Pigment epithelium-derived factor (PEDF) plays an important role in insulin resistance (IR). The study aims to investigate the effect of rosiglitazone, an insulin sensitizer, on PEDF production and release both in vivo and in vitro. Male SD rats were divided into normal control group, high-fat group, and rosiglitazone group. Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 adipocytes and HepG2 cells were established by the hyperinsulinemic method. Glucose uptake was examined to validate IR of adipocytes, and phosphorylation of protein kinase B and glycogen synthesis kinase 3β were examined to validate IR of HepG2 cells. Rosiglitazone, 2-chloro-5-nitro-N-phenylbenzamide (GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ), and compound C (inhibitor of AMP-activated protein kinase [AMPK]) were used for the in vitro intervention. In vivo, the high-fat group showed increased serum PEDF levels, which negatively correlated with insulin sensitivity, whereas the rosiglitazone treatment decreased the serum PEDF and down-regulated PEDF expression in fat and liver of the obese rats, concomitant with significantly enhanced insulin sensitivity. In vitro, the IR cells showed increased PEDF secretion and expression, whereas rosiglitazone lowered PEDF secretion and expression, accompanied with increased insulin sensitivity. Interestingly, combination with 2-chloro-5-nitro-N-phenylbenzamide did not influence the effect of rosiglitazone on PEDF. However, rosiglitazone stimulated AMPK phosphorylation in fat and liver of the obese rats, whereas in vitro, when combined with compound C, the effect of rosiglitazone on PEDF was abrogated. In summary, rosiglitazone inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation rather than peroxisome proliferator-activated receptor-γ, and changes of PEDF induced by rosiglitazone are closely associated with IR improvement.

Electric-field-induced second harmonic generation (EFISH), a third-order nonlinear process, arises from the interaction between the electric field of an external bias and that of two incident photons. EFISH can be used to dynamically control the nonlinear optical response of materials and is therefore promising for active nonlinear devices. However, it has been challenging to achieve a strong modulation with EFISH in conventional nonlinear materials. Here, we report a large tunability of an EFISH signal from a subwavelength-thick polymer film sandwiched between a transparent electrode and a metallic mirror. By exploiting the band-edge-enhanced third-order nonlinear susceptibility of the organic conjugated polymer, we successfully demonstrate a gigantic EFISH effect with a modulation ratio up to 422% V- 1 at a pumping wavelength of 840 nm. The band-edge-enhanced EFISH opens new avenues for modulating the intensity of SHG signals and for controlling nonlinear electro-optic interactions in nanophotonic devices.

Pigment epithelium-derived factor (PEDF) plays an important role in obesity-induced insulin resistance (IR). The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro.

Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter. Thus, blocking glutamate flux using riluzole (an amyotropic lateral sclerosis approved drug) can selectively kill CR cells in vitro and in vivo. However, we discovered here that glutathione suppression is not the primary pathway in eradicating the CR cells. Riluzole can lead to further decrease in NAD+ (nicotinamide adenine dinucleotide) and lactate dehydrogenase-A (LDHA) expressions which in turn further heightened oxidative stress in CR cells. LDHA knocked-down cells became hypersensitive to riluzole treatments and possessed increased levels of ROS. Addition of NAD+ re-stabilized LDHA and reversed riluzole induced cell death. Thus far, no drugs are available which could overcome cisplatin resistance or kill cisplatin resistant cells. CR cells possess high levels of ROS and undergo metabolic reprogramming. These metabolic adaptations can be exploited and targeted by riluzole. Riluzole may serve as a dual-targeting agent by suppression LDHA and blocking xCT antiporter. Repurposing of riluzole should be considered for future treatment of cisplatin resistant lung cancer patients.