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1.
J Drug Target ; : 1-46, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960252

RESUMO

The specific tumor microenvironment plays a crucial role in the occurrence and development of tumors. Among them, the abnormal structure and function of blood vessels in the tumor microenvironment are obvious characteristics of the tumor. Abnormal blood vessels with high leakage can lead to impaired blood perfusion and non-specific leakage of blood components into the surrounding interstitial spaces. They create a hypoxic and acidic microenvironment for tumors, which supports the occurrence of malignant tumors and increases the possibility of tumor cell invasion and metastasis. The formation of abnormal vascular also enhances immunosuppression and prevents the delivery of chemotherapy drugs to deeper tumors. Therefore, the normalization of tumor blood vessels is a very promising approach to improve anti-tumor efficacy, aiming to restore the structural integrity of vessels and improve drug delivery efficiency and anti-tumor immunity. In this review, we have summarized strategies to improve cancer treatment that via nano drug delivery technology regulates the normalization of tumor blood vessels. The treatment strategies related to the structure and function of tumor blood vessels such as angiogenesis factors, tumor-associated macrophages, tumor vascular endothelial cells, tumor-associated fibroblasts, and immune checkpoints in the tumor microenvironment were mainly discussed. The normalization of tumor blood vessels presents new opportunities and challenges for the more efficient delivery of nanoparticles to tumor tissues and cells and an innovative combination of treatments for cancer.

2.
Sci Rep ; 11(1): 8529, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879822

RESUMO

This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student's caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children's health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.


Assuntos
/epidemiologia , Exercício Físico/psicologia , Tempo de Tela , Privação do Sono/epidemiologia , Estudantes/psicologia , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Inquéritos e Questionários
3.
Acta Biomater ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33894351

RESUMO

The combination of chemotherapy and gene therapy has been indicated as a promising approach for cancer therapy. However, this combination strategy is still faced a challenge by the lack of suitable carriers to co-loaded chemotherapeutic drug and gene into one single nanoplatform. In this study, a tumor-targeted HC/pIL-12/polyMET micelleplexes were developed for the co-loading and co-delivery of cisplatin (CDDP) and plasmid encoding interleukin-12 gene (pIL-12), which would be utilized to generate synergistic actions through chemotherapy sensitization and microenvironment modulation. The HC/pIL-12/polyMET exhibited desirable particle size, superior serum stability, effective intracellular CDDP release and pIL-12 transfection efficiency. More important, the HC/pIL-12/polyMET generated the enhanced LLC cell proliferation inhibition and apoptosis induction efficiency. The long-circulating HC/pIL-12/polyMET micelleplexes promoted the accumulation of CDDP and pIL-12 in tumor site, which resulted in significantly inhibiting the growth of lung cancer, and prolonging the overall survival of tumor-bearing mice. The underlying immune mechanism demonstrated the combination of CDDP and pIL-12 activated immune effector cells to release IFN-γ and induced M1-type differentiation of tumor-related macrophages, thereby generating synergistic chemoimmunotherapy effect. Taken together, this study may provide an effective strategy for drug/gene co-delivery and cancer chemoimmunotherapy. STATEMENT OF SIGNIFICANCE: Chemoimmunotherapy has been indicated as an approach to improve efficacy of cancer therapy. Herein, a tumor-targeted micelleplexes (HC/pIL-12/polyMET) were developed for the co-delivery of cisplatin (CDDP) and plasmid encoding IL-12 gene (pIL-12), which can employ the synergistic effects through chemotherapy sensitization and microenvironment modulation. The HC/pIL-12/polyMET exhibited desirable particle size, superior serum stability, high gene transfection efficiency and antitumor activity on tumor cell proliferation inhibition and apoptosis induction. More importantly, the long-circulating HC/pIL-12/polyMET micelleplexes could effectively accumulate in tumor sites and then rapidly release the CDDP and pIL-12, significantly inhibit the growth of lung cancer. This strategy provides a new concept for chemo-gene combination with a strengthened overall therapeutic efficacy of chemoimmunotherapy.

4.
J Cell Biochem ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33852174

RESUMO

LASS2 is a novel tumor-suppressor gene and has been characterized as a ceramide synthase, which synthesizes very-long acyl chain ceramides. However, LASS2 function and pathway-related activity in prostate carcinogenesis are still largely unexplored. Here, we firstly report that LASS2 promotes ß-catenin degradation through physical interaction with STK38, SCYL2, and ATP6V0C via the ubiquitin-proteasome pathway, phosphorylation of LASS2 is essential for ß-catenin degradation, and serine residue 248 of LASS2 is illustrated to be a key phosphorylation site. Furthermore, we find that dephosphorylation of LASS2 at serine residue 248 significantly enhances prostate cancer cell growth and metastasis in vivo, indicating that phosphorylated LASS2 inhibits prostate carcinogenesis through negative regulation of Wnt/ß-catenin signaling. Thus, our findings implicate LASS2 as a potential biomarker and therapeutic target of prostate cancer.

5.
Plants (Basel) ; 10(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799872

RESUMO

Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2) is the key antioxidant system in animals. In a previous study, we identified a probable KEAP1 ortholog in rice, OsKEAP1, and demonstrated that the downregulation of OsKEAP1 could alter the redox system and impair plant growth, as well as increase the susceptibility to abscisic acid (ABA) in seed germination. However, no NRF2 orthologs have been identified in plants and the mechanism underlying the phenotype changes of downregulated oskeap1 mutants is yet unknown. An in silico search showed that OsABI5 is the gene that encodes a protein with the highest amino acid identity score (38.78%) to NRF2 in rice. In this study, we demonstrated that, via yeast two-hybrids analysis and bimolecular fluorescence complementation assays, OsKEAP1 interacted with OsABI5 via its Kelch repeat domain in the nucleus. In germinating seeds, the expression of OsKEAP1 was significantly downregulated in oskeap1-1 (39.5% that of the wild-type (WT)) and oskeap1-2 (64.5% that of WT), while the expression of OsABI5 was significantly increased only in oskeap1-1 (247.4% that of WT) but not in oskeap1-2 (104.8% that of WT). ABA (0.5 µM) treatment significantly increased the expression of OsKEAP1 and OsABI5 in both the oskeap1 mutants and WT, and 4 days post treatment, the transcription level of OsABI5 became significantly greater in oskeap1-1 (+87.2%) and oskeap1-2 (+55.0%) than that in the WT. The ABA-responsive genes (OsRab16A and three late embryogenesis abundant genes), which are known to be activated by OsABI5, became more responsive to ABA in both oskeap1 mutants than in the WT. The transcript abundances of genes that regulate OsABI5, e.g., OsSnRK2 (encodes a kinase that activates OsABI5), OsABI1, and OsABI2 (both encode proteins binding to OsSnRK2 and are involved in ABA signaling) were not significantly different between the two oskeap1 mutants and the WT. These results demonstrated that OsKEAP1 played a role in the ABA response in rice seed germination via regulating OsABI5, which is the key player in the ABA response. In-depth analyses of the components and their action mode of the KEAP1-NRF2 and ABA signaling pathways suggested that OsKEAP1 likely formed a complex with OsABI5 and OsKEG, and OsABI5 was ubiquitinated by OsKEG and subsequently degraded under physiological conditions; meanwhile, under oxidative stress or with increased an ABA level, OsABI5 was released from the complex, phosphorylated, and transactivated the ABA response genes. Therefore, OsKEAP1-OsABI5 bore some resemblance to KEAP1-NRF2 in terms of its function and working mechanism.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33813699

RESUMO

The occurrence and distribution of antibiotics and antibiotic resistance genes (ARGs) in natural water has attracted worldwide attention. Antibiotic and ARG pollution in the surface water of drinking water sources might directly/indirectly affect human health. In this study, the distribution of 38 antibiotics, 10 ARGs, 2 integrons, and 16S r DNA in river-type water sources in a large city of China were monitored in winter, which was a period with high level of antibiotic pollution. The results showed that 20 antibiotics were detected with different detection frequencies. The antibiotic pollution in December 2019 was relatively high, with the total concentrations of antibiotics ranging from 281.95 to 472.42 ng/L, followed by that in January 2020 (191.70-337.29 ng/L) and November 2019 (161.25-309.72 ng/L). Sulfacetamide was dominant in November 2019 (23.52-219.00 ng/L) and in January 2020 (113.18-209 ng/L), while norfloxacin in December 2019 (146.72-290.20 ng/L). All the target antibiotics posed low or medium risk for aquatic organisms, and posed low health risk for mankind. Sul1 and erm36 were the predominant ARGs, and intI1 was the predominant integron in drinking water sources. Only tetA showed positive correlations with its corresponding antibiotic (tetracycline). The rest of ARGs showed no correlations with antibiotics or positive / negative correlations with their non-corresponding antibiotics. Overall, the antibiotics and ARG pollution in these water sources was relatively low. These findings provided some reference data for the distribution of antibiotics and ARGs in river-type drinking water sources of large cities in China.

7.
Nat Commun ; 12(1): 1689, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727548

RESUMO

Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.


Assuntos
Biomimética , Bivalves/química , Sistemas de Liberação de Medicamentos , Mucosa Bucal/fisiologia , Adesividade , Administração Bucal , Animais , Linhagem Celular , Dexametasona/farmacologia , Di-Hidroxifenilalanina/química , Liberação Controlada de Fármacos , Humanos , Indóis/toxicidade , Masculino , Mucinas/química , Muco/química , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/toxicidade , Polímeros/toxicidade , Álcool de Polivinil/química , Álcool de Polivinil/toxicidade , Ratos Sprague-Dawley , Espectrofotometria Ultravioleta , Suínos , Distribuição Tecidual
8.
Biochem Pharmacol ; : 114453, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33545119

RESUMO

A novel PMet-P(cdmPEG2K) polymeric micellar carrier was developed for tumor-targeted co-delivery of DOX and nucleic acids (NA), based on polymetformin and a structure designed to lose the PEG shell in response to the acidic extracellular tumor environment. NA/DOX co-loaded micelleplexes exhibited enhanced inhibition of cell proliferation compared to DOX-loaded micelles, and displayed a higher level of cytotoxicity at an acidic pH (6.8) which mimicks the tumor microenvironment. The PMet-P(cdmPEG2K) micelles achieved significantly improved transfection with either a reporter plasmid or Cy3-siRNA, and enhanced DOX intracellular uptake in 4T1.2 cells at pH 6.8. Importantly, PMet-P(cdmPEG2K) micelles showed excellent pEGFP (EGFP expression plasmid) transfection in an aggressive murine breast cancer (4T1.2) model. By using a plasmid encoding IL-12 (pIL-12), we investigated the combined effect of chemotherapy and gene therapy. PMet-P(cdmPEG2K) micelles co-loaded with DOX and pIL-12 were more effective at inhibiting tumor growth compared to micelles loaded with DOX or pIL-12 alone. In addition, this micellar system was effective in co-delivery of siRNA and DOX into tumor cells. Our results suggest that PMet-P(cdmPEG2K) has the potential for chemo and nucleic acid combined cancer therapy.

9.
Microb Cell Fact ; 20(1): 29, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530990

RESUMO

BACKGROUND: Cembranoids are one kind of diterpenoids with multiple biological activities. The tobacco cembratriene-ol (CBT-ol) and cembratriene-diol (CBT-diol) have high anti-insect and anti-fungal activities, which is attracting great attentions for their potential usage in sustainable agriculture. Cembranoids were supposed to be formed through the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, yet the involvement of mevalonate (MVA) pathway in their synthesis remains unclear. Exploring the roles of MVA pathway in cembranoid synthesis could contribute not only to the technical approach but also to the molecular mechanism for cembranoid biosynthesis. RESULTS: We constructed vectors to express cembratriene-ol synthase (CBTS1) and its fusion protein (AD-CBTS1) containing an N-terminal GAL4 AD domain as a translation leader in yeast. Eventually, the modified enzyme AD-CBTS1 was successfully expressed, which further resulted in the production of CBT-ol in the yeast strain BY-T20 with enhanced MVA pathway for geranylgeranyl diphosphate (GGPP) production but not in other yeast strains with low GGPP supply. Subsequently, CBT-diol was also synthesized by co-expression of the modified enzyme AD-CBTS1 and BD-CYP450 in the yeast strain BY-T20. CONCLUSIONS: We demonstrated that yeast is insensitive to the tobacco anti-fungal compound CBT-ol or CBT-diol and could be applied to their biosynthesis. This study further established a feasibility for cembranoid production via the MVA pathway and provided an alternative bio-approach for cembranoid biosynthesis in microbes.

10.
Sci Rep ; 11(1): 4048, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603029

RESUMO

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

11.
J Hazard Mater ; 404(Pt B): 124020, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049558

RESUMO

Environmental pollution has become a concern for public health. As endocrine disruptors, organophosphate esters (OPEs) causes many diseases via human exposure. However, there is limited research on the risk of OPE exposure to female-specific cancers. Blood measurements are biomarkers for chemical exposures by their definition. Thus, in the present study, 11 OPEs were analyzed in the plasma of patients with 4 female-specific tumors. 2-Ethylhexyl diphenyl phosphate (EHDPP) was detected at the highest levels in all groups. The Spearman correlation test results showed significantly positive correlations between some OPEs in each group, which indicated that those OPEs had similar sources and/or behaved similarly in the patients of each group. However, compared with different patient groups, obvious differences in the correlation results were noted, implying the differences in the metabolism of OPEs between different groups. The results of the correlation analysis showed that EHDPP concentration was associated with the risk of breast cancer (p < 0.05), while tri-n-butyl phosphate (TNBP), tris (methylphenyl) phosphate (TMPP), triphenyl phosphate (TPHP), and EHDPP concentrations were associated with the risk of cervical cancer (p < 0.05 or p < 0.01). These findings indicated that OPEs were associated with the risk of breast and cervical cancer.


Assuntos
Retardadores de Chama , Neoplasias , China , Monitoramento Ambiental , Ésteres , Feminino , Retardadores de Chama/análise , Humanos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Organofosfatos/toxicidade
12.
ACS Appl Mater Interfaces ; 13(1): 97-111, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33354968

RESUMO

Zeolitic imidazolate framework-8 (ZIF-8) is an important type of metal organic framework and has found numerous applications in the biomedical field. Our previous studies have demonstrated that nano ZIF-8-based titanium implants could promote osseointegration; however, its osteogenic capacity and the related mechanisms in bone regeneration have not been fully clarified. Presented here is a nanoscale ZIF-8 that could drive rat bone mesenchymal stem cell (rBMSC) differentiation into osteoblasts both in vitro and in vivo, and interestingly, nano ZIF-8 exhibited a better osteogenic effect compared with ionic conditions of Zn at the same concentration of Zn2+. Moreover, the cellular uptake mechanisms of the nanoparticles were thoroughly clarified. Specifically, nano ZIF-8 could enter the rBMSC cytoplasm probably via caveolae-mediated endocytosis and macropinocytosis. The intracellular and extracellular Zn2+ released from nano ZIF-8 and the receptors involved in the endocytosis may play a role in inducing activation of key osteogenic pathways. Furthermore, through transcriptome sequencing, multiple osteogenic pathways were found to be upregulated, among which nano ZIF-8 primarily phosphorylated ERK, thus activating the canonical mitogen-activated protein kinase pathway and promoting the osteogenesis of rBMSCs. Taken together, this study helps to elucidate the mechanism by which nano ZIF-8 regulates osteogenesis and suggests it to be a potential biomaterial for constructing multifunctional composites in bone tissue engineering.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estruturas Metalorgânicas/uso terapêutico , Nanopartículas/uso terapêutico , Alginatos/química , Animais , Osso e Ossos/citologia , Osso e Ossos/lesões , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Endocitose/fisiologia , Hidrogéis/química , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/metabolismo , Nanopartículas/química , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Pinocitose/fisiologia , Ratos Sprague-Dawley , Zinco/química , Zinco/metabolismo
13.
Food Chem ; : 128600, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33221101

RESUMO

The contents of phenolic compounds, especially flavonoids, and antioxidant activity of rice (Oryza sativa, Os) and Chinese wild rice (Zizania latifolia, Zl) harvested in China were compared. Zl possessed significantly higher contents of total phenolics, flavonoids, and proanthocyanidins and exhibited higher antioxidant activity than in the Os Xian group, the Os Geng group, and red rice. The flavonoid contents of Os and Zl were compared using a UHPLC-QqQ-MS-based metabolomics approach. A total of 159 flavonoids were identified, among which 78 showed differential expression (72 up-regulated and six down-regulated in the Zl group). The Kyoto Encyclopaedia of Genes and Genomes annotation and classification indicated that the differentially expressed flavonoids were mainly related to anthocyanin biosynthesis. Moreover, candidate genes for flavonoid biosynthesis in Os and Zl were identified in this study. Compared with non-pigmented and red rice, Zl may be more nutritious and is thus considered a better source of natural antioxidants.

14.
Small ; : e2005639, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169499

RESUMO

The disordered dendritic growth of Li metal seriously hampers the practical application of lithium metal batteries. Great efforts are devoted to suppress the growth of dendrites, it is still necessary to explore measures of controlling dendritic growth and pave ways for normal cell operation in presence of dendrites. Herein, a modification technique of Li metal anode by a periodic Ni mesh with micrometer-sized grid is proposed for interfacial engineering. Periodic patterned Ni mesh is prepared using a novel laser direct-writing technique combined with selective electrodeposition process. The growth of Li dendrites is regulated under the effect of unique electric field distribution by the introduction of the Ni mesh. It is noteworthy that the controlled lateral growth of dendrites is successfully realized by the internal structure modification instead of any external electric or magnetic field as has been previously reported. The resultant anode exhibits a stable cycling performance with ultralow overpotential of 6-8 mV for over 1000 h at the current density of 0.5 mA cm-2 . It also presents superior electrochemical performance when assembled against LiFePO4 cathode into full cells, with an initial capacity of 133 mA h g-1 and a stable cycling performance over 160 cycles.

15.
Earths Future ; 8(9): e2019EF001331, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32999892

RESUMO

Precipitation extremes are among the most serious consequences of climate change around the world. The observed and projected frequency and intensity of extreme precipitation in some regions will greatly influence the social economy. The frequency of extreme precipitation and the population and economic exposure were quantified for a base period (1986-2005) and future periods (2016-2035 and 2046-2065) based on bias corrected projections of daily precipitation from five global climatic models forced with three representative concentration pathways (RCPs) and projections of population and gross domestic product (GDP) in the shared socioeconomic pathways (SSPs). The RCP8.5-SSP3 scenario produces the highest global population exposure for 2046-2065, with nearly 30% of the global population (2.97 × 109 persons) exposed to precipitation extremes >10 days/a. The RCP2.6-SSP1 scenario produces the highest global GDP exposure for 2046-2065, with a 5.56-fold increase relative to the base period, of up to (2.29 ± 0.20) × 1015 purchasing power parity $-days. Socioeconomic effects are the primary contributor to the exposure changes at the global and continental scales. Population and GDP effects account for 64-77% and 78-91% of the total exposure change, respectively. The inequality of exposure indicates that more attention should be given to Asia and Africa due to their rapid increases in population and GDP. However, due to their dense populations and high GDPs, European countries, that is, Luxembourg, Belgium, and the Netherlands, should also commit to effective adaptation measures.

16.
J Mol Cell Biol ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049034

RESUMO

Metastases are the main cause of cancer-related mortality in breast cancer. Although significant progress has been made in the field of tumor metastasis, the exact molecular mechanisms involved in tumor metastasis are still unclear. Here, we report that ATOH8-V1, a novel isoform of ATOH8, is highly expressed in breast cancer and is a negative prognostic indicator of survival for patients. Forced expression of ATOH8-V1 dramatically enhances, while silencing of ATOH8-V1 decreases the metastasis of breast cancer cell lines. Moreover, ATOH8-V1 directly binds to the RhoC promoter and stimulates the expression of RhoC, which in turn enhances the metastasis of breast cancer. Altogether, our data demonstrate that ATOH8-V1 is a novel pro-metastatic factor that enhances cancer metastasis, suggesting that ATOH8-V1 is a potential therapeutic target for treatment of metastatic cancers.

17.
J Biochem Mol Toxicol ; : e22639, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051984

RESUMO

Doxorubicin (DOX) is a very effective broad-spectrum anticancer drug, yet its clinical application is badly restricted due to its serious side effects. Citronellal (CT), a specialized metabolite of plants found in Cymbopogon spp., is proved to exhibit many beneficial properties. In the current study, we intended to investigate the effect of CT on DOX-induced hepatotoxicity in rats. Rats were treated with CT (200 mg/kg b.w./day orally), and given DOX (2.5 mg/kg b.w./week, intraperitoneally) to induce hepatotoxicity for six consecutive weeks. The results showed that CT administration could attenuate the DOX-induced pathological changes of liver tissues and ameliorated the inappropriate alteration of liver function biomarkers (serum glutamic aspartate aminotransferase, glutamic pyruvic transaminase, and albumin) in serum and oxidative stress parameters (malondialdehyde, superoxide dismutase, and reduced glutathione) in the liver. Moreover, CT mitigated the Bax/Bcl-2 ratio and caspase-3 expression to inhibit cell apoptosis. Further study indicated that CT therapy could enhance the protein levels of p-PI3K, p-Akt, and CD31 in the liver. These results demonstrate that CT can ameliorate DOX-induced hepatotoxicity in rats mediated by antioxidative stress, antiapoptosis, and proangiogenesis.

18.
Iran J Public Health ; 49(7): 1232-1241, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33083289

RESUMO

Background: To investigate the effect of perceptual stress reduction control intervention on the level of symptomatic groups at different time points in breast cancer. Methods: A total of 124 breast cancer patients were divided into intervention group and control group, 62 cases in each group. Perioperative nursing and chemotherapy nursing were given to the control group, and the intervention group was given the interventional stress reduction control intervention. The level of symptom clusters of different time points were compared between the two groups. Results: The incidence and severity of myelosuppression in the intervention group were slightly lower than those in the control group. The adverse reactions of bone marrow suppression at T3 were much lower than those in the control group, and the differences were significant (P=0.003, P=0.043). The control group had higher incidence and more severe symptoms of nausea, vomiting and diarrhea than the intervention group (P=0.002, P=0.042). The symptoms of breast pain and swelling at T1 in the intervention group were significantly lower than those in the control group (P=0.000, P=0.000). There was no significant difference in breast symptoms between the two groups at T2 and T3 (p>0.05). At the time of T2 and T3 of chemotherapy, the health promotion behavior scores of the intervention group were higher than the control group, and the difference was statistically significant (PT2=0.000, PT3=0.000). Conclusion: Perceptual stress reduction control intervention can effectively relieve bone marrow suppression, digestive tract discomfort and breast symptoms, and promote health promotion behavior.

19.
Plants (Basel) ; 9(11)2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33121183

RESUMO

The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2) module is a key component in the detoxification and antioxidant system in animals, which plays crucial roles in cell homeostasis and cytoprotection, and consequently in carcinogenesis and disease development. However, this system seems to have diverged throughout evolution across different organisms, and the question of whether a similar system exists in plants has thus far remained unresolved. In this study, a KEAP1 ortholog was identified in rice (Oryza sativa L., OsKEAP1) and its properties were characterized via in silico and laboratory studies. To reveal OsKEAP1's function, two knockdown mutants, oskeap1-1 and oskeap1-2, were generated by targeted mutagenesis in the 5' untranslated region (UTR) using the CRISPR-Cas9 system. In silico analysis showed that OsKEAP1 has a Kelch-repeat domain which is identical to those of animals and a plant-specific development and cell death (DCD) domain in place of the broad-complex, tramtrack, bric-a-brac (BTB) domain found in animals. Orthologs of OsKEAP1 are present across plant species and all have the DCD domain and the Kelch-repeat domain. OsKEAP1 was proven to be localized to both the cytoplasm and nucleus, in contrast to the exclusive cytoplasm localization of animal KEAP1. Single nucleotide insertions in the 5' UTR significantly reduced the transcription level of OsKEAP1 in the oskeap1-1 and oskeap1-2 mutants. The oskeap1 mutations greatly impaired plant growth and development, resulting in significant declines in a majority of agronomic and yield-related traits, i.e., plant height, panicle length, grain number per plant, and seed-set rate. The downregulation of OsKEAP1 increased the levels of H2O2, malondialdehyde, and proline while significantly decreasing the expression of two catalase genes in seedlings grown under normal and salt-stressed conditions. The changes in the above phenotypes are either positively or negatively correlated with the degree of OsKEAP1 downregulation. Altogether, we identified a probable KEAP1 ortholog in rice, revealed its unique subcellular localization, and demonstrated its important functions in vegetative and reproductive growth via regulation of the antioxidant response in plants.

20.
Opt Express ; 28(18): 26531-26542, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32906925

RESUMO

An efficient approach to obtain high shielding effectiveness (SE) in transparent shielding in an optical window field is proposed and demonstrated by fabricating an embedded double-layer metallic mesh (DLMM) comprised of randomly structured Ni meshes on both sides of a flexible substrate, employing a facile and low-cost double-sided nanoimprinting method. The unique nonperiodic random structure contributes to uniform diffraction and eliminates the Moiré fringe generated by double-layer periodic meshes, ensuring high imaging quality for optical applications. The designed DLMM films simultaneously achieve strong shielding in the X-band and high transmittance in the visible spectrum, demonstrating a high transmittance of 88.7% at the 550-nm wavelength and a SE of 46.9 dB at a frequency of 8.2 GHz. An ultra-high SE of 80 dB is achieved at 64.2% transmittance, which reveals the highest reported SE over a metallic mesh for transparent shielding, indicating the high potential for this transparent electromagnetic interference shielding material for practical optical applications.

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