SGLT2i improves kidney senescence by down-regulating the expression of LTBP2 in SAMP8 mice.

Senescent kidney can lead to the maladaptive repairment and predispose age-related kidney diseases. Here, we explore the renal anti-senescence effect of a known kind of drug, sodium-dependent glucose transporters 2 inhibitor (SGLT2i). After 4 months intragastrically administration with dapagliflozin on senescence-accelerated mouse prone 8 (SAMP8) strain mice, the physiologically effects (lowering urine protein, enhancing glomerular blood perfusion, inhibiting expression of senescence-related biomarkers) and structural changes (improving kidney atrophy, alleviating fibrosis, decreasing glomerular mesangial proliferation) indicate the potential value of delaying kidney senescence of SGLT2i. Senescent human proximal tubular epithelial (HK-2) cells induced by H2 O2 also exhibit lower senescent markers after dapagliflozin treatment. Further mechanism exploration suggests LTBP2 have the great possibility to be the target for SGLT2i to exert its renal anti-senescence role. Dapagliflozin down-regulate the LTBP2 expression in kidney tissues and HK-2 cells with senescent phenotypes. Immunofluorescence staining show SGLT2 and LTBP2 exist colocalization, and protein-docking analysis implies there is salt-bridge formation between them; these all indicate the possibility of weak-interaction between the two proteins. Apart from reducing LTBP2 expression in intracellular area induced by H2 O2 , dapagliflozin also decrease the concentration of LTBP2 in cell culture medium. Together, these results reveal dapagliflozin can delay natural kidney senescence in non-diabetes environment; the mechanism may be through regulating the role of LTBP2.

Michelson interferometer based phase demodulation for stable time transfer over 1556 km fiber links.

Time transfer based on phase modulation schemes has attracted extensive attention in recent years. We propose and experimentally demonstrate an adjustable and stable Michelson interferometer (MI) with a DC phase tracking algorithm for two-way time transfer. Time signal with one pulse per second (1 PPS) is loaded on an optical carrier modulated in phase and demodulated by a Michelson interferometer. The whole compact and cost-effective demodulator is symmetrical with a single coupler to split and recombine optical waves, flexible with one photodetector and a bias tee to separate the DC signal and recovery pulses and stable with a phase modulator to compensate for the drift-phase noise. We show the implementation of modulation and demodulation of the time signal and obtain the stability of 2.31 × 10-11 at 1000 s averaging time. We then demonstrate two-way time transfer over 1556 km lab fibers. The experimental result shows time interval stability of 1 PPS with 5.62 × 10-11 at 1000 s averaging time. It has the potential to transfer time signals in long-distance fiber optic links.

Prebiotics, Probiotics and Nutrients in Cardiovascular and Kidney Disease.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) are the leading causes of mortality and health burden worldwide [...].

Lean non-alcoholic fatty liver disease and risk of incident diabetes in a euglycaemic population undergoing health check-ups: A cohort study.

INTRODUCTION: Convincing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and an increased risk of diabetes; however, the association between lean NAFLD and incident diabetes, and especially differences according to gender, have not been reported thus far. This study therefore aimed to investigate whether lean NAFLD and overweight/obese NAFLD confer the same excess risk of new-onset diabetes in both genders. METHODS: Our longitudinal study was performed in 14,482 euglycaemic adults who had participated in a health checkup programme. Fatty liver was diagnosed by abdominal ultrasonography. The outcome of interest was incident diabetes. RESULTS: Over the median 6.0 years of follow-up, 356 cases of diabetes were diagnosed. After adjusting for sociodemographic and other potential confounders, the fully adjusted HR (95% CI) for incident diabetes in lean NAFLD vs lean without NAFLD patients was 2.58 (95% CI: 1.68-3.97) in the total cohort. Corresponding HRs were 5.53 (95% CI: 2.30-13.30) and 2.02 (95% CI: 1.24-3.31) for women and men, respectively. Post-hoc analysis revealed that the relative risk for developing diabetes was similar between lean and overweight/obese NAFLD groups whether in the entire study population or in subgroups stratified by gender (all P> 0.05). CONCLUSION: Lean NAFLD is indeed a risk factor for incident type 2 diabetes in both genders, although the effect appeared to be more pronounced in women than in men. Further investigations are now needed to obtain a better understanding of the natural history of NAFLD in lean subjects.