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Background Reendothelialisation is the natural pathway that inhibits neointimal hyperplasia and in-stent restenosis. Circulating endothelial progenitor cells (EPCs) derived from bone marrow (BM) might contribute to endothelial repair. However, the temporal and spatial distributions of reendothelialisation and neointimal hyperplasia after EPC transplantation in injured arteries are currently unclear. Methods A carotid balloon injury (BI) model was established in Sprague-Dawley rats, and PKH26-labelled BM-derived EPCs were transplanted after BI. The carotid arteries were harvested on the first, fourth, seventh, and 14th day post-injury and analysed via light-sheet fluorescence microscopy and pathological staining (n = 3). EPC and human umbilical vein endothelial cell culture supernatants were collected, and blood samples were collected before and after transplantation. The paracrine effects of VEGF, IGF-1, and TGF-β1 in cell culture supernatants and serum were analysed by enzyme-linked immunosorbent assay (n = 4). Results Transplanted EPCs labelled with PKH26 were attached to the injured luminal surface the first day after BI. In the sham operation group, the transplanted EPCs did not adhere to the luminal surface. From the fourth day after BI, the mean fluorescence intensity of PKH26 decreased significantly. However, reendothelialisation and inhibition of neointimal hyperplasia were significantly promoted by transplanted EPCs. The degree of reendothelialisation of the EPC7d and EPC14d groups was higher than that of the BI7d and BI14d groups, and the difference in neointimal hyperplasia was observed between the EPC14d and BI14d groups. The number of endothelial cells on the luminal surface of the EPC14d group was higher than that of the BI14d group. The number of infiltrated macrophages in the injured artery decreased in the EPC transplanted groups. Conclusions Transplanted EPCs had chemotactic enrichment and attached to the injured arterial luminal surface. Although decreasing significantly after the fourth day at the site of injury after transplantation, transplanted EPCs could still promote reendothelialisation and inhibit neointimal hyperplasia. The underlying mechanism is through paracrine cytokines and not differentiation into mature endothelial cells.

Background CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46–9.00] months for GP arm and 6.07 (95% CI 5.32–6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration ClinicalTrials.gov, NCT01287624.

Background: Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options and poor prognosis. Gemcitabine plus carboplatin (GC) is one of the preferred chemotherapeutic regimens for patients with metastatic triple-negative breast cancer(mTNBC), with a median progression-free survival(PFS) of 4.6 months in the first-line patients (O'Shaughnessy J, et al. J Clin Oncol 2014). Gemcitabine plus cisplatin (GP) has also demonstrated promising efficacy and safety in the first-line phase III trial of mTNBC, with a median PFS of 7.7 months (Hu XC, Lancet Oncol 2015). A recent analysis, based on data derived from a cohort of 379 mTNBC patients, indicated that patients receiving cisplatin-based regimen as the first-line chemotherapy showed better PFS compared with other platinum agents (8.0 vs 4.3 months, P = 0.03) (Zhang J, et al. Oncotarget 2015). To further investigate the superiority between carboplatin and cisplatin when combined with gemcitabine, this phase II study was conducted to directly compare the efficacy and safety of GP with GC in the first-line treatment for patients with metastatic triple negative breast cancer. Trial Design: This prospective phase II, single center, open-label, randomized study has been designed to compare the efficacy and safety of GP with GC as the first-line treatment for mTNBC. Patients are randomized 1:1 to receive gemcitabine (1250 mg/m2, D1,8) plus cisplatin (75 mg/m2, D1) or gemcitabine (1000mg/m2, D1,8) plus carboplatin (area under the curve 2 mg × min/mL, D1,8) every 21 days until disease progression or intolerable toxicity. Eligibility Criteria: Patients with histologically confirmed triple negative metastatic breast cancer, with no prior chemotherapy in metastatic setting will be included in this trial. Eligible patients must be between 18 and 70 years of age with a performance status of 0–1, adequate organ function and at least one RECIST 1.1-measurable lesion. Specific Aims: The primary endpoint is PFS. Secondary endpoints include objective response rate, safety and overall survival. Statistical Methods: The sample size of the present study was determined based on the results of two phase III clinical trials: the median PFS for patients receiving GC and GP as the first-line treatment for mTNBC was 4.6 and 7.7 months, respectively. This design was hypothesized that GP would be superior to GC in terms of efficacy. Thus, in order to detect an improvement of median PFS from 4.6 months to 7.7 months, with 80% power and a 1-sided type I error of 0.05, 136 patients would be required. Considering a drop-out rate of 10%, a total of 150 patients planned to be enrolled. Present Accrual and Target Accrual: Target accrual: 150. Present accrual (2017/5/24): 83 Contact information: Contact: Xichun Hu, MD, PHD xchu2009@hotmail.com Biyun Wang, MD pro_wangbiyun@163.com ClinicalTrials.gov Identifier: NCT02341911. Citation Format: Gong C, Cao E, Wang Z, Zhang J, Wang L, Cao J, Zhang S, Tao Z, Li T, Zhao Y, Li Y, Wang B, Hu X. A phase II randomized trial of gemcitabine plus cisplatin(GP) vs. gemcitabine plus carboplatin (GC) as the first-line treatment for patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-05-01.

This study sought to assess whether the objective response (OR, including complete response and partial response) of first-line chemotherapy can predict overall survival (OS) for patients with metastatic triple-negative breast cancer (mTNBC) in both clinical trial and a real-world setting. The survival predictable parameters were assessed in two independent cohorts, the training cohort of 236 patients as part of a phase 3 trial (CBCSG006, Trial registration number NCT0128762) and the validation cohort of 360 patients from the real-world setting. Univariable and multivariable Cox proportional hazard models were applied to explore associations with progression-free survival and OS in the training cohort and then in the validation cohort. OR (OR vs non-OR, HR, 0.438, p

Flurochloridone (FLC) is a widely used herbicide in developing countries. Although the testes are a target organ for FLC in rats, the adverse effects of FLC on testes have not been fully elucidated. To clarify them, we performed RNA-seq analysis using the testes of FLC-treated rats from our previous subchronic toxicity tests. Unilateral testes of three male rats from solvent control groupand three FLC-treated groups (3 mg/kg, 31.25 mg/kg and 125 mg/kg) were used for RNA extraction. A poly A selection protocol coupled with an Illumina TruSeq RNA-Seq library protocol was used to construct RNA-Seq libraries. Principal component analysis (PCA), differentially expressed gene (DEG) analysis, and hierarchical clustering analysis (HCA) were conducted using R. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to understand the biological characteristics of the DEGs using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The results indicated that many up-regulated DEGs were enriched in pathways associated with testicular injury, such as mitogen-activated protein kinase (MAPK) signaling, lysosome and focal adhesion. Many down-regulated DEGs were enriched in pathways associated with testicular reproduction function, such as sexual reproduction, spermatogenesis and germ cell development. Moreover, we confirmed the oral no-observed-adverse-effect level (NOAEL) of 3 mg/kg in subchronic toxicity test, because the overall testicular gene expression in 3 mg/kg FLC-treated group was similar to that of the solvent control group. In 31.25 mg/kg and 125 mg/kg groups, DEGs revealed that testicular injury was related to oxidative stress.

Fluorochloridone (FLC) is a herbicide used worldwide that is thought to be safe. However, due to its potential genotoxicity, cytotoxicity, and even systematic toxicity, there are increasing concerns about human exposure to this compound. Thus, the metabolism and bioactivation of FLC was investigated. After oral administration to mice, 27 metabolites were identified by ultrahigh performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry and with further structural identification by nuclear magnetic resonance spectroscopy. Hydroxylation and oxidative dechlorination were the major phase I pathways, while glutathione (GSH) and N-acetylcysteine conjugations were two major phase II pathways, indicating the formation of a reactive intermediate. In vitro microsomal and cytosolic studies revealed that a GSH conjugate (M13) was the predominant metabolite of FLC formed through a nucleophilic SN2 substitution of 3-Cl by GSH; this pathway is NADPH independent and accelerated by glutathione S-transferase (GST). Further, a kinetic study showed that M13 formation in both human liver microsomes and cytosols obeyed typical Michaelis-Menten kinetics. The maximum clearance (Vmax/Km) of GSH conjugation in human liver microsomes was approximately 5.5-fold higher than human liver cytosol, thus implying that microsomal GST was mainly responsible for M13 formation. These findings are important for understanding the potential hazard of human exposure to FLC.

Background The nuclear factor erythroid 2-related factor 2 (Nrf2) is a potential molecular target for cancer chemoprevention. Si–Wu–Tang (SWT), a popular traditional Chinese medicine for women's health, was reported with a novel activity of cancer prevention. Purpose The present study was aimed to identify the bioactive constituents in SWT responsible for the Nrf2 activating and cancer preventive activity and explore the pharmacological mechanisms. Methods Nine compounds detectable from various batches of SWT were ranked using in silico molecular docking based on their ability to interfere the forming of Nrf2-Keap1 complex. The predicted Nrf2 activating effect was validated using the antioxidant response element (ARE) luciferase reporter assay and quantitative RT-PCR analysis for select Nrf2 regulated genes Hmox1, Nqo1 and Slc7a11. The antimutagenic activity of the compounds were determined by the Ames test. The chemopreventive activity of these compounds were assessed on EGF-induced neoplastic transformation of JB6 P+ cells, an established non-cancerous murine epidermal model for studying tumor promotion and identifying cancer preventive agents. These compounds were further characterized using luciferase reporter assay on EGF-induced activation of AP-1, a known transcription factor mediating carcinogenesis. Results Three of the nine compounds predicted as Nrf2 activators by molecular docking, gallic acid (GA), Z-liguistilide (LIG), and senkyunolide A (SA), were confirmed with highest potency of increasing the Nrf2/ARE promoter activity and upregulating the expression of Hmox1, Nqo1 and Slc7a11. In addition, GA, LIG and SA exhibited an antimutagenic activity against the direct mutagen 2-nitrofluorene while no mutagenic effects were observed at the same time in Ames test. At nontoxic concentrations, GA, LIG, and SA inhibited EGF-induced neoplastic transformation of JB6 P+ cells. Combined treatment of GA, LIG and SA, in the same ratio as detected in SWT, showed enhanced effect against JB6 transformation compared with that of the single compound alone. GA, LIG and SA, alone or in combination, suppressed EGF-induced activation of AP-1. Conclusion We identified three bioactive constituents in SWT responsible for the Nrf2 activating and cancer preventive activity. This study provides evidence supporting novel molecular basis of SWT in cancer prevention.

Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex mixture with many constituents, including flavonol glycosides and terpene lactones. The National Toxicology Program 2-year cancer bioassay found that G. biloba leaf extract targets the liver, thyroid gland, and nose of rodents; however, the mechanism of G. biloba leaf extract-associated carcinogenicity remains unclear. In the current study, the in vitro genotoxicity of G. biloba leaf extract and its eight constituents was evaluated using the mouse lymphoma assay (MLA) and Comet assay. The underlying mechanisms of G. biloba leaf extract-associated genotoxicity were explored. Ginkgo biloba leaf extract, quercetin, and kaempferol resulted in a dose-dependent increase in the mutant frequency and DNA double-strand breaks (DSBs). Western blot analysis confirmed that G. biloba leaf extract, quercetin, and kaempferol activated the DNA damage signaling pathway with increased expression of γ-H2AX and phosphorylated Chk2 and Chk1. In addition, G. biloba leaf extract produced reactive oxygen species and decreased glutathione levels in L5178Y cells. Loss of heterozygosity analysis of mutants indicated that G. biloba leaf extract, quercetin, and kaempferol treatments resulted in extensive chromosomal damage. These results indicate that G. biloba leaf extract and its two constituents, quercetin and kaempferol, are mutagenic to the mouse L5178Y cells and induce DSBs. Quercetin and kaempferol likely are major contributors to G. biloba leaf extract-induced genotoxicity.

Purpose: Patients with metastatic triple-negative breast cancer (mTNBC) typically have a poor prognosis and limited treatment options. Previous study showed biweekly combination of vinorelbine and oxaliplatin (NVBOX) at doses of 30 mg/m2 and 90 mg/m2, respectively, is highly active and well tolerated as first-line treatment for patients with metastatic breast cancer. The purpose of this study (NCT 01528826) was to prospectively evaluate the efficacy and toxicity of NVBOX in second- or third-line mTNBC. Methods: Eligible patients were female with 18–70 years old and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and had mTNBC that had progressed after 1or 2 prior chemotherapy regimens in the metastatic setting. A period of 4 weeks (NVBOX twice) was considered as one treatment cycle and the maximum cycles were 6. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Results: Between Dec 2011 and Nov 2012, forty-four patients were recruited [median age 47; 77.3% with viceral metastasis, 100% had been exposed to anthracyclines and/or taxanes; 56.8% cis/carbo-platin pretreated for MBC; 38.6% with time to progression (TTP) of 1-2 previous regimens before recruitment ≤ 3 months]. The overall response rate was 31.6% (1 complete response, 11 partial responses) and 10 achieved stable diseases (7 lasting more than 6 months) in 38 evaluable patients. After a median follow-up of 12.8 months, the median PFS and OS were 4.3 (95% CI, 3.6–5.0) months and 12.6 (95% CI, 8.1–17.0) months, respectively. PFS was significantly shorter in patients with disease free interval (DFI) ≤ 1year (HR = 2.10; 95% CI, 1.05–4.21; P = 0.037) and TTP of 1-2 previous regimens before recruitment ≤ 3 months (HR = 3.39; 95% CI, 1.66–6.89; P < 0.001). Also, these two factors were two independent predictors for the poor OS (HR = 5.45; 95% CI, 2.08–14.32; P < 0.001 and HR = 4.09; 95% CI, 1.73–9.68; P < 0.001). For 34 second line patients, prior platinum in the first line was a factor significantly compromise the PFS (HR = 2.29; 95% CI, 1.03–5.10; P = 0.043). Dose adjustment happened in 14 patients (31.8%) due to adverse events (AEs). Grade 3/4 hematologic toxicities were neutropenia (70.5%), thrombocytopenia (27.3%) and anemia (15.9%). Four patients experienced febrile neutropenia. The most frequent grade 3/4 non-hematologic toxicities were constipation (20.5%) and vomiting (11.4%). Two patients developed grade 3 NVBOX-related peripheral neurotoxicity. There were no treatment-related deaths. Conclusion: We conclude that biweekly NVBOX regimen is effective with a good safety profile in the second- or third-line mTNBC, which warrants further investigation in a phase III study. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-06.

Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women's diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT's activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF)-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in 'Sensitivity to Carcinogenesis' (SENCAR) mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA), and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB.

Aim: In this study, we aimed to explore the toxic mechanisms of cardiovascular injuries induced by ambient fine particulate matter (PM2.5) in atherosclerotic-susceptible ApoE−/− mice. An acute toxicological animal experiment was designed with PM2.5 exposure once a day, every other day, for three days. Methods: ApoE−/− and C57BL/6 mice were randomly categorized into four groups, respectively (n = 6): one control group, three groups exposed to PM2.5 alone at low-, mid-, and high-dose (3, 10, or 30 mg/kg b.w.). Heart rate (HR) and electrocardiogram (ECG) were monitored before instillation of PM2.5 and 24 h after the last instillation, respectively. Cardiac function was monitored by echocardiography (Echo) after the last instillation. Biomarkers of systemic oxidative injuries (MDA, SOD), heart oxidative stress (MDA, SOD), and NAD(P)H oxidase subunits (p22phox, p47phox) mRNA and protein expression were analyzed in mice. The results showed that PM2.5 exposure could trigger the significant increase of MDA, and induce the decrease of heart rate variability (HRV), a marker of cardiac autonomic nervous system (ANS) function with a dose–response manner. Meanwhile, abnormal ECG types were monitored in mice after exposure to PM2.5. The expression of cytokines related with oxidative injuries, and mRNA and protein expression of NADPH, increased significantly in ApoE−/− mice in the high-dose group when compared with the dose-matched C57BL6 mice, but no significant difference was observed at Echo. In conclusion, PM2.5 exposure could cause oxidative and ANS injuries, and ApoE−/− mice displayed more severe oxidative effects induced by PM2.5.

A ninety-day toxicity and toxicokinetics of flurochloridone (FLC) were studied in male Wistar rats with oral administration at doses of 3 mg/kg and 10 mg/kg respectively, following the previous study. Apparent toxicity to reproductive system of male rats was still observed at the dose of 10 mg/kg, trace amounts of FLC were still detected 24 hours after administration, testicular weight, epididymal weight and serum testosterone were significantly reduced and sperm abnormalities in epididymis were significantly increased. No abnormalities were found in 3 mg/kg group, it indicated that no-observed-adverse-effect level (NOAEL) of FLC in male rats was 3 mg/kg/day, far below the dose of 20 mg/kg/day reported by European Food Safety Authority (EFSA). Therefore, more attention should be paid to this herbicide.

The ninety day toxicity and toxicokinetics of fluorochloridone (FLC) were accessed in Wistar rats. Animals were gavaged with FLC at doses of 31.25 mg/kg, 125 mg/kg and 500 mg/kg for ninety days, followed by thirty days for recovery. On the 1st, 60th, 75th and 90th days of the dosing phase, plasma of ten animals of all groups treated with FLC was collected for toxicokinetic analysis of FLC by an UPLC-MS/MS method. Numerous changes in body weight, hematology, serum chemistry, and organ weight ratios were observed by the 45th and 90th dosing day. Most changes in groups treated with FLC were absent on the last recovery day. Testis and epididymis lesions were consistently seen in histopathological observations on the 45th, 90th dosing day and the last recovery day. Repeated administration of FLC increased the level of testosterone in serum in male rats on the 90th dosing day. FLC plasma concentrations could be detected in all animal drug-treated groups during the dosing phase, and a dose proportional relationship was seen between FLC dose and AUC or Cmax. This study will support future studies on the mechanism of FLC-induced toxicity.

Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong and Paeoniae, is one of the most popular Chinese medicines for women's diseases. Previously we showed that SWT was able to upregulate genes in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, suggesting a potential application for cancer chemoprevention. The present study examined the chemopreventive activity of SWT using models of skin carcinogenesis. In JB6 P+ cells, a non-cancerous murine epidermal cell line for studying skin tumor promotion, SWT inhibited epidermal growth factor (EGF)-induced neoplastic transformation. In a 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine skin tumorigenesis model, both topical and oral treatment of SWT inhibited epidermal hyperplasia, proliferating cell nuclear antigen expression, and H-ras mutations induced by DMBA treatment. In addition, SWT exhibited a significant antimutagenic activity against DMBA-induced mutagenicity, determined by the Ames Test using Salmonella typhimurium TA100 in the presence of metabolic activator S9 system. To identify active components in SWT, among nine compounds previously reported in commercial SWT products, in silico molecular docking analysis predicted some as potential Nrf2 activators due to an ability of interfering the forming of Nrf2-Keap1 complex. Three of these compounds, gallic acid, Z-liguistilide and senkyunolide A, were confirmed with highest potency of increasing the antioxidant response element luciferase reporter activity, inducing Nrf2-regulated genes Hmox1, Slc7A11 and Nqo1, and inhibiting EGF-induced JB6 P+ transformation. Further mechanistic studies showed that SWT and the three compounds suppressed EGF-induced activation of the activator protein 1 (AP-1), an essential transcription factor involved in skin carcinogenesis. The antimutagenic activity for the three compounds was also confirmed with the Ames Test. In conclusion, these results provide evidence that SWT and its constituents are able to prevent skin cancer, at least partly, by activating the Nrf2 pathway and blocking the activation of AP-1. Thus, this widely used Chinese medicinal formula may provide a promising option toward preventing skin cancer or may be other types of cancer. Citation Format: Kevin Huang, Mandy Liu, Suhui Zhang, Steven Yeung, Andy Chang, Li Qian, Payal Chatterjee, Rui Li, Su Zhou, Nan Mei, Zhijun Wang, Cyrus Parsa, Robert Orlando, Yun Luo, Ying Huang. Skin cancer prevention by traditional Chinese medicinal formula Si-Wu-Tang and its constituents. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5252.

Two novel cryptand-based [2]rotaxanes were synthesized by a facile one-pot reaction from three neutral precursors: easily accessible cryptand host 1 and commercially available 4,4'-bipyridine and 3,5-di-tert-butylbenzyl bromide. Their structures were confirmed by (1)H NMR, 2D NMR, HRMS and X-ray analysis. Moreover, two [2]pseudorotaxanes based on the same cryptand hosts and dibenzyl viologen guest 3 were also demonstrated both in solution and in the solid state, which are different from previously reported [3]pseudorotaxane-like complexes formed by dimethyl viologen guest 2 and the cryptands.