Targeted Quantification of Glutathione/Arginine Redox Metabolism Based on a Novel Paired Mass Spectrometry Probe Approach for the Functional Assessment of Redox Status.

Glutathione (GSH) redox control and arginine metabolism are critical in regulating the physiological response to injury and oxidative stress. Quantification assessment of the GSH/arginine redox metabolism supports monitoring metabolic pathway shifts during pathological processes and their linkages to redox regulation. However, assessing the redox status of organisms with complex matrices is challenging, and single redox molecule analysis may not be accurate for interrogating the redox status in cells and in vivo. Herein, guided by a paired derivatization strategy, we present a new ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based approach for the functional assessment of biological redox status. Two structurally analogous probes, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and newly synthesized 2-methyl-6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (MeAQC), were set for paired derivatization. The developed approach was successfully applied to LPS-stimulated RAW 264.7 cells and HDM-induced asthma mice to obtain quantitative information on GSH/arginine redox metabolism. The results suggest that the redox status was remarkably altered upon LPS and HDM stimulation. We expect that this approach will be of good use in a clinical biomarker assay and potential drug screening associated with redox metabolism, oxidative damage, and redox signaling.

FNICM: A New Methodology To Identify Core Metabolites Based on Significantly Perturbed Metabolic Subnetworks.

Metabolomics has emerged as a powerful tool in biomedical research to understand the pathophysiological processes and metabolic biomarkers of diseases. Nevertheless, it is a significant challenge in metabolomics to identify the reliable core metabolites that are closely associated with the occurrence or progression of diseases. Here, we proposed a new research framework by integrating detection-based metabolomics with computational network biology for function-guided and network-based identification of core metabolites, namely, FNICM. The proposed FNICM methodology is successfully utilized to uncover ulcerative colitis (UC)-related core metabolites based on the significantly perturbed metabolic subnetwork. First, seed metabolites were screened out using prior biological knowledge and targeted metabolomics. Second, by leveraging network topology, the perturbations of the detected seed metabolites were propagated to other undetected ones. Ultimately, 35 core metabolites were identified by controllability analysis and were further hierarchized into six levels based on confidence level and their potential significance. The specificity and generalizability of the discovered core metabolites, used as UC's diagnostic markers, were further validated using published data sets of UC patients. More importantly, we demonstrated the broad applicability and practicality of the FNICM framework in different contexts by applying it to multiple clinical data sets, including inflammatory bowel disease, colorectal cancer, and acute coronary syndrome. In addition, FNICM was also demonstrated as a practicality methodology to identify core metabolites correlated with the therapeutic effects of Clematis saponins. Overall, the FNICM methodology is a new framework for identifying reliable core metabolites for disease diagnosis and drug treatment from a systemic and a holistic perspective.

Reactive oxygen species contribute to delirium-like behavior by activating CypA/MMP9 signaling and inducing blood-brain barrier impairment in aged mice following anesthesia and surgery.

Postoperative delirium (POD) is common in the elderly and is associated with poor clinical outcomes. Reactive oxygen species (ROS) and blood-brain barrier (BBB) damage have been implicated in the development of POD, but the association between these two factors and the potential mechanism is not clear. Cyclophilin A (CypA) is a specifically chemotactic leukocyte factor that can be secreted in response to ROS, which activates matrix metalloproteinase 9 (MMP9) and mediates BBB breakdown. We, therefore, hypothesized that ROS may contribute to anesthesia/surgery-induced BBB damage and delirium-like behavior via the CypA/MMP9 pathway. To test these hypotheses, 16-month-old mice were subjected to laparotomy under 3% sevoflurane anesthesia (anesthesia/surgery) for 3 h. ROS scavenger (N-acetyl-cysteine) and CypA inhibitor (Cyclosporin A) were used 0.5 h before anesthesia/surgery. A battery of behavior tests (buried food test, open field test, and Y maze test) was employed to evaluate behavioral changes at 24 h before and after surgery in the mice. Levels of tight junction proteins, CypA, MMP9, postsynaptic density protein (PSD)-95, and synaptophysin in the prefrontal cortex were assessed by western blotting. The amounts of ROS and IgG in the cortex of mice were observed by fluorescent staining. The concentration of S100ß in the serum was detected by ELISA. ROS scavenger prevented the reduction in TJ proteins and restored the permeability of BBB as well as reduced the levels of CypA/MMP9, and further alleviated delirium-like behavior induced by anesthesia/surgery. Furthermore, the CypA inhibitor abolished the increased levels of CypA/MMP, which reversed BBB damage and ameliorated delirium-like behavior caused by ROS accumulation. Our findings demonstrated that ROS may participate in regulating BBB permeability in aged mice with POD via the CypA/MMP9 pathway, suggesting that CypA may be a potential molecular target for preventing POD.

Dexmedetomidine Combined with Femoral Nerve Block Provides Effective Analgesia Similar to Femoral Nerve Combined with Sciatic Nerve Block in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Study.

BACKGROUND: Total knee arthroplasty (TKA) is a severe traumatic procedure, and femoral nerve block (FNB) combined with a sciatic nerve block (SNB) is widely used in TKA. However, injury of the sciatic nerve is clinically reported. Dexmedetomidine (DEX) could reduce stress and inflammation, as well as improve pain in TKA. This study aims to observe the analgesic impact of DEX combined with FNB in TKA. METHODS: Eighty-eight patients undergoing TKA were included and randomly divided into two groups: DF group (FNB combined with DEX 0.6µg/kg before surgery, followed by DEX 0.2-0.4µg/kg/h until articular closure) and SF group (FNB combined with SNB). Each nerve was blocked with 0.375% ropivacaine 20mL, and all patients received general anesthesia routinely. The primary endpoint was the pain visual analog scale (VAS) score during activities at postoperative 24 hours. RESULTS: There was no statistical difference in the pain VAS scores at any time point. The mean duration of analgesia for patients with rescue analgesic requests was comparable between the two groups: 25.4 ± 6.3 hours in the DF group vs 24.8 ± 6.4 hours in the SF group (two-sample t-test, p=0.738). The total dose of sufentanil was similar between groups (P=0.355). The maintenance dose of propofol and dose of rescue analgesics were comparable (all P>0.05). There were no statistical differences in the incidence of adverse events. However, the time to extubate in the DF group was significantly longer than those in the SF group (P<0.001). CONCLUSION: DEX combined with FNB could provide effective analgesia similar to SNB combined with FNB in TKA. CLINICAL TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on November 17, 2019 (identifier: ChiCTR1900027552).

Measurement of Intracellular Nitric Oxide with a Quantitative Mass Spectrometry Probe Approach.

Nitric oxide (NO) is a molecule of physiological importance, and the function of NO depends on its concentration in biological systems, particularly in cells. Concentration-based analysis of intracellular NO can provide insight into its precise role in health and disease. However, current methods for detecting intracellular NO are still inadequate for quantitative analysis. In this study, we report a quantitative mass spectrometry probe approach to measure NO levels in cells. The probe, Amlodipine (AML), comprises a Hantzsch ester group that reacts with NO to form a pyridine, Dehydro Amlodipine (DAM). Quantification of DAM by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) allows specific measurement of intracellular NO levels. Notably, the AML/NO reaction proceeds rapidly (within 1 s), which is favorable for NO detection considering its large diffusivity and short half-life. Meanwhile, studies under simulated physiological conditions revealed that the AML response to NO is proportional and selective. The presented UPLC-MS/MS method showed high sensitivity (LLOQ = 0.24 nM) and low matrix interference (less than 15%) in DAM quantification. Furthermore, the mass spectrometry probe approach was demonstrated by enabling the measurement of endogenous and exogenous NO in cells. Hence, the quantitative UPLC-MS/MS method developed using AML as a probe is expected to be a new method for intracellular NO analysis.

Individualized Treatment and Palliative Care for A 90-Year-Old Patient with Primary Gastric Diffuse Large-B Cell Lymphoma: 4 Year Follow-up and Inspiration.

A 90-year-old man was diagnosed with primary gastric diffuse large B-cell lymphoma (PGDLBL) by PET/CT examination, gastroscopy, biopsy and histopathological analysis at a regular physical check in April, 2016. The patient received R-CO chemotherapy (rituximab, cyclophosphamide, and vincristine) and radiotherapy subsequently, with enteral nutritional treatment through 3-cavity nasogastric tube due to development of pyloric obstruction. To satisfy patient's strong desire of eating by himself, we performed surgery of exploratory laparotomy and Roux-en-Y gastric bypass (RGB) to relieve pylorus obstruction. Postoperatively, the patient resumed oral feeding, supplemented by nasogastric tube feeding at 1350 - 1550 Kcal daily. He is now 94 years old with fairly well nutrition and normal communication. The outcome of 4 year follow-up suggests that nutritional treatment and palliative medicine are important for improving prognosis and life-quality of very elderly patients with end-stage tumors apart from the effective chemotherapy, radiotherapy, and surgery.

Autophagic degradation of PML promotes susceptibility to HSV-1 by stress-induced corticosterone.

Rationale: Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that can cause a variety of clinical syndromes including mucocutaneous disease and HSV-1 encephalitis (HSE). Here, we characterize the molecular mechanisms underlying the susceptibility to HSV-1 under stressful conditions. Methods: Restraint stress and corticosterone (CORT, a primary stress hormone) were respectively used to establish HSV-1 susceptible model in vivo and in vitro. Viral titers were determined by plaque assay. Western blotting, immunofluorescence, transmission electron microscopy (TEM), qRT-PCR, H&E staining, IHC staining and flow cytometry were employed to evaluate virus-related protein expressions and detect the activation of autophagy. Loss- and gain-function assays, co-immunoprecipitation (co-IP) technique and autophagy agonist/antagonist treatments were applied in mechanistic experiments. Results: Restraint stress increased the susceptibility of mouse brain to HSV-1. Similarly, CORT treatment enhanced the susceptibility of neural cells to HSV-1. Furthermore, PML protein level in HSV-1 infected brain tissues and neural cells was remarkably decreased by stress treatment in vivo or CORT treatment in vitro, while its transcriptional level was not affected. Notably, a striking decline in protein expressions of ICP27 and gB was observed in PML-overexpressing cells, which was reversed by CORT treatment. By contrast, protein expression of gB was increased by knockdown with si-PML in virus-infected SH-SY5Y cells. We further discovered that CORT-driven PML degradation was dependent on the activation of autophagy in a ULK1-independent manner, rather than proteasome pathway. Bafilomycin A1 (BaF1) attenuated the augmentation effect of CORT on HSV-1 infection. The expressions of viral proteins were reduced in LC3-depleted cells, and the degradation of PML by CORT-induced autophagy was prevented in cells with LC3 knockdown by RNAi. Interestingly, PML was revealed to interact with the autophagic cargo receptor P62 and the autophagic effector protein LC3. Additionally, CORT failed to increase gB protein level when PML was silenced, providing direct evidence linking autophagic degradation of PML and CORT-induced virus susceptibility. Conclusion: Our results revealed that restraint stress/CORT increased HSV-1 susceptibility by delivering PML into autolysosomes for degradation. The results obtained from in vitro and in vivo models not only demonstrated the adverse effects of stress on HSV-1 infection, but also systematically investigated the underlying molecular mechanisms. These discoveries broaden our understanding of the interplay between host and viruses, and a comprehensive understanding of the role of autophagy in viral infection will provide information for future development of innovative drugs against viral infection.

Effect of sulfur-fumigation process on ginseng: Metabolism and absorption evidences.

ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation has been developed to prevent insects and molds during post-harvest handling of Panax ginseng C.A. Mey (ginseng) in the near decades. Our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives (SFCDs), the artifacts with unknown toxicity. However, whether the biotransformation could be occurred and absorption characteristics between ginsenosides and SFCDs are still needed to further investigate. AIM OF THE STUDY: To evaluate the effect of sulfur-fumigation process on ginseng through comparing the metabolic profile and absorption characteristics between ginsenoside Rg1, Re and their SFCDs. MATERIALS AND METHODS: Intestinal microflora and liver S9 fraction were utilized to compare the metabolic profile, and single-pass intestinal perfusion and Caco-2 cell models were applied to compare the absorption characteristics, between Rg1, Re and their SFCDs. RESULTS: Rg1 and Re were metabolized to 7 none sulfur-containing metabolites, while their SFCDs were metabolized to 18 sulfur-containing metabolites. The intestinal absorption and transport of Rg1 and Re were much greater than their SFCDs. Besides, the uptakes of Rg1 and Re were transport-dependent, but their SFCDs were non-transport-dependent. CONCLUSION: Ginsenosides and their SFCDs could not be bio-transformed with each other and their absorption characteristics were quite different, which suggested that sulfur-fumigation is not a feasible post-harvest process of ginseng.

Screening of Biomarkers Related to Ovarian Maturation and Spawning in Blunt Snout Bream (Megalobrama amblycephala) Based on Metabolomics and Transcriptomics.

In fish breeding practices, gamete maturity of females is vital to reproductive success. For some species, it is possible to estimate the female maturation status based on abdomen observation, but quite difficult for some species which mature at big size. To screen out the potential biomarker in fish blood relating to female maturation, we employed the approach integrating the UPLC-MS/MS and RNA-seq techniques to investigate the metabolites and genes reflecting the sexual maturation and spawning of female blunt snout bream Megalobrama amblycephala. The study included four groups, 1-year-old immature female individuals, 2-year-old immature female individuals, 2-year-old sexually mature female individuals, and 2-year-old sexually mature female individuals after 24 h of successful spawning. The upregulated metabolites in mature females were involved in "steroid hormone biosynthesis," "metabolic pathways," "glycerophospholipid metabolism," etc. compared with those of immature individuals. As the key intermediate of steroid hormone biosynthesis, 17α-hydroxypregnenolone exhibited the highest level in 2-year-old mature females than in the immature females. Meanwhile, the metabolites (i.e., dodecanoic acid and myristic acid) participating in fatty acid synthesis exhibited much lower levels in the females after spawning than those before spawning. In addition to the metabolites, the genes involved in ovarian steroidogenesis were significantly upregulated in the 2-year-old immature females compared to the 1-year-old immature females, indicating that the ovarian steroidogenesis plays important roles in ovarian development of M. amblycephala at the early stages. The significant upregulation of genes (i.e., itpr1, camk2, and mekk2) involved in the "GnRH signaling pathway" was observed in the mature females compared with the immature females, which indicated that the estrogen levels increased after female maturation in M. amblycephala. Moreover, many genes (e.g., gck, creb1, tf2-9, ryr2, asgr1, and creb1) regulating insulin secretion and thyroid hormone synthesis were significantly downregulated after female spawning. The dynamics of gene expression and metabolites observed in this study provide novel cues for guiding fish practical artificial reproduction.

Epidemiological and Immunological Features of Influenza Viruses in Hospitalized Children with Influenza Illness in Hangzhou.

Objectives: We evaluated the epidemiological features and various inflammatory markers in hospitalized children with influenza virus infection in China. Methods: The real-time RT-PCR assay was performed for detection and genotyping of influenza A and B virus. Th1/Th2 cytokines, WBC, and CRP were determined in influenza virus positive children. Results: H1N1 and Yamagata were the prevalent genotypes of influenza A and B virus in Hangzhou, respectively. IL-2, IL-10, and CRP were significantly increased and IFN-γ was decreased in children with severe Influenza A virus infection, and TNF-α and IFN-γ levels were found to be significantly lower in children with severe Influenza B virus infection. Conclusion: Increased IL-2, IL-10, and CRP with decreased IFN-γ may indicate a severe influenza A virus infection, and decreased TNF-α and IFN-γ may indicate a severe influenza B virus infection in children.

Chemical constituents from common vetch (Vicia sativa L.) and their antioxidant and cytotoxic activities.

Vicia sativa L. (common vetch) is a potential food source for both human beings and animals because of its abundant nutritional composition. There is a lack of phytochemical study on the whole plant, and thus the objective of this study was to investigate the isolation of phytochemicals and evaluate their biological activities. A new flavanol, (2R,3S)-3,3'-dihydroxy-4',7-dimethoxyflavanol (1), together with nine known compounds, two flavones (2-3), one coumarin (4), and six oleanane triterpenoids (5-10), was obtained from Vicia sativa L.. The structure of the new compound 1 was determined via its NMR spectra, IR and CD data. Compound 3 displayed the potential of the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging effect in antioxidant test. In terms of cytotoxic activities, compound 3 showed moderate cytotoxic activities against three human tumor cells, especially HeLa cells.

Correction: Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material.

Correction for 'Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material' by Wei-Tao Dou et al., Chem. Commun., 2019, 55, 13235-13238.

Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material.

Protein C receptor (PROCR) is a recently discovered transmembrane biomarker for several tissue stem cells and is highly expressed in triple-negative breast cancer (TNBC) patient-derived xenografts. Herein, to enrich the toolbox for the biochemical evaluation of PROCR, we have developed a peptide-functionalized fluorogenic 2D material based on the self-assembly between a fluorescent peptide probe and thin-layer molybdenum disulfide. The material developed was suitable for the sensitive detection of PROCR recombinant protein in buffer solution and the fluorescence imaging of TNBC cells that express high levels of PROCR.

Genetic polymorphisms of ARID5B rs7089424 and rs10994982 are associated with B-lineage ALL susceptibility in Chinese pediatric population.

BACKGROUND: Several ARID5B single nucleotide polymorphisms (SNPs) were confirmed to be significantly associated with the susceptibility of childhood acute lymphoblastic leukemia (ALL) based on Caucasian populations in previous studies. Similar investigations in Asian populations were less. The aim of this study is to explore the relationship between ARID5B SNPs rs7089424, rs10994982, and the risk of ALL in Chinese pediatric population. METHODS: A total of 190 pediatric ALL patients and 270 controls were enrolled in this study. PCR amplification combined with mass spectrometry were used to evaluate the genotypes of ARID5B rs7089424 and rs10994982. χ test was used in allele frequencies and genotype distributions of the SNPs for analyzing statistical differences between patients and controls. RESULTS: There were significant differences in the risk allele frequencies of ARID5B rs7089424 and rs10994982 between B-lineage ALL (B-ALL) patients and controls (rs7089424, G allele: p = 0.001; rs10994982, A allele: p = 0.000). The genotype distributions of ARID5B rs7089424 and rs10994982 were also statistically different in B-ALL patients compared with controls (rs7089424, p = 0.004; rs10994982, p = 0.001). Further analyzing the relevance of ARID5B rs7089424 and rs10994982 genotypes to clinical risk classification of ALL showed GG genotype of rs7089424 and AA genotype of rs10994982 were strikingly correlated with the medium-risk and low-risk groups of B-ALL. Finally, GG and GT genotypes of rs7089424 and AA genotype of rs10994982 seemed to be responsible for the hyperdiploid subtype susceptibility of childhood B-ALL. CONCLUSION: ARID5B rs7089424 and rs10994982 might serve as genetic susceptibility markers for B-ALL in Chinese pediatric population. Moreover, the two ARID5B SNPs are associated with the risk of B-hyperdiploid ALL, which had a better therapeutic response than other ALL subtypes.

Comparison of OA-2000 and IOL Master 500 using in cataract patients with high myopia.

This study was designed to compare optical biometry measurements and predicted refraction in cataract patients with high myopia [axial length (AL) ≥26 mm] using OA-2000 and IOL Master 500. Ocular biometry measurements were performed using both biometers before surgery. Uneventful cataract surgery was performed in all patients. Postoperative manifest refraction was obtained 3wk after surgery or later. A total of 67 eyes were examined. The AL, keratometry (K), and anterior chamber depth (ACD) of the two biometers showed excellent agreement. Predicted errors were similar and a strong positive correlation was observed (r=0.909). Out of 21 eyes (31.34%) with unsuccessful AL readings using the IOL Master 500, 20 eyes of them could be measured using OA-2000. Therefore, the biometric parameters measured by the two biometers showed good agreement. However, OA-2000 had a lower AL measurement failure rate.

Paeonol: pharmacological effects and mechanisms of action.

Paeonia suffruticosa possesses various medicinal benefits and has been used extensively in traditional oriental medicine for thousands of years. Paeonol is the main component isolated from the root bark of Paeonia suffruticosa. The pharmacological effects of Paeonia suffruticosa are mostly attributed to paeonol. Paeonol injection has been successfully applied in China for nearly 50 years for inflammation/pain-related indications. Currently, the dosage forms of paeonol approved by China Food and Drug Administration include tablet, injection, and external preparations such as ointment and adhesive plaster. So far, the clinical applications of paeonol are mainly focusing on the anti-inflammatory activity. Studies of other pharmacological activities of paeonol are developing rapidly, and which may play an important role in the future. Besides, substantial mechanisms of pharmacological action of paeonol have been clarified in recent years. In this review, we summarize the pharmacological effects anti-inflammatory, neuroprotective, anti-tumor, anti-cardiovascular diseases and associated mechanisms of action of paeonol up to date.

Iridoid Derivatives with Cytotoxic Activity from Pedicularis uliginosa Bunge.

Three new iridoids, rel-(4aR,7S,7aS)-7-hydroxy-7-methyl-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carbaldehyde (1), 1-methoxy-7-methyl-1,3,5,6-tetrahydrocyclopenta[c]pyran-4-carbaldehyde (2), and rel-(1R,4S,4aS,7R,7aR)-7-methylhexahydro-1,4-(epoxymethano)cyclopenta[c]pyran-3(1H)-one (3), together with seven known analogues, were isolated from the 95 % EtOH extract of the whole plants of Pedicularis uliginosa Bunge. Their structures were elucidated via extensive NMR spectroscopy and mass spectral data. In terms of inhibitory effects on human tumor cells, compounds 1, 2, 6, 7, and 8 exhibited better inhibitory activities against ACHN cells than the positive control (vinblastine).

Succinate induces synovial angiogenesis in rheumatoid arthritis through metabolic remodeling and HIF-1α/VEGF axis.

BACKGROUND AND PURPOSE: In response to hypoxic succinate accumulates in arthritis synovium, however, the implication is little known. This study aims to investigate whether succinate could act as a metabolic signal linking metabolic alternation with angiogenesis in arthritis synovium. EXPERIMENTAL APPROACH: The interaction between elevated succinate and VEGF production was examined in endothelial cells. Succinate production, HIF-1α induction and angiogenesis in the hypoxic synovium of collagen-induced arthritis rats were also investigated. KEY RESULTS: Intracellular succinate promoted VEGF production and induced angiogenic response dependent on HIF-1α induction in endothelial cells. Luciferase reporter assay showed that succinate increased VEGF expression through gene promoter activation dependent on HIF-1α induction. Intracellular succinate released into intercellular space, where extracellular succinate activated succinate receptor G-protein-coupled receptor 91 (GPR91) and induced VEGF production, further exacerbating angiogenesis. In addition, TGF-ß1 treatment increased succinate production due to the reversal of succinate dehydrogenase (SDH) activation, and consistently, SDH inhibitor dimethyl malonate reduced angiogenesis in the arthritis synovium. CONCLUSION AND IMPLICATIONS: More than an intermediate, succinate functioned as a signaling molecule to link metabolic reprograming with angiogenesis. Intracellular succinate induced angiogenesis through HIF-1α induction, while extracellular succinate acted on GPR91 activation, working together to disturb energy metabolism and exacerbate inflammation and angiogenesis in arthritis synovium. Our work suggested that suppression of SDH could prevent succinate accumulation and inhibit angiogenesis via blocking HIF-1α/VEGF axis. This finding not only provides a novel insight into angiogenesis, but also reveals a potential therapeutical strategy to attenuate revascularization in arthritis.

Mechanisms of Lung Cancer Caused By Cooking Fumes Exposure: A Minor Review△.

Cooking fumes (CFs) are mixtures of many toxic components, such as aldehydes, heterocyclic amines, polycyclic aromatic hydrocarbons, fat aerosols and particulate matters. CFs exposure has been proven to be associated with many diseases. Lung cancer takes the leading place among the diseases being reported caused by CFs exposure. Molecular and biochemical studies have found that CFs exposure may lead to lung cancer by gene damage, formation of reactive oxygen species, blockage of related proteins' function, and even cell death. However, reviews about the mechanisms of how CFs exposure leads to lung cancer are still lacking. Elucidation of the mechanisms of lung cancer caused by CFs exposure may provide a new insight into the prevention of lung cancer caused by CFs exposure, as well as laying the foundation for the toxicity study of CFs. In this minor review, the mechanisms of how CFs exposure leads to lung cancer were summarized and discussed.

UPLC/ESI-QTOF-MS-based metabolomics survey on the toxicity of triptolide and detoxication of licorice.

Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.