The associated risk of phthalate exposure, both parent compounds in the home and their metabolites in urine, to childhood allergic and respiratory morbidity, after adjusting for exposures of indoor ...pollutants, especially bioaerosols, was comprehensively assessed. Levels of five phthalates in settled dust from the homes of 101 children (3–9 years old) were measured, along with their corresponding urinary metabolites. Other environmental risk factors, including indoor CO2, PM2.5, formaldehyde, 1,3‐β‐d‐glucan, endotoxin, allergen and fungal levels, were concomitantly examined. Subject’s health status was verified by pediatricians, and parents recorded observed daily symptoms of their children for the week that the home investigation visit took place. Significantly increased level of benzylbutyl phthalate, in settled dust, was associated with test case subjects (allergic or asthmatic children). Higher levels of dibutyl phthalate and its metabolites, mono‐n‐butyl phthalate, and mono‐2‐ethylhexyl phthalate were found to be the potential risk factors for the health outcomes of interest. Similarly, indoor fungal exposure remained a significant risk factor, especially for reported respiratory symptoms. The relative contribution from exposure to phthalates and indoor biocontaminants in childhood allergic and respiratory morbidity is, for the first time, quantitatively assessed and characterized.
Practical Implications
For asthmatic and allergic children living in subtropical and highly developed environments like homes in Taiwan, controlling environmental exposure of phthalates may be viewed as equally important as avoiding indoor microbial burdens, for the management of allergy‐related diseases. It is also recognized that multidisciplinary efforts will be critical in realizing the true underlying mechanisms associated with these observations.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
With continued climate changes, soil drought stress has become the main limiting factor for crop growth in arid and semi‐arid regions. A typical characteristic of drought stress is the burst of ...reactive oxygen species (ROS), causing oxidative damage. Plant‐associated microbes, such as arbuscular mycorrhizal fungi (AMF), can regulate physiological and molecular responses to tolerate drought stress, and they have a strong ability to cope with drought‐induced oxidative damage via enhanced antioxidant defence systems. AMF produce a limited oxidative burst in the arbuscule‐containing root cortical cells. Similar to plants, AMF modulate a fungal network in enzymatic (e.g. GmarCuZnSOD and GintSOD1) and non‐enzymatic (e.g. GintMT1, GinPDX1 and GintGRX1) antioxidant defence systems to scavenge ROS. Plants also respond to mycorrhization to enhance stress tolerance via metabolites and the induction of genes. The present review provides an overview of the network of plant − arbuscular mycorrhizal fungus dialogue in mitigating oxidative stress. Future studies should involve identifying genes and transcription factors from both AMF and host plants in response to drought stress, and utilize transcriptomics, proteomics and metabolomics to clarify a clear dialogue mechanism between plants and AMF in mitigating oxidative burst.
The dialogue of arbuscular mycorrhizal fungi and host plants confers a mitigating drought‐induced oxidative burst in hosts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Fragile histidine triad (FHIT) loss by the two-hit mechanism of loss of heterozygosity and promoter hypermethylation commonly occurrs in non-small cell lung cancer (NSCLC) and may confer cisplatin ...resistance in NSCLC cells. However, the underlying mechanisms of FHIT loss in cisplatin resistance and the response to cisplatin-based chemotherapy in NSCLC patients have not yet been reported. In the present study, inhibition concentration of 50% cell viability induced by cisplatin (IC50) and soft agar growth and invasion capability were increased and decreased in FHIT-knockdown and -overexpressing cells, respectively. Mechanistically, Slug transcription is upregulated by AKT/NF-κB activation due to FHIT loss and, in turn, Slug suppresses PUMA expression; this decrease of PUMA by FHIT loss is responsible for cisplatin resistance. In addition, cisplatin resistance due to FHIT loss can be conquered by AKT inhibitor-perifosine in xenograft tumors. Among NSCLC patients, low FHIT, high p-AKT, high Slug and low PUMA were correlated with shorter overall survival, relapse-free survival and poorer response to cisplatin-based chemotherapy. Therefore, the AKT inhibitor perifosine might potentially overcome the resistance to cisplatin-based chemotherapy in NSCLC patients with low-FHIT tumors, and consequently improve the outcome.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Impressive performance of hybrid perovskite solar cells reported in recent years still awaits a comprehensive understanding of its microscopic origins. In this work, the intrinsic Hall mobility and ...photocarrier recombination coefficient are directly measured in these materials in steady-state transport studies. The results show that electron-hole recombination and carrier trapping rates in hybrid perovskites are very low. The bimolecular recombination coefficient (10(-11) to 10(-10) cm(3) s(-1)) is found to be on par with that in the best direct-band inorganic semiconductors, even though the intrinsic Hall mobility in hybrid perovskites is considerably lower (up to 60 cm(2) V(-1) s(-1)). Measured here, steady-state carrier lifetimes (of up to 3 ms) and diffusion lengths (as long as 650 μm) are significantly longer than those in high-purity crystalline inorganic semiconductors. We suggest that these experimental findings are consistent with the polaronic nature of charge carriers, resulting from an interaction of charges with methylammonium dipoles.
The dual role of the microRNA-29 (miR-29) family in tumor progression and metastasis in solid tumors has been reported. Evidence for the role of miR-29 in tumor malignancy and its prognostic value in ...overall survival (OS) and relapse-free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting. Mechanistic studies presented herein demonstrated that c-Myc suppressed the expression of miR-29b, promoting soft agar growth and invasion capability in lung cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc is responsible for soft agar growth and invasiveness mediated by FHIT loss due to promoter methylation. Among patients, low expression of miR-29b and FHIT was more common in tumors with high c-Myc expression than in tumors with low c-Myc expression. Kaplan-Meier and Cox regression analysis showed that tumors with high c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than their counterparts. In conclusion, the decrease in the expression of miR-29b by c-Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b expression using the c-Myc inhibitor might be helpful in suppressing tumor aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC patients with tumors with low expression of FHIT.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aims/hypothesis
Sirtuin-1 (SIRT1) is a potential therapeutic target to combat insulin resistance and type 2 diabetes. This study aims to identify a microRNA (miRNA) targeting SIRT1 to regulate ...hepatic insulin sensitivity.
Methods
Luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were measured by real-time PCR. Insulin signalling was detected by immunoblotting and glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor and SIRT1-deficient hepatocytes. The role of
miR-181a
in vivo was explored with adenovirus and locked nucleic acid antisense oligonucleotides.
Results
miR-181a
targets the 3′ untranslated region (3′UTR) of
Sirt1
mRNA through a
miR-181a
binding site, and downregulates SIRT1 protein abundance at the translational level.
miR-181a
is increased in insulin-resistant cultured hepatocytes and liver, and in the serum of diabetic patients. Overexpression of
miR-181a
decreases SIRT1 protein levels and activity, and causes insulin resistance in hepatic cells. Inhibition of
miR-181a
by antisense oligonucleotides increases SIRT1 protein levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic expression of
SIRT1
abrogates the effect of
miR-181a
on insulin sensitivity, and inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the improvement in insulin sensitivity induced by antisense
miR-181a
. In addition, overexpression of
miR-181a
by adenovirus impairs hepatic insulin signalling, and intraperitoneal injection of locked nucleic acid antisense oligonucleotides for
miR-181a
improves glucose homeostasis in diet-induced obesity mice.
Conclusions/interpretation
miR-181a
regulates SIRT1 and improves hepatic insulin sensitivity. Inhibition of
miR-181a
might be a potential new strategy for treating insulin resistance and type 2 diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Resistance mutations A2058G and A2059G, within the 23S rRNA gene of Treponema pallidum, have been reported to cause treatment failures in patients receiving azithromycin for syphilis. Genotyping of ...T. pallidum strains sequentially isolated from patients with recurrent syphilis is rarely performed. From September 2009 to August 2013, we collected 658 clinical specimens from 375 patients who presented with syphilis for genotyping to examine the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and tp0548 gene, and to detect A2058G and A2059G point mutations by restriction fragment length polymorphism. Treponemal DNA was identified in 45.2% (n = 298) of the specimens that were collected from 216 (57.6%) patients; 268 (40.7%) specimens tested positive for the 23S rRNA gene, and were examined for macrolide resistance. Two isolates (0.7%) harboured the A2058G mutation, and no A2059G mutation was identified. A total of 14 strains of T. pallidum were identified, with 14f/f (57.5%) and 14b/c (10.0%) being the two predominant strains. Forty patients who presented with recurrent episodes of syphilis had T. pallidum DNA identified from the initial and subsequent episodes, with five cases showing strain discrepancies. One patient had two strains identified from different clinical specimens collected in the same episode. Our findings show that 14f/f is the most common T. pallidum strain in Taiwan, where the prevalence of T. pallidum strains that show A2058G or A2059G mutation remains low. Different genotypes of T. pallidum can be identified in patients with recurrent episodes of syphilis.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Colorectal cancer (CRC) development has been associated with increased proportions of Bacteroides fragilis and certain Streptococcus, Fusobacterium, and Peptostreptococcus species in the intestinal ...microbiota. We investigated associations between bacteremia from specific intestinal microbes and occurrence of CRC.
We performed a retrospective study after collecting data on 13,096 adult patients (exposed group) in Hong Kong hospitalized with bacteremia (identified by blood culture test) without a previous diagnosis of cancer from January 1, 2006 through December 31, 2015. We collected data on intestinal microbes previously associated with CRC (genera Bacteroides, Clostridium, Filifactor, Fusobacterium, Gemella, Granulicatella, Parvimonas, Peptostreptococcus, Prevotella, Solobacterium, and Streptococcus). Clinical information, including patient demographics, comorbid medical conditions, date of bacteremia, and bacterial species identified, were collected. The incidence of biopsy-proved CRC was compared between the exposed and unexposed (patients without bacteremia matched for age, sex, and comorbidities) groups.
The risk of CRC was increased in patients with bacteremia from B fragilis (hazard ratio HR = 3.85, 95% CI = 2.62–5.64, P = 5.5 × 10−12) or Streptococcus gallolyticus (HR = 5.73, 95% CI = 2.18–15.1, P = 4.1 × 10−4) compared with the unexposed group. In addition, the risk of CRC was increased in patients with bacteremia from Fusobacterium nucleatum (HR = 6.89, 95% CI = 1.70–27.9, P = .007), Peptostreptococcus species (HR = 3.06, 95% CI = 1.47–6.35, P = .003), Clostridium septicum (HR = 17.1, 95% CI = 1.82–160, P = .013), Clostridium perfringens (HR = 2.29, 95% CI = 1.16–4.52, P = .017), or Gemella morbillorum (HR = 15.2, 95% CI = 1.54–150, P = .020). We observed no increased risk in patients with bacteremia caused by microbes not previously associated with colorectal neoplasms.
In a retrospective analysis of patients hospitalized for bacteremia, we associated later diagnosis of CRC with B fragilis and S gallolyticus and other intestinal microbes. These bacteria might have entered the bloodstream from intestinal dysbiosis and perturbed barrier function. These findings support a model in which specific members of the intestinal microbiota promote colorectal carcinogenesis. Clinicians should evaluate patients with bacteremia from these species for neoplastic lesions in the colorectum.
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Resveratrol (RES) is a naturally occurring and effective drug for tumor prevention and treatment. However, its low levels of aqueous solubility, stability, and poor bioavailability limit its ...application, especially when used as a free drug. In this study, RES was loaded into peptide and sucrose liposomes (PSL) to enhance the physico-chemical properties of RES and exploit RES delivery mediated by liposomes to effectively treat breast cancer. RES loaded PSL (the complex: PSL@RES) were stable, had a good RES encapsulation efficiency, and prolonged RES-release
in vitro
. PSL@RES was exceptionally efficient for inhibiting the growth of cancer cells, as the IC
50
of PSL@RES in MCF-7 cells was found to be only 20.89 μmol L
−1
. The therapeutic efficacy of PSL@RES was evaluated in mice bearing breast cancer. The results showed that PSL@RES at a dosage of 5 mg kg
−1
was more effective than 10 mg kg
−1
free RES, and PSL@RES inhibited tumor growth completely at a dosage of 10 mg kg
−1
. PSL@RES induced apoptosis in breast tumor by upregulation of p53 expression. This then downregulated Bcl-2 and upregulated Bax, thereby inducing Caspase-3 activation. More importantly, encapsulation of RES within peptide liposomes greatly reduced the toxicity of free RES to mice. Overall, the simple formulation of liposomal nanocarriers of RES developed in this study produces satisfactory outcomes to encourage further applications of liposomal carriers for the treatment of breast cancer.
RES encapsulated in tri-peptide liposome led to obvious apoptosis of tumor cells and great inhibition of tumors at low doses, and significantly decreased the toxicity of RES to mice.
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