Polydatin ameliorates chemotherapy-induced cognitive impairment (chemobrain) by inhibiting oxidative stress, inflammatory response, and apoptosis in rats.

Most breast cancer survivors receiving chemotherapy have severe cognitive impairment, often referred to as "chemobrain." Polydatin (PLD) is known to have many biological activities. Thus, this study aimed to determine whether symptoms of chemobrain can be prevented or relieved by PLD. The chemobrain models were established by intraperitoneal injection of doxorubicin (DOX, 2 mg/kg) in rats once a week for 4 weeks (DOX group and DOX+PLD group). In the PLD group and DOX+PLD group, PLD (50 mg/kg) was administered orally to rats every day. We found that PLD treatment significantly protected against DOX-induced learning and memory impairment, restored hippocampal histopathological architecture. Furthermore, PLD suppressed DOX-induced oxidative stress through up-regulating Nrf2, inhibited inflammatory response by activating the NF-κB pathway, and reduced hippocampal apoptosis. Therefore, the present study indicated that PLD offered neuroprotection against DOX-induced chemobrain. PLD may assist in preventing chemobrain after chemotherapy in patients with cancers.

Antcin C ameliorates neuronal inflammation due to cerebral haemorrhage by inhibiting the TLR-4 pathway.

INTRODUCTION: This study investigated the protective effects of antcin C against cerebral haemorrhage injury. MATERIAL AND METHODS: Cerebral haemorrhage was treated with antcin C 100 mg/kg i.p. at 60 min after the induction of cerebral injury. Neurological scores and volumes of cerebral injury were assessed to determine the effects of antcin C, based on oxidative stress and serum mediators of inflammation by ELISA. qRT-PCR was used to estimate the mRNA expression of Toll-like receptor 4 (TLR-4) and interleukin-1 receptor-associated kinase 4 (IRAK4) proteins in the cerebral tissue of rats with cerebral haemorrhage. Western blot assay and histopathology were also performed. RESULTS: The findings suggest that treatment with antcin C reduced the neurological scores and volumes of cerebral injury in cerebral injured rats. Parameters of oxidative stress and cytokine levels were reduced in the serum of the antcin C-treated group compared with the negative control group. Treatment with antcin C ameliorated the expression of TLR-4, IRAK4, and zonula occludens-1 (ZO-1) proteins in the cerebral tissue of cerebral injured rats. CONCLUSIONS: The results revealed that treatment with antcin C protected against cerebral haemorrhage damage by controlling microglia inflammation through the TLR-4 pathway.

Water Stable [Tb4] Cluster-Based Metal-Organic Framework as Sensitive and Recyclable Luminescence Sensor of Quercetin.

A novel 3D metal-organic framework (MOF){[Tb3(CBA)2(HCOO)(µ3-OH)4(H2O)]·2H2O·0.5DMF} n (S-1) was synthesized by the solvothermal method. The crystal structure indicates that [Tb4O4] cubane clusters self-assemble into an infinite chain by sharing vertex, which is further linked to adjacent chains through 1,1-cyclobutanedicarboxylic acid ligand (H2CBA), resulting in a honeycomb arrayed framework. S-1 possesses excellent water stability and still retains intact structure after exposure to water for 10 weeks or boiling water for 10 weeks. Interestingly, S-1 acts as a luminescence sensor to selectively and sensitively detect quercetin with the limit of detection (LOD) as low as 0.23 ppm (7.6 × 10-7 M). The relationship between relative luminescence intensity and concentration obeys linear in the range of 0-300 ppm (0-993 µM), which allows quantitative detection of quercetin. Importantly, S-1 can be reused at least six times with almost no change in luminescent intensity. Compared with the high performance liquid chromatography-mass spectrometry (HPLC-MS) method, S-1 was used to determine the content of quercetin in onionskin and apple peel samples with satisfactory results. Furthermore, a portable S-1 test paper is also developed and expected to be applied in practice. To our knowledge, S-1 is the first example of MOFs as luminescent sensor for quercetin.

Recombinant Osteopontin Improves Neurological Functional Recovery and Protects Against Apoptosis via PI3K/Akt/GSK-3ß Pathway Following Intracerebral Hemorrhage.

BACKGROUND This study aimed to investigate the potential neuroprotective effect of recombinant osteopontin (r-OPN) on apoptotic changes via modulating phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK-3ß) signaling in a rat model of intracerebral hemorrhage (ICH). MATERIAL AND METHODS We subjected 10-12-week-old Sprague-Dawley male rats (n=120) to injection of autologous blood into the right basal ganglia to induce ICH or sham surgery. ICH animals received vehicle administration, r-OPN (4 µL/pup), or r-OPN combined with phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (86 ng/pup) at 30 min after injury. Neurological scores and rotarod latencies were evaluated on days 1-5 post-ICH. Brain water content was evaluated on days 1-3 post-ICH. The number of apoptotic cells changes were evaluated by terminal deoxynucleotidyl transferase-mediated 2-deoxyuridine 5-triphosphate-biotin nick-end labeling (TUNEL) and hematoxylin staining. Apoptosis-related proteins Bcl-2, Bax, and cleaved caspase-3 (CC3), and the phosphorylation levels of Akt and GSK-3b were assayed by Western blot. RESULTS Neurological deficits, rotarod latencies, and brain water content following ICH were reduced in the r-OPN group compared to the vehicle group. r-OPN also attenuated cell death in ICH. Furthermore, treatment with r-OPN significantly increased p-Akt expression and decreased p-GSK-3ß. These effects were associated with a decrease in the Bax/Bcl-2 ratio and the suppression of CC3 at 24 h after ICH. Importantly, all the beneficial effects of r-OPN in ICH were abrogated by the PI3K inhibitor wortmannin. CONCLUSIONS r-OPN may provide a wide range of neuroprotection by suppressing apoptosis through the PI3K/Akt/GSK-3ß signaling pathway after ICH.

Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury.

BACKGROUND/AIMS: Traumatic brain injury (TBI) is a major public health problem in the world and causes high rates of mortality and disability. Recent evidence suggests that vitamin D (VD) has neuroprotective actions and can promote function recovery after TBI. In vitro and in vivo studies have demonstrated that autophagy could be enhanced following supplementation with an active metabolite of VD (calcitriol). However, it is unclear whether autophagy participates in the protective effects of calcitriol after TBI. To test this hypothesis, we examined the protective effects of calcitriol on TBI-induced neurological impairment and further investigated whether calcitriol could modulate autophagy dysfunction-mediated cell death in the cortex region of rat brain. METHODS: Eighty-five male rats (250-280 g) were randomly assigned to sham (n=15), TBI model (TBI, n=35) and calcitriol treatment (calcitriol, n=35) groups. Rats were injected intraperitoneally with calcitriol (1 µg/kg) at 30 min, 24 h and 48 h post-TBI in the calcitriol group. The lysosomal inhibitor, chloroquine (CQ), was used to evaluate autophagic flux in the TBI and calcitriol groups. Neurological functions were evaluated via the modified neurological severity score test at 1-7 days after TBI or sham operation, and the terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick-end labeling method was used to evaluate the ability of calcitriol to inhibit apoptosis. The expression of VDR, LC3 and p62 proteins was measured by western blot analysis at 1, 3 and 7 days post-injury Results: Calcitriol treatment attenuated mNSS at 2-7 days post-TBI (P < 0.05 versus TBI group). Calcitriol dramatically increased VDR protein expression compared with the untreated counterparts at 1, 3 and 7 days post-TBI (P < 0.05). The rate of apoptotic cells in calcitriol-treated rats was significantly reduced compared to that observed in the TBI group (P < 0.05). The LC3II/LC3I ratio was decreased in the cortex region at 1, 3 and 7 days post-TBI in rats treated with calcitriol (p < 0.05 versus TBI group), and the p62 expression was also attenuated (p < 0.05 versus TBI group). The LC3II/LC3I ratio in the calcitriol group was significantly increased when pretreated with CQ (P < 0.05). CONCLUSION: Calcitriol treatment activated VDR protein expression and attenuated neurological deficits in this rat TBI model. The protective effects might be associated with the restoration of autophagy flux and the decrease in apoptosis in the cortex region of rat brain.