Kaempferide ameliorates cisplatin-induced nephrotoxicity via inhibiting oxidative stress and inducing autophagy.

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 µM) and kaempferol (10 µM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.

Application of contrast-enhanced sonography with time-intensity curve analysis to explore hypervascularity in Achilles tendinopathy by using a rabbit model.

OBJECTIVES: The purpose of this study was to investigate the ability of contrast-enhanced sonography in staging and grading hypervascularity in tendinopathic tissues by using a rabbit model. METHODS: Fourteen rabbits were injected with 100 and 50 µL of collagenase in their left and right Achilles tendons, respectively. The vascularity was assessed by non-contrast-enhanced and contrast-enhanced power Doppler sonography on day 0 (baseline) and days 1, 7, and 14 after collagenase injections. Color pixels within targeted areas were plotted according to time and analyzed by a curve-fitting method. RESULTS: Non-contrast-enhanced power Doppler sonography failed to differentiate vascularity at various stages or between bilateral tendons, whereas contrast-enhanced sonography showed that the peak color pixel amount reached its maximum on day 1 and declined over time in tendons treated with 100 µL of collagenase. A similar trend was observed in tendons receiving 50 µL of collagenase. For comparisons between bilateral tendons, higher vascularity was detected in those treated with more collagenase on day 1 or 7. Time-intensity curve analysis revealed rapid microbubble replenishment in both tendons during their initial phase after collagenase injections. CONCLUSIONS: Contrast-enhanced sonography discriminated the vascularity of various injury grades at different time points after collagenase injections. Time-intensity curve analysis detailed the hemodynamics in tendinopathic tissues, which helped differentiate vascularity in acute inflammatory from later degenerative phases.

Reducing lesion aberration by dual-frequency focused ultrasound ablations.

Discrepancies between hyperecho-predicted necrosed volume in ultrasound (US) images and the actual size of a thermal lesion might cause incomplete ablation or damage normal structures during high intensity focused US (HIFU) ablations. A novel dual-frequency sonication procedure is proposed to reduce this discrepancy. HIFU transducers of either 1 or 3.5 MHz were applied to transparent tissue-mimicking phantoms and ex vivo bovine liver samples. A diagnostic probe and a charge-coupled device (CCD) camera were used to record lesion formation in real time, allowing for comparison of the sizes of the hyperechoes in US images and the protein denaturing area on optical images. Bovine liver specimens were segmented to reveal the lesion's terminal sizes. Differences between actual lesion volume and hyperechoes in US images were demonstrated to be dependent on acoustic frequency and intensity. At a low frequency (1 MHz), the hyperechoes appeared to be larger than the actual volume, but the difference decreased with the duration of ablation. In contrast, at a high frequency (3.5 MHz), the hyperechoes were smaller for ablations lasting longer than 10 s. Moreover, given certain low-intensity conditions, lesions were formed without detectable hyperechoes (3.5 MHz), or hyperechoes appeared before a visible lesion was formed (1 MHz). Dual frequency sonications (low frequency followed by high frequency) produce more stable and larger lesions, and with less position shift, which might be useful for designing future ablation strategies.