Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model.</p> <p>Results</p> <p>Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord.</p> <p>Conclusions</p> <p>These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.</p

EFFECTS OF LOW CONCENTRATIONS OF ROTENONE UPON MITOHORMESIS IN SH-SY5Y CELLS

The mitochondrial toxin rotenone exerts cytotoxicity via overproduction of reactive oxygen species (ROS) and depolarization of the mitochondrial membrane. We investigated the effects of rotenone (12.5, 25, 50, 100 nmol/L) on mitochondrial biogenesis and the potential roles of ROS production in SH-SY5Y cells. Mitochondrial biogenesis was assessed by counting the number of mitochondria, determining protein expression of peroxisome proliferator-activated receptor γ coactivator α (PGC1-α) and its regulator, SIRT1, and oxygen consumption. ROS production and levels of reduced glutathione (GSH) and oxidized glutathione(GSSG) were also determined. Compared with controls, rotenone (12.5 nmol/L) significantly increased the quantity of mitochondria and amount of oxygen consumption, whereas rotenone at \u3e12.5 nmol/L decreased the quantity of mitochondria and amount of oxygen consumption. GSH contents and GSH/GSSG were also significantly enhanced by rotenone at 12.5 nmol/L and decreased by rotenone at \u3e12.5 nmol/L. Except for ROS production and SIRT1 protein expression, all concentration–response relationships showed a typical inverted-U shape. ROS production was continually increased in cells treated with rotenone. These data indicate that low concentrations of rotenone can induce mitohormesis, which may be attributed to ROS production

Silica-Lipid Hybrid Microparticles as Efficient Vehicles for Enhanced Stability and Bioaccessibility of Curcumin

Kurkumin je aktivni sastojak koji ima višestruku ulogu, no njegova je uporaba ograničena zbog slabe topljivosti u vodi i stabilnosti, a time i slabe biološke raspoloživosti. Stoga je svrha ovoga rada bila osmisliti kako zaobići ta ograničenja. Postupkom emulgiranja dobivena je nanoemulzija s kurkuminom, a nakon toga sušenjem u vakuumu hibridne mikročestice nanoemulzije u silicijevom dioksidu. Udjel kurkumina u nanoemulziji bio je (0,30±0,02) %, a u mikročesticama (0,67±0,02) %. FTIR i XDR analizom utvrđeno je da je kurkumin u mikročesticama inkapsuliran u poroznom amorfnom silicijevom dioksidu. Antioksidacijska aktivnost kurkumina in vitro nije se smanjila nakon inkapsulacije. Simulacijom probave in vitro utvrđeno je da je biološka raspoloživost kurkumina u nanoemulziji i mikročesticama bila veća nego u kontrolnom uzorku. Stabilnost mikročestica ostala je ista tijekom 6 tjedana skladištenja u mraku pri temperaturama od 4, 25 i 40 °C. Osim toga, pokazalo se da su pri izlaganju svjetlosti, mikročestice imale bolju kemijsku stabilnost od nanoemulzije. Pri koncentraciji nanoemulzije manjoj od 45 μg/mL preživljavanje stanica bilo je veće od 80 %. Stoga možemo zaključiti da mikročestice mogu poslužiti kao nosači kurkumina te poboljšati njegovu topljivost, stabilnost pri izlaganju svjetlosti te biološku raspoloživost.Curcumin is an active ingredient with multiple functions, but its application is often restricted due to its poor water solubility, weak stability, and consequently low bioaccessibility. Based on this, the aim of this work is to develop a new vehicle to overcome these restrictions. Here we developed a curcumin-loaded nanoemulsion and then curcumin-loaded silica-lipid hybrid microparticles through emulsification and vacuum drying, respectively. The loading of curcumin in the nanoemulsion and microparticles was (0.30±0.02) and (0.67±0.02) %, respectively. FTIR and XRD analyses of microparticles revealed that curcumin was encapsulated in porous, amorphous silica. In vitro antioxidant activities showed that the encapsulation would not affect the antioxidant activity of curcumin. In vitro simulated digestion indicated that nanoemulsion and microparticles had higher curcumin bioaccessibility than the control group. The storage stability of microparticles remained the same during 6 weeks in the dark at 4, 25 and 40 °C. Moreover, the microparticles had a better chemical stability than nanoemulsion under the light. The cell viability was over 80 % when the concentration of nanocarriers was less than 45 μg/mL. Hence, the microparticles could be a promising means to load curcumin and improve its solubility, light stability and bioaccessibilit

Therapeutic effects of total saikosaponins from Radix bupleuri against Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive dysfunction in the elderly, with amyloid-beta (Aβ) deposition and hyperphosphorylation of tau protein as the main pathological feature. Nuclear factor 2 (Nrf2) is a transcription factor that primarily exists in the cytosol of hippocampal neurons, and it is considered as an important regulator of autophagy, oxidative stress, and inflammation. Total saikosaponins (TS) is the main bioactive component of Radix bupleuri (Chaihu). In this study, it was found that TS could ameliorate cognitive dysfunction in APP/PS1 transgenic mice and reduce Aβ generation and senile plaque deposition via activating Nrf2 and downregulating the expression of β-secretase 1 (BACE1). In addition, TS can enhance autophagy by promoting the expression of Beclin-1 and LC3-II, increasing the degradation of p62 and NDP52 and the clearance of phosphorylated tau (p-tau), and reducing the expression of p-tau. It can also downregulate the expression of nuclear factor-κB (NF-κB) to inhibit the activation of glial cells and reduce the release of inflammatory factors. In vitro experiments using PC12 cells induced by Aβ, TS could significantly inhibit the aggregation of Aβ and reduce cytotoxicity. It was found that Nrf2 knock-out weakened the inhibitory effect of TS on BACE1 and NF-κB transcription in PC12 cells. Moreover, the inhibitory effect of TS on BACE1 transcription was achieved by promoting the binding of Nrf2 and the promoter of BACE1 ARE1. Results showed that TS downregulated the expression of BACE1 and NF-κB through Nrf2, thereby reducing the generation of Aβ and inhibiting neuroinflammation. Furthermore, TS can ameliorate synaptic loss and alleviate oxidative stress. In gut microbiota analysis, dysbiosis was demonstrated in APP/PS1 transgenic mice, indicating a potential link between gut microbiota and AD. Furthermore, TS treatment reverses the gut microbiota disorder in APP/PS1 mice, suggesting a therapeutic strategy by remodeling the gut microbe. Collectively, these data shows that TS may serve as a potential approach for AD treatment. Further investigation is needed to clarify the detailed mechanisms underlying TS regulating gut microbiota and oxidative stress

Recommendation for a contouring method and atlas of organs at risk in nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy

Background and purpose To recommend contouring methods and atlas of organs at risk (OARs) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy, in order to help reach a consensus on interpretations of OARs delineation. Methods and materials Two to four contouring methods for the middle ear, inner ear, temporal lobe, parotid gland and spinal cord were identified via systematic literature review; their volumes and dosimetric parameters were compared in 41 patients. Areas under the receiver operating characteristic curves for temporal lobe contouring were compared in 21 patients with unilateral temporal lobe necrosis (TLN). Results Various contouring methods for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord lead to different volumes and dosimetric parameters (P < 0.05). For TLN, D1 of PRV was the most relevant dosimetric parameter and 64 Gy was the critical point. We suggest contouring for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord. A CT-MRI fusion atlas comprising 33 OARs was developed. Conclusions Different dosimetric parameters may hinder the dosimetric research. The present recommendation and atlas, may help reach a consensus on subjective interpretation of OARs delineation to reduce inter-institutional differences in NPC patients. © 2013 Elsevier Ireland Ltd. All rights reserved.published_or_final_versio

Selection of Pru p 3 hypoallergenic peach and nectarine varieties

To the Editor, Peach is an important fruit consumed worldwide. However, it is also one of the most frequently reported allergenic fruits.1 Component diagnosis of peach allergy indicates Pru p 1, Pru p 2, Pru p 3, Pru p 4, Pru p 7, and Pru p 9 are involved.2, 3 Pru p 3 is the dominant allergen responsible for severe allergic reaction,4 and it is considered to be the primary sensitizer to other LTPs in Mediterranean and Central Europe.5 The levels of Pru p 3 differ between varieties.6 To date, measurement of Pru p 3 in a limited number of peach and nectarines from Spain, United States, and Italy has been reported.7 Significant variation of allergen concentration in processed foods containing peach has also been observed.8 The content of Pru p 3 of peach/nectarine determines the potential risk for peach allergic patients. China is the origin of peach with representative genetic diversity to be explored for hypoallergenic varieties.9 A core collection of 103 varieties cultivated in Jiaxing, Zhejiang Province were selected to represent this diversity, including 23 nectarines and 80 peach varieties (with fruit hair, round or flat, 77 cultivated, three wild) (Table S1). The soluble solid content (SSC), ripening date, and peach aroma intensity were recorded. Specific methods are detailed in the Supporting Information. Pru p 3 was quantified by ELISA based on our previous research.6info:eu-repo/semantics/publishedVersio

The Tumor-Log Odds of Positive Lymph Nodes-Metastasis Staging System, a Promising New Staging System for Gastric Cancer after D2 Resection in China

BACKGROUND: In this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover, we compared them with the 7(th) edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection. METHODS: A total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7(th) edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the -2log likelihood and the hazard ratio. RESULTS: The cut points of lymph node ratio (LNR) were set as 0, 0-0.3, 0.3-0.6, 0.6-1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as≤-0.5, -0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis showed that TLM staging system was better than the TRM or TNM system for the prognostic evaluation. CONCLUSIONS: The TLM system was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection

Molecular footprints of domestication and improvement in soybean revealed by whole genome re-sequencing

BACKGROUND: Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed. RESULTS: A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified. CONCLUSIONS: Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits