis. However, the functions of eicosanoids in NPDR are still unknown. In this study, we investigated the eicosanoids profile difference in plasma between type 2 diabetes with NPDR or not. A total of 50 patients with type 2 diabetes were recruited and divided into non-DR (NDR) group and NPDR group based on fundus photographs. The eicosanoids profiles in plasma were determined by LC-MS/MS. Adhesion and transwell assay were used to detect the adhesion and migration effects of metabolites on primary bovine retinal pericyte cells (BRPC), respectively. Streptomycin (STZ)-induced diabetic mouse model was used to test the protective effects of selected metabolites according to retinal immunofluorescence staining and fluorescence confocal microscopy. Prostaglandin 2α (PGF2α) was decreased significantly in NPDR group compared to NDR group and negatively correlated with NPDR. In vitro, PGF2α was found to accelerate adhesion and migration by activating prostaglandin F receptor (FP receptor) and subsequent increasing RhoA activity in primary bovine retinal pericyte. Administration of PGF2α analogue diminished the damage on retinal capillary in an STZ-induced diabetic mouse model. Our results suggested that PGF2α may be a protective factor in the progression of NPDR in T2D patients. The protective mechanism of PGF2α was to increase pericyte mobility through FP receptor/RhoA pathway.