Modulation of IGF1R Signaling Pathway by GIGYF1 in High Glucose-Induced SHSY-5Y Cells.

Grb10 (growth factor receptor-bound protein 10)-interacting GYF protein 1 (GIGYF1) can modulate insulin-like growth factor 1 receptor (IGF1R) signaling pathway, which plays an important role in regulating diabetes-associated cognitive impairment, by linking to Grb10 adapter. However, it remains unclear whether endogenous GIGYF1 expression is associated with the development of diabetes-related cognitive impairment. In this study, we measured the expression level of GIGYF1, Grb10, phosphorylated IGF1R/IGF1R, phosphorylated AKT serine/threonine protein kinase/protein kinase B (AKT)/AKT, and phosphorylated extracellular signal-regulated kinase (ERK)/ERK in human neuroblastoma SHSY-5Y cells. Meanwhile, we detected cell apoptosis, proliferation, and migration. Our results showed that the percentage of apoptotic cells increased along with the increasing concentrations of glucose (0-200 mM). The expression of GIGYF1 had a significant increase in the presence of 25 mM concentration of glucose in SHSY-5Y cells. In addition, high glucose augmented the expression of IGF1R and Grb10, but decreased the expression of p-IGF1R, p-AKT, and p-ERK. However, GIGYF1 knockdown reversed the decline in the expression of p-IGF1R, p-AKT, and p-ERK. In addition, knocking down GIGYF1 promoted the proliferation and migration of SHSY-5Y cells, but inhibited the apoptosis in SHSY-5Y cells. These results demonstrate that the expression of GIGYF1 can regulate IGF1R signaling pathway in high glucose-induced SHSY-5Y cells.

Early Assessment of the Risk Factors for Diabetic Retinopathy Can Reduce the Risk of Peripheral Arterial and Cardiovascular Diseases in Type 2 Diabetes.

BACKGROUNDS: There is still a lack of consensus about how to assess the risk of peripheral arterial disease (PAD) and cardiovascular disease (CVD) in patients with diabetic retinopathy (DR). AIMS: We investigated the risk factors for DR and their association with PAD and CVD in patients with type 2 diabetes (T2D). METHODS: A total of 1,421 patients diagnosed with T2D participated in this study. DR stages were classified as non-DR, nonproliferative DR (NPDR), or proliferative DR (PDR). Logistic regression analysis was employed to analyze risk factors associated with DR. RESULTS: NPDR and PDR patients had higher systolic blood pressure (SBP) and higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) than the non-DR group (p < 0.05). The prevalence of abnormal ankle-brachial index (ABI) in the non-DR, NPDR, and PDR groups was 7.00, 10.80, and 13.96%, respectively (p < 0.05) and the prevalence of peripheral arterial plaques was 68.48, 81.38, and 80.56%, respectively (p < 0.001). Logistic regression analysis showed that DR (vs. non-DR) was associated with peripheral arterial plaques (OR = 2.07), SBP ≥130 mm Hg (OR = 1.53) and levels of hemoglobin (Hb)A1c (OR = 2.11) and TC (OR = 1.42). CONCLUSION: PAD is commonly associated with NPDR and PDR. Hypercholesterolemia is an important risk factor for the development of PAD and CVD in patients with DR. Our results suggest that a routine ABI test, duplex ultrasonography, and obtaining a lipid profile for DR patients may help to reduce the occurrence of PAD and CVD.

Amelioration of Diabetic Mouse Nephropathy by Catalpol Correlates with Down-Regulation of Grb10 Expression and Activation of Insulin-Like Growth Factor 1 / Insulin-Like Growth Factor 1 Receptor Signaling.

Growth factor receptor-bound protein 10 (Grb10) is an adaptor protein that can negatively regulate the insulin-like growth factor 1 receptor (IGF-1R). The IGF1-1R pathway is critical for cell growth and apoptosis and has been implicated in kidney diseases; however, it is still unknown whether Grb10 expression is up-regulated and plays a role in diabetic nephropathy. Catalpol, a major active ingredient of a traditional Chinese medicine, Rehmannia, has been reported to possess anti-inflammatory and anti-aging activities and then used to treat diabetes. Herein, we aimed to assess the therapeutic effect of catalpol on a mouse model diabetic nephropathy and the potential role of Grb10 in the pathogenesis of this diabetes-associated complication. Our results showed that catalpol treatment improved diabetes-associated impaired renal functions and ameliorated pathological changes in kidneys of diabetic mice. We also found that Grb10 expression was significantly elevated in kidneys of diabetic mice as compared with that in non-diabetic mice, while treatment with catalpol significantly abrogated the elevated Grb10 expression in diabetic kidneys. On the contrary, IGF-1 mRNA levels and IGF-1R phosphorylation were significantly higher in kidneys of catalpol-treated diabetic mice than those in non-treated diabetic mice. Our results suggest that elevated Grb10 expression may play an important role in the pathogenesis of diabetic nephropathy through suppressing IGF-1/IGF-1R signaling pathway, which might be a potential molecular target of catalpol for the treatment of this diabetic complication.

Transient behavior at the nanoscale.

Transient and steady state responses of a system to an input are well-known features of materials and systems in science and engineering. These responses depend on the intrinsic parameters of the system and on the nature of the input. We find that a system comprised of nanosized features no longer shows the typical stationary characteristics as their microscopic or solid-state counterparts. Interestingly, because of the chemistry of the nanostructure, thermal motion of the atoms, and external fields, the nanosized system shows extended electrical transient behavior, compatible with highly nonlinear features such a negative differential resistance and hysteresis.

Atomistic nature of transient and steady-state responses.

We find experimentally that a system comprised of nanosized features no longer shows fixed steady characteristics as in solid-state devices, and instead, because of the chemistry of the nanostructure, the thermal motion of the atoms, and the external fields, the nanosized system shows intermittent behavior, that is, transient behavior. This transient response for nanosized systems might misguide conclusions regarding observed negative differential resistance (NDR) which is due to the collective nuclei rearrangements to more stable conformations under the presence of an applied field yielding, in many cases, resonances between conformations that can sustain during the steady-state period. This NDR yields peculiar behavior that needs to be considered to design molecular and nanoelectronic devices. In addition, the commonly sharp contrast between transient and steady responses blurs at the nanoscale. In nanosize systems, the time constants or transient response times depend on the velocity of the rearrangements of the atoms in the system or molecule.

Encoding information using molecular vibronics.

Signals carrying information are encoded in molecular vibrational waves (vibronics) rather than in electric currents as widely done in microelectronics. We demonstrate theoretically that signals can be transmitted along a long polypeptide molecule; the signal is modulated in a terahertz carrier corresponding to a frequency of an intrinsic vibrational mode of the backbone of the polypeptide, via amplitude and frequency modulations. The modulated carrier is coupled as a vibrational wave to the polypeptide at one end of the molecule and propagates for more than 168 angstroms towards the other end. Digital signal processing techniques are used to recover the modulated signals.

Transmission of vibronic signals in molecular circuits.

It is proposed and demonstrated using molecular dynamics and digital signal processing techniques that molecular vibrations can be used to transport signals in molecular circuits, revealing that signals transmitted along polypeptide molecules by a frequency-modulated carrier in the terahertz domain consume only 0.2 eV to successfully transfer one information bit; this energy is several orders of magnitude smaller than the several thousands of electronvolts needed using electrons in present electronic devices.

Clustering effects on discontinuous gold film NanoCells.

Reproducible negative differential resistance (NDR)-like switching behavior is observed in NanoCells. This behavior is attributed to the formation of filaments and clusters between the discontinuous gold films. Control experiments are performed by self-assembly of insulating molecules between the gold islands and conducting molecules on these islands. Additional control experiments are performed by removing the filaments and clusters between islands using a piranha bath. The results are consistent with theoretical predictions and extend the domain of molecular electronics based in organic molecules to include nanosized clusters as active units. This facilitates a scenario where synthetically accessible organic molecules, with defined characteristics, can be adjusted by metallic nanoclusters as an in situ fine-tuning element, able to compensate for the lack of addressing in the nanosize regime.