Piceatannol Protects against High Glucose-Induced Injury of Renal Tubular Epithelial Cells via Regulating Carbonic Anhydrase 2.

INTRODUCTION: We here evaluated the efficacy of piceatannol (PIC) in high glucose (HG)-induced injury of renal tubular epithelial cells HK-2. METHODS: After the establishment of an HG-induced cell injury model and the treatment with PIC at both high and low concentrations and/or acetazolamide (ACZ, the inhibitor of carbonic anhydrase 2 [CA2]), MTT and flow cytometry assays were carried out to confirm the viability and apoptosis of HK-2 cells. The levels of oxidative stress markers lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS), the ratio of glutathione/oxidized glutathione (GSH/GSSG), and the CA2 activity were determined. Both quantitative reverse-transcription polymerase chain reaction and Western blot were used to calculate the expressions of CA2 (the predicted target gene of PIC via intersecting the data from bioinformatic analyses) and AKT pathway-related (phosphatase and tensin homolog [PTEN], phosphorylated [p]-AKT, AKT) and apoptosis-related proteins (Bcl-2 and cleaved caspase-3). RESULTS: HG suppressed cell viability and the levels of GSH/GSSG ratio, CA2, pThr308-AKT/AKT, pSer473-AKT/AKT, and Bcl-2, while promoting cell apoptosis, the levels of LDH, MDA, and ROS, and the expressions of PTEN and cleaved caspase-3. All effects of HG were reversed by PIC at a high concentration. CA2 was predicted and identified as the target of PIC. In HG-treated HK-2 cells, additionally, ACZ reversed the effects of PIC on the viability, apoptosis, and levels of both oxidative stress markers and AKT pathway- and apoptosis-related factors. CONCLUSION: PIC protects against HG-induced injury of HK-2 cells via regulating CA2.

Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen.

The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.

Synaptically silent sensory hair cells in zebrafish are recruited after damage.

Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is challenging in many species. To overcome this challenge, we used optical indicators to investigate mechanotransduction among collections of hair cells in intact zebrafish. Our imaging reveals a previously undiscovered disconnect between hair-cell mechanosensation and synaptic transmission. We show that saturating mechanical stimuli able to open mechanically gated channels are unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells. Although synaptically silent, latent hair cells can be rapidly recruited after damage, demonstrating that they are synaptically competent. Therefore synaptically silent hair cells may be an important reserve that acts to maintain sensory function. Our results demonstrate a previously unidentified level of complexity in sculpting sensory transmission from the periphery.

Therapeutic Effects of a Traditional Chinese Medicine Formula Plus Tamoxifen vs. Tamoxifen for the Treatment of Mammary Gland Hyperplasia: A Meta-Analysis of Randomized Trials.

As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients' life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09-4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28-0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72-2.71; P < 0.00001) and decrease the size of breast lump (MD: -0.67; 95% CI: -0.86 to -0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH.

A randomized trial of Chinese medicine Lirukang Granule combined with psychological intervention for cyclomastopathy and menoxenia.

OBJECTIVE: To observe the influence of therapy with Chinese medicine Lirukang Granule (, LRKG) combined with psychological intervention on anxiety states and sex hormones in patients with cyclomastopathy and menoxenia. METHODS: A total of 470 subjects were randomly assigned to three groups by the net-central randomization system, the treatment group (161 patients, treated with LRKG and psychological intervention), the Chinese medicine group (157 patients, treated with LRKG), and the psychological intervention group (152 patients, treated with psychological intervention). The dose of LRKG was 12 g three times per day; psychological intervention included establishing relations, cognitive intervention and psychological persuasion, 30-40 min per session, once a week. The therapy duration for all groups was three months. The efficacy was compared and anxiety state/State-Trait Anxiety Invertory (STAI) scoring was measured before and after treatment. The serum estradiol (E2), progesterone (P), prolactin (PRL) and follicle stimulating hormone (FSH) levels of 60 patients selected randomly from each group during the luteal phase were measured before and after treatment, and a group of 20 healthy women were evaluated for comparison. A follow-up was arranged for one year after treatment. RESULTS: Thirty subjects were lost to follow-up. (1) Comparison of efficacy: the markedly effective rate and the total effective rate of the treatment group were 86.67% (131/150) and 98.00% (147/150), respectively; of the Chinese medicine group, 64.58% (93/144) and 90.27% (130/144), respectively; and of the psychological intervention group, 0% (0/146) and 3.42% (5/146), respectively. The markedly effective rate and the total effective rate in the treatment group were significantly higher than those in the Chinese medicine and psychological intervention groups (P < 0.05). (2) Comparison of STAI scoring: STAI scoring was decreased dramatically in the treatment group after treatment compared with that of the Chinese medicine group (P < 0.01), but there was no significant difference compared with the psychological intervention group. (3) Comparison of levels of sex hormones: E2, P, PRL and FSH of the three patient groups were disordered before treatment, and significantly different from healthy women (P < 0.01). After treatment, the levels of P and FSH of the treatment group were significantly increased (P < 0.01), E2 and PRL were significantly reduced, which were also significantly decreased compared with the psychological intervention groups (P < 0.01). (4) FOLLOW-UP: the markedly effective rate and the total effective rate of the treatment group remained higher than those of the other two groups after one year of treatment (P < 0.05). (5) Adverse reactions: no obvious adverse reactions were found among the three groups. CONCLUSIONS: Therapy with Chinese medicine combined with psychological intervention was effective for short-term and long-term treatment of cyclomastopathy and menoxenia. The mechanism might be related to the regulation of sex hormones.