Abstract We synthesized a cationic microbubble (CMB) with the aim of enhancing its DNA-carrying capacity to improve targeted gene transfection of the ischemic heart for cardiac regeneration. We ...previously reported that ultrasound-targeted microbubble destruction (UTMD) employing the commercial Definity microbubble (MB) successfully transfected genes into rodent hearts, but the transfection efficiency was modest. We synthesized a CMB and compared its DNA-carrying capacity and reporter gene transfection efficiency with the Definity MB. The CMB bound 70% more plasmid DNA than the Definity MB. UTMD-mediated gene delivery with the CMB enhanced both transfection efficiency and gene expression. In vivo studies assessed the ability of the CMB to deliver the therapeutic AKT gene to the ischemic rat myocardium and evaluated the effects on apoptosis, angiogenesis, and cardiac function. AKT transfection with the CMB reduced infarct size ( p < 0.05), increased infarct thickness ( p < 0.05), reduced apoptosis ( p < 0.05), increased vascular density ( p < 0.05), and improved cardiac perfusion and function ( p < 0.05) compared to the Definity MB. Delivery of AKT with the CMB resulted in greater cardiac functional improvements compared to the Definity MB. UTMD therapy with this CMB provides an efficient platform for the targeted delivery of factors required to regenerate the ischemic heart and preserve cardiac function.
Previous studies have shown that phthalate exposure in childhood is associated with the development of respiratory problems. However, few studies have assessed the relative impact of prenatal and ...postnatal exposure to phthalates on the development of asthma later in childhood. Therefore, we assessed the impact of prenatal and postnatal phthalate exposure on the development of asthma and wheezing using a Taiwanese birth cohort. A total of 430 pregnant women were recruited, and 171 (39.8%) of them had their children followed when they were aged 2, 5, and 8 years. The International Study of Asthma and Allergies in Childhood questionnaire was used to assess asthma and wheezing symptoms and serum total immunoglobulin E levels were measured at 8 years of age. Urine samples were obtained from 136 women during their third trimester of pregnancy, 99 children at 2 years of age, and 110 children at 5 years. Four common phthalate monoester metabolites in maternal and children's urine were measured using liquid chromatography-electrospray ionization-tandem mass spectrometry. Maternal urinary mono-benzyl phthalate MBzP concentrations were associated with an increased occurrence of wheezing in boys at 8 years of age (odds ratio OR = 4.95 (95% CI 1.08-22.63)), for upper quintile compared to the others) after controlling for parental allergies and family members' smoking status. Urinary mono-2-ethylhexyl phthalate MEHP levels over the quintile at 2-year-old were associated with increased asthma occurrence (adjusted OR = 6.14 (1.17-32.13)) in boys. Similarly, the sum of di-2-ethyl-hexyl phthalate DEHP metabolites at 5 years was associated with asthma in boys (adjusted OR = 4.36 (1.01-18.86)). Urinary MEHP in maternal and 5-year-old children urine were significantly associated with increased IgE in allergic children at 8 years. Prenatal and postnatal exposure to phthalate was associated with the occurrence of asthma in children, particularly for boys.
Main conclusion
We discovered and identified a series of characteristic substances, including one new polyketide, epicorepoxydon B, of the important pathogenic fungus,
Epicoccum sorghinum
, of ...sorghum. The fungal extract and some isolated polyketides are sensitive to a malignant triple-negative breast cancer cell line, MDA-MB-231.
Sorghum (Kaoliang) grain is an important crop with high economic value and several applications. In Taiwan, sorghum has been used in the wine industry, and “Kinmen Kaoliang Liquor” is a well-known Asian brand. Fungal contamination is one of the major threats affecting the production of sorghum grain resulting in economic losses as well as human and animal health problems. Several fungal species can infect sorghum grain and generate some toxic secondary metabolites.
Epicoccum sorghinum
is one of the major fungal contaminants of sorghum grains and a potent producer of mycotoxins such as tenuazonic acid (TeA). However, except for TeA, few studies focused on chemical compounds produced by this fungus. To explore the potential biological and toxic effects of
E. sorghinum
, a chemical investigation was carried out on the ethyl acetate extract of the fungus because it showed cytotoxic activity against a triple-negative breast cancer cell line, MDA-MB-231 (54.82% inhibition at 20 µg/mL). One new polyketide, epicorepoxydon B (
1
), along with six known compounds including 4,5-dihydroxy-6-(6′-methylsalicyloxy)-2-hydroxymethyl-2-cyclohexenl-one (
2
), epicorepoxydon A (
3
), 3-hydroxybenzyl alcohol (
4
), 6-methylsalicylic acid (
5
), gentisyl alcohol (
6
), and 6-(hydroxymethyl)benzene-1,2,4-triol (
7
) were obtained, and their structures were established by the interpretation of their MS and NMR spectroscopic data. The cytotoxic activity of all isolated polyketides
1
–
7
was evaluated, and compounds
2
,
6
, and
7
exhibited potent activities against A549, HepG2, and MDA-MB-231 human cancer cell lines with IC
50
value ranging from 1.86 to 18.31 μM. The structure–activity relationship of the isolated compounds was proposed.
Graphic abstract
Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the ...real-world database to investigate
in vivo
protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD).
In vitro
, human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA), and western blot analysis. The
in vivo
effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For
in vivo
study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.
Previous studies have shown associations between prenatal phthalate exposure and neurobehavioral changes in children. However, few studies have focused on neonatal neurobehavioral development. This ...study aimed to examine the associations between prenatal phthalate exposure and neonatal neurobehavioral development in the early days of life after birth.
This cohort study included 283 mother-infant pairs who participated in the Taiwan Mother Infant Cohort Study during 2012–2015. Each mother was interviewed, and urine samples were collected during the third trimester of pregnancy (weeks 29–40). Eleven common phthalate metabolites in maternal urine were analyzed. The Chinese version of the Neonatal Neurobehavioral Examination was used to evaluate early infant neurobehavioral development within five days of birth. We performed multiple linear regressions to explore the associations between phthalate exposure and neonatal neurobehavioral development. Sex differences in the association between phthalate metabolites and neonatal neurobehaviors were noted. Among girls, tertiles of phthalate metabolite concentrations were associated with worse behavioral responses and tone and motor patterns in the high-molecular-weight phthalate (HMW) and low-molecular-weight phthalate (LMW) groups. Girls in the highest tertile of di-2-ethylhexyl phthalate (DEHP) and mono-isobutyl phthalate (MiBP) had a negative association with tone and motor patterns. Girls in the highest tertile of mono-n-butyl phthalate (MnBP) and MiBP showed a negative association with behavioral responses. In contrast, tertiles of phthalate metabolite exposure were associated with improved neurobehaviors in mono-methyl phthalate (MMP) among boys. The highest tertile of MMP was positively associated with behavioral responses, primitive reflexes, and tone and motor patterns. Our findings suggest that maternal phthalate exposure affects neonatal neurobehavioral development in a sex-specific manner. Despite the relatively small sample size, our findings add to the existing research linking maternal phthalate exposure to neonatal neurobehavioral development. Additional research is needed to determine the potential long-term effects of prenatal phthalate exposure on children.
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•The association between neurobehavioral development and phthalate exposure differed by sex.•DEHP and MiBP are associated with poor tone and motor patterns in female infants.•MnBP and MiBP are associated with poor behavioral response in female infants.•MMP is positively associated with male neurobehavioral development scores.
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•Interconnected porous Ti-Nb-Zr-Sn scaffold is made by electron beam melting method.•Alkali treatment creates outer porous topography and inner dense layer on scaffold.•Collagen is ...immobilized on alkali-treated scaffold by cross-linker procyanidin.•The surface treatments enhance corrosion resistance and cell response of scaffold.•The proposed surface-treated alloy scaffold has potential as biomedical implants.
We present a unique way of combining alkali treatment and natural cross-linker, procyanidin, to create submicron-porous structure (pore size 100–300 nm) and immobilize type I collagen on the surface of electron beam melted β-type Ti-24Nb-4Zr-8Sn (Ti2448) alloy scaffold with interconnected porosity. Scanning electron microscopy and transmission electron microscopy showed a hybrid layer, an outer submicron-porous layer and an inner dense layer, was formed on the interconnected Ti2448 alloy scaffold surface. X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and Sirius red staining analysis confirmed the collagen was successfully immobilized on the scaffold. The dense inner oxide layer mainly provided Ti2448 alloy scaffold with enhanced corrosion resistance. The Ti2448 alloy scaffolds, with and without surface treatments, were potentially non-cytotoxic; particularly, the type I collagen-immobilized Ti2448 alloy scaffold via procyanidin cross-linking showed better adhesion of human bone marrow mesenchymal stem cells. The proposed simple and unique surface treatment simultaneously enhances the corrosion resistance and cell adhesion of interconnected porous Ti2448 alloy scaffold without causing cytotoxicity and shows great potential for biomedical implant applications.
Landscape patterns in urban regions are usually influenced by human-induced change in land cover in the processes of urbanization. Landscape spatial patterns have profound implications for the ...functions of ecological systems, and landscape diversity is an effective parameter representing landscape spatial patterns. However, the dynamics of landscape diversity in response to urbanization and its relationships with other aspects of landscape patterns have not been adequately discussed in the context of urban regions. Moreover, the significance of spatial distributions and local differences in landscape diversity within urban regions has received minimal attention. To further understand landscape diversity this study conducted a series analysis of landscape metrics to describe the spatiotemporal pattern of landscape diversity within the Taipei metropolitan region between 1971 and 2005. The landscape metrics were also analyzed to present the characteristics of landscape patterns and examine the correlations of metrics. The dynamics of intra-level landscape diversity in response to urbanization and its relationships with other aspects of landscape patterns were revealed by a series of metric analyses. The spatial distributions and local differences of landscape diversity were revealed to identify the areas where landscape diversity significantly changed in Taipei metropolitan region. This study also identified the regular pattern of landscape diversity in response to the process of urbanization and tested the theory of urban growth.
Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear.
This ...study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD).
In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD.
Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs.
Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure.
Ti-24Nb-4Zr-8Sn (Ti2448), a new β-type Ti alloy, consists of nontoxic elements and exhibits a low uniaxial tensile elastic modulus of approximately 45 GPa for biomedical implant applications. ...Nevertheless, the bio-corrosion resistance and biocompatibility of Ti2448 alloys must be improved for long-term clinical use. In this study, a rapid electrochemical anodization treatment was used on Ti2448 alloys to enhance the bio-corrosion resistance and bone cell responses by altering the surface characteristics. The proposed anodization process produces a unique hybrid oxide layer (thickness 50-120 nm) comprising a mesoporous outer section and a dense inner section. Experiment results show that the dense inner section enhances the bio-corrosion resistance. Moreover, the mesoporous surface topography, which is on a similar scale as various biological species, improves the wettability, protein adsorption, focal adhesion complex formation and bone cell differentiation. Outside-in signals can be triggered through the interaction of integrins with the mesoporous topography to form the focal adhesion complex and to further induce osteogenic differentiation pathway. These results demonstrate that the proposed electrochemical anodization process for Ti2448 alloys with a low uniaxial tensile elastic modulus has the potential for biomedical implant applications.
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