Human bocavirus 1 (HBoV1) is an emerging human-pathogenic respiratory virus. We characterized two important features of HBoV1 infection in polarized primary human airway epithelia (HAE). Apical HBoV1 infection of HAE at a low multiplicity of infection causes disruption of the tight junction barrier, loss of cilia, and epithelial cell hypertrophy, which are hallmarks of the airway epithelial damage caused by HBoV1 infection. HBoV1 also infects HAE from the basolateral surface productively, although less efficiently, and this also leads to the characteristic airway epithelial damage. Human bocavirus 1 (HBoV1), first discovered in 2005 (1), is a temporary member in the genus Bocavirus of the Parvoviridae family (2). Recently, mounting evidence has indicated that HBoV1 is one of the etiological agents of acute respiratory tract infections (ARTI), especially those causing wheezing in young children (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The pseudostratified and well-differentiated primary human airway epithelium (HAE) culture model, which grows and differentiates human tracheobronchial epithelial cells at an air-liquid interface (ALI), is the best in vitro model of the human airway epithelium (15,16). HAE culture has been used to model infections with a wide range of respiratory viruses (17-24), including HBoV1 (25, 26). We recently established, for the first time, an infectious plasmid clone of the complete genome of HBoV1, and we generated HBoV1 virions from HEK293 cells transfected with this clone. We demonstrated that the reversegenetics-generated HBoV1 virions productively infect HAE at a high multiplicity of infection (MOI; ϳ750 viral genome copies [VGC] per cell) and cause cytopathogenesis (26). In this report, we extended our study to the efficacy of the HBoV1 infection and showed evidence of its high infectivity in polarized primary HAE culture at extremely low MOIs. Additionally, we demonstrate that HBoV1 is capable of infecting HAE from the basolateral surface, despite a slower progression.Progeny HBoV1 virions in apical washes of infected HAE are highly infectious in polarized primary HAE. In our previous study, we produced HBoV1 virions from HEK293 cells transfected with the HBoV1 infectious clone, which were further concentrated and purified through cesium chloride equilibrium ultracentrifugation (26). During this process, significant viral inactivation occurred (27), and the precise infectivity of the virus was difficult to determine. However, progeny virions were persistently secreted from the apical surface of infected HAE at a high titer (ϳ1.0 ϫ 10 7 VGC/l) (26). Hence, we hypothesized that the progeny virions washed from the apical surface mimic naturally secreted virions from HBoV1-infected lung airways and thus are highly contagious.To test this hypothesis, we obtained polarized primary HAE cultures in Millicell inserts of 0.6 cm 2 (Millipore) from the Tissue and Cell Culture Core of the Center for Gene Therapy, University of Iowa. These cultures were made by growing isolated human airway (t...

Doxorubicin is widely prescribed in the chemotherapy of haematological malignancies and solid tumours. The major side effect of doxorubicin is oxidative injury-related cardiotoxicity, which has dramatically hindered its usage. Procyanidins from grape seeds are potent free radical scavengers that have been shown to protect against anthracyclineinduced cardiotoxicity. In the present study, we tested whether procyanidins would prevent the doxorubicin-induced cardiotoxicity in rats. Rats were intraperitoneally treated with doxorubicin at a cumulative dose of 15 mg/kg with and without pre-administration of procyanidins. Our data showed that doxorubicin led to cardiac function deterioration, myocardial injury and increased oxidative stress in cardiac tissues. The cardiac function deterioration by doxorubicin included increased QT-interval and ST-interval in electrocardiograph (ECG) and decreased left ventricular developed pressure. Doxorubicininduced myocardial injury was shown by the increased creatine kinase, alanine aminotransferase and aspartate aminotransferase in serum as well as in myocardial lesions. Pretreatment with procyanidin (150 mg/kg daily) effectively hindered the adverse effects of doxorubicin, such as myocardial injury and impaired heart function. Procyanidin pretreatment attenuated cytoplasmic vacuolization, increased left ventricular developed pressure and improved the ECG. The cardioprotective effect of procyanidin corresponded to the decrease of lipid peroxidation and the increase of cardiac antioxidant potency in doxorubicintreated rats that were also given procyanidin. An in vitro cytotoxic study showed that procyanidins did not attenuate the antineoplastic activity of doxorubicin to A549 adenocarcinoma cells. All the above lines of evidence suggest that procyanidins protect cardiomyocytes from doxorubicin-induced cardiotoxicity via suppression of oxidative stress.

The aim of this study is to identify the minor compounds in Jing liqueur, determine the concentration of metals, amino acids, and polysaccharides, and evaluate their Nrf2 activity and cytotoxicity. Jing liqueur that contains Chinese medicine is one of the best-selling liqueurs in China, which is also marketed in the United States. Totally, we have isolated 189 minor compounds including one new molecule (7) from a concentrated Jing liqueur, with the concentrations of most isolated compounds at micromolar levels. The structures of all these compounds were determined by using MS and NMR (1D and 2D) or by comparison of their chemical and physical data with reported values in the literatures. Besides, the concentrations of iron (0.52 mg/L), zinc (0.21 mg/L), calcium (11.0 mg/L), L-proline (2.33 mg/L), L-arginine (1.73 mg/L), total amino acids (9.84 mg/L), and total polysaccharides (337.4 mg/L) were determined. Jing liqueur, the five fractions and most of the compounds isolated from Jing liqueur were screened for their activities in the Nrf2-ARE and MTT assays. At 5.2 mg/mL the crude enhanced the Nrf2 activity. At 80 μg/mL, fraction IV weakly but fraction V strongly activated Nrf2. Among the compounds screened in the Nrf2 assay, eighteen activated Nrf2 at 40 μg/mL and compounds 51 and 126 from fraction V were the most active. The crude, all the five fractions, and Nrf2 activators were not cytotoxic toward HepG2 cells. In conclusion, Jing liqueur contains different classes of compounds including flavonoids, terpenoids, alkaloids, coumarins, cinnamic acid or coumaric acid, and phenyl ethanol (or acetic acid) derivatives, benzoquinone, naphthoquinone, anthraquinones or phenanphrene derivatives, xanthones, chromone, and γ-pyrone derivatives, lignans, other aromatic compounds, and others. Jing liqueur and the eighteen compounds, which were isolated from Jing liqueur, could activate Nrf2 without any cytotoxicity.

Juices, wine, coffee, and cocoa are rich sources of natural polyphenolic compounds that have potent antioxidant activities proven by in vitro and in vivo studies. These polyphenolic compounds quench reactive oxygen and nitrogen species (RONS) or reactive free radicals and act as natural antioxidants which are also able to protect against reactive oxygen species (ROS)-mediated oxidative damage, which elevates cellular antioxidant capacity to induce antioxidant defense mechanisms by modulating transcription factors. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor encoded in humans. It is activated as a result of oxidative stress and induces the expression of its target genes. This is one of the most important cellular defense mechanisms against oxidative stress. However, the oxidative stress alone is not enough to activate Nrf2. Hence phytochemicals, especially polyphenolics, act as natural Nrf2 activators. Herein, this review discusses the natural products identified in juices, coffee, cocoa and wines that modulate Nrf2 activity in cellular systems.