Magnetic resonance imaging with upconversion nanoprobes capable of crossing the blood-cerebrospinal fluid barrier.

The central nervous system (CNS) maintains homeostasis with its surrounding environment by restricting the ingress of large hydrophilic molecules, immune cells, pathogens, and other external harmful substances to the brain. This function relies heavily on the blood-cerebrospinal fluid (B-CSF) and blood-brain barrier (BBB). Although considerable research has examined the structure and function of the BBB, the B-CSF barrier has received little attention. Therapies for disorders associated with the central nervous system have the potential to benefit from targeting the B-CSF barrier to enhance medication penetration into the brain. In this study, we synthesized a nanoprobe ANG-PEG-UCNP capable of crossing the B-CSF barrier with high targeting specificity using a hydrocephalus model for noninvasive magnetic resonance ventriculography to understand the mechanism by which the CSF barrier may be crossed and identify therapeutic targets of CNS diseases. This magnetic resonance nanoprobe ANG-PEG-UCNP holds promising potential as a safe and effective means for accurately defining the ventricular anatomy and correctly locating sites of CSF obstruction.

Concentrations, Sources and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons in Chinese Herbal Medicines.

The determination and evaluation of 16 polycyclic aromatic hydrocarbons (PAHs) in seven Chinese herbal medicines (CHMs) were conducted through a rapid and straightforward extraction and purification method, coupled with GC-MS. A sample-based solid-phase extraction (SPE) pretreatment technique, incorporating isotopic internal standards, was employed for detecting various medicinal parts of CHMs. The assay exhibited linearity within the range of 5 to 500 ng/mL, with linear coefficients (R2) for PAHs exceeding 0.999. The recoveries of spiked standards ranged from 63.37% to 133.12%, with relative standard deviations (RSDs) ranging from 0.75% to 14.54%. The total PAH content varied from 176.906 to 1414.087 µg/kg. Among the 16 PAHs, phenanthrene (Phe) was consistently detected at the highest levels (47.045-168.640 µg/kg). Characteristic ratio analysis indicated that oil, coal, and biomass combustion were the primary sources of PAHs in CHMs. The health risk associated with CHMs was assessed using the lifetime carcinogenic risk approach, revealing potential health risks from the consumption of honeysuckle, while the health risks of consuming Lycium chinense berries were deemed negligible. For the other five CHMs (glycyrrhizae, Coix lacryma, ginseng, lotus seed, seed of Sterculia lychnophora), the health risk from consumption fell within acceptable ranges. Furthermore, sensitivity analyses utilizing Monte Carlo exposure assessment methods identified PAH levels in CHMs as health risk sensitizers. It is crucial to recognize that the consumption of herbal medicines is not a continuous process but entails potential health risks. Hence, the monitoring and risk assessment of PAH residues in CHMs demand careful attention.

Association of MRI Features and Adverse Maternal Outcome in Patients With Placenta Accreta Spectrum Disorders After Abdominal Aortic Balloon Occlusion.

BACKGROUND: MRI features may be associated with adverse maternal outcome in patients with placenta accreta spectrum (PAS) disorders even with abdominal aortic balloon occlusion (AABO). PURPOSE: This study aimed to identify risk factors of MRI for association with adverse maternal outcome in patients with PAS disorders after AABO. STUDY TYPE: Retrospective. POPULATION: Clinical and MRI features of 80 patients were retrospectively reviewed from October 2016 to August 2021. A total of 40 patients had adverse maternal outcomes including intrapartum/peripartum bleeding >1000 mL and/or emergency hysterectomy after AABO. SEQUENCE: Half-Fourier acquisition single-shot turbo spin echo and gradient echo imaging True fast imaging with steady-state precession (True-FISP) at 1.5T MR scanner. ASSESSMENT: MRI features were evaluated by three radiologists and were tested for any association with adverse maternal outcome. STATISTICAL TESTS: Interobserver agreement was calculated with kappa (k) statistics. Association between MRI features and adverse maternal outcomes were evaluated by univariate and multivariate analyses. A nomogram was constructed based on the logistic regression. RESULTS: The interobserver agreement ranged from fair to substantial (k = 0.379-0.783). Multivariate analyses revealed that short cervical length (OR: 4.344), abnormal intraplacental vascularity (OR: 6.005), placental bulge (OR: 9.085), and myometrial interruption (OR: 9.550) were independent risk factors for adverse maternal outcomes. The combination of four risk factors together demonstrated the highest AUC of 0.851 (95% CI 0.769-0.933) with a sensitivity and specificity of 77.5% and 72.5%, respectively and then a nomogram composed of the above four risk factors was constructed to represent the probability of adverse maternal outcome. DATA CONCLUSION: The nomogram demonstrated the association between MRI features and patient's poor outcome after undergoing AABO and C-section delivery for PAS. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Effects of acupuncture on obstructive sleep apnea-hypopnea syndrome: A meta-analysis.

Our study aimed to systematically evaluate the effect of acupuncture in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Literature search of four Chinese databases and six English databases for studies published from the inception of each database to March 1, 2022 and identify relevant studies published in Chinese or English. Related randomized controlled trials of acupuncture for the treatment of OSAHS were included to analyze the efficacy of acupuncture. Two researchers independently reviewed all of the retrieved studies to screen for eligible studies and extract the required relevant data. Included studies were subjected to a methodological quality assessment using the Cochrane Manual 5.1.0, and to a meta-analysis using Cochrane Review Manager version 5.4. A total of 19 studies with 1365 participants were examined. Compared with the control group, the apnea-hypopnea index, lowest oxygen saturation, Epworth Sleepiness Scale, interleukin-6, tumor necrosis factor α, and nuclear factor κ-B indicators all exhibited statistically significant changes. Thus, acupuncture was effective in alleviating the state of hypoxia and sleepiness and reduced the inflammatory response and disease severity among reported patients with OSAHS. Therefore, acupuncture could be widely used in the clinical treatment of OSAHS patients as a complementary strategy and warrants further study.

Two new alkaloids produced by Dothideomycetes sp. BMC-101 isolated from the Magnolia grandiflora.

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

Insights into the trihelix transcription factor responses to salt and other stresses in Osmanthus fragrans.

BACKGROUND: Osmanthus fragrans is an evergreen plant with high ornamental and economic values. However, they are easily injured by salt stress, which severely limits their use in high salinity areas. The trihelix transcription factor (TF) family, as one of the earliest discovered TF families in plants, plays an essential part in responses to different abiotic stresses, and it has potential functions in improving the salt-tolerance capability of O. fragrans. RESULTS: In this study, 56 trihelix genes (OfGTs) were first identified in O. fragrans and then divided into five subfamilies in accordance with a phylogenetic tree analysis. The OfGTs were found to be located randomly on the 20 O. fragrans chromosomes, and an analysis of gene replication events indicated that the OfGT gene family underwent strong purification selection during the evolutionary process. The analysis of conserved motifs and gene structures implied that the OfGT members in the same subfamily have similar conserved motifs and gene structures. A promoter cis-elements analysis showed that all the OfGT genes contained multiple abiotic and hormonal stress-related cis-elements. The RNA-seq data suggested that the OfGTs have specific expression patterns in different tissues, and some were induced by salt stress. The qRT-PCR analysis of 12 selected OfGTs confirmed that OfGT1/3/21/33/42/45/46/52 were induced, with OfGT3/42/46 being the most highly expressed. In addition, OfGT42/OfGT46 had a co-expression pattern under salt-stress conditions. OfGT3/42/46 were mainly localized in the nuclei and exhibited no transcriptional activities based on the analysis of the subcellular localization and transcriptional activity assay. Furthermore, the expression levels of most of the selected OfGTs were induced by multiple abiotic and hormonal stresses, and the expression patterns of some OfGTs were also highly correlated with gibberellic acid and methyl jasmonate levels. Remarkably, the transient transformation results showed lower MDA content and increased expression of ROS-related genes NbAPX in transgenic plants, which implying OfGT3/42/46 may improve the salt tolerance of tobacco. CONCLUSIONS: The results implied that the OfGT genes were related to abiotic and hormonal stress responses in O. fragrans, and that the OfGT3/42/46 genes in particular might play crucial roles in responses to salt stress. This study made a comprehensive summary of the OfGT gene family, including functions and co-expression patterns in response to salt and other stresses, as well as an evolutionary perspective. Consequently, it lays a foundation for further functional characterizations of these genes.

Transjugular Intrahepatic Portosystemic Shunt for Portal Vein Cavernous Transformation: A Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is technically challenging in the treatment of portal vein cavernous transformation (PVCT), and there is no high-quality evidence regarding whether it is an option for patients with PVCT. We carried out a systematic review and meta-analysis to assess the feasibility and safety of TIPS for PVCT. METHODS: Systematic search of PubMed, Chinese National Knowledge Infrastructure (CNKI) database, Cochrane Library, Embase, and Wanfang database through December 2021 for appropriate studies reporting efficacy and safety in patients with PVCT undergoing TIPS. The main outcome included the technical success rate, postoperative rebleeding rate, postoperative hepatic encephalopathy rate, stent patency rate, preoperative, and postoperative portal pressure. RESULTS: Ten studies, including 292 patients were included. Our results showed that TIPS was technically successful in 82.97% (95% confidence interval [CI]: 77.14%-88.41%, p = 0.297) with low heterogeneity (I2 = 18.39%, p = 0.279). Postoperative rebleeding occurred in 9.56% (95% CI: 4.55%-16.77%, p = 0.073) with moderate heterogeneity (I2 = 46.45%, p = 0.06). Postoperative hepatic encephalopathy occurred in 18.55% (95% CI: 9.23%-27.05%, p = 0.343) with moderate heterogeneity (I2 = 48.62%, p = 0.049). Stent patency during follow-up was in 78.43% (95% CI: 70.74%-85.20%, p = 0.805) with low heterogeneity (I2 = 0%, p = 0.654). Postoperative portal pressure significantly reduced (WMD = 12.79 mm Hg, 95% CI: 12.09-13.48 mm Hg, p < 0.00001) with high heterogeneity (I2 = 61.4%, p = 0.02). Both Begg test and funnel plot showed that there was no significant publication bias. CONCLUSIONS: TIPS is feasible and safe in patients with PVCT and PVCT should not be considered an absolute contraindication to TIPS.

Dothideomins A-D, Antibacterial Polycyclic Bisanthraquinones from the Endophytic Fungus Dothideomycetes sp. BMC-101.

Four new bisanthraquinones, dothideomins A-D (1-4), were identified from Dothideomycetes sp. BMC-101, an endophytic fungus isolated from Magnolia grandiflora L. leaves. Their chemical structures were established by NMR analysis, single-crystal X-ray crystallography, and ECD analysis. Dothideomins A-D (1-4) were characterized by an unusual 6/6/6/5/6/3/6/6 octocyclic scaffold (1 and 2) and a 6/6/6/5/6/6/6 heptacyclic scaffold (3 and 4), respectively. All compounds, especially 1 and 3, exhibited potent antibacterial activity with MIC values ranging from 0.4 to 0.8 µg/mL.

Accuracy of quantitative diffusion-weighted imaging for differentiating benign and malignant pancreatic lesions: a systematic review and meta-analysis.

BACKGROUND: A variety of imaging techniques can be used to evaluate diffusion characteristics to differentiate malignant and benign pancreatic lesions. The diagnostic performance of diffusion parameters has not been systematic assessed. PURPOSE: We aimed to investigate the diagnostic efficacy of quantitative diffusion-weighted imaging (DWI) for pancreatic lesions. METHODS: A literature search was conducted using the PubMed, Embase, and Cochrane Library databases for studies from inception to March 30, 2020, which involves the quantitative diagnostic performance of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) in the pancreas. Studies were reviewed according to inclusion and exclusion criteria. The quality of articles was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUATAS-2). A bivariate random-effects model was used to evaluate pooled sensitivities and specificities. Univariable meta-regression analysis was used to test the effects of factors that contributed to the heterogeneity. RESULTS: A total of 31 studies involving 1558 patients were ultimately eligible for data extraction. The lowest heterogeneity was found in specificity of perfusion fraction (f) with the I2 value was 17.97% and Cochran p value was 0.28. However, high heterogeneities were found for the other parameters (all I2 > 50%). There was no publication bias found in funnel plot (p = 0.30) for the apparent diffusion coefficient (ADC) parameter. The pooled sensitivities for ADC, f, pure diffusion coefficient (D), and pseudo diffusivity coefficient (D*) were 83%, 81%, 76%, and 84%, respectively. The pooled specificities for ADC, f, D, and D* were 87%, 83%, 69%, and 81% respectively. The areas under the curves for ADC, f, D, and D* were 0.92, 0.87, 0.79, and 0.87 respectively. CONCLUSION: Quantitative DWI and IVIM have a good diagnostic performance for differentiating malignant and benign pancreatic lesions. KEY POINTS: • IVIM has high sensitivity and specificity (84% and 83%, respectively) for differential diagnosis of pancreatic lesions, which is comparable to that of the ADC (83% and 87%, respectively). • The ADC has an excellent diagnostic performance for differentiating malignant from benign IPMNs (sensitivity, 0.83; specificity, 0.92); the f has the best diagnostic performance for differentiating pancreatic carcinoma from PNET (sensitivity, 0.85; specificity, 0.85). • For the ADC, using a maximal b value < 800 s/mm2 has a higher diagnostic accuracy than ≥ 800 s/mm2; performing in a high field strength (3.0 T) system has a higher diagnostic accuracy than a low field strength (1.5 T) for pancreatic lesions.

Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90.

Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 µg·mL-1. In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2). Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.

The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis.

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 µM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 µM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives.

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 µM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

Anti-cancer effects of methanol-ethyl acetate partitioned fraction from Magnolia grandiflora in human non-small cell lung cancer H1975 cells.

Non-small cell lung cancer (NSCLC) constitutes nearly 85% of all cases of lung cancer. Drug resistance, dose-limiting toxicity, and metastasis in NSCLC eventually reduce the efficacy of chemotherapeutics. In this study, we have shown that the methanol-ethyl acetate partitioned fraction from Magnolia grandiflora L. seeds (MEM) exhibit potential anti-cancer activities against NSCLC H1975 cells in vivo and in vitro. MEM significantly inhibited the proliferation of H1975 cells in a concentration- and time-dependent manner. Further, MEM exhibited potent anti-tumor efficacy and low toxicity in nude mice bearing H1975 tumors. Our study also showed that MEM could induce cellular apoptosis in H1975 cells by down-regulating the protein expression levels of Akt and p-Akt-473, and by increasing the ratio of Bax/Bcl-2. Also, MEM significantly inhibited metastasis-related cell invasion and migration of H1975 cells, which associated with the down-regulation of HIF-1α, MMP-2, and MMP-9 protein expression levels. Thus, our data shows that MEM may be an effective fraction of M. grandiflora in NSCLC treatment.

Synthesis and in vitro antitumor evaluation of honokiol derivatives.

Honokiol is a natural bioactive neolignan and has been widely researched and structural modified as an anticancer agent. In this paper, 18 honokiol derivatives were synthesized and investigated for their antitumor activity. Among these, the promising compound 5a exhibited much higher anti-proliferative activity with IC50 value of 10.41 µM. Transwell assays showed that 5a could significantly inhibit the invasion and migration of I-10 cells at 2.5 µM, which was further confirmed by the western blotting experiments with down-regulation of the HIF-1α and its associated downstream proteins MMP-2 and MMP-9. Overall, these results provided useful suggestion for further structural optimization of honokiol derivatives.

Enzymatic biosynthesis and biological evaluation of novel 17-AAG glucoside as potential anti-cancer agents.

A novel 17-allylamino-17-demethoxygeldanamycin (17-AAG) glucoside (1) was obtained from in vitro enzymatic glycosylation using a UDP-glycosyltransferase (YjiC). The water-solubility of compound 1 was approximately 10.5 times higher than that of the substrate, 17-AAG. Compound 1 showed potential anti-proliferative activities against five human cancer cell lines, with IC50 values ranging from 5.26 to 28.52 µM. Further studies also indicated that compound 1 could inhibit the growth of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (Akt, c-Raf, Bcl-2, and HIF-1α). In addition, compound 1 showed greater potential anti-tumor efficacy than 17-AAG in nude mice xenografted with CNE-2Z cells. Therefore, we suggest that in vitro enzymatic glycosylation is a powerful approach for the structural optimization of 17-AAG.

Penispirozines A-H, Three Classes of Dioxopiperazine Alkaloids with Spirocyclic Skeletons Isolated from the Mangrove-Derived Penicillium janthinellum.

Eight new dioxopiperazine alkaloids, penispirozines A-H (1-8), were discovered from the mangrove-derived fungus Penicillium janthinellum HDN13-309. Their structures were elucidated by spectroscopic analysis, TDDFT-ECD calculations, and X-ray diffraction. Compound 1 had an unusual pyrazino[1,2]oxazadecaline coupled with a thiophane ring system, and compound 2 possessed a 6/5/6/5/6 pentacyclic ring system with two rare spirocyclic centers. Interestingly, compounds 3-8 were distinguished by not only the existence of a spiro-thiophane or spiro-furan ring system but also the chirality of the pentacyclic moiety. Compounds 3 and 4 increased the expression of the two relevant phase II detoxifying enzymes SOD2 and HO-1 at 10 µM.

Irregularly Bridged Epipolythiodioxopiperazines and Related Analogues: Sources, Structures, and Biological Activities.

Epipolythiodioxopiperazines (ETPs) are a class of biologically active fungal secondary metabolites characterized by a bridged polysulfide piperazine ring. Regularly, the sulfide functionality is attached in the α-positions of the dioxopiperazine scaffold. However, ETPs possessing irregular sulfur bridges have rarely been explored. This review summarizes that 83 compounds of this subtype have been isolated and characterized since the discovery of gliovirin in 1982. Herein, particular emphasis is given to the isolation, chemistry, and biological activity of this subtype. For a better understanding, a relevant summary focusing on the source microorganisms and their taxonomy is provided and will help elucidate the fascinating chemistry and biology of these unusual ETPs.

Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging and anticancer drug delivery.

BACKGROUND: Glioma is the deadliest brain cancer in adults because the blood-brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma single-photon emission computed tomography (SPECT) imaging and anticancer drug delivery. RESULTS: This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol (mPEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99mTc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac2O), the CTX-modified PEI (mPEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The formed mPEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the mPEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99mTc via DTPA, the 99mTc-labeled complex could help to visualize the drug accumulation in tumors of glioma-bearing mice and the drug delivery into the brains of rats through SPECT imaging. CONCLUSIONS: These results indicate the potential of the developed PEI-based nanocomplex in facilitating glioma-targeting SPECT imaging and chemotherapy.

Potentially toxic element (PTE) levels in maize, soil, and irrigation water and health risks through maize consumption in northern Ningxia, China.

BACKGROUND: Industrial and agricultural activities result in elevated levels of potentially toxic elements (PTEs) in the local environment. PTEs can enter the human body through the food chain and pose severe health risks to inhabitants. In this study, PTE levels in maize, soil, and irrigation water were detected, and health risks through maize consumption were evaluated. METHODS: Maize, soil, and irrigation water samples were collected in northern Ningxia, China. Inductively coupled plasma-optical emission spectrometry was applied to determine the contents of six PTEs. Bioaccumulation factor was used to reflect the transfer potential of a metal from soil to maize. Health risks associated with maize consumption were assessed by deterministic and probabilistic estimation. Sensitivity analysis was performed to determine variables that pose the greatest effect on health risk results. RESULTS: The levels of Pb and Cr in maize exceeded the standards, while the PTE levels in soil and irrigation water did not exceed the corresponding standards. The bioaccumulation factor values of the six PTEs in maize were all lower than 1 and followed the order of Cd > Zn = As > Cr > Cu > Pb. The hazard index (0.0986) was far less than 1 for all inhabitants implying no obvious non-carcinogenic risk. The carcinogenic risk value was 3.261 × 10- 5, which was lower than the maximum acceptable level of 1 × 10- 4 suggested by United States Environmental Protection Agency (USEPA). Females were at greater risk than males, and the age group of below 20 years had the greater risk among all the groups evaluated. Approximately 0.62% of inhabitants exceeded the level for non-carcinogenic risk, while 8.23% exceeded the level for carcinogenic risk. The As concentration and daily intake of maize contributed 35.8, and 29.4% for non-carcinogenic risk results as well as 61.0 and 18.5% for carcinogenic risk results. CONCLUSIONS: Maize was contaminated by Pb and Cr, whereas the associated soil and irrigation water were not contaminated by PTEs. Inhabitants would not suffer obvious harmful health risks through maize consumption. Arsenic level and daily intake of maize were the most sensitive factors that impact health risks.

Bishonokiol A inhibits breast cancer cell invasion and migration by suppressing hypoxia inducible factor-1α.

Hypoxia inducible factor-1α (HIF-1α) plays a central role in cell survival, invasion, metastasis and angiogenesis, and also is emerging as an important target in anti-cancer drug discovery. In the present study, bishonokiol A, a dimeric neolignan isolated from Magnolia grandiflora, was identified as a novel HIF-1α inhibitor. We here demonstrated that in a dose-dependent manner, bishonokiol A inhibited metastasis-related cell invasion and migration of cobalt chloride (CoCl2)-induced MCF-7 and MDA-MB-231 cells, associating with the reduction in HIF-1α levels. Transfection of MDA-MB-231 cells with HIF-1α small interfering ribonucleic acid (siRNA) resulted in a reduction in cell invasion and migration. Furthermore, we found that bishonokiol A not only inhibited the synthesis of HIF-1α protein and protein kinase B (AKT-473) phosphorylation without affecting the expression of HIF-1α mRNA or ubiquitination degradation, but also inhibited the expression of matrix metalloproteinase-9 (MMP-9) and promoter activity. Nude mice bearing MDA-MB-231 cells incubation were treated with bishonokiol A and results showed that bishonokiol A exhibited potent antitumor activity and low toxicity. Therefore, we suggest that bishonokiol A may be a potential inhibitor of HIF-1α and effective antitumor agent for breast cancer.