Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Neurodegenerative diseases (NDs) have posed significant challenges to public health, and it is crucial to understand their mechanisms in order to develop effective therapeutic strategies. Recent studies have highlighted the potential role of selenium in ND pathogenesis, as it plays a vital role in maintaining cellular homeostasis and preventing oxidative damage. However, a comprehensive analysis of the association between selenium and NDs is still lacking. METHOD: Five public databases, namely PubMed, Web of Science, EMBASE, Cochrane and Clinical Trials, were searched in our research. Random model effects were chosen, and Higgins inconsistency analyses (I2), Cochrane's Q test and Tau2 were calculated to evaluate the heterogeneity. RESULT: The association of selenium in ND patients with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) was studied. A statistically significant relationship was only found for AD patients (SMD = -0.41, 95% CI (-0.64, -0.17), p < 0.001), especially for erythrocytes. However, no significant relationship was observed in the analysis of the other four diseases. CONCLUSION: Generally, this meta-analysis indicated that AD patients are strongly associated with lower selenium concentrations compared with healthy people, which may provide a clinical reference in the future. However, more studies are urgently needed for further study and treatment of neurodegenerative diseases.

Preliminary exploration of method for screening efficacy markers compatibility in TCM prescriptions based on Q-markers: Anti-inflammatory activity of Dachaihu decoction as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu Decoction (DD), a classic Chinese herbal prescription, is composed of radix of Bupleurum chinense DC. (Chaihu), radix of Scutellaria baicalensis Georgi (Huangqin), radix of Paeonia lactiflora Pall. (Baishao), rhizoma of Pinellia ternata (Thunb.) Breit. (Banxia), fructus of Citrus aurantium L. (Zhishi), rhizoma of Zingiber officinale Rosc. (Shengjiang), fructus of Ziziphus jujuba Mill. (Dazao) and rhizoma of Rheum officinale Baill. (Dahuang). DD has the traditional effects of soothing the liver, relieving depression and clearing heat from the stomach, and is mainly used to treat heat stagnation in the liver and stomach. AIM OF THE STUDY: Dachaihu decoction (DD), a classic prescription commonly used in clinical practice for the treatment of pancreatitis and cholecystitis. Although its pharmacological effects are clear, the efficacy components and mechanism of action remain intricate and difficult to clarify. MATERIALS AND METHODS: The action targets and components of the anti-inflammatory activity of DD were predicted by network pharmacology; the effective components and targets were verified by HPLC and qPCR; the efficacy markers of DD were further screened by in vitro experiments; the pharmacological value of DD and its components compatibility were evaluated by in vitro experiments. RESULTS: The key targets MMP9, JAK2, MAP2K1 and NR3C1 were screened by network pharmacology; HPLC analysis showed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were identified as potential efficacy markers of DD; molecular docking combined with qPCR verification suggested that baicalin, naringin, neohesperidin, hesperidin and baicalein and wogonoside had certain ability to regulate above targets; in vitro studies revealed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 could inhibit the release of NO, pancreatic lipase and α-glucosidase; after comprehensive comparison and analysis, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were selected as the efficacy markers of DD; in vivo studies indicated that DD and its efficacy markers (components compatibility) had definite therapeutic effects on guinea pigs with cholecystitis. CONCLUSIONS: The efficacy markers of DD including naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 can be used as components compatibility to exert anti-inflammatory activity. In addition, a method for obtaining the compatibility of efficacy markers by simplifying the prescription is initially established.

Discovery of a traditional Chinese herbal combination for the treatment of atopic dermatitis: saposhnikoviae radix, astragali radix and cnidium monnieri.

Atopic dermatitis (AD) is a skin disease characterized by pruritus. The present study aimed to discover a herbal combination with anti-allergic and anti-inflammatory activities to treat AD. First, the anti-allergic and anti-inflammatory activities of herbs were evaluated by RBL-2H3 degranulation and HaCaT inflammatory models. Subsequently, the optimal proportion of herbs was determined by uniform design-response surface methodology. The effectiveness and synergistic mechanism was further verified. Cnidium monnieri (CM) suppressed ß-hexosaminidase (ß-HEX) release, saposhnikoviae radix (SR), astragali radix (AR), and CM inhibited the release of IL-8 and MCP-1. The optimal proportion of herbs was SR∶AR∶CM = 1: 2: 1. The in vivo experiments results indicated that the topical application of combination at high (2 ×) and low (1 ×) doses improved dermatitis score and epidermal thickness, and attenuated mast cell infiltration. Network pharmacology and molecular biology further clarified that the combination resisted AD by regulating the MAPK, JAK signaling pathways, and the downstream cytokines such as IL-6, IL-1ß, IL-8, IL-10, and MCP-1. Overall, the herbal combination could inhibit inflammation and allergy, improving AD-like symptoms. The present study discovers a promising herbal combination, worthy of further development as a therapeutic drug for AD.

Zinc homeostasis may reverse the synergistic neurotoxicity of heavy metal mixtures in Caenorhabditis elegans.

Heavy metal mixtures can cause nerve damage. However, the combined effects of metal mixtures are extremely complex and rarely studied. Zinc (Zn) homeostasis plays an integral role in neural function, but the role of Zn homeostasis in the toxicity of metal mixtures is not well understood. Here, we investigated the combined effects of manganese (Mn), lead (Pb) and arsenic (As) on nerves and the effect of Zn homeostasis on metal toxicity. Caenorhabditis elegans (Maupas, 1900) were exposed to single and multiple metals for 8 days, their movement, behavior, neurons and metal concentration were detected to evaluate the combined effect of metal mixtures. After nematodes were co-treated with metal mixtures and Zn, the nerve function, Zn concentration and redox balance were detected to evaluate the effect of Zn homeostasis on metal toxicity. The results showed that Mn + Pb and Pb + As mixtures induced synergistic toxicity for nematode nerves, which damaged movement, behavior and neurons, and decreased Zn concentration. While Zn supplementation recovered Zn homeostasis and promoted redox balance on nematodes, and then improved the nerve function. Our study demonstrated the combined effects of metal mixtures and the neuroprotective effect of Zn homeostasis. Therefore, assessment of metal mixtures toxicity should consider their interaction and the impacts of essential metals homeostasis.

Identification of a novel farnesoid X receptor agonist, kaempferol-7-O-rhamnoside, a compound ameliorating drug-induced liver injury based on virtual screening and in vitro validation.

Farnesoid X receptor (FXR), a bile acid receptor, plays an essential role in maintaining bile acid and liver homeostasis and has been recognized as an essential target for drug-induced liver injury (DILI). This study aimed to identify potential FXR agonists by virtual screening, molecular dynamics (MD) simulation, and biological assays. First, an in-house Traditional Chinese medicine compound database was screened using a virtual approach based on molecular docking to reveal potential FXR agonists. Secondly, MD was applied to analyze the process of agonist binding. Finally, the acetaminophen (APAP)-induced L02 cells model evaluated the pharmacodynamic activity of agonists treating DILI. Virtual screening results showed that kaempferol-7-O-rhamnoside was confirmed as the FXR agonist. MD results showed that kaempferol-7-O-rhamnoside could stably bind the FXR. In addition, in vitro cell-based assay showed that kaempferol-7-O-rhamnoside could promote the expression of the FXR gene and inhibit the Cyp7a1 gene expression in APAP-induced cells, significantly reducing the activities of AST, AKP and ROS, and enhancing the expression of GSH. The current study confirmed that kaempferol-7-O-rhamnoside might improve liver function by promoting proliferation, ameliorating oxidative stress, and regulating FXR target genes as observed in vitro. Therefore, in this study, discovering the FXR agonist, kaempferol-7-O-rhamnoside, provides valuable guidance for developing novel drugs against DILI.

Analysis of Research Status and Development Trend of Nanotoxicology of Liliaceae Medicinal Plants.

The research status and development trend of nanotoxicology of Liliaceae medicinal plants were analyzed. In the research, the toxicology of Liliaceae medicinal plants was investigated by the preparation method of silver nanoparticles. By means of spectral curve experiment, the present situation of nanotoxicology of Liliaceae medicinal plants was analyzed, and then its subsequent development trend was analyzed. In this process, Liliaceae medicinal plants could be used effectively, which could create great economic benefits. In the application of the above scheme, the toxicological degradation of Liliaceae medicinal plants could be controlled at about 96%. The high-dose silver nanoparticles could reach 100 µM, and the silver nitrate could reach 10 or 30 µM.

Gender-specific effects of prenatal mixed exposure to serum phthalates on neurodevelopment of children aged 2-3 years:the Guangxi Birth Cohort Study.

Phthalates have been shown to have adverse effects on neurodevelopment, which may be gender-specific. However, the association between prenatal mixed exposure to phthalates and children's neurodevelopment remains inconsistent. We measured 15 prenatal serum phthalate levels and evaluated children's neurodevelopmental indicators using Gesell Developmental Schedule (GDS) (n = 750). Generalized linear regression was fitted to examine the association. Among boys, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) had adverse effects on gross motor [odds ratio (OR): 7.38, 95% confidence interval (CI):1.42, 38.46]. For gross motor in boys, joint effect was discovered between mono-2-ethylhexyl phthalate (MEHP) and MEHHP. Moreover, synergistic effects were found for MEHP with vanadium and cadmium, and antagonistic effects for MEHP with magnesium, calcium, titanium, iron, copper, selenium, rubidium, and strontium. We did not find statistically significant relationships in girls. In the 1st trimester, adverse effects were identified between mono-2-ethyl-5-oxoyhexyl phthalate (MEOHP) and adaptation (P = 0.024), and monomethyl phthalate (MMP) with social area (P = 0.017). In the 2nd trimester, MEHHP had adverse effects on social area (P = 0.035). In summary, we found boys may be more vulnerable to the neurotoxicity than girls in gross motor, and we also discovered the detrimental effects of phthalates on children's neurodevelopment in the 1st and 2nd trimesters. Therefore, the supplementation of appropriate elements in the 1st and 2nd trimesters may help reduce the adverse effects of phthalates on children's neurodevelopment, especially among boys.

[Research status and strategy of quality control of medicinal and edible food].

As China is implementing "Healthy China" strategy, medicinal and edible food has attracted unprecedented attention due to the dual attributes of food and medicine. However, there is a lack of the quality control standard and the existing quality control research cannot fully reflect the dual attributes of medicinal and edible food, which consequently restrict the development of medicinal and edible food industry. This study reviewed the research status and proposed the strategy of quality control in line with the dual attribu-tes of medicinal and edible food, and clarified the research contents of quality control of medicinal and edible food of different types to provide references for the follow-up quality control of medicinal and edible food.

Causal relationships between blood calcium, iron, magnesium, zinc, selenium, phosphorus, copper, and lead levels and multisystem disease outcomes in over 400,000 Caucasian participants.

BACKGROUND & AIMS: Metal elements have been associated with a wide range of clinical outcomes. The available epidemiological evidence for these associations is often inconsistent and suffers from confounding and reverse causation. We aimed to explore the broad clinical effects of varying blood metal element levels and possible underlying mechanisms. METHODS: We performed a two-sample Mendelian randomization (MR) analysis by using metal element-associated genetic loci as instrumental variable to evaluate the causal associations between blood metal element levels and 1050 disease outcomes in a UK Biobank cohort. A total of 408,910 White British participants were enrolled in the analysis. We further used the metal element-related genes and disease-related genes to construct a protein-protein interaction (PPI) network. RESULTS: Eight metal elements were associated with 63 diseases in total. Notably, we found nine pairs of suggestive evidence between two different metal elements for the same disease. Selenium and lead share some of the associated clinical outcomes, including diabetes mellitus, type 2 diabetes, lymphoid leukemia, and acute pharyngitis. Lead and zinc share the associated disease of acquired hypothyroidism. Iron and copper share the associated disease of arthropathies. Copper and zinc share the associated disease of occlusion of cerebral arteries. Calcium and zinc share the associated disease of arthropathies. In addition, the PPI network provided potential links between metal elements and disease outcomes at the genetic level. CONCLUSIONS: Our MR study of eight metal elements comprehensively characterized their shared and unique clinical effects, highlighting their potential causal roles in multiple diseases. Given the modifiable nature of blood metal elements and the potential for clinical interventions, these findings warrant further investigation.

Selenium Status in Patients with Chronic Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The potential role of selenium in preventing chronic liver diseases remains controversial. This meta-analysis aimed to summarize the available evidence from observational studies and intervention trials that had evaluated the associations between body selenium status and chronic liver diseases. METHODS: We comprehensively searched MEDLINE, Embase, Web of Science, and Cochrane Library from inception to April 2021. The study protocol was registered at PROSPERO (CRD42020210144). Relative risks (RR) for the highest versus the lowest level of selenium and standard mean differences (SMD) with 95% confidence intervals (CI) were pooled using random-effects models. Heterogeneity and publication bias were evaluated using the I2 statistic and Egger's regression test, respectively. RESULTS: There were 50 studies with 9875 cases and 12975 population controls in the final analysis. Patients with hepatitis (SMD = -1.78, 95% CI: -2.22 to -1.34), liver cirrhosis (SMD = -2.06, 95% CI: -2.48 to -1.63), and liver cancer (SMD = -2.71, 95% CI: -3.31 to -2.11) had significantly lower selenium levels than controls, whereas there was no significant difference in patients with fatty liver diseases (SMD = 1.06, 95% CI: -1.78 to 3.89). Moreover, the meta-analysis showed that a higher selenium level was significantly associated with a 41% decrease in the incidence of significant advanced chronic liver diseases (RR = 0.59, 95% CI: 0.49 to 0.72). CONCLUSION: Our meta-analysis suggested that both body selenium status and selenium intake were negatively associated with hepatitis, cirrhosis, and liver cancer. However, the associations for fatty liver diseases were conflicting and need to be established in prospective trials.

[Extracts of Poria cocos polysaccharides improves alcoholic liver disease in mice via CYP2E1 and NF-κB inflammatory pathways].

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.

Discovery of Therapeutic Candidates for Diabetic Retinopathy Based on Molecular Switch Analysis: Application of a Systematic Process.

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

Causal Effect of Genetically Determined Blood Copper Concentrations on Multiple Diseases: A Mendelian Randomization and Phenome-Wide Association Study.

Exposures to copper have become a health concern. We aim to explore the broad clinical effects of blood copper concentrations. A total of 376,346 Caucasian subjects were enrolled. We performed a Mendelian randomization and phenome-wide association study (MR-PheWAS) to evaluate the causal association between copper and a wide range of outcomes in UK Biobank, and we constructed a protein-protein interaction network. We found association between blood copper concentrations and five diseases in the overall population and nine diseases in male. MR analysis implicated a causal role of blood copper in five diseases (overall population), including prostate cancer (OR = 0.87, 95% CI 0.77-0.98), malignant and unknown neoplasms of the brain and nervous system (OR = 0.58, 95% CI 0.38-0.89), and hypertension (OR = 0.94, 95% CI 0.90-0.98), essential hypertension (OR = 0.94, 95% CI 0.90-0.98) and cancer of brain and nervous system (OR = 0.63, 95% CI 0.41-0.98). For male, except for dysphagia being newly associated with blood copper (OR = 1.39, 95% CI 1.18-1.63), other MR results were consistent with the overall population. In addition, the PPI network showed possible relationship between blood copper and four outcomes, namely brain cancer, prostate cancer, hypertension, and dysphagia. Blood copper may have causal association with prostate cancer, malignant and unknown neoplasms of the brain and nervous system, hypertension, and dysphagia. Considering that copper is modifiable, exploring whether regulation of copper levels can be used to optimize health outcomes might have public health importance. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00052-3.

Periconceptional iron supplementation and risk of gestational diabetes mellitus: A prospective cohort study.

AIMS: Iron supplementation has been recommended for healthy pregnancy, but concerns have been raised regarding the potential adverse effects. We sought to examine the impact of periconceptional iron supplement use on subsequent gestational diabetes mellitus (GDM) risk. METHODS: Participants (N = 5101) with information on periconceptional micronutrient supplementation and diagnosis of GDM were involved. Information on iron supplementation and general characteristics were collected at enrollment and follow-up visits. GDM was diagnosed by oral glucose tolerance tests (OGTT) conducted at 24-28 weeks of gestation. Robust Poisson regression model was used to estimate the relative risks (RRs) and 95% confidence intervals (CI) for the effect of iron supplement use on GDM. RESULTS: 10.5% of the participants were diagnosed with GDM and the incidence was significantly higher in users with iron >30 mg/d for more than 3 months (Iron >30-L) than in nonusers. Adjusted RRs (95% CI) were 1.53 (1.21, 1.93) in Iron >30-L group, 1.14 (0.80, 1.61) in users with iron >30 mg/d for<3 months (Iron > 30-S) and 1.15 (0.86, 1.54) in users with iron ≤30 mg/d for any duration (Iron ≤30) respectively, compared to nonusers. This link in Iron >30-L group was even stronger (adjusted RR: 1.70, 95% CI: 1.25, 2.31) when restricting the analysis among primiparous and iron-replete participants without family history of diabetes. There were no significant differences in birth outcomes among groups. CONCLUSIONS: Periconceptional iron supplementation >30 mg/d for long-term was associated with increased GDM risk. The need and safety of prophylactic iron supplement in iron-replete pregnant women should be reconsidered.

Higher dietary vitamin C intake is associated with a lower risk of gestational diabetes mellitus: A longitudinal cohort study.

BACKGROUND & AIMS: Oxidative stress has been implicated in the pathogenesis of gestational diabetes mellitus (GDM). Vitamin C as natural antioxidant may help to increase the body's antioxidant capacity. The study is aimed to determine whether vitamin C intake during pregnancy is associated with lower risk of GDM. METHODS: Women with singleton pregnancy and without any history of diabetes were drawn from the ongoing Tongji Maternal and Child Health Cohort (TMCHC). Oral glucose tolerance tests (OGTT) were conducted during weeks 24-28 of gestation to screen for GDM. A validated food frequency questionnaire (FFQ) was used to assess dietary intake during mid pregnancy. Use of multivitamins and specific supplements of vitamin C was assessed by questionnaires. Odds ratios (ORs) of GDM risk were calculated by logistic regression models, adjusted for potential confounders. RESULTS: 344 (11.4%) of the 3009 women were diagnosed with GDM. Dietary vitamin C intake was inversely associated with the risk of GDM. Women with above adequate dietary vitamin C intake (more than 200 mg/day) experienced lower odds of GDM (OR 0.68, 95% CI: 0.49-0.95) than those with adequate intake (115-200 mg/day). There was no association between the total consumption of vitamin C and the risk of GDM (OR 1.04, 95% CI: 0.71-1.53). CONCLUSION: This data suggests that higher dietary consumption of vitamin C during pregnancy is independently associated with lower odds of GDM. Above 200 mg/day of dietary vitamin C intake may help reduce the odds of GDM. However, no such association between total vitamin C intake and the risk of GDM was found. Hence, sufficient vegetables and fruits rich in vitamin C should be recommended to protect pregnant women from developing gestational diabetes.

Low serum folate status in the second trimester increase the risk of low birthweight in Chinese women.

AIM: This study aimed to explore the influence of maternal folate and vitamin B12 (B12) status during pregnancy on the incidence of low birthweight (LBW) infants. METHODS: A total of 6203 eligible women registered in seven hospitals in southern China, and 230 cases with singleton live births and 382 controls were matched for further analyses. The concentrations of serum folate and B12 were detected with chemiluminescence microparticle immunoassay on ARCHITECT i2000-1. Conditional logistic regression was used to evaluate the effects of folate and B12 levels on LBW. RESULTS: Maternal serum folate levels increased basically with increasing the period of folic acid supplementation (P trend <0.001). Moreover, maternal serum folate and B12 levels gradually decreased with the increase of gestational age (P < 0.001). Conditional logistic regressions analysis results showed increased odds ratios (OR) for LBW from the fourth to first folate quartiles (P trend <0.01) in the second trimester. Compared with the women in the highest quartile, those in the lowest quartile of serum folate in the second trimester were found with higher risk of LBW (adjusted OR = 1.67, 95% confidence interval [CI]: 1.02-2.73). However, no significant association was observed between serum folate and LBW in the first trimester or third trimester. In addition, serum B12 exhibited no significant association with LBW. CONCLUSIONS: Low serum folate levels in the second trimester significantly increases the risk of LBW amongst Chinese women with singleton pregnancies.

A NIR-controlled cage mimicking system for hydrophobic drug mediated cancer therapy.

Most chemotherapeutic drugs commonly suffer from several shortcomings, including the lack of aqueous solubility, limited stability and adverse side effects. Although caging strategy has recently been employed as an effective approach to conceal and stabilize these drugs to achieve light-activated cancer therapy, it is plagued by the sophisticated drug modification process and deleterious solvent usage. In addition, using UV or Visible light to remove photocaged group is restricted to its limited tissue penetration ability in and phototoxicity. In this paper, by anchoring photochromic spiropyran on the mesoporous silica coated upconversion nanoparticles (UCNP-SP), we design a NIR-controlled cage mimicking system. Our results indicate that hydrophobic drug can be concealed inside the channels of the nanocarrier with high stability and "uncaged" via NIR irradiation-triggered hydrophobicity-hydrophilicity switch of the spiropyran molecules, finally inducing drug release and recovering their bioactivity. Moreover, under NIR illumination, the UV/Visible emissions from UCNP can also efficaciously initiate the generation of reactive oxygen species (ROS) by Curcumin, further improving the therapeutic efficiency. Both in vitro and in vivo experimental results validate that NIR irradiated nanosystem can produce remarkably enhanced antitumor efficiency.

A GO-Se nanocomposite as an antioxidant nanozyme for cytoprotection.

GO-Se nanocomposites are fabricated with excellent glutathione peroxidase (GPx)-like properties to protect cells against oxidative stress. Compared with SeNPs, the GO-Se nanozymes exhibit higher GPx-mimic catalytic efficiency. Cell experiments further confirm their excellent cytoprotection capacity.

Vascular CXCR4 Expression Promotes Vessel Sprouting and Sensitivity to Sorafenib Treatment in Hepatocellular Carcinoma.

Purpose: C-X-C chemokine receptor type 4 (CXCR4) is known to be involved in both developmental and adult angiogenesis; however, its role in tumor angiogenesis remains largely unknown. Here, the role of vascular CXCR4 in regulating vascular structure in hepatocellular carcinoma (HCC) was assessd, and the clinical value of CXCR4 was explored.Experimental Design: The expression of CXCR4 in HCC was determined by IHC and immunofluorescence. Characteristics of CXCR4+ cells were determined by in vitro and mice experiments. Kaplan-Meier survival analysis was used to determine the correlation of CXCR4 expression with prognosis.Results: We found that CXCR4 is selectively expressed on a fraction of tumor endothelial cells (TECs) in HCC tissues, but not on the hepatic endothelium in peritumoral area. High levels of CXCR4 on TECs tended to develop a sinusoidal vasculature in tumors and predicted poor prognosis for patients with HCC. CXCR4+ endothelial cells (EC) displayed the functional features of tip cells, with increased expression of tip cell-related markers. Functional studies revealed that CXCR4 could directly promote vessel sprouting in vitro and in vivo Interestingly, sorafenib treatment reduced the frequency of CXCR4+ ECs in culture and inhibited the formation of sinusoidal vasculature and growth of CXCR4High xenograft tumors. Moreover, high CXCR4 vascular density in resected tumor tissues before sorafenib treatment was associated with prolonged survival in patients with advanced HCC treated with sorafenib.Conclusions: These data revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. Clin Cancer Res; 23(15); 4482-92. ©2017 AACR.

Metal-organic-framework-supported immunostimulatory oligonucleotides for enhanced immune response and imaging.

We have demonstrated the ability of iron carboxylate metal-organic frameworks to efficiently deliver unmethylated cytosine-phosphate-guanine oligonucleotides. The nanoconjugates induced a stronger immune response than did free cytosine-phosphateguanine oligonucleotides and showed T2-magnetic resonance imaging ability both in vitro and in vivo.