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Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti-ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE-induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose-dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis.

The high porosity and versatile structures of metal–organic frameworks (MOFs) as new theranostic platforms have drawn broad attention and have been widely explored. This has inspired the use of MOFs to encapsulate various functional nanoparticles within the frameworks to further develop and extend the biomedical applications in drug delivery and bioimaging. Herein, we fabricated yolk–shell magnetic composites Fe3O4@Co/Zn-ZIF towards magnetic resonance (MR) imaging-guided chemotherapy by combining a controlled encapsulation process with a mild phase transformation under solvothermal conditions. The designed yolk–shell composites Fe3O4@Co/Zn-ZIF exhibited high doxorubicin (DOX) loading capacity, pH-responsive release characteristics, good biocompatibility and strong T2-weighted MR imaging contrast enhancement. The hollow structure Co/Zn-ZIF serving as a shell could collapse under low pH conditions, and achieved controlled release of drugs. Dopamine-modified Fe3O4 nanoparticles (Fe3O4–DA NPs) as the core could confer Fe3O4@Co/Zn-ZIF with outstanding MR imaging capacity and facile magnetic separation. This strategy sheds light on a new way to develop multifunctional drug delivery systems by using hollow structures of MOFs as hosts for different functional nanoparticles.

Beta amyloid (Aβ) is a key component of parenchymal Aβ plaques and vascular Aβ fibrils, which lead to cerebral amyloid angiopathy (CAA) in Alzheimer’s disease (AD). Recent studies have revealed that Aβ contained in the cerebrospinal fluid (CSF) can re-enter into brain through paravascular spaces. However, whether Aβ in CSF may act as a constant source of pathogenic Aβ in AD is still unclear. This study aimed to examine whether Aβ pathology could be worsened when CSF Aβ level was enhanced by intra-cisternal infusion of aged brain extract containing abundant Aβ in TgCRND8 host mice. TgCRND8 mouse is an AD animal model which develops predominant parenchymal Aβ plaques in the brain at as early as 3 months of age. Here, we showed that single intracisternal injection of Aβ seeds into TgCRND8 mice before the presence of Aβ pathology induced robust prion-like propagation of CAA within 90 days. The induced CAA is mainly distributed in the cerebral cortex, hippocampus and thalamus of TgCRND8 mice. Surprisingly, despite the robust increase in CAA levels, the TgCRND8 mice had a marked decrease in parenchymal Aβ plaques and the plaques related neuroinflammation in the brains compared with the control mice. These results amply indicate that Aβ in CSF may act as a source of Aβ contributing to the growth of vascular Aβ deposits in CAA. Our findings provide experimental evidence to unravel the mechanisms of CAA formation and the potential of targeting CSF Aβ for CAA.

Fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) is an extensively used carbamate insecticide. Its developmental neurotoxicity and the underlying mechanisms have not been well investigated. In this study, zebrafish embryos were exposed to various concentrations of BPMC from 6 hpf (hours post fertilization, hpf) to 120 hpf. BPMC induced developmental toxicity with reduced motility in larval zebrafish. The spinal cord neutrophil infiltration, increased ROS production, caspase 3 and 9 activation, central nerve and peripheral motor neuron damage, axon and myelin degeneration were observed in zebrafish treated with BPMC generally in a dose-dependent manner. The expression of eight marker genes for nervous system function or development, namely, a1-tubulin, shha, elavl3, gap43, syn2a, gfap, mbp and manf, was significantly downregulated following BPMC exposure. AChE activity reduction and ache gene expression suppression was also found significantly in BPMC-treated zebrafish. These results indicate that BPMC is highly toxic to zebrafish and that BPMC induces zebrafish developmental neurotoxicity through pathways involved in inflammation, oxidative stress, degeneration and apoptosis.

HNF1A-AS1 is a cancer-related lncRNA. Elevated expression of HNF1A-AS1 has been observed in various malignancies including esophageal squamous cell carcinoma (ESCC). However, the role of HNF1A-AS1 in ESCC has not been fully understood. This study aimed to investigate the potential role of HNF1A-AS1 in ESCC. Expression of HNF1A-AS1, miRNA (miR)-298, and transcription factor 4 (TCF4) was detected using qRT-PCR. The interactions between HNF1A-AS1 and miR-298 or miR-298 and TCF4 were evaluated. Short hairpin RNAs (shRNAs) were used to knock down HNF1A-AS1 (sh-HNF1A-AS1). The EMT and stemness of ESCC cells were detected. HNF1A-AS1 was overexpressed in ESCC tumor tissues and cells. miR-298 was validated as a direct target of HNF1A-AS1. sh-HNF1A-AS1 significantly inhibited EMT and stemness of ESCC cells. The high expression of miR-298 significantly inhibited the expression of TCF4, and further inhibited the expression of N-cadherin and stemness-related genes. Animal experiments showed that sh-HNF1A-AS1 significantly inhibited tumor growth and increased the level of miR-298 in tissues. In conclusion, knockdown of HNF1A-AS1 could inhibit EMT and stemness by regulating the miR-298/TCF4 axis.

Fe3O4@Cu/C and Fe3O4@CuO composites were achieved using nanoparticle-encapsulated MOFs Fe3O4@HKUST-1 as both a precursor and a self-sacrificing template. Fe3O4@HKUST-1 was thermally converted into magnetic Fe3O4@Cu/C and Fe3O4@CuO composites in different atmosphere (N2 and air). The resulting composites not only kept superparamagnetic characteristics, but also exhibited improved peroxidase-like catalytic activity and high stability when compared to the precursor Fe3O4@HKUST-1. The morphology, crystal structure, magnetic and porous properties of Fe3O4@Cu/C and Fe3O4@CuO composites were characterized, and the kinetics parameters and the influence factors on the peroxidase-mimicking activity such as temperature, pH and H2O2 concentration were evaluated. On account of the excellent peroxidase-like activity, the as-prepared Fe3O4@Cu/C and Fe3O4@CuO composites were successfully used for the catalytic removal of methylene blue (MB) dye with H2O2 oxidant. This work provides an effective way to fabricate highly reactive MOFs-derived biomimetic catalysts, which have potential applications in bioassays and pollutant degradation. Fe3O4@Cu/C and Fe3O4@CuO composites were achieved using Fe3O4 nanoparticle-encapsulated HKUST-1 as self-sacrificial templates and demonstrated excellent peroxidase-like activity.

The high performance of catalysts relies largely on the meticulous design of hierarchical hollow micro/nanostructures with more active sites and superb structural tenability. Herein, we developed a simple strategy to design and fabricate CoFe2O4/CuO (sub)microcages using core-shell dual-MOF heterostructures (FeII-Co PBAs@HKUST-1) as both the precursor and self-sacrificing template. The derivation of metal oxide composites from dual-MOF heterostructures is challenging, and this method could overcome the difficulty caused by the possible lattice mismatch between the different MOFs. Uniform core-shell dual-MOF structures FeII-Co PBAs@HKUST-1 were first fabricated and then converted to CoFe2O4/CuO (sub)microcages by thermal annealing in air. The resulting CoFe2O4/CuO (sub)microcages were extensively characterized and exhibited remarkable catalytic performance with an excellent stability and magnetic recyclability for the reduction of 4-nitrophenol to 4-aminophenol by NaBH4. In addition, CoFe2O/CuO (sub)microcages were also found to be highly active for catalytic reduction of methylene blue (MB) by NaBH4 in an aqueous solution. The results show that CoFe2O4/CuO (sub)microcages have potential application for organic pollutants degradation and environmental rehabilitation.

Objective: To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of intravenous immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice. Methods: A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until June 30, 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs. We used random-effects models (or fixed-effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis. Results: From a total of 420 entries identified via searches, 8 RCTs involving 1,450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time, and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1 g/kg/day) had shorter fever clearance time (p < 0.05), shorter rash regression (p< 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05). Conclusion: The high-dose group has a better prognosis; however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD.

Brusatol is a main bioactive component derived from the Chinese medicinal plant Brucea javanica, which is traditionally used for the treatment of dysentery (also known as ulcerative colitis, UC). Previously, we have designed a novel brusatol self-microemulsifying drug delivery system (BR-SMEDDS) to increase its solubility and bioavailability, and enhance its bioactivities. In the present study, we established 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model in vivo and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro, to investigate the potential anti-inflammatory effect and underlying mechanism of BR-SMEDDS. Disease activity index (DAI) including body weight, stool consistency and gross bleeding was measured. Macroscopic and histological evaluations of colons were conducted. Relevant molecular events were determined by ELISA, qRT-PCR, immunohistochemistry or Western blotting. The results showed that BR notably inhibited the productions of TNF-α, pro-IL-1β, PGE2 and NO, and suppressed the NF-κB signaling pathway in LPS-stimulated macrophages. In parallel with the vitro experimental results, BR significantly attenuated diarrhea, colonic shortening, macroscopic damage and histological injury. BR treatment also increased the levels of TGF-β and IL-4, decreased the contents of IL-1β and IL-18, and elevated the levels of CAT, GSH and SOD in the colons. Furthermore, BR also markedly activated the Nrf2 expression and suppressed the NLRP3 inflammasome activation. Taken together, the anti-UC effect of BR might be intimately associated with the suppression of NF-κB and NLRP3-mediated inflammatory responses, and regulation of Nrf2-mediated oxidative stress. BR might have the potential to be further developed into a promising therapeutic agent for colitis treatment.

Graphical abstract, Highlights • In the same content, Nano-HO could effectively enhance the bioactivity of HO remarkably and prolonged its circulation time in rats. • Nano-HO improved cognitive deficits in TgCRND8 mice. • Nano-HO suppressed neuroinflammatory response (TNF-α, IL-Iβ, IL-6) inhibited the activation of microglia, astrocyte and A-β plaque burdens in TgCRND8 mice. • Nano-HO ameliorated AD through regulating APP processing, preventing tau hyperphosphorylation and modulating JNK/CDK5/GSK-3β pathway. • Nano-HO regulated the composition and structure of gut microbiota to protect the gut microflora and its stability., Introduction Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer’s disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy. Objectives A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size and excellent stability was developed in this study to improve the solubility and bioavailability of HO. The anti-AD effects of Nano-HO was determined. Methods Male TgCRND8 mice were daily orally administered Nano-HO or HO at the same dosage (20 mg/kg) for 17 consecutive weeks, followed by assessment of the spatial learning and memory functions using the Morris Water Maze test (MWMT). Results Our pharmacokinetic study indicated that the oral bioavailability was greatly improved by Nano-HO. In addition, Nano-HO significantly improved cognitive deficits and inhibited neuroinflammation via suppressing the levels of TNF-α, IL-6 and IL-1β in the brain, preventing the activation of microglia (IBA-1) and astrocyte (GFAP), and reducing β-amyloid (Aβ) deposition in the cortex and hippocampus of TgCRND8 mice. Moreover, Nano-HO was more effective than HO in modulating amyloid precursor protein (APP) processing via suppressing β-secretase, as well as enhancing Aβ-degrading enzymes like neprilysin (NEP). Furthermore, Nano-HO more markedly inhibited tau hyperphosphorylation via decreasing the ratio of p-Tau (Thr 205)/tau and regulating tau-related apoptosis proteins (caspase-3 and Bcl-2). In addition, Nano-HO more markedly attenuated the ratios of p-JNK/JNK and p-35/CDK5, while enhancing the ratio of p-GSK-3β (Ser9)/GSK-3β. Finally, Nano-HO prevented the gut microflora dysbiosis in TgCRND8 mice in a more potent manner than free HO. Conclusion Nano-HO was more potent than free HO in improving cognitive impairments in TgCRND8 mice via inhibiting Aβ deposition, tau hyperphosphorylation and neuroinflammation through suppressing the activation of JNK/CDK5/GSK-3β signaling pathway. Nano-HO also more potently modulated the gut microbiota community to protect its stability than free HO. These results suggest that Nano-HO has good potential for further development into therapeutic agent for AD treatment.

Our previous study revealed that Epimedii Folium (EF) and Codonopsis Radix (CNR) significantly promoted tumor growth on a subcutaneous mouse model of prostate cancer (PCa) via enhancing the mRNA and protein expressions of androgen receptor (AR), while Astragali Radix (AGR) inhibited tumor growth via suppressing the protein expression of AR. In the present study, we aimed to investigate the potential interactions between EF, CNR or AGR and AR antagonist (abiraterone acetate [ABI]) on the tumor growth using subcutaneous and orthotopic PCa mouse models. EF, CNR, AGR and ABI were intragastrically given to mice once every 2 days for 4 weeks. The pharmacokinetics of ABI were evaluated in the plasma of rats when combined with EF, CNR, or AGR. Our results demonstrated that EF or CNR could weaken the anti-tumor effects of ABI via increasing the AR expression involving activation of the PI3K/AKT and Rb/E2F pathways and decreasing the bioavailability of ABI, while AGR could enhance the anti-tumor effects of ABI through suppressing the AR expression via inhibiting the activations of PI3K/AKT and Rb/E2F pathways and increasing the bioavailability of ABI. These findings imply that cautions should be exercised when prescribing EF and CNR for PCa patients.

Background Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer’s disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy. A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size and excellent stability was developed in this study to improve the solubility and bioavailability of HO. Methods Male TgCRND8 mice were administered with Nano-HO or HO at the same dosage (20 mg/kg) by oral gavage daily for 17 consecutive weeks, followed by assessment of the spatial learning and memory functions with the Morris Water Maze test (MWMT). Results Nano-HO and HO could significantly improve cognitive deficits and inhibit neuroinflammation via suppressing the levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and IL-1β in the brain, preventing the activation of microglia (IBA-1) and astrocyte (GFAP), and reducing β-amyloid (Aβ) deposition in the cortex and hippocampus of TgCRND8 mice. In addition, Nano-HO and HO could modulate amyloid precursor protein (APP) processing and phosphorylation via suppressing β-secretase including β-site APP cleaving enzyme-1 (BACE-1) and phosphorylated APP (Thr 668), inhibiting γ-secretase including presenilin-1 (PS-1) and anterior pharynx-defective-1 (APH-1), as well as enhancing Aβ-degrading enzymes such as insulin degrading enzyme (IDE) and neprilysin (NEP). Moreover, Nano-HO remarkably inhibited tau hyperphosphorylation via decreasing the levels of p-tau (Thr 205) and p-tau (Ser 404), as well as regulating tau-related apoptosis proteins including caspase-3 and Bcl-2. Furthermore, Nano-HO and HO markedly attenuated the ratios of p-JNK/JNK and p-35/CDK5, while enhancing the ratio of p-GSK-3β (Ser9)/GSK-3β. On the other hand, Nano-HO and HO prevented the alterations on the composition of gut microbiota in TgCRND8 mice. Conclusions Nano-HO was more effective than regular HO in improving cognitive impairments in TgCRND8 mice via inhibiting Aβ deposition, tau hyperphosphorylation and neuroinflammation through suppressing the activation of JNK/CDK5/GSK-3β signaling pathway. Nano-HO was also more potently modulate the gut microbiota community to protect its stability as compared with that of regular HO. Our results amply indicated that HO with nano-sized drug delivery system has good potential for further development into therapeutic agent for AD treatment.

Many prostate cancer (PCa) patients in Mainland China and other Asian countries often use Chinese herbal medicines as an adjuvant treatment while receiving Western medicines. However, concerns have been raised about the potential herb-drug interaction when using herbal medicines containing phytoandrogens.This study aimed to investigate the effects of the selected 21 Chinese herbal medicines on the proliferation and tumor growth using the relevant in vitro and in vivo models of PCa.After treatment of LNCaP and 22Rv1 cells with different concentrations of 70% ethanol extracts of the 21 selected herbal medicines for 48 h, the proliferative activity, the effects on androgen receptor (AR) and prostate specific antigen (PSA) were determined. The anti-tumor effects of the 21 herbs on PCa growth were also investigated on a subcutaneous mouse model of PCa.The results showed that Epimedii Folium (EF) and Codonopsis Radix (CNR) could significantly increase the cell viability in LNCaP cells (p 0.05 for both) and 22Rv1 cells (p 0.05 for both), protein expressions of AR in LNCaP cells (p 0.05 for both) and 22Rv1 cells (p 0.05 for both), and PSA (p 0.05 for both) in LNCaP cells. EF, CNR, and Cistanches Herba (CCH) markedly accentuated the tumor growth (p 0.05 for three drugs) and AR expression (p 0.05 for three herbs) in tumor tissues. On the other hand, treatment with Astragali Radix (AGR), Chuanxiong Rhizoma (CXR) and Bruceae Fructus (BF) significantly inhibited the cell viability in LNCaP cells (p 0.05, p 0.05 and p 0.001, respectively) and in 22Rv1 cells (p 0.05, p 0.05 and p 0.001, respectively), and the protein expression of AR in LNCaP cells (p 0.05 for three herbs) and 22Rv1 cells (p 0.05, p 0.05 and p 0.001, respectively), and the protein expression of PSA (p 0.05 for three herbs) in LNCaP cells, as well as tumor growth (p 0.05 for three herbs) and the AR expression (p 0.05 for AGR and CXR, p 0.001 for BF) in tumor tissues.Our results revealed that AGR, CXR and BF suppressed the PCa development via inhibition of AR expression, while EF, CNR and CCH promoted the development and progression of PCa via enhancement of AR expression. The results strongly suggest that caution should be exercised when using androgenic Chinese herbal medicines in PCa patients.

To evaluate the diagnostic value of T-cells enzyme linked immunospot (TSPOT.TB) in the children with tuberculosis.The clinical data was retrieved from 2 348 children who underwent TSPOT.TB test in the Children's Hospital of Chongqing Medical University from January 2017 to December 2017. The diagnostic value of TSPOT.TB in the children with tuberculosis was analyzed.In the diagnosis of children tuberculosis, the sensitivity of TSPOT.TB was 84.0%, the specificity was 99.1%, the positive predictive value was 93.1%, and the negative predictive value was 97.8%. To the area under receiver operating characteristic (ROC) curve of TSPOT.TB, the area under the curve (TSPOT.TB has high diagnostic value in the children with tuberculosis, which can rapidly assist to diagnose pediatric tuberculosis.

Yao-Xing Dou,1,2,* Jiang-Tao Zhou,3,4,* Tong-Tong Wang,2 Yan-Feng Huang,1 Vicky Ping Chen,5 You-Liang Xie,1 Zhi-Xiu Lin,6 Jian-Sheng Gao,7 Zi-Ren Su,1 Hui-Fang Zeng2 1Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Pharmacy, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA; 6School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 7Guangzhou Baiyunshan Mingxing Pharmaceutical Co. Ltd., Guangzhou, People’s Republic of China *These authors contributed equally tothiswork Background: Bruceine D (BD) is a major bioactive component isolated from the traditional Chinese medicinal plant Brucea javanica which has been widely utilized to treat dysentery (also known as ulcerative colitis [UC]). Methods: To improve the water solubility and absolute bioavailability of BD, we developed a self-nanoemulsifying drug delivery system (SNEDDS) composing of MCT (oil), Solutol HS-15 (surfactant), propylene glycol (co-surfactant) and BD. The physicochemical properties and pharmacokinetics of BD-SNEDDS were characterized, and its anti-UC activity and potential mechanism were evaluated in TNBS-induced UC rat model. Results: The prepared nanoemulsion has multiple beneficial aspects including small mean droplet size, low polydispersity index (PDI), high zeta potential (ZP) and excellent stability. Transmission electron microscopy showed that nanoemulsion droplets contained uniform shape and size of globules. Pharmacokinetic studies demonstrated that BD-SNEDDS exhibited enhanced pharmacokinetic parameters as compared with BD-suspension. Moreover, BD-SNEDDS significantly restored the colon length and body weight, reduced disease activity index (DAI) and colon pathology, decreased histological scores, diminished oxidative stress, and suppressed TLR4, MyD88, TRAF6, NF-κB p65 protein expressions in TNBS-induced UC rat model. Conclusion: These results demonstrated that BD-SNEDDS exhibited highly improved oral bioavailability and advanced anti-UC efficacy. In conclusion, our current results provided a foundation for further research of BD-SNEDDS as a potential complementary therapeutic agent for UC treatment. Keywords: bruceine D, self-nanoemulsifying drug delivery system, physicochemical properties, pharmacokinetics, anti-inflammation, anti-colitis activity

This study aimed to investigate the prophylactic effect of selenium-enriched Cordyceps militaris (CS) against triptolide-induced acute hepatotoxicity. Rats were intragastrically administrated with CS and ordinary Cordyceps militaris (CM) for 7 consecutive days prior to triptolide intoxication. Triptolide elevated levels of serum aminotransferases, total cholesterol and caused severe liver injury. However, CS remarkably inhibited the increases of these parameters and pathological damages. The action mechanisms might be associated with its antioxidant property by enhancing antioxidant enzymes activities and triggering nuclear factor E2-related factor 2 (Nrf2) translocation and downstream genes expression. Besides, CS prevented cellular apoptosis through up-regulating Bcl-2/Bax ratio and down-regulating cytochrome c and caspase-3 cleavage. Constituent analyses showed that CS had higher amounts of cordycepin, selenium, selenocystine and polysaccharides than CM. In conclusion, CS effectively prevented triptolide-induced hepatotoxicity via activating Nrf2 pathway and inhibiting hepatocyte apoptosis, suggesting that it could be a promising hepatic protector and a befitting nutraceutical supplement.

A novel molecular imprinting polymer (MIP)-based electrochemical senor, consisting of Fe3O4 nanobeads and gold nanoparticles on a reduced graphene oxide (RGO) substrate, was fabricated to detect ractopamine (RAC) in water using the reversible addition fragmentation chain transfer (RAFT) polymerization technique. The Au nanoparticles widely dispersed on RGO can significantly increase the response current for RAC detection in water, which is confirmed by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and theoretical calculations. By means of the differential pulse voltammetry technique, the as-prepared MIP-based electrode shows a dynamic linear range of 0.002 to 0.1 μM with a correlation coefficient of 0.992 and a remarkably low detection limit of 0.02 nM (S/N = 3). Additionally, the sensor exhibits high binding affinity and selectivity towards RAC with excellent reproducibility. Our study demonstrates the potential for the proposed electrochemical sensors in monitoring organic pollutants in water.

Brusatol (BR) is one of the main bioactive components derived from Brucea javanica, a medicinal herb historically used in the treatment of dysenteric disorders (also known as ulcerative colitis(UC)). Due to its poor aqueous solubility, a novel brusatol self-microemulsifying drug delivery system (BR-SMEDDS) nanoformulation with smaller size, higher negative zeta potential and drug content, and excellent stability was developed. The appearance of BR-SMEDDS remained clear and transparent, and transmission electron microscopy showed microemulsion droplets to be spherical with homogeneous distribution. Pharmacokinetic parameters indicated that oral bioavailability was greatly improved by BR-SMEDDS as compared with aqueous suspension. Meanwhile, the anti-colitis activity of BR-SMEDDS was evaluated on dextran sodium sulfate (DSS)-induced colitis mice model. The result illustrated that the nano-formation significantly reduced the body weight loss, recovered colon length, decreased disease activity index and microscopic score, regulated immune-inflammatory cytokines, diminished oxidative stress and repressed the colonic expression of myeloid differentiation factor 88 (MyD88), toll-like receptor 4 (TLR4) and nuclear factor kappa B p65 (NF-κB p65) proteins. Our findings demonstrated for the first time that BR could effectively attenuate colonic inflammation in mice, at least partially, via favorable regulation of anti-oxidative and anti-inflammatory status and inhibition of the TLR4-linked NF-κB signaling pathway. The BR nano-formulation was superior to BR suspension and sulphasalazine, in treating experimental UC, and exhibited similar effect with azathioprine, with much smaller dosage. The enhanced anti-UC effect of BR might be intimately associated with the improved pharmacokinetic property by SMEDDS. The developed nano-delivery system might thus be a promising candidate for colitis treatment.

Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC.

// Yan-Feng Huang 1 , Da-Jian Zhu 2 , Xiao-Wu Chen 3 , Qi-Kang Chen 2 , Zhen-Tao Luo 3 , Chang-Chun Liu 3 , Guo-Xin Wang 3 , Wei-Jie Zhang 3 and Nv-Zhu Liao 2 1 Department of Traditional Chinese Medicine, Shunde Hospital of Southern Medical University, Guangdong 528300, China 2 Department of Gastrointestinal Surgery, Shunde Women and Children’s Hospital Affiliated to Jinan University, Guangdong 528300, China 3 Department of Gastrointestinal Surgery, Shunde Hospital of Southern Medical University, Guangdong 528300, China Correspondence to: Da-Jian Zhu, email: zhudajian2016@126.com Keywords: curcumin, colorectal cancer, irinotecan, ROS, ER stress Received: May 13, 2016 Accepted: February 27, 2017 Published: April 04, 2017 ABSTRACT Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan’s effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca 2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.

Ethnopharmacological relevance Brucea javanica is an important traditional medicinal herb used for the treatment of dysentery, malaria, inflammation and cancer in southeast Asia for many years. However, the anti-inflammatory mechanism of Brucea javanica in the treatment of dysentery (also known as ulcerative colitis, UC) has not been fully illuminated. Brucea javanica oil emulsion (BJOE) is the major active and most common application form of Brucea javanica oil (BJO), which has a variety of pharmacological activities. The aim of this study was to investigate the potential anti-inflammatory effect of BJOE and possible mechanism of action on dextran sulfate sodium (DSS)-induced UC in mice. Materials and methods The components of BJOE were determined by gas chromatography-mass spectrometry (GC-MS). Balb/C mice with dextran sulfate sodium (DSS, 30 mg/mL) induced colitis were treated with BJOE (0.5, 1 and 2 g/kg) and two positive drugs (sulfasalazine, SASP, 200 mg/kg; and azathioprine, AZA, 13 mg/kg) once daily by gavage for 7 days. Mice in normal control group and DSS group were orally given the same volume of distilled water and soybean lecithin suspension (0.15 g/kg) respectively. The effects of BJOE on DSS-induced UC were assessed by determination of body weight loss, disease activity index (DAI), colon length, histological analysis, as well as levels of pro-inflammatory cytokines. The mRNA expression of MPO, iNOS and COX-2 in colon tissues was detected by qRT-PCR. In addition, NF-κB p65, p-p65 and IκB-α, p-IκBα protein expression levels in colon tissues were investigated using Western blotting. Results The major components of BJOE were found to be oleic acid (62.68%) and linoleic acid (19.53%) as detected by GC-MS. Our results indicated that BJOE, SASP and AZA showed beneficial effect on DSS-induced colitis in mice, and significantly reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, decreased histological scores, and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-17 and IFN-γ) as compared with the DSS group. In addition, the mRNA expression of MPO, iNOS and COX-2 induced by DSS treatment was remarkably inhibited by BJOE, SASP or AZA treatments. Furthermore, when compared with DSS-treated mice, the activation of NF-κB was significantly inhibited by AZA and BJOE treatment. Conclusions Our study shows that BJOE possessed appreciable anti-inflammatory effect against murine experimental UC induced by DSS. The protective mechanism of BJOE may involve inhibition of NF-κB signal transduction pathways and subsequent down-regulation of inflammatory mediators. These findings suggest that BJOE might be an efficacious and promising therapeutic approach for the treatment of UC. Our investigation might also provide experimental evidence for the traditional application of Brucea javanica in the treatment of dysentery and might add new dimension to the clinical indications for BJOE.

Triptolide (TP) is the major active component of Tripterygium wilfordii Hook F (TWHF) and possesses multiple pharmacological effects. However, hepatotoxicity of TP which is one of the toxic properties slows its progression in clinical application. 18β-Glycyrrhetinic acid (GA) is the main bioactive ingredient of Licorice (Glycyrrhiza glabra L.), a herbal medicine famous for its detoxification. This study aims to investigate whether GA possesses protective effect against TP-induced hepatotoxicity in rats. TP interference markedly elevated serum levels of ALT, AST, and ALP, caused evident liver histopathological changes, and elevated hepatic TNF-α, IL-6, IL-1β, and IFN-γ as well as nuclear translocation of NF-κB. TP also significantly elevated liver MDA and declined hepatic activities of SOD, CAT, and GSH-Px. Assay of TUNEL and apoptosis proteins (Bax, Bcl-2, and active caspase-3) showed that TP induced severe hepatocellular apoptosis. In contrast, low-dose GA (50 mg/kg) significantly reversed TP-induced changes above. However, high-dose GA (100 mg/kg) had no such effect. Overall, these findings indicated that low-dose GA but not high-dose GA exhibited a protective effect against TP-induced hepatotoxicity in rats by anti-inflammation, antioxidation, and antiapoptosis, which suggests that the doses of GA/Licorice should be carefully considered when used together with TWHF or TWHF preparations.

The fabricated TiO2@MIL-100 composite not only demonstrates high capacity in adsorption of Rhodamine B (RhB) but also plays an important role as a “molecule pump” which offers excellent features and facilitates the following degradation of RhB with exceptionally high efficiency.

Highly efficient extraction of peptides from serum is critical for finding serum biomarkers using mass spectrometry, which still remains a great challenge. Currently, a bottom-up proteomics approach has been applied to discover serum biomarkers. However, the approach was labor intensive, time and cost consuming, and cannot meet the requirements for clinical application. In this work, Fe3O4/C@MIL-100 composites were synthesized to efficiently capture peptides from microwave-assisted formic acid digests of BSA and human serum prior to MALDI-TOF MS analysis. Fe3O4/C@MIL-100 composites exhibited size-selective adsorption performance, thus providing a rapid and convenient approach to enrich low-abundance peptides. Notably, the peptides’ mass fingerprinting of serum digestions between type 2 diabetes mellitus (T2DM) and healthy persons were distinguishable, which indicated the potential ability of this technique for T2DM diagnosis and rapid biomarker discovery.

Purpose: To evaluate the therapeutic effects of combined atlas fracture with type II (C1-type II) odontoid fractures and to outline a management strategy for it. Patients and Methods: Twenty three patients with C1-type II odontoid fractures were treated according to our management strategy. Nonoperative external immobilization in the form of cervical collar and halo vest was used in 13 patients with stable atlantoaxial joint. Surgical treatment was early performed in 10 patients whose fractures with traumatic transverse atlantal ligament disruption or atlantoaxial instability. The visual analog scale (VAS), neck disability index (NDI) scale, and American Spinal Injury Association (ASIA) scale at each stage of followup were then collected and compared. Results: Compared to pretreatment, the VAS score, NDI score, and ASIA scale were improved among both groups at followup evaluation after treatment. However, in the nonsurgical group, one patient (1/11) developed nonunion which required surgical treatment in later stage and one patient (1/13) with halo vest immobilization had happened pin site infection. Two patients of the surgical group (2/11) had appeared minor complications: occipital cervical pain in one case and cerebrospinal fluid leakage in one case. Two patients (2/23) were excluded from nonsurgical treatment group because their followup period was less than 12 months. Twenty one patients were followed up regularly with an average of 23.9 months (range 15–45 months). Conclusions: We outlined our concluding management principle for the treatment of C1-type II odontoid fractures based on the nature of C1 fracture and atlantoaxial stability. The treatment principle can obtain satisfactory results for the management of C1-type II odontoid fractures.

Oxidative and inflammatory damage has been suggested to play important roles in the pathogenesis of skin photoaging. Andrographolide sodium bisulfate (ASB) is a soluble derivative of andrographolide and has known antioxidant and anti‑inflammatory properties. In the present study, cellular experiments were designed to investigate the molecular mechanisms underlying the effect of ASB in relieving ultraviolet (UV)‑induced photo‑damage. Following ASB pretreatment and UV irradiation, the apoptosis and necrosis of HaCaT cells were investigated by Hoechst 33342/propidium iodide staining. Reactive oxygen species (ROS) production was investigated using a DCFH‑DA fluorescence probe. Furthermore, the protein expression levels of p65, NF‑κB inhibitor‑α, nuclear factor E2‑related factor 2 (Nrf2) and kelch‑like ECH‑associated protein 1 (keap1) were measured via western blotting and immunofluorescence analyses. Furthermore, NF‑κB‑mediated cytokines were assessed by ELISA, and Nrf2‑mediated genes were detected by reverse transcription‑quantitative PCR. Pretreatment with ASB markedly increased cell viability, decreased cell apoptosis and decreased UV‑induced excess ROS levels. In addition, ASB activated the production of Nrf2 and increased the mRNA expression levels of glutamate‑cysteine ligase catalytic subunit and NAD(P)H quinone oxidoreductase 1, while ASB downregulated the protein expression of p65 and decreased the production of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α. These results suggested that ASB attenuates UV‑induced photo‑damage by activating the keap1/Nrf2 pathway and downregulating the NF‑κB pathway in HaCaT keratinocytes.

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn’s disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

A hexa-coordinate 3,5-pyridinedicarboxylic acid and imidazole react with copper chloride in the ethanol aqueous solution, water solution, and copper chloride in an N,N-dimethylformamide aqueous to ...

Ethnopharmacological relevance Existing evidences suggest that Radix Astragali and its polysaccharides composition (APS) can improve muscle mass, but the mechanisms need more research. Aim of the study In this study, we aimed to examine the effects of APS on muscle wasting at molecular level in 5/6 nephrectomised rats. Materials and methods We performed 5/6 nephrectomy or sham operation in 160 6-week-old Sprague–Dawley rats, and feed animals with or without 2% APS for 155 days. After treatment, we compared the change of weight, muscle fibre, protein metabolism, pro-inflammatory factors (TNF-α, IL-15, CRP) and oxidative factors (MDA, SOD) among each group. In addition, we detected the Akt/mTOR, ubiquitin proteasome, autophagy signalling and AA transporters in vivo and in vitro. Results Data in vivo show 2% APS could alleviate weight loss and improve protein metabolism in nephrectomised rats. The levels of serum pro-inflammatory factors and oxidative factors were restored by APS treatment. In molecular levels, APS restored Akt/mTOR, MAFbx, MuRF1, Atg7, LC3B-II/LC3B-I and SLC38A2 which changed in nephrectomised rats. Data in vitro show the optimal dose of APS is 0.2 mg/mL, and SLC38A2 siRNA attenuated the effects of 0.2 mg/mL APS on atrophy and autophagy. Conclusions Our results suggested APS could improve muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling, and SLC38A2 may be one of potential targets.

Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.

Emodin, a major component of Rheum palmatum, has been reported to significantly protect neural tissue against apoptosis and autophagy. However, the effects and underlying mechanisms of action of emodin in muscle atrophy are still poorly defined. In this study, we investigated the protective effects and the underlying mechanisms by which emodin acts on tumor necrosis factor alpha (TNF-α)-induced apoptosis and autophagy in mouse C2C12 myoblasts. Emodin, at various concentrations, decreased TNF-α-induced apoptosis in C2C12 myoblasts, which were analyzed by Hoechst 33342 staining and annexin V/PI analysis. Emodin also inhibited the collapse of the mitochondrial membrane potential and the generation of reactive oxygen species in TNF-α-stimulated C2C12 myoblasts. Consistent with these results, the expression of Bcl-2 was increased, whereas the expression of Bax, cleaved-caspase 3 and cleaved-PARP was decreased after emodin treatment. These data demonstrate that emodin attenuated apoptosis in TNF-α-stimulated C2C12 myoblasts through mitochondrial signaling pathways. In addition, emodin inhibited autophagy in TNF-α-stimulated C2C12 myoblasts by suppressing the expression of LC3-II, Beclin-1 and Atg7. Emodin also resulted in the upregulation of the phosphorylated forms of Akt. Taken together, these results suggest that emodin inhibited apoptosis and autophagy in TNF-α-induced C2C12 myoblasts, possibly through the activation of phosphorylated Akt. Our findings suggest that emodin could be a potential therapeutic agent in the treatment of muscle atrophy.

Two novel metal-organic complexes [Cu4(2,2′-bipy)4Cl4(Hima)4].4H2O (1), [Co2(H2Pimdc)6(H2PDA)3].6H2O(2)(Hima=1H-imidazole-1-acetic acid, 2,2′-bipy=2,2′-bipyridyl, H2Pimdc=2-propyl-4,5-imidazoledica...

A simple hydrofluoric acid-free one-pot method was developed for the preparation of three functionalized magnetic MIL-101 composites (Fe3O4–NH2@MIL-101, Fe3O4–COOH@MIL-101 and Fe3O4/C@MIL-101). As magnetic solid-phase extraction materials, they exhibited a remarkable preconcentration ability for estrone (E1), 17β-estradiol (E2), estriol (E3) and bisphenol-A (BPA). However, because the incorporated magnetic particles were decorated with different surface functional groups, the three magnetic MIL-101 composites exhibited certain differences in extraction efficiency of the four target estrogens. Herein, the Fe3O4–NH2@MIL-101 composite as an adsorbent was applied for magnetic solid-extraction coupled with high performance liquid chromatography (HPLC) to determine the estrogens content in aqueous samples. The dominant parameters affecting enrichment efficiency including extraction time, sample pH, extraction temperature and desorption conditions were investigated. Under the optimized conditions, the developed method showed good linearity within the range of 0.2–100 μg L−1, low detection limits (0.06–0.22 μg L−1) and high repeatability (RSD, 5.9–8.3%). The recoveries were between 80.6 and 99.6% with the spiked level of 10 μg L−1. The proposed method was successfully applied to determine the estrogens content in real water samples.

Herein, we report a new strategy based on non-aqueous sol–gel reaction for in situ fabrication of TiO2@MIL-53 core–shell composites, and systematically show the excellent performance of the composites for exceptionally enhanced adsorption and degradation of nonionic organics, including Sudan red III, Sudan red IV, Sudan red I and vat pink.

Osteoarthritis (OA) is a chronic arthropathy that occurs in the middle-aged and elderly population. The present study aimed to identify gene signature differences between synovial cells from OA synovial membrane with and without inflammation, and to explain the potential mechanisms involved. The differentially expressed genes (DEGs) between 12 synovial membrane with inflammation and 12 synovial membrane without inflammation from the dataset GSE46750 were identified using the Gene Expression Omnibus 2R. The DEGs were subjected to enrichment analysis, protein-protein interaction (PPI) analysis and module analysis. The analysis results were compared with text-mining results. A total of 174 DEGs were identified. Gene Ontology enrichment results demonstrated that functional molecules encoded by the DEGs primarily had extracellular location, molecular functions predominantly involving ‘chemokine activity’ and ‘cytokine activity’, and were associated with biological processes, including ‘inflammatory response’ and ‘immune response’. The Kyoto Encyclopedia of Genes and Genomes results demonstrated that DEGS may function through pathways associated with ‘rheumatoid arthritis’, ‘chemokine signaling pathway’, ‘complement and coagulation cascades’, ‘TNF signaling pathway’, ‘intestinal immune networks for IgA production’, ‘cytokine-cytokine receptor interaction’, ‘allograft rejection’, ‘Toll-like receptor signaling pathway’ and ‘antigen processing and presentation’. The top 10 hub genes [interleukin (IL)6, IL8, matrix metallopeptidase (MMP)9, colony stimulating factor 1 receptor, FOS proto-oncogene, AP1 transcription factor subunit, insulin-like growth factor 1, TYRO protein tyrosine kinase binding protein, MMP3, cluster of differentiation (CD)14 and CD163] and four gene modules were identified from the PPI network using Cytoscape. In addition, text-mining was used to identify the commonly used drugs and their targets for the treatment of OA. It was initially verified whether the results of the present study were useful for the study of OA treatment targets and pathways. The present study provided insight for the molecular mechanisms of OA synovitis. The hub genes and associated pathways derived from analysis may be targets for OA treatment. IL8 and MMP9, which were validated by text-mining, may be used as molecular targets for the OA treatment, while other hub genes require further validation.

Colorectal cancer stem cells (CSCs), characterized by self-renewal ability and high expression of proliferative genes, contribute to the chemoresistance of colorectal cancer (CRC). We aimed to identify the molecular mechanisms underlying CRC chemoresistance through comprehensive bioinformatics screenings and experimental confirmation of gene functions. We found that high expression of FGF1 intracellular binding protein (FIBP) was correlated with chemoresistance and poor prognosis in CRC patients. Therefore, the chemoresistant CRC cell line HCT116-CSC with high expression of the stem cell markers CD44 and CD133 was established for further phenotypic tests. FIBP knockdown inhibited proliferation, enhanced chemotherapy effects, and attenuated the stemness markers of CRC cells in vivo and in vitro. Through RNA-seq and gene set enrichment analysis, we identified cyclin D1 as a key downstream target in FIBP-regulated cell cycle progression and proliferation. Moreover, FIBP bound to GSK3β, inhibited its phosphorylation at Tyr216, and activated β-catenin/TCF/cyclin D1 signaling in HCT116-CSCs. Additional GSK3β knockdown reversed the FIBP silencing-induced inhibition of proliferation and decreased stemness marker expression in HCT116-CSCs. Furthermore, DNA methylation profiling suggested that FIBP regulated the stemness of CRC cells via methylation activity that was dependent on GSK3β but independent of β-catenin signaling. Our data illuminate the potential of FIBP as a novel therapeutic target for treating chemoresistant CRC through inhibition of GSK3β-related signaling.

Silymarin has been used in the treatment of a number of liver diseases for a long time, but its efficacy in preventing triptolide induced acute hepatotoxicity has not been reported previously. The present study aimed to assess the protective effect of silymarin against triptolide (TP)-induced hepatotoxicity in rats. Rats were orally administrated with silymarin (50, 100 and 200 mg/kg) for 7 days and received intraperitoneal TP (2 mg/kg) on the day 8. Hepatic injuries were comprehensively evaluated in terms of serum parameters, morphological changes, oxidative damage, inflammation and apoptosis. The results demonstrated that TP-induced increases in serum parameters, including alanine transaminase, aspartate aminotransferase, alkaline phosphatase, total cholesterol and γ-glutamyl transpeptidase, which were determined using a biochemical analyzer, and histopathological alterations and hepatocyte apoptosis as determined by hematoxylin and eosin and TUNEL staining, respectively, were prevented by silymarin pretreatment in a dose-dependent manner. TP-induced depletions in the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione S-transferase and catalase, and glutathione levels, were also significantly reversed by silymarin, as determined using specific kits. Additionally, silymarin dose-dependently exhibited inhibitory effects on malonaldehyde content in the liver. The production of proinflammatory cytokines was investigated using ELISA kits, and the results demonstrated that silymarin dose-dependently inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and IL-1β in the liver. To determine the mechanism of silymarin, western blot analysis was performed to investigate the protein expression of phosphorylated (p)-p38 and p-c-Jun N-terminal kinase (JNK) of the TNF-α induced inflammatory response and apoptotic pathways. Silymarin significantly blocked p38 and JNK phosphorylation and activation. Additionally, the expression of the proapoptotic proteins cytochrome c, cleaved caspase-3 and Bcl-2-associated X was also reduced following treatment with silymarin, as determined by ELISA, western blotting and immunohistochemistry, respectively. In conclusion, silymarin was demonstrated to dose-dependently protect rat liver from TP-induced acute hepatotoxicity, with the high dose (200 mg/kg) achieving a superior effect. This protective effect may be associated with the improvement of antioxidant and anti-inflammatory status, as well as the prevention of hepatocyte apoptosis. Therefore, silymarin may have the potential to be applied clinically to prevent TP-induced acute hepatotoxicity.

A novel molecularly imprinted electrochemical sensor based on Fe3O4 nanobeads immobilized on graphene (Fe3O4-MIP@RGO) has been developed for detecting 17β-estradiol (17β-E2) in water using reversible addition fragmentation chain transfer (RAFT) polymerization technique. 17β-E2 can be detected by this electrochemical sensor through the response current change before and after binding 17β-E2. The Fe3O4-MIP@RGO-based sensor amplifies the response current in differential pulse voltammetry measurement, allowing the detection limit reaching 0.819 nM in a wide linear range from 0.05 to 10 μM. Moreover, Fe3O4-MIP@RGO-based sensor exhibits high selectivity and sensitivity towards 17β-E2. This MIP electrochemical sensor has a promising potential in the detection of 17β-E2 in water.

The aim is to study the effects and underlying mechanisms of astragalus polysaccharide (APS) on the peroxide-induced injury in C2C12 myoblasts in vitro. Cell viability in the presence or absence of APS was detected by the methyl thiazolyl tetrazolium colorimetric assay. The autophagosomes were observed by electron microscopy to examine the influence of APS on autophagy caused by H2O2 in C2C12 cells, and the percentage of apoptosis cells was measured by flow cytometry. To further confirm the effect of H2O2 on C2C12 cells, the protein expression of LC3 and RARP, which are the markers of autophagy and apoptosis, respectively, was analyzed by Western blot, as well as the expression levels of p-p70S6K, p70S6K, Bcl-2, Bax, cyto-C, and Caspase-3, to reveal the underlying mechanisms. We observed multiple effects of APS on C2C12 functionality. APS treatment of C2C12 cells at 1 mg/mL reduced cell viability to less than 70 %, and analysis by electron microscopy revealed that APS also reduced the number of H2O2-induced autophagosome formation. Similarly, APS abated the H2O2-mediated increase in cell apoptosis, which was accompanied by the inhibition of LC3 II and RARP that are normally upregulated by H2O2. The expression of p-p70S6K and p70S6K, however, remained unchanged in C2C12 cells in the Control, H2O2 and H2O2 + APS groups. In addition, APS promoted the expression of protein Bcl-2 in H2O2-treated C2C12 cells, but did not change Bax, thus reducing the Bax/Bcl-2 ratio that in turn prevented the release of cytochrome c and the activation of caspase-3. APS inhibits the autophagy and apoptosis induced by peroxide injury in C2C12 myoblasts through two independent signaling pathways: the mTOR-independent pathway for the inhibition of autophagy, and the caspase-3-dependent pathway for the suppression of apoptosis.

Three new metal-organic complexes, [Cd4(2,3-Pdc)4 · 4H2O] (I), [Fe4(2,3-Pdc)4 · 12H2O] (II), [Ba8(2,3-Pdc)4 · 12H2O] (III) (2,3-Pdc = 2,3-pyridinedicarboxylic acid), have been synthesized and characteristic by IR spectrum, elemental analysis, single-crystal X-ray diffraction, thermogravimetric analysis. X-ray structure analysis shows that complex I is 3D structure, complex II and complex III are 1D chain structures (CIF files CCDC nos. 1002757 (I), 1002888 (II) and 1002980 (III)). 2,3-Pdc has many kinds of coordination mode, so it can form many different of coordination polymers. Complexes can be packed by the weak C-H⋯O, N-H⋯O and π-π interactions.