Migration Patterns and Potential Risk Assessment of Trace Elements in the Soil-Plant System in the Production Area of the Chinese Medicinal Herb Scrophularia ningpoensis Hemsl.

Scrophularia ningpoensis Hemsl. holds a prominent place among Chinese medicinal herbs. Assessing the soil-plant system of its origin is crucial for ensuring medication safety. Although some trace elements are essential for the normal functioning of living organisms, exposure to higher concentrations is harmful to humans, so in order to assess the possible health risk of trace elements in the soil-plant system of Scrophularia ningpoensis Hemsl. origin for human assessment, we used non-carcinogenic risk (HI) and carcinogenic risk (CR) for their evaluation. In this paper, the following trace elements were studied in the soil-Scrophularia ningpoensis Hemsl. system: manganese (Mn), iron (Fe), cobalt (Co), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As) and lead (Pb). Correlation and structural equation analyses showed that the effect of soil in the root zone on the plant was much greater than the effect of soil in the non-root zone on the plant. The single-factor pollution index (Pi) showed that the soil in the production area of Scrophularia ningpoensis Hemsl. was polluted to a certain extent, notably with Pb showing the highest average Pi values of 0.94 and 0.89 in the non-root and root zones, respectively. Additionally, the Nemerow composite pollution indices (PN) for both zones indicated an alert range. Regarding health risks, exposure to soil in the non-root zone posed higher non-carcinogenic risk (HI) and carcinogenic risk (CR) compared to the root zone, although neither zone presented a significant carcinogenic risk. The potential non-carcinogenic risk (HI) and carcinogenic risk (CR) from consuming Scrophularia ningpoensis Hemsl. leaves and stems were more than ten times higher than that of roots. However, the carcinogenic risk (CR) values for both the soil and plant of interest in the soil- Scrophularia ningpoensis Hemsl. system did not exceed 10-4, and therefore no significant carcinogenic risk existed.

Recent developments of hydroxamic acid hybrids as potential anti-breast cancer agents.

Histone deacetylase inhibitors not only possess favorable effects on modulating tumor microenvironment and host immune cells but also can reactivate the genes silenced due to deacetylation and chromatin condensation. Hydroxamic acid hybrids as promising histone deacetylase inhibitors have the potential to address drug resistance and reduce severe side effects associated with a single drug molecule due to their capacity to simultaneously modulate multiple targets in cancer cells. Accordingly, rational design of hydroxamic acid hybrids may provide valuable therapeutic interventions for the treatment of breast cancer. This review aimed to provide insights into the in vitro and in vivo anti-breast cancer therapeutic potential of hydroxamic acid hybrids, together with their mechanisms of action and structure-activity relationships, covering articles published from 2020 to the present.

Downregulation of miR-599 predicts poor outcome in cervical cancer patients and promotes the progression of cervical cancer.

OBJECTIVE: Cervical cancer remains a leading cause of gynecological cancer-related death. In this study, we aimed to investigate the expression pattern of miR-599 and its prognostic significance in cervical cancer. MATERIALS AND METHODS: The RT-qPCR analysis was used to detect the expression levels of miR-599 in cervical cancer tissues and cell lines. The association between miR-599 expression and clinical characteristics of cervical cancer patients was analyzed using the χ2 test. The Kaplan-Meier analysis and multivariate Cox proportional hazards model were used to explore the prognostic significance of miR-599. Then, CCK-8 assays, transwell migration, and invasion assays were used to assess the effects of miR-599 on tumor cell proliferation, migration, and invasion of cervical cancer cells, respectively. RESULTS: miR-599 expression was significantly downregulated in cervical cancer tissues and cells compared with non-cancerous tissues and HaCaT cells, respectively. Statistical analysis revealed that miR-599 expression was associated with lymph node metastasis and FIGO stage. The miR-599 expression was an independent prognostic factor for overall survival. Functionally, overexpression of miR-599 suppressed cell proliferation, migration, and invasion of cervical cancer cells, while downregulation of miR-599 had opposite effects. CONCLUSION: miR-599 acts as a tumor suppressor in cervical cancer that inhibiting cell proliferation, migration, and invasion of cervical cancer cells, suggesting that miR-599 may be a potential prognostic biomarker and novel targeted strategy for cervical cancer.

Tetraspanin 1 (TSPAN1) promotes growth and transferation of breast cancer cells via mediating PI3K/Akt pathway.

The incidence and mortality of breast cancer rank first among all types of female tumors. To improve patients' prognosis with advanced breast cancer, new and more effective targets still need to be explored and identified. Tetraspanin 1 (TSPAN1) is highly expressed in several cancers and affects the progression of these tumors. However, there are few studies focused on its role in breast cancer. Previous study showed that TSPAN1 promoted epithelial-mesenchymal transition (EMT) and metastasis, and whether TSPAN1 could promote breast cancer via regulating EMT needs further study. In this study, we found high TSPAN1 expression in breast cancer tumor samples and cell lines which was confirmed by bioinformation analysis. The ablation of TSPAN1 suppressed the growth, and motility of breast cancer cells. We further found that TSPAN1 affected the EMT and mediated the PI3K/Akt pathway in breast cancer cells. In addition, TSPAN1 depletion suppressed tumor growth of breast cancer in mice. In summary, we thought TSPAN1 suppressed growth and motility of breast cancer via mediating EMT and PI3K/AKT pathway, and could serve as a potential target for treatment of breast cancer.

Structural characterization and protective effects of polysaccharide from Gracilaria lemaneiformis on LPS-induced injury in IEC-6 cells.

This study was aimed to characterize Gracilaria lemaneiformis polysaccharides and evaluate their protective effects on Lipopolysaccharide-induced injury in IEC-6 cells. The G. lemaneiformis polysaccharide was degraded by UV/H2O2 treatment and purified to three fractions named GLP-1.0 M, GLP-1.4 M and GLP-1.6 M. The purified fractions were mainly composed of galactose, glucose and xylose. The structural analysis showed that GLP-1.6 M was a typical sulfated red alga polysaccharide containing the linear backbone of ß-(1 â†’ 3)- and α-(1 â†’ 4)-linked galactosyl residues, anhydro-galactose units. In the Lipopolysaccharide-induced IEC-6 cells model, GLP-1.6 M exerted the strongest in vitro anti-inflammatory activity by inhibiting the release and expressions of tumor necrosis factor-α, interleukin-6 and interleukin-1ß by 89.93%, 67.82% and 38.06%, respectively. Meanwhile, GLP-1.6 M enhanced the intestinal barrier function via up-regulating the expressions of tight junctions and mucin. Therefore, the purified polysaccharide from G. lemaneiformis could be a promising candidate for maintaining intestinal health in the food and pharmaceutical industries.

In vivo Anticancer Potential of Hydroxamic Acid Derivatives.

Notwithstanding the noteworthy advances in its treatment, cancer remains one of the most serious threatens to humans across the world. Hydroxamic acid derivatives, the potential inhibitors of Histone Deacetylases (HDACs), could inhibit cancer cell proliferation, induce cell differentiation, apoptosis and autophagy, and suppress angiogenesis, invasion as well as metastasis through diverse signaling pathways. Thus, hydroxamic acid derivatives exhibit promising activity against cancers and are useful scaffolds in modern anticancer drug discovery. The purpose of the present review article is to summarize the recent developments (Jan, 2011-Jan, 2021) in hydroxamic acid derivatives with insights into their in vivo anticancer potential and mechanisms of action.

Structural characteristics and anti-inflammatory activity of UV/H2O2-treated algal sulfated polysaccharide from Gracilaria lemaneiformis.

The study aimed to study the effects on structural characteristics and anti-inflammatory activities of algal sulfated polysaccharides isolated from Gracilaria lemaneiformis (GLP) after a combined treatment of UV irradiation (average irradiance of 6500 mJ/cm2) and H2O2 (50 mmol/L) for various time periods up to 60 min. After a 30-min treatment, the molecular weight and particle size of GLP was decreased by 15 and 2.6 fold, respectively with small but significant decrease in the contents of total sugars, uronic acids and proteins. There seemed to have no starch and the presence of longer side chains of branches in the GLP samples before and after UV/H2O2 treatment based on the I2-KI assay. Scanning electron microscope and atomic force microscope analysis confirmed that the UV/H2O2 treatment could modify the surface morphology of GLP. GLP treated for 5 min possessed the strongest in vitro anti-inflammatory activity by inhibiting the production of nitric oxide, tumor necrosis factor-α and interleukin-6 by 60.49%, 62.81% and 36.29%, respectively in IEC-6 cells when compared to the model. Therefore, UV/H2O2 treatment had the potential to enhance the anti-inflammatory activity of algal sulfated polysaccharides.

ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/ß-catenin pathway via modulating NuSAP1 expression.

Breast cancer is one of the most prevalent malignancies in women worldwide. Although great advancements have been achieved in the diagnosis and treatment of breast cancer, the prognosis of patients with breast cancer is still poor due to distal recurrence and metastasis after surgery. This study aimed to assess the role of ankyrin repeat domain 22 (ANKRD22) in the progression of breast cancer and investigate the molecular mechanism. Using immunohistochemistry, we demonstrated that the expression level of ANKRD22 in human breast cancer tissues was significantly higher than that in normal breast tissues. ANKRD22 knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells, as confirmed by BrdU, colony formation, transwell, and immunoblot assays. Immunoblot assays further indicated that ANKRD22 regulated the expression of nucleolar and spindle-associated protein 1 (NuSAP1) and then caused the activation of Wnt/ß-catenin signaling pathway. Moreover, overexpression of NUSAP1 reversed the inhibitory effects of ANKRD22 knockdown on the proliferation, invasion, and EMT of breast cancer cells. In summary, this study demonstrated that ANKRD22 enhanced breast cancer cell malignancy by activating the Wnt/ß-catenin pathway via modulating NuSAP1 expression, which might shed light on new therapeutic approaches for breast cancer.

Current scenario of indole derivatives with potential anti-drug-resistant cancer activity.

Cancer chemotherapy is frequently hampered by drug resistance, so the resistance to anticancer agents represents one of the major obstacles for the effective cancer treatment. Indole derivatives have the potential to act on diverse targets in cancer cells and exhibit promising activity against drug-resistant cancers. Moreover, some indole-containing compounds such as Semaxanib, Sunitinib, Vinorelbine, and Vinblastine have already been applied in clinics for various kinds of cancer even drug-resistant cancer therapy. Thus, indole derivatives are one of significant resources for the development of novel anti-drug-resistant cancer agents. This review focuses on the recent development of indole derivatives with potential therapeutic application for drug-resistant cancers, and the mechanisms of action, the critical aspects of design as well as structure-activity relationships, covering articles published from 2010 to 2020.

Multifunctional Edge-Activated Carbon Nitride Nanosheet-Wrapped Polydimethylsiloxane Sponge Skeleton for Selective Oil Absorption and Photocatalysis.

Developing green 3D porous materials integrating multitasking environmental remediation with high efficiency and reusability is considered to be a promising sustainable approach and is urgently required. Herein, we have successfully prepared a facile, ecofriendly, and robust multifunctional composite sponge of carbon nitride (CN) nanosheets wrapping an elastomer polydimethylsiloxane (PDMS) skeleton without harsh treatments. The composite sponge (CN@PDMS) exhibits excellent hydrophobic and superoleophilic properties with a water contact angle of 133.2°. This sponge also shows high selective absorption of organic solvents and oils with high recyclability after 10 absorption cycles. Furthermore, the CN@PDMS sponge has a high ability for demulsification of the oil-in-water emulsion as well. The as-prepared sponge displays high thermal stability, retaining 82.16% of its original weight up to 550 °C, and extraordinary prolonged stability in harsh corrosive solutions over 35 h compared with the pristine PDMS sponge. Additionally, the CN@PDMS sponge exhibits a high ability for adsorption and photodegradation of rhodamine B under visible light irradiation with self-cleaning and high reusability over 5 runs. Such a sustainable strategy would provide new ways for broad environmental applications.

A preliminary report: genistein attenuates cerebral ischemia injury in ovariectomized rats via regulation of the PI3K-Akt-mTOR pathway.

Stroke is a leading cause of disability and death in the worldwide. Therefore, prevention of stroke is critically important. Genistein, a natural phytoestrogen extracted from soybeans, has been found to be a potential neuroprotective agent for stroke prevention. However, the role of genistein and its underlying mechanism in ovariectomized rats has been rarely evaluated. In this study, ovariectomized rats were treated with genistein (10 mg/kg) or vehicle daily for two weeks before they received middle cerebral artery occlusion (MCAO) and reperfusion. Seventy-two hours after reperfusion, the neurological function was evaluated by Garcia test, infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride staining; and neuronal damage and cell apoptosis were detected by Nissl and Tunel staining in the ischemic penumbra, respectively. In addition, Western blotting was used to detect the activity of PI3K-Akt-mTOR signal pathway in the ischemic penumbra in different groups. And we found that genistein treatment in ovariectomized rats significantly improved neurological outcomes, reduced infarct volumes, decreased neuronal damage and cell apoptosis, and increased the activity of PI3K-Akt-mTOR signal pathway. Our findings indicated that treatment genistein could alleviate neuronal apoptosis induced by cerebral ischemia in ovariectomized rats via promoting the activity of PI3K-Akt-mTOR signal pathway, which provides a new molecular mechanism for the neuroprotective effects of genistein against stroke.

Comparing the disrupting effects of short-, medium- and long-chain chlorinated Paraffins on cell viability and metabolism.

With the phasing out of short-chain chlorinated paraffins (SCCPs), the production and emissions of medium- and long-chain chlorinated paraffins (MCCPs and LCCPs) are expected to increase. In this study, cell viability assay and pseudotargeted metabolomics approach were adopted to define and compare the toxic effects induced by SCCPs, MCCPs and LCCPs. The dose response curves indicated that three CP mixtures with comparable chlorine contents produced similar inhibitory effects on cell viability. At exposure concentration of 100 µg/L, three CP mixtures all induced significant increases in levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and a significant reduction in level of adenosine triphosphate production (ATP), and produced similar impact intensities on overall metabolism. A stronger perturbation in phospholipid and fatty acid metabolism was observed in all CP exposure groups. In comparison with SCCPs and MCCPs, LCCPs produced a stronger suppressive effect on amino acid transport across cell membrane and induced an opposite effect on purine metabolism. Furthermore, the toxicity mechanism and possible health risks of the three types of CPs were discussed. MCCPs shared the most similar cytotoxicity and metabolic perturbation with SCCPs, suggesting that there should be concern about using MCCPs as alternatives to SCCPs.

Development of a lipovitellin-based sandwich ELISA for determination of vitellogenin in the marine medaka Oryzias melastigma.

A lipovitellin (Lv) based sandwich enzyme-linked immunosorbent assay (ELISA) was developed to quantify vitellogenin (Vtg) in marine medaka (Oryzias melastigma). Lv and Vtg were purified from the unfertilized eggs and the whole body homogenates (WBH) of estradiol (E2)-exposed fish. The purified Lv sample appeared as three clear bands (118, 112 and 100 kDa) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and was identified as an Lvs mixture from VtgAa and VtgAb by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. Polyclonal antibody against marine medaka VtgAa was also raised. Compared with Vtg, Lv was more stable to heat stress (37 °C for 8 h or 4 °C for a week) and repeated freeze/thaw stress. In addition, western blot analysis revealed that marine medaka Vtg and Lv had similar immunogenicity. Therefore, in this study, Lv was applied instead of Vtg as the standard to establish an ELISA. The Lv standard curve was parallel to serial WBH dilutions of E2-exposed fish, and the absorbance values were very low in control male samples, suggesting the specificity and feasibility of the method for Vtg quantification. The developed assay was sensitive with the detection limit of 3.1 ng/mL and had a working range between 15.6 and 500 ng/mL. The intra- and inter-assay coefficients of variation were both below 5%. Moreover, the standard curves of Lv antigen treated under different stresses were almost identical, indicating high robustness of the assay. Overall, our study provides an important methodology reference for quantification of marine medaka Vtg.

Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats.

Short-chain chlorinated paraffins (SCCPs) are known to disturb thyroid hormone (TH) homeostasis in rodents. However, the mechanism remains to be fully characterized. In this study, male Sprague Dawley rats received SCCPs (0, 1, 10, or 100mg/kg/day) via gavage once a day for consecutive 28days. Plasma and hepatic TH concentrations, thyrocyte structure, as well as thyroid and hepatic mRNA and protein levels of genes associated with TH homeostasis were examined. Moreover, we performed molecular docking to predict interactions between constitutive androstane receptor (CAR), a key regulator in xenobiotic-induced TH metabolism, with different SCCP molecules. Exposure to SCCPs significantly decreased the circulating free thyroxine (T4) and triiodothyronine (T3) levels, but increased thyroid-stimulating hormone (TSH) levels by a feedback mechanism. Decreased hepatic T4 and increased hepatic T3 levels were also seen after 100mg/kg/day SCCPs exposure. SCCPs didn't show any significant effects on the expression of thyroid TH synthesis genes or thyrocyte structure. However, stimulation effects were observed for mRNA and protein levels of hepatic uridine diphosphoglucuronosyl transferase (UGT) 1A1 and organic anion transporter 2, suggesting an accelerated TH metabolism in rat liver. The increased cytochrome P450 2B1 but not 1A1 mRNA and protein levels indicated that the CAR signaling was activated by SCCPs exposure. According to docking analysis, SCCPs form hydrophobic interactions with CAR and the binding affinity shows dependency on chlorine content. Overall, our data showed that CAR implicated enhancement of hepatic TH influx and degradation could be the main cause for SCCPs induced TH deficiency in male rats.

A metabolomics strategy to assess the combined toxicity of polycyclic aromatic hydrocarbons (PAHs) and short-chain chlorinated paraffins (SCCPs).

The combined toxicity of mixed chemicals is usually evaluated according to several specific endpoints, and other potentially toxic effects are disregarded. In this study, we provided a metabolomics strategy to achieve a comprehensive understanding of toxicological interactions between mixed chemicals on metabolism. The metabolic changes were quantified by a pseudotargeted analysis, and the types of combined effects were quantitatively discriminated according to the calculation of metabolic effect level index (MELI). The metabolomics strategy was used to assess the combined effects of polycyclic aromatic hydrocarbons (PAHs) and short-chain chlorinated paraffins (SCCPs) on the metabolism of human hepatoma HepG2 cells. Our data suggested that exposure to a combination of PAHs and SCCPs at human internal exposure levels could result in an additive effect on the overall metabolism, whereas diverse joint effects were observed on various metabolic pathways. The combined exposure could induce a synergistic up-regulation of phospholipid metabolism, an additive up-regulation of fatty acid metabolism, an additive down-regulation of tricarboxylic acid cycle and glycolysis, and an antagonistic effect on purine metabolism. SCCPs in the mixture acted as the primary driver for the acceleration of phospholipid and fatty acid metabolism. Lipid metabolism disorder caused by exposure to a combination of PAHs and SCCPs should be an important concern for human health.

An in vivo assay performed using multiple biomarkers related to testosterone synthesis and conversion for assessing the androgenic potency of refuse leachate.

Refuse leachate is likely an important source of androgens. However, common in vitro bioassays underestimate the potential androgenic activity of leachate, owing to non-receptor-mediated mechanisms that modify the balance of sex hormones and promote the accumulation of endogenous androgens. This study aimed to develop an in vivo assay by using multiple biomarkers related to testosterone synthesis and conversion for assessing the potential androgenic activity of refuse leachate sampled from a municipal solid waste treatment plant in Qingdao, China. The results indicated that exposure to leachate increased the levels of testosterone and luteinizing hormone, but decreased those of 17ß-estradiol in both male and female goldfish (Carassius auratus), suggesting a potential androgenic activity. Further, Leydig cell hyperplasia and decreased gonadal P450 aromatase mRNA levels were observed; these alterations might promote the biosynthesis of testosterone and hinder the conversion of testosterone to 17ß-estradiol, which in turn enhance testosterone accumulation. Exposure to leachate also resulted in reproductive impairments, including decreased gonadosomatic index and plasma vitellogenin levels of female goldfish, as well as decreased testicular enzyme activities in male goldfish. The integrated use of biochemical, molecular, and histological markers not only improved our understanding of the androgenic effects of leachate but also verified the reliability and validity of the results. Therefore, the in vivo bioassay described in this study might allow the investigation of the androgenic effects of other complex contaminant mixtures in the future.

Refuse leachate exposure causes changes of thyroid hormone level and related gene expression in female goldfish (Carassius auratus).

To elucidate the potential thyroid disrupting effects of refuse leachate on females, female goldfish (Carassius auratus) were exposed to 0.5% diluted leachates from each step of a leachate treatment process (i.e. raw leachate before treatment, after membrane bioreactor treatment, and the final treated leachate) for 21days. Raw leachate exposure caused disturbances in the thyroid cascade of female fish, as evidenced by the elevated plasma 3,3',5-triiodo-l-thyronine (p<0.05) and thyroid-stimulating hormone (p<0.01) levels as well as up-regulated hepatic and gonadal type I deiodinase (p<0.01), type II deiodinase (p<0.01) and thyroid receptor (p<0.05) mRNA levels. Thyroid disrupting potency decreased markedly as raw leachate progressed through the "membrane bioreactor + reverse osmosis" treatment but could still be detected in the treated leachate. As our results indicated, thyroid system in female goldfish was more sensitive to leachate exposure than that of the male fish.

An integrated approach combining chemical analysis and an in vivo bioassay to assess the estrogenic potency of a municipal solid waste landfill leachate in Qingdao.

Various adverse effects related to landfill leachate have made leachates an important issue in past decades, and it has been demonstrated that landfill leachate is an important source of environmental estrogens. In this study, we employed chemical analysis of some already evaluated estrogenic substances, in combination with a bioassay using several specific biomarkers (e.g., plasma vitellogenin and sex steroids, enzyme activity of gonad gamma-glutamyl transpeptidase, and gonadosomatic index) to evaluate the estrogenic activities in outlets from different stages of the leachate treatment process. The results indicated that 5 environmental estrogens (4-t-octylphenol, bisphenol A, di-ethyl phthalate, di-n-butyl phthalate, and diethylhexyl phthalate) were detected by a gas chromatography-mass spectrometry, and the concentrations in leachate samples were 6153 ng/L, 3642 ng/L, 2139 ng/L, 5900 ng/L, and 9422 ng/L, respectively. Leachate (1∶200 diluted) induced the synthesis of plasma vitellogenin and led to decreased enzyme activity of gonad gamma-glutamyl transpeptidase and gonadosomatic index in male goldfish (Carassius auratus) after a 28-day exposure, while increased circulating 17ß-estradiol level was also observed in males exposed to treated effluent. Although the target EEs were partially removed with removal rates varying from 87.2% to 99.77% by the "membrane bioreactor+reverse osmosis+aeration zeolite biofilter" treatment process, the treated effluent is still estrogenic to fish. The method combined chemical techniques with the responses of test organisms allowing us to identify the group of estrogen-like chemicals so that we were able to evaluate the overall estrogenic effects of a complex mixture, avoiding false negative assessments.