The characterization of traditional Chinese medicine natures and flavors using network pharmacology integrated strategy.

Background and aim: Due to the complexity of TCM ingredients and medication compatibility, TCM cannot be used like chemical medicines. The theory of "Four Natures and five Flavors" provides a theoretical basis for the use of TCM. "Four Natures and five Flavors" are originated from pharmacological rules based on clinical practices. Whereas, How to describe and characterize "Natures"(Warm, Hot, Cold and Cool) and "Flavors" (Pungent, Sour, Sweet, Bitter and Salty) scientifically remain the issue that needs to be solved. The aim of this study is to establish the TCM characterization models based on the integrated pharmacology network strategy and provide a deeper understanding of TCM theory. Experimental procedure: Five "Pungent-Neutral", nine "Sweet-Neutral and nine "Bitter-Neutral" TCMs were selected to characterize the "Flavors" (Pungent, Sweet and Bitter). Nine "Pungent-Warm" and nine "Bitter-Cold" TCMs were selected to characterize the "Natures" (Warm and Cold). The screened chemical ingredients were analyzed by classification and the screened characteristics targets were analyzed by GO and KEGG enrichment analysis. Results and conclusion: In the "Pungent" group, flavonoids are the most. "Pungent" may have immune-regulatory effects and potential anticancer activity. In the "Sweet" group, isoflavones are the most. "Sweet" are related to effectively invigorate health. Fatty acids in the "Warm" group are the most. Flavonoids in the "Cold' group are far more than other components. "Warm" and "Cold" are both related to fatty acid and energy metabolism.

Lysine-Polydopamine Nanocrystals Loaded with the Codrug Abemaciclib-Flurbiprofen for Oral Treatment of Cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) combined with chemotherapeutic agents for the treatment of colorectal cancer (CRC) are a promising therapeutic strategy. NSAIDs can effectively boost the antitumor efficacy of chemotherapeutic agents by inhibiting the synthesis of COX-2. However, hazardous side effects and barriers to oral drug absorption are the main challenges for combination therapy with chemotherapeutics and NSAIDs. To address these issues, a safe and effective lysine-polydopamine@abemaciclib-flurbiprofen (Flu) codrug nanocrystal (Lys-PDA@AF NCs) was designed. Abemaciclib (Abe), a novel and effective inhibitor of the CDK4/6 enzyme, and Flu were joined to prepare Abemaciclib-Flu codrug (AF) by amide bonds, and then the AF was made into nanocrystals. Lysine-modified polydopamine was selected as a shell to encapsulate nanocrystals to enhance intestinal adhesion and penetration and lengthen the duration time of drugs in vivo. Nuclear magnetic resonance, Fourier transform infrared, Massspectrometry, X-ray photoelectron spectroscopy, Transmission electron microscopy, and drug loading were used to evaluate the physicochemical characteristics of the nanocrystals. In our study, Abe and Flu were released to exert their synergistic effect when the amide bond of AF was broken and the amide bond was sensitive to cathepsin B which is overexpressed in most tumor tissues, thus increasing the selectivity of the drug to the tumor. The results showed that Lys-PDA@AF NCs had higher cytotoxicity for CRC cell with an IC50 of 4.86 µg/mL. Additionally, pharmacokinetics showed that Abe and Flu had similar absorption rates in the Lys-PDA@AF NCs group, improving the safety of combination therapy. Meanwhile, in vivo experiments showed that Lys-PDA@AF NCs had excellent antitumor effects and safety. Overall, it was anticipated that the created Lys-PDA@AF NCs would be a potential method for treating cancer.

Norsesquiterpenes from the Latex of Euphorbia dentata and Their Chemical Defense Mechanisms against Helicoverpa armigera.

Euphorbia dentata (Euphorbiaceae), an invasive weed, is rarely eaten by herbivorous insects and could secrete a large amount of white latex, causing a serious threat to local natural vegetation, agricultural production and human health. In order to prevent this plant from causing more negative effects on humans, it is necessary to understand and utilize the chemical relationships between the latex of E. dentata and herbivorous insects. In this study, three new norsesquiterpenes (1-3), together with seven known analogues (4-10), were isolated and identified from the latex of E. dentata. All norsesquiterpenes (1-10) showed antifeedant and growth-inhibitory effects on H. armigera with varying levels, especially compounds 1 and 2. In addition, the action mechanisms of active compounds (1-3) were revealed by detoxifying enzyme (AchE, CarE, GST and MFO) activities and corresponding molecular docking analyses. Our findings provide a new idea for the development and utilization of the latex of E. dentata, as well as a potential application of norsesquiterpenes in botanical insecticides.

Dual Tumor Exosome Biomarker Co-recognitions Based Nanoliquid Biopsy for the Accurate Early Diagnosis of Pancreatic Cancer.

Pancreatic cancer, with extremely limited treatment options and poor prognosis, urgently needs a breakthrough in early diagnosis and monitoring. Tumor exosomes (T-Exos) detection is presently one of the most clinically significant liquid biopsy approaches for non-invasive pancreatic cancer early diagnosis, which, unfortunately, cannot be applied as a routine diagnostic tool until a number of obstacles, such as unsatisfactory specificity and sensitivity, as well as labor-intensive purification and analysis procedures by ultracentrifugation and enzyme-linked immunosorbent assay, are overcome. Here, we report a facile nanoliquid biopsy assay for the especially specific, ultrasensitive yet economical T-Exos detection by a dual specific biomarker antigen co-recognition and capturing strategy, which is enabled by grafting two corresponding capture antibodies on magnetic nanoparticles and gold nanoparticles, for the accurate detection of target tumor exosomes. This approach exhibits excellent specificity and ultrahigh sensitivity of detecting as low as 78 pg/mL pancreatic cancer exosome specific protein GPC1. Successful screening of 21 pancreatic cancer samples from 22 normal control cases with the enhanced specificity and sensitivity ensures the promising non-invasive monitoring and diagnosis for early stage pancreatic cancer.

Rapid detection of the biomarker for cystinuria by a metal-organic framework fluorescent sensor.

Arginine (Arg) is considered a valuable biomarker for various diseases, including cystinuria, and its concentration level holds significant implications for human health. To achieve the purposes of food evaluation and clinical diagnosis, it is imperative to develop a rapid and facile method for selective and sensitive determination of Arg. In this work, a novel fluorescent material (Ag/Eu/CDs@UiO-66) was synthesized by encapsulating carbon dots (CDs), Eu3+ and Ag + into UiO-66. This material can serve as a ratiometric fluorescent probe for detecting Arg. It exhibits a high sensitivity with a detection limit of 0.74 µM and a relatively broad linear range from 0-300 µM. After dispersing the composite Ag/Eu/CDs@UiO-66 in an Arg solution, the red emission of Eu3+ center at 613 nm was significantly enhanced, while the characteristic peak of CDs center at 440 nm remained unchanged. Therefore, a ratio fluorescence probe could be constructed based on the peak height ratio of the two emission peaks to achieve selective detection of Arg. In addition, the remarkable ratiometric luminescence response induced by Arg results in a significant color transition from blue to red under UV-lamp for Ag/Eu/CDs@UiO-66, which was convenient for visual analysis.

SH3BP1 Regulates Melanoma Progression Through Race1/Wace2 Signaling Pathway.

Background: SH3-domain binding protein-1 (SH3BP1), which specifically inactivates Rac1 and its target protein Wave2, has been shown to be an important regulator of cancer metastasis. However, the effects of SH3BP1 in melanoma progression remain unclear. The current study aimed to explore the function of SH3BP1 in melanoma and its possible molecular mechanism. Methods: TCGA database was used to analyze the expression of SH3BP1 in melanoma. Then, reverse transcription-quantitative polymerase chain reaction was performed to detect the expression of SH3BP1 in melanoma tissues and cells. Next, genes related to SH3BP1 were analyzed by LinkedOmics database, and protein interactions were analyzed by STRING database. These genes were further subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In addition, the signaling pathway of SH3BP1 action was screened by bioinformatics analysis. Finally, the function of SH3BP1 and its mediated signaling pathway in melanoma progression were investigated in vitro and in vivo. Results: SH3BP1 was significantly upregulated in melanoma tissues and cells. The pathways regulated by SH3BP1 are closely related to the occurrence and development of tumors. And we found that overexpression of SH3BP1 promoted the proliferation, migration, and invasion of melanoma cells by increasing Rac1 activity and Wave2 protein levels in vitro. Similarly, overexpression of SH3BP1 facilitated melanoma progression by upregulating Wave2 protein expression in vivo. Conclusion: In summary, this study revealed for the first time that SH3BP1 promoted melanoma progression through Rac1/Wave2 signaling pathway, providing a new therapeutic target for melanoma.

UPLC-Q-Exactive-based rats serum metabolomics for characterization of traditional Chinese medicine Natures and Flavors.

ETHNOPHARMACOLOGY RELEVANT: "Four Natures and five "Flavors" comes from the high generalization of medicine pharmacological rules from clinical practice by ancients. "Flavor" and "Natures"are both descriptions of the effect properties of traditional Chinese medicine. At present, researchers have realized that the "Flavors" (Pungent, Sour, Sweet, Bitter and Salty) are related to the different pharmacological effects of treatment. The "Natures" (Warm, Hot, Cold and Cool) are closely related to energy and substance metabolism and contribute to the effect of the "Flavors". Since "Four Natures and five Flavors" are the rules derived from clinical practice, how to describe and characterize "Natures" and "Flavors" scientifically is still a problem that needs to be solved. AIM OF THE STUDY: the aim is to objectively further understand the scientific connotations of properties ("Flavors"and "Natures") from the perspective of metabolomics and characterize them by metabolites. MATERIALS AND METHOD: "Pungent-Neutral", "Sweet-Neutral and "Bitter-Neutral" TCMs were selected to characterize the "Flavors" (Pungent, Sweet and Bitter). "Pungent-Warm" and "Bitter-Cold" were selected to characterize the "Natures" (Warm and Cold). The rat serum metabolomics was performed on UHPLC-Q-Exactive. Metabolites were identified through the metabolites databases and related literature. RESULTS: The "Flavors" and "Natures" metabolites were identified, respectively, including four "Pungent", four "Sweet" and thirteen "Bitter" characterized metabolites and thirteen "Cold" and sixteen "Warm"related metabolites. CONCLUSIONS: The "Natures" characterized metabolites show the "Natures" are closely related to lipid and energy metabolism. The "Warm" may promote lipid metabolism to produce ATP to generate energy through bile acid metabolism and purine metabolism. The "Cold" may inhibit lipid metabolism to generate ATP to decrease energy through the way of tryptophan metabolism and purine metabolism. The "Flavors" characteristic metabolites can provide a theoretical basis for the rules of the "Flavors". These metabolites can also be used to characterize TCM's "Natures" and "Flavors" in the development of traditional Chinese medicine resources and quality control.

Nanocatalytic bacteria disintegration reverses immunosuppression of colorectal cancer.

Tumor-associated bacteria (TAB) play a critically important role in regulating the microenvironment of a tumor, which consequently greatly deteriorates the therapeutic effects by chemo- and radiotherapy deactivation and, more considerably, leads to substantial immunosuppression. On the contrary, herein we propose a nanocatalytic tumor-immunotherapeutic modality based on the bacteria disintegration by bacteria-specific oxidative damage under magnetic hyperthermia for highly effective immune response activation-promoted tumor regression. A monodispersed and superparamagnetic nanocatalytic medicine modified by arginyl-glycyl-aspartic acid (RGD) and (3-carboxypropyl)triphenylphosphonium bromide (TPP), named as MNP-RGD-TPP herein, has been synthesized, which features selective accumulation at the TAB by the electrostatic affinity, enabling effective TAB disintegration by the nanocatalytic Fenton reaction producing abundant cytotoxic hydroxyl radicals in situ under alternating magnetic field-induced hyperthermia. More importantly, the lipopolysaccharide has been metabolically secreted from the destructed TAB as pathogen-associated molecular patterns (PAMPs) to M1-polarize tumor-associated macrophages (TAMs) and promote the maturation of dendritic cells (DCs) for innate immuno-response activation of TAMs, followed by cytotoxic T lymphocytes awakening under the PAMPs presentation by the mature DCs against tumor cells. The integrated innate and adaptive immunity activations based on this TAB-promoted nanocatalytic immunomedicine, instead of magnetic heating-induced hyperthermia or the released Fe2+/Fe3+ Fenton agent, has been found to achieve excellent therapeutic efficacy in an orthotopic colorectal cancer model, demonstrating the great potential of such an integrated immunity strategy in clinical tumor immunotherapy.

Dual Inhibitions on Glucose/Glutamine Metabolisms for Nontoxic Pancreatic Cancer Therapy.

Glucose and glutamine are two principal nutrients in mammalian cells that provide energy and biomass for cell growth and proliferation. Especially in cancer cells, glutamine could be a main alternative for energy and biomass supply once glucose metabolism is suppressed. Therefore, single inhibition of enzymes in either glucose metabolism or glutaminolysis, though maybe efficient in vitro, is far from being satisfactory for efficient in vivo cancer therapy. Here, we proposed a new strategy for dual inhibitions on both glucose and glutamine metabolisms concurrently by silencing mutated gene Kras and glutaminase 1 (GLS1) via nanomaterial-based siKras and siGLS1 delivery, rather than conventional highly toxic chemodrugs. Such a combination therapy could overcome the challenge that glucose and glutamine are alternatives to each other in the biosynthesis and energy production for cancer cells, resulting in much elevated treatment efficacy. In addition, layered double hydroxide (LDH), the siRNA carrier, enables an enhanced gene delivery efficiency compared to the commercial transfection agent Lipofectamine 2000. Briefly, Mg-Al LDH nanosheets, loaded with siKras and siGLS1 onto their surfaces by electrostatic adsorption, could release siRNA from lysosomes into the cytoplasm via the proton sponge effect of LDH, favoring the siRNA stability and gene silencing efficiency enhancements. The thus released siRNA could downregulate the expressions of Kras, GLS1, and other enzymes involved in glucose metabolism, resulting in the downregulations of ATP and other metabolites. Such a biosafe LDH/siRNA nanomedicine is able to efficiently suppress the growth of xenografts through cancer cell proliferation suppression, displaying its great potential as a simultaneous glucose/glutamine metabolism coinhibitor for treating pancreatic cancer.

Enhanced periphyton biodegradation of endocrine disrupting hormones and microplastic: Intrinsic reaction mechanism, influential humic acid and microbial community structure elucidation.

Endocrine-disrupting compounds (EDCs), as well as microplastics, have drawn global attention due to their presence in the aquatic ecosystem and persistence in wastewater treatment plants (WWTPs). In the present study, for simultaneous bio-removal of two EDCs, 17α-ethinylestradiol (EE2), bisphenol A (BPA), and a microplastic, polypropylene (PP) four kinds of periphytic biofilms were employed. Additionally, the effect of humic acid (HA) on the removal efficacy of these biofilms was evaluated. It was observed that EE2 and BPA (0.2 mg L-1 each) were completely (∼100%) removed within 36 days of treatment; and the biodegradation of EE2, BPA, and PP was significantly enhanced in the presence of HA. Biodegradation of EE2 and BPA was evaluated through Ultra-high performance liquid chromatography (UHPLC), and Gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) was used to determine the mechanism of degradation. Gel permeation chromatography (GPC) and SEM had validated the biodegradation of PP (5.2-14.7%). MiSeqsequencing showed that the community structure of natural biofilm changed after the addition of HA, as well as after the addition of EDCs and PP. This change in community structure might be a key factor regarding variable biodegradation percentages. The present study revealed the potential of periphytic biofilms for the simultaneous removal of pollutants of different chemical natures, thus provides a promising new method for wastewater treatment applications.

Intratumoral synthesis of nano-metalchelate for tumor catalytic therapy by ligand field-enhanced coordination.

The iron gall ink-triggered chemical corrosion of hand-written documents is a big threat to Western cultural heritages, which was demonstrated to result from the iron gall (GA-Fe) chelate-promoted reactive oxygen species generation. Such a phenomenon has inspired us to apply the pro-oxidative mechanism of GA-Fe to anticancer therapy. In this work, we construct a composite cancer nanomedicine by loading gallate into a Fe-engineered mesoporous silica nanocarrier, which can degrade in acidic tumor to release the doped Fe3+ and the loaded gallate, forming GA-Fe nanocomplex in situ. The nanocomplex with a highly reductive ligand field can promote oxygen reduction reactions generating hydrogen peroxide. Moreover, the resultant two-electron oxidation form of GA-Fe is an excellent Fenton-like agent that can catalyze hydrogen peroxide decomposition into hydroxyl radical, finally triggering severe oxidative damage to tumors. Such a therapeutic approach by intratumoral synthesis of GA-Fe nano-metalchelate may be instructive to future anticancer researches.

Bio-remediation approaches for alleviation of cadmium contamination in natural resources.

Cadmium (Cd) is a harmful heavy metal that can cause potent environmental and health hazards at different trophic levels through food chain. Cd is relatively non-biodegradable and persists for a long time in the environment. Considering the potential toxicity and non-biodegradability of Cd in the environment as well as its health hazards, this is an urgent issue of international concern that needs to be addressed by implicating suitable remedial approaches. The current article specifically attempts to review the different biological approaches for remediation of Cd contamination in natural resources. Further, bioremediation mechanisms of Cd by microbes such as bacteria, fungi, algae are comprehensively discussed. Studies indicate that heavy metal resistant microbes can be used as suitable biosorbents for the removal of Cd (up to 90%) in the natural resources. Soil-to-plant transfer coefficient (TC) of Cd ranges from 3.9 to 3340 depending on the availability of metal to plants and also on the type of plant species. The potential phytoremediation strategies for Cd removal and the key factors influencing bioremediation process are also emphasized. Studies on molecular mechanisms of transgenic plants for Cd bioremediation show immense potential for enhancing Cd phytoremediation efficiency. Thus, it is suggested that nano-technological based integrated bioremediation approaches could be a potential futuristic path for Cd decontamination in natural resources. This review would be highly useful for the biologists, chemists, biotechnologists and environmentalists to understand the long-term impacts of Cd on ecology and human health so that potential remedial measures could be taken in advance.

UHPLC-MS/MS method for simultaneously detecting 16 tryptamines and their metabolites in human hair and applications to real forensics cases.

Tryptamines are hallucinogenic substances many of which have appeared recently as novel psychoactive substances (NPS). Herein, we describe the establishment of a rapid UHPLC-MS/MS quantitative method for the targeted screening of 16 tryptamines of abuse in hair. Twenty milligram pieces of hair were pulverized below 4 °C in 0.5 mL of deionized water containing 0.1% formic acid and an internal standard (2 ng/mL psilocin-d10 and psilocybin-d4). After subsequent centrifugation, 5 µL of the supernatant was injected into a LC-MS/MS system fitted with a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm). The column was gradient eluted at 0.3 mL/min with mobile phases composed of 20 mmol/L ammonium acetate, 5% acetonitrile, and 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Limits of detection ranged between 0.1 and 20 pg/mg, with limits of quantitation ranging from 3 to 50 pg/mg. The calibration curves for all analytes were linear (r > 0.992). Accuracies varied between 91% and 114%, with intraday precision RSDs < 14% and interday precision RSDs of between 1.3% and 14%. The recoveries of all tryptamines were in the 85-115% range, with the matrix effect ranging from 95% to 112%. The validated method was successfully used to analyse 191 hair samples from suspected tryptamine users, 77 of which were 5-MeO-DiPT-positive, while the 16 tryptamines and their metabolites were not detected in the remaining 114 hair samples. 5-MeO-DiPT and its 5-MeO-NiPT, 5-OH-DiPT, and 4-OH-DiPT metabolites were concurrently detected in 34 hair samples. 5-MeO-DiPT, as the parent drug, was the parent substance found in the hair samples.

Efficient Gene Therapy of Pancreatic Cancer via a Peptide Nucleic Acid (PNA)-Loaded Layered Double Hydroxides (LDH) Nanoplatform.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors with extremely poor prognosis due to the later stage diagnosis when surgical resection is no longer applicable. Alternatively, the traditional gene therapy which drives pancreatic cancer cells into an inactive state and inhibiting the proliferation and metastasis, presents potentials to safely inhibit pancreatic cancer progression, but unfortunately has received limited success to date. Here, an efficient gene therapy of pancreatic cancer is shown via a peptide nucleic acid (PNA)-loaded layered double hydroxides (LDHs) nanoplatform. Compared with the traditional DNA- or RNA-based gene therapies, the gene therapy using PNA features great advantages in recognizing and hybridizing with the target mutant sequences to form PNA-DNA hybrids with significantly enhanced stability due to the absence of electrostatic repulsion, and the constrained flexibility of the polyamide backbone. Moreover, ultrasmall LDHs are engineered to load PNA and the obtained PNA-loaded LDH platform (LDHs/PNA) is capable of efficiently and selectively targeting the intranuclear mutant sequences thanks to the proton sponge effect. Treatments with LDHs/PNA demonstrate markedly inhibited growth of pancreatic cancer xenografts via a cancer cell proliferation suppression mechanism. The results demonstrate the great potentials of LDHs/PNA as a highly promising gene therapy agent for PDAC.

Analysis of pesticide residues in commercially available chenpi using a modified QuEChERS method and GC-MS/MS determination.

To ensure the safety of the commercially available chenpi, a convenient and fast analytical method was developed for the determination of 133 pesticide residues in chenpi using gas chromatography-tandem mass spectrometry (GC-MS/MS). In this study, different extraction solvents, redissolution solvents and adsorbents were tested according to the recovery and purification effect to obtain a modified QuEChERS method. The samples were extracted with acetonitrile. During the clean-up step, octadecyl-modified silica (C18) and graphitized carbon black (GCB) were selected, and aminopropyl (NH2) was used instead of primary secondary amine (PSA) because of its weaker ion exchange capacity which had little effect on the recovery of ditalimfos. Samples were quantified by matrix-matched calibration with internal standards. All pesticides showed good linearity in the respective range, both with values of r 2 > 0.99. The average recoveries of the pesticides spiked samples ranged from 70.0% to 112.2% with the RSDs of 0.2%-14.4%. The modified QuEChERS method was validated and applied to twenty real samples. Five pesticides were found in eight batches, but no pesticide exceeded the maximum residue limits (MRL, MRL reference to European commission).

Determination of 5-MeO-DIPT in Human Urine Using Gas Chromatography Coupled with High-Resolution Orbitrap Mass Spectrometry.

5-Methoxy-N,N-Diisopropyltryptamine (5-MeO-DIPT) is a designer hallucinogen derived from tryptamine and its use has been banned by many countries. In this study, a qualitative and quantitative method was developed for determining 5-MeO-DIPT in urine by gas chromatography high-resolution mass spectrometry. 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N-isopropyltryptamine (5-MeO-IPT) were identified as 5-MeO-DIPT metabolites in abusers' urine. 5-MeO-DIPT was extracted from urine by liquid-liquid extraction with ethyl acetate under alkaline conditions. The extract was analyzed by GC-Orbitrap-MS in full scan mode with a resolution of 60,000 full width at half maxima (FWHM). The linear range of this method was 2-300 ng/mL with r > 0.99, and the limit of detection was 1 ng/mL. The accuracy and precision were 93-108.7% and 3.1-10.3%, respectively. This method is simple and sensitive. It has been successfully used to detect 5-MeO-DIPT in drug abusers' urine, which showed that the concentrations of 5-MeO-DIPT were between 1 and 2.8 ng/mL. 5-OH-DIPT and 5-MeO-IPT, two urinary major metabolites of 5-MeO-DIPT, were identified in urine samples from 5-MeO-DIPT users. Furthermore, the stability of 5-MeO-DIPT in human urine was investigated. It was discovered that the concentration of 5-MeO-DIPT in urine decreased by 22.8, 33.2 and 38.2% after samples were stored for 24 h at 25°C, 5 days at 4°C and 7 days at 4°C, respectively. And 5-MeO-DIPT in urine were stable after they were stored for 30 days at -20°C. Therefore, it is recommended that urine should be stored under freezing conditions before performing 5-MeO-DIPT analysis.

Novel drug isolated from mistletoe (1E,4E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one for potential treatment of various cancers: synthesis, pharmacokinetics and pharmacodynamics.

(1E,4E)-1,7-Bis(4-hydroxyphenyl)hepta-1,4-dien-3-one (DHDK) is a novel curcuminoid analogue isolated from mistletoe. DHDK exhibits better anti-tumour activity, higher bioavailability and superior stability than curcumin. DHDK is difficult to isolate from Viscum coloratum, but it can be synthesised. MTT (methylthiazolyldiphenyl tetrazolium bromide) assay was used to evaluate the in vitro cytotoxic activity of synthesised DHDK on 12 cancer cell lines. Results showed that DHDK exhibited excellent potential as an anticancer agent, especially for breast and lung cancer. Efficacy was further evaluated in vivo by using MCF-7 breast cancer models. DHDK showed a dose-dependent relationship without weight reduction, mortality growth inhibition or tissue toxicity. Pharmacokinetics and tissue distribution statistics were determined by LC-ESI-MS/MS. This work provided preliminary data on this natural compound and could open up new prospects for changing related parameters to improve drug efficacy.

Rapid characterization of chemical constituents of Gansuibanxia decoction by UHPLC-FT-ICR-MS analysis.

Gansuibanxia decoction (GSBXD) is one of the most famous traditional Chinese medicine (TCM). It is a herbal formula used for treating hydrops, such as cancerous ascites, pleural effusion, pericardial effusion, etc. However, the chemical constituents of GSBXD were still unclear. In this study, an UHPLC-FT-ICR-MS method was established and applied to the separation and characterization of the chemical constituents of GSBXD. A total of 62 components were chemically defined or tentatively identified, including diterpenoids, triterpenoids, flavonoids, monoterpene glycosides and alkaloids. The results is meaningful for a better understanding of the material basis of GSBXD and can be the basis for its further in vitro and in vivo studies.

Investigation of the mechanism of incompatible herb pair gansui-gancao-induced hepatotoxicity and nephrotoxicity and the attenuated effect of gansuibanxia decoction by UHPLC-FT-ICR-MS-based plasma metabonomic analysis.

Gansui-Gancao is one of the "eighteen incompatible herb pairs" which was recorded 2000 years ago according to TCM (Traditional Chinese Medicine) theory for their toxicity when using together. Nevertheless, Gansuibanxia decoction contained the herb pair have satisfactory effect on the treatment of cancerous ascites, pericardial effusion, etc. The present study aimed to investigate the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction using UHPLC-FT-ICR-MS in a metabonomic perspective. Rats were divided into four groups administrated with different herb combination extracts for successive 14 days. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to plot the metabolic state and screen the potential biomarkers in plasma. A total of 20 biomarkers contributed to the separation of Gansui-Gancao group and control group were tentatively identified mainly involved in 7 metabolic pathways related to hepatotoxicity and nephrotoxicity. The contents of these biomarkers were adjusted to normal levels in Gansuibanxia decoction group. Thus, the results of our study reveled the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction in a metabonomic perspective and it's valuable for better understanding the "eighteen incompatible madicaments" of TCM theory.

Development of a high-throughput screening analysis for 288 drugs and poisons in human blood using Orbitrap technology with gas chromatography-high resolution accurate mass spectrometry.

The screening analysis for drugs and poisons always symbolizes the capabilities of a forensic laboratory. Due to the rapid emergence of new compounds in clinical and forensic intoxication cases, sensitive and specific methods are necessary for the screening of wide range of target compounds. A novel high-throughput screening method has been developed for the toxicological analysis of 288 drugs and poisons in human blood using Orbitrap technology with gas chromatography-high resolution mass spectrometry (GC-HRMS). This method allows for the fast detection and identification of high-throughput forensically important drugs and poisons, e.g., drugs of abuse (cocaine, amphetamines, synthetic cannabinoids, opiates, hallucinogen), sedative-hypnotics, antidepressants, non-steroidal anti-inflammatory drugs, pesticides (acaricides, fungicides, insecticides, nematicides), and cardiovascular agents in one single GC-Q Exactive run. After a simple extraction with ethyl ether and buffer, following centrifugation, the supernatant was injected into the system. For detection, spiked blood samples were analyzed by Orbitrap-GC-HRMS using an electrospray ionization in full scan mode with a scan range from 40 to 650 (m/z). The identification of drugs and poisons in the samples was carried out by searching the accurate molecular mass of characteristic fragment ions, ion rations and retention time (RT) against the in-house library that we developed with 70 ev electron energy. The limit of detection (LOD) for most compounds (249 in a total of 288 compounds) was below 100 ng/mL. For selectivity, no substances have been identified in drug-free blood samples from six different sources, and the method was suitable for the recovery and the carryover. The coefficient of variation (CV) of the RTs was below 0.99% in all reproducibility experiments. Mass accuracy was always better than 3 ppm, corresponding to a maximum mass error of 1.04 millimass units (mmu). The developed method was applied to 136 real samples from forensic cases, demonstrating its suitability for the sensitive and fast screening of high-throughput drugs in human blood samples.