Recent tobacco smoking, restaurant and in-car secondhand smoke exposure are associated with depressive symptoms among young adults: a population-based cross-sectional analysis.

The purpose of this study was to evaluate the association between recent tobacco smoking, household secondhand smoke exposure, confined space secondhand smoke exposure and depressive symptoms in young adults after adjustments for each other. Data from NHANES 2013-2018 were extracted. A total of 4129 young adults age 18-35 years (mean age 26.11 ± 5.39 years, 2021 males and 2108 females) were included. Depressive symptoms were screened by PHQ-9. Recent tobacco smoking was assessed through question "smoked tobacco in the last 5 days?". Household secondhand smoke exposure was assessed through question "living with a smoker who smoked inside the house?". Confined space secondhand smoke exposure was assessed by SSEQ. Binary logistic regression models were performed to analyze the associations. Significant association were observed in recent tobacco smoking (OR = 1.593, 95% CI 1.318-1.926) and confined space secondhand smoke exposure (OR = 1.399, 95% CI 1.185-1.651), but not in household secondhand smoke exposure (P = 0.108). Among the different settings of confined space secondhand smoke exposure, restaurant (OR = 1.732, 95% CI 1.120-2.678) and in-car (OR = 1.350, 95% CI 1.102-1.652) exposure were significantly associated with depressive symptom after after fully adjustments.

Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation.

Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1ß, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.

Dietary gallic acid as an antioxidant: A review of its food industry applications, health benefits, bioavailability, nano-delivery systems, and drug interactions.

Gallic acid (GA), a dietary phenolic acid with potent antioxidant activity, is widely distributed in edible plants. GA has been applied in the food industry as an antimicrobial agent, food fresh-keeping agent, oil stabilizer, active food wrap material, and food processing stabilizer. GA is a potential dietary supplement due to its health benefits on various functional disorders associated with oxidative stress, including renal, neurological, hepatic, pulmonary, reproductive, and cardiovascular diseases. GA is rapidly absorbed and metabolized after oral administration, resulting in low bioavailability, which is susceptible to various factors, such as intestinal microbiota, transporters, and metabolism of galloyl derivatives. GA exhibits a tendency to distribute primarily to the kidney, liver, heart, and brain. A total of 37 metabolites of GA has been identified, and decarboxylation and dihydroxylation in phase I metabolism and sulfation, glucuronidation, and methylation in phase Ⅱ metabolism are considered the main in vivo biotransformation pathways of GA. Different types of nanocarriers, such as polymeric nanoparticles, dendrimers, and nanodots, have been successfully developed to enhance the health-promoting function of GA by increasing bioavailability. GA may induce drug interactions with conventional drugs, such as hydroxyurea, linagliptin, and diltiazem, due to its inhibitory effects on metabolic enzymes, including cytochrome P450 3A4 and 2D6, and transporters, including P-glycoprotein, breast cancer resistance protein, and organic anion-transporting polypeptide 1B3. In conclusion, in-depth studies of GA on food industry applications, health benefits, bioavailability, nano-delivery systems, and drug interactions have laid the foundation for its comprehensive application as a food additive and dietary supplement.

Comprehensive review of the phytochemistry, pharmacology, pharmacokinetics, and toxicology of alkamides (2016-2022).

Alkamides refer to a class of natural active small-molecule products composed of fatty acids and amine groups. These compounds are widely distributed in plants, and their unique structures and various pharmacological activities have caught the attention of scholars. This review provides a collection of literatures related to the phytochemistry, pharmacological effects, pharmacokinetics, and toxicity of alkamides published in 2016-2022 and their summary to provide references for further development of this class of ingredients. A total of 234 components (including chiral isomers) were summarized, pharmacological activities, such as anti-inflammatory, antitumor, antidiabetic, analgesic, neuroprotective, insecticidal, antioxidant, and antibacterial, and miscellaneous properties of alkamides were discussed. In addition, the pharmacokinetic characteristics and toxicity of alkamides were reviewed. However, information on the pharmacological mechanisms of the action, drug safety, and pharmacokinetics of alkamides is limited and thus requires further investigation and evaluation.

Protoberberine alkaloids: A review of the gastroprotective effects, pharmacokinetics, and toxicity.

BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

Skin irritation assessment and potential mechanism of Capparis spinosa L. fruits.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Capparis spinosa L. fruits (CSF) are often used topically in Uyghur folk medicine in treating rheumatic diseases with remarkable efficacy. However, it has noticed severe skin irritation after a short time application with high dose of CSF, which limited long-term clinical use. To date, there is almost no research related to skin irritation of CSF. AIM OF THE STUDY: This study was intended to perform the first systematic assessment of morphological and histological changes in skin after stimulation with CSF. Furthermore, potential irritant components in CSF and related mechanisms were explored by in vitro transdermal techniques, network pharmacology, molecular docking, and experimental validation. MATERIALS AND METHODS: Skin changes after single and multiple stimulations with CSF were observed and subjected to skin irritation response scoring, irritation strength assessment, and histopathological analysis. In addition, in vitro transdermal technology, liquid chromatography-mass spectrometry (LC-MS) method, network pharmacology, molecular docking, and experimental validation were used to further exploit underlying skin irritant components and possible mechanisms of action. RESULTS: CSF induced significant morphological (erythema and edema) and histological (epidermal thickening and inflammatory infiltration) changes in skin of mice, which were similar to the clinical presentation of irritation contact dermatitis (ICD). The ethyl acetate fraction of CSF (CFEAF) was the main source of CSF-induced skin irritation. Kaempferol, flazin, and gallic acid were potential major irritant compounds. Moreover, CFEAF, kaempferol, flazin, and gallic acid could increase the levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-17A (IL-17A) to promote skin inflammation. The potential mechanism of CSF-induced skin irritation may be activation of the nuclear factor kappa-B (NF-κB) signaling pathway, including phosphorylation of NF-κB p65 (p65) and nuclear factor-kappa B inhibitor alpha (IκBα). CONCLUSION: Kaempferol, flazin, and gallic acid are potential skin irritant components from CSF. Altogether, they induce skin irritation responses through promoting the release of the inflammatory factors TNF-α and ICAM-1, as well as activating the NF-κB signaling pathway. In addition, IL-17A may be an important pro-inflammatory factor in skin irritation.

Jiedu Fuzheng decoction improves the proliferation, migration, invasion and EMT of non-small cell lung cancer via the Wnt/ß-catenin pathway.

OBJECTIVES: This study aimed to investigate the effect of Jiedu Fuzheng decoction (JFD) in non-small cell lung cancer (NSCLC) and its potential therapeutic mechanism. RESULTS: We prepared JFD-medicated serum from rats and treated NSCLC cells (A549 and NCI-H1650) with 0.5, 1, and 2 mg/mL JFD-medicated serum. CCK-8 and colony formation assays were used to detect cell proliferation. Transwell assays showed that JFD attenuated cell migration and invasion. JFD and SKL2001 (Wnt/ß-catenin activator) were simultaneously used to treat NSCLC cells to verify that JFD regulated the biological behavior of NSCLC via Wnt/ß-catenin signaling. It was found that 2 mg/mL JFD had the most significant effect on the activity of NSCLC cells. JFD attenuated proliferation and metastasis but increased the proportion of apoptotic cells. At the same time, JFD downregulated N-cadherin, vimentin and ß-catenin protein expression in cancer cells. SKL2001 could restore the improvement of JFD on proliferation, metastasis and apoptosis. CONCLUSION: This study confirmed that JFD suppressed the occurrence and development of NSCLC by regulating Wnt/ß-catenin signaling and provided a novel therapeutic scheme for NSCLC.

Risk of second cancer in esophageal squamous cell carcinoma and adenocarcinoma survivors: a population-based analysis in SEER dataset.

Background: Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients. Methods: This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992-2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients' characteristics. Results: After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51-1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02-1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87-15.79), stomach (SIR: 3.03, 95% CI: 1.77-4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47-8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96-2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52-0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23-5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02-1.54), and kidney (SIR: 1.57, 95% CI: 1.05-2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11-1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50-0.76 for regional stage; sHR: 0.27, 95% CI: 0.20-0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40-0.56 for regional stage; sHR: 0.10, 95% CI: 0.07-0.13 for distant stage). Conclusions: Both ESCC and EAC patients are at considerable risk of certain types of second cancer.

Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-ß-induced epithelial-mesenchymal transition via directly targeting TGFßR1.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-ß-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-ß receptor type-1 (TGFßR1) and abrogated the kinase activity of TGFßR1, thereby blocking the TGF-ß-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFßR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFßR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFßR1 were found to be crucial for the interaction of ITSN with TGFßR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-ß-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFßR1 in TNBC metastasis, but also provide a leading compound targeting TGFßR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFßR1 inhibitor.

Sinapis Semen: A review on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics.

Sinapis Semen (SS), the dried mature seed of Sinapis alba L. and Brassica juncea (L.) Czern. et Coss., is one of the traditional Chinese medicinal materials with a wide range of pharmacological effects being used for asthma, cough and many other ailments. SS is also widely used in food agriculture, medicine and other industries in North America and South Asia. More recently, the research on SS has gradually intensified and increased. However, there is no systematic review of SS. In this review, through literature exploration and analysis, the research advance on phytochemistry, pharmacology, toxicity, analytical methods and pharmacokinetics of SS was aggregated initially. Total 144 compounds have been isolated and identified from SS. Among them, glucosinolates and their hydrolysates and volatile oils are the main active ingredients and important chemical classification markers. SS has a wide range of pharmacological effects, especially in cough suppressing, asthma calming, anti-inflammatory, neuroprotective, cardiovascular protective, inhibiting androgenic effects, anti-tumor, and skin permeation promoting effects. Sinapine and sinapic acid are the main active ingredients of SS for its medicinal effects. However, SS has a strong skin irritation, presumably related to the time of application, the method of processing, and original medicinal plants. This review will provide useful data for the follow-up research and safe and reasonable clinical application of SS.

Herb-drug interactions between Panax notoginseng or its biologically active compounds and therapeutic drugs: A comprehensive pharmacodynamic and pharmacokinetic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbs, along with the use of herb-drug interactions (HDIs) to combat diseases, are increasing in popularity worldwide. HDIs have two effects: favorable interactions that tend to improve therapeutic outcomes and/or minimize the toxic effects of drugs, and unfavorable interactions aggravating the condition of patients. Panax notoginseng (Burk.) F.H. Chen is a medicinal plant that has long been commonly used in traditional Chinese medicine to reduce swelling, relieve pain, clear blood stasis, and stop bleeding. Numerous studies have demonstrated the existence of intricate pharmacodynamic (PD) and pharmacokinetic (PK) interactions between P. notoginseng and conventional drugs. However, these HDIs have not been systematically summarized. AIM OF THE REVIEW: To collect the available literature on the combined applications of P. notoginseng and drugs published from 2005 to 2022 and summarize the molecular mechanisms of interactions to circumvent the potential risks of combination therapy. MATERIALS AND METHODS: This work was conducted by searching PubMed, Scopus, Web of Science, and CNKI databases. The search terms included "notoginseng", "Sanqi", "drug interaction," "synergy/synergistic", "combination/combine", "enzyme", "CYP", and "transporter". RESULTS: P. notoginseng and its bioactive ingredients interact synergistically with numerous drugs, including anticancer, antiplatelet, and antimicrobial agents, to surmount drug resistance and side effects. This review elaborates on the molecular mechanisms of the PD processed involved. P. notoginseng shapes the PK processes of the absorption, distribution, metabolism, and excretion of other drugs by regulating metabolic enzymes and transporters, mainly cytochrome P450 enzymes and P-glycoprotein. This effect is a red flag for drugs with a narrow therapeutic window. Notably, amphipathic saponins in P. notoginseng act as auxiliary materials in drug delivery systems to enhance drug solubility and absorption and represent a new entry point for studying interactions. CONCLUSION: This article provides a comprehensive overview of HDIs by analyzing the results of the in vivo and in vitro studies on P. notoginseng and its bioactive components. The knowledge presented here offers a scientific guideline for investigating the clinical importance of combination therapies. Physicians and patients need information on possible interactions between P. notoginseng and other drugs, and this review can help them make scientific predictions regarding the consequences of combination treatments.

Capparis spinosa L. as a potential source of nutrition and its health benefits in foods: A comprehensive review of its phytochemistry, bioactivities, safety, and application.

Capparis spinosa L. (C. spinosa) is an edible plant with health-promoting benefits. C. spinosa possesses various biological activities, including antioxidant, antidiabetic, anticancer, hepatoprotective, neuroprotective, anti-inflammatory, anti-arthritic, antibacterial, and insecticidal effects. The active compounds associated with these effects mainly include flavonoids, phenolic acids, alkaloids, volatile oils, fatty acids, and polysaccharides. Moreover, C. spinosa has considerable nutritional value. Apart from being a food condiment, it belongs to a class of functional ingredients that act as preservatives and antioxidants in food products. C. spinosa has also shown good potential applications in novel food packaging materials. In this article, in addition to systematically reviewing the botanical characteristics, traditional edible uses, phytochemical composition, bioactivities and safety of C. spinosa, we highlight for the first time its potential applications in the foods. The findings will provide critical information for the future development of C. spinosa into a multifunctional food product with essential roles in health benefits.

Simultaneous determination of cordycepin and its metabolite 3'-deoxyinosine in rat whole blood by ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry and its application to accurate pharmacokinetic studies.

Cordycepin from Cordyceps possesses excellent pharmacological properties, including anti-inflammation and anti-tumor effects, therefore representing a potential alternative medicine. However, doubts about the pharmacokinetic results of cordycepin had been raised in the previous study due to its rapid deamination. The organic solvent methanol was immediately added to terminate the degradation of cordycepin in anticoagulated blood samples and enable the accurate evaluation of pharmacokinetics in vivo. A sensitive and selective ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry method was developed and validated to simultaneously determine cordycepin and its deamination metabolite 3'-deoxyinosine using 2-chloroadenosine as an internal standard in rat whole blood. The calibration curves of cordycepin and 3'-deoxyinosine showed excellent linearity within the concentration range of 1.05-10 000.00 ng/ml with acceptable accuracy, precision, selectivity, recovery, matrix effect, and stability. This method was successfully applied to the pharmacokinetic study of cordycepin and its metabolite in rat blood. The effect of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride on the pharmacokinetics of cordycepin was investigated. In summary, the reliable pharmacokinetic parameters of cordycepin and its deamination metabolite 3'-deoxyinosine in rat blood were successfully elucidated. Erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride considerably prolonged the half-life of cordycepin in vivo.

Response to neoadjuvant immune checkpoint inhibitors and chemotherapy in Chinese patients with esophageal squamous cell carcinoma: the role of tumor immune microenvironment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) through programmed cell death 1 blockade improve the survival outcomes of patients with advanced esophageal squamous cell carcinoma (ESCC). Recently, the use of neoadjuvant immunotherapy for the treatment of ESCC has been gradually increasing. We aimed to evaluate the efficacy of neoadjuvant treatment of ICIs with chemotherapy and explore tumor microenvironment (TME) immune profiles of ESCC samples during neoadjuvant therapy. METHODS: Patients with previously untreated, resectable, locally advanced ESCC (stage II or III) in Harbin Medical University Cancer Hospital were enrolled. Each patient received two to four cycles of neoadjuvant ICIs combined with chemotherapy before surgical resection. The TME immune profiles of formalin-fixed paraffin-embedded tumor samples at baseline and after surgery were evaluated by multiplex staining and multispectral imaging. RESULTS: In all, 18 patients were enrolled, and all patients received surgery with R0 resection. The postoperative pathological evaluation indicated that 7 (38.9%) patients had a pathological complete response (pCR) and 11 (61.1%) patients had a partial response. The neoadjuvant therapeutic regimens had acceptable side effect profiles. The TME immune profiles at baseline observed higher densities of stroma CD3 + , PD-1 + , and PD-1 + CD3 + cells in pCR patients than in non-pCR patients. Comparing TME immune profiles before and after neoadjuvant treatment, an increase in CD8 + T cells and a decrease in CD163 + CD68 + M2-like macrophage cells were observed after neoadjuvant treatment. CONCLUSIONS: Neoadjuvant ICIs combined with chemotherapy produced a satisfactory treatment response, demonstrating its anti-tumor efficacy in locally advanced ESCC. Further large-scale studies are required to understand the role of tumor immunities and ICIs underlying ESCC.

The in vitro/in vivo metabolic pathways analysis of lobetyol, lobetyolin, and lobetyolinin, three polyacetylenes from Codonopsis Radix, by UHPLC-Q/TOF-MS and UHPLC-MS/MS.

Polyacetylenes, lobetyol, lobetyolin and lobetyolinin, are responsible for antitumor, antioxidant, anti-inflammatory, immunomodulatory activities of Codonopsis Radix. However, their metabolic pathways are still unknown. The study was purposed to investigate the metabolism of three polyacetylenes in vitro and in vivo by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Moreover, a rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative and semi-quantitative determination of lobetyol and its 12 metabolites to investigate the metabolic stability and metabolic phenotypes. A total of 47, 30 and 34 metabolites of lobetyol, lobetyolin and lobetyolinin were found in all samples. These metabolites are produced through extensive pathways, mainly involving oxidation, glucuronidation and glutathione conjugation. Lobetyol showed good metabolic stability in liver microsomes. The results of both recombinant human CYP enzymes and chemical inhibition experiments confirmed that CYP2C19, 1A1, 2C9, and 1A2 are the major isozymes mediating lobetyol metabolism.

Detection and Removal of Aristolochic Acid in Natural Plants, Pharmaceuticals, and Environmental and Biological Samples: A Review.

Aristolochic acids (AAs) are a toxic substance present in certain natural plants. Direct human exposure to these plants containing AAs leads to a severe and irreversible condition known as aristolochic acid nephropathy (AAN). Additionally, AAs accumulation in the food chain through environmental mediators can trigger Balkan endemic nephropathy (BEN), an environmental variant of AAN. This paper presents a concise overview of the oncogenic pathways associated with AAs and explores the various routes of environmental exposure to AAs. The detection and removal of AAs in natural plants, drugs, and environmental and biological samples were classified and summarized, and the advantages and disadvantages of the various methods were analyzed. It is hoped that this review can provide effective insights into the detection and removal of AAs in the future.

Uptake, Translocation, and Fate of Carcinogenic Aristolochic Acid in Typical Vegetables in Soil-Plant Systems.

When Aristolochia plants wilt and decay, aristolochic acids (AAs) are released into the soil, causing soil contamination. It has been demonstrated that aristolochic acid can be accumulated and enriched in crops through plant uptake. However, there is a lack of systematic studies on the migration and accumulation of AAs in a realistic simulated soil environment. In this study, Aristolochia herbal extracts were mixed with soil for growing three typical vegetables: lettuce, celery, and tomato. The contents of AAs in the above-mentioned plants were determined by an established highly sensitive LC-MS/MS method to study the migration and accumulation of AAs. We found that AAs in the soil can be transferred and accumulated in plants. AAs first entered the roots, which were more likely to accumulate AAs, and partially entered the above-ground parts. This further confirms that AAs can enter the food chain through plants and can have serious effects on human health. It was also shown that plants with vigorous growth and a large size absorbed AAs from the soil at a faster rate. The more AAs present in the soil, the more they accumulated in the plant.

Advances in Research on Bioactivity, Toxicity, Metabolism, and Pharmacokinetics of Usnic Acid In Vitro and In Vivo.

Lichens are among the most widely distributed plants on earth and have the longest growth cycle. Usnic acid is an abundant characteristic secondary metabolite of lichens and the earliest lichen compound used commercially. It has diverse pharmacological activities, such as anti-inflammatory, antibacterial, antiviral, anticancer, antioxidant, and photoprotective effects, and promotes wound healing. It is widely used in dietary supplements, daily chemical products (fodder, dyes, food, perfumery, and cosmetics), and medicine. However, some studies have found that usnic acid can cause allergic dermatitis and drug-induced liver injury. In this paper, the bioactivity, toxicity, in vivo and in vitro metabolism, and pharmacokinetics of usnic acid were summarized. The aims were to develop and utilize usnic acid and provide reference for its future research.

The association between biomarkers of acrylamide and cancer mortality in U.S. adult population: Evidence from NHANES 2003-2014.

The association between acrylamide (AA) and the development of cancer has been extensively discussed but the results remained controversial, especially in population studies. Large prospective epidemiological studies on the relationship of AA exposure with cancer mortality were still lacking. Therefore, we aimed to assess the association between AA biomarkers and cancer mortality in adult population from National Health and Nutrition Examination Survey (NHANES) 2003-2014. We followed 3717 participants for an average of 10.3 years. Cox regression models with multivariable adjustments were performed to determine the relationship of acrylamide hemoglobin adduct (HbAA) and glycidamide hemoglobin adduct (HbGA) with cancer mortality. Mediation analysis was conducted to demonstrate the mediated role of low-grade inflammation score (INFLA-score) in this correlation. Compared with the lowest quintile, participants with the highest quintile of HbAA, HbGA and HbAA+HbGA had increased cancer mortality risk, and the hazard ratios(HRs) were 2.07 (95%CI:1.04-4.14) for HbAA, 2.39 (95%CI:1.29-4.43) for HbGA and 2.48 (95%CI:1.28-4.80) for HbAA+HbGA, respectively. And there was a considerable non-linearity association between HbAA and cancer mortality (p for non-linearity = 0.0139). We further found that increased INFLA-score significantly mediated 71.67% in the effect of HbGA exposure on increased cancer mortality risk. This study demonstrates that hemoglobin biomarkers of AA are positively associated with cancer mortality in adult American population and INFLA-score plays a mediated role in this process. Our findings can raise public awareness of environmental and dietary exposure to acrylamide and remind people to refrain from smoking or having acrylamide-rich foods.

One-pot H/D exchange and low-coordinated iron electrocatalyzed deuteration of nitriles in D2O to α,ß-deuterio aryl ethylamines.

Developing a step-economical approach for efficient synthesis of α,ß-deuterio aryl ethylamines (α,ß-DAEAs) with high deuterium ratios using an easy-to-handle deuterated source under ambient conditions is highly desirable. Here we report a room-temperature one-pot two-step transformation of aryl acetonitriles to α,ß-DAEAs with up to 92% isolated yield and 99% α,ß-deuterium ratios using D2O as a deuterium source. The process involves a fast α-C - H/C - D exchange and tandem electroreductive deuteration of C ≡ N over an in situ formed low-coordinated Fe nanoparticle cathode. The moderate adsorptions of nitriles/imine intermediates and the promoted formation of active hydrogen (H*) on unsaturated Fe sites facilitate the electroreduction process. In situ Raman confirms co-adsorption of aryl rings and the C ≡ N group on the Fe surface. A proposed H*-addition pathway is confirmed by the detected hydrogen and carbon radicals. Wide substrate scope, parallel synthesis of multiple α,ß-DAEAs, and successful preparation of α,ß-deuterated Melatonin and Komavine highlight the potential.