Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death.

BACKGROUND/AIMS: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. METHODS: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). RESULTS: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. CONCLUSION: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction.

BACKGROUND/AIMS: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. METHODS: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. RESULTS: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. CONCLUSION: LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

Ru(ii) polypyridyl complex-incorporated and folate-conjugated vehicle for cancer cell imaging and photoinduced inactivation.

Ru(ii) polypyridyl complexes have been expected as promising therapeutic agents against cancer owing to its DNA photocleavage activity. However, the lack of cell selectivity poses a significant obstacle to their practical application. Herein, the strategy combining cell-specific imaging with photoinduced cell death based on [Ru(phen)2(dppz)](2+) has been developed by incorporating [Ru(phen)2(dppz)](2+) into folate-conjugated liposomes. The cells overexpressing folate receptors could specifically recognize this vehicle and be imaged through the luminescence of [Ru(phen)2(dppz)](2+). Thereafter, the delivered [Ru(phen)2(dppz)](2+) interacted with DNA in cells and led to photoinduced cell death. This work provided a possible alternative for cancer diagnosis and therapy.

A fast and biocompatible living virus labeling method based on sialic acid-phenylboronic acid recognition system.

The sialic acid (SA)-phenylboronic acid (PBA) recognition system is of particular interest in the bioconjugation field, because it is simple, fast, efficient, and biocompatible. In this paper, we report a novel method for reversibly labeling living virus with quantum dots (QDs) by taking advantage of this SA-PBA recognition system. The QDs were initially modified with PBA (QDs-PBA) to target them to the surface of vesicular stomatitis virus (VSV), which has abundant with SA on its envelope. The QDs-PBA was of good monodispersity and strong fluorescence, and could be conjugated with VSV by simply incubating with native VSV for 10 min at 37 °C, producing QDs-VSV that was capable of being imaged at the single virion level. The labeling efficiency attained 83 ± 4.3 % (mean ± SD); meanwhile, the activity and recognition ability of the labeled virus were minimally affected. This method was simple, rapid, and reversible. This work promotes the virus labeling development to a new step. That is, native viruses can be reversibly labeled without any modification.