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1.
JCI Insight ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591955

RESUMO

Recent advances in proteomic technologies have made high throughput profiling of low abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across two large longitudinal cohorts (n=2,839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic and clinical data from humans to nominate one specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Further, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (WFIKKN2) was in turn associated with fasting glucose, hemoglobin A1c and HOMA-IR measurements in humans. In addition to identifying novel disease markers and potential pathways in T2DM, we provide publicly available data to be leveraged for new insights about gene function and disease pathogenesis in the context of human metabolism. .

2.
Int J Biol Macromol ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33592267

RESUMO

7α-Hydroxysteroid dehydrogenase (7α-HSDH) plays an important role in the efficient biotransformation of taurochenodeoxycholic acid (TCDCA) to tauroursodeoxycholic acid (TUDCA). In this paper, a novel NADP(H)-dependent 7α-HSDH (named J-1-1) was discovered, heterologously expressed in Escherichia coli and biochemically characterized. J-1-1 exhibited high enzymatic activities. The specific activities of J-1-1 toward TCDCA, glycochenodeoxycholic acid (GCDCA) and ethyl benzoylacetate (EBA) were 188.3 ±â€¯0.2, 217.6 ±â€¯0.4, and 20.0 ±â€¯0.2 U·mg-1, respectively, in 50 mM Glycine-NaOH, pH 10.5. Simultaneously, J-1-1 showed high thermostability; 73% of its activity maintained after heat treatment at 40 °C for 100 h. Particularly noteworthy is that magnesium ion could stabilize the structure of J-1-1, resulting in the enhancement of its enzymatic activity and thermostability. The enzymatic activity of J-1-1 increased 40-fold in the presence of 50 mM Mg2+, and T0.5 increased by approximately 6 °C. Furthermore, after heat treatment at 40 °C for 20 min, the control group only retained 52% of the residual enzyme activity, while the residual enzyme activity of the experimental group was still 77% of the J-1-1 enzyme activity with Mg2+ and without heat treatment. These properties of 7α-HSDH would be expected to contribute to more extensive applications in the biotransformation of related substrates.

3.
Aging (Albany NY) ; 122021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535170

RESUMO

HOXA6 gene plays a role of the oncogene in various cancers. Nonetheless, its effect on gastric cancer (GC) occurrence and development is still unclear. We analysed whether HOXA6 interacts with the PBX2 protein using the STRING database. The molecular mechanism by which HOXA6 synergizes with PBX2 in GC metastasis is not fully understood. Here, we found that the expression of HOXA6 was increased in GC tissues and cell lines. The upregulation of HOXA6 was closely associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients based on tissue microarray (TMA) data. Moreover, the overexpression of HOXA6 promoted, whereas siRNA-mediated repression of HOXA6 inhibited, the cell proliferation, migration, and invasion of GC cells. Furthermore, HOXA6 could physically interact with and stabilize PBX2. In addition, HOXA6 and PBX2 expression was positively correlated in GC cells and tissue. HOXA6 and PBX2 suppression in GC cells also led to decreased migration and invasion potential in vitro. In vivo, HOXA6 was shown to cooperate with PBX2 to enhance cell metastasis via orthotopic implantation. These data indicate that HOXA6 promotes cell proliferation, migration, and invasion and that the HOXA6-PBX2 axis may be a useful biomarker for disease progression in GC.

4.
Sci Rep ; 11(1): 3145, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542345

RESUMO

Recognizing that family data provide unique advantage of identifying rare risk variants in genetic association studies, many cohorts with related samples have gone through whole genome sequencing in large initiatives such as the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. Analyzing rare variants poses challenges for binary traits in that some genotype categories may have few or no observed events, causing bias and inflation in commonly used methods. Several methods have recently been proposed to better handle rare variants while accounting for family relationship, but their performances have not been thoroughly evaluated together. Here we compare several existing approaches including SAIGE but not limited to related samples using simulations based on the Framingham Heart Study samples and genotype data from Illumina HumanExome BeadChip where rare variants are the majority. We found that logistic regression with likelihood ratio test applied to related samples was the only approach that did not have inflated type I error rates in both single variant test (SVT) and gene-based tests, followed by Firth logistic regression that had inflation in its direction insensitive gene-based test at prevalence 0.01 only, applied to either related or unrelated samples, though theoretically logistic regression and Firth logistic regression do not account for relatedness in samples. SAIGE had inflation in SVT at prevalence 0.1 or lower and the inflation was eliminated with a minor allele count filter of 5. As for power, there was no approach that outperformed others consistently among all single variant tests and gene-based tests.

5.
Eur J Immunol ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547649

RESUMO

Intestinal trefoil factor 3 (TFF3) plays an important role in repairing the intestinal mucosa. However, the detailed mechanism regarding immune regulation by TFF3 is not well defined. Here, we reported that treatment of mouse BM cells and human peripheral blood mononuclear cells from healthy volunteers with TFF3 activated polymorphnuclear myeloid-derived suppressor cells (PMN-MDSCs) in vitro. We also found that prostaglandin E2 is a major TFF3-mediated MDSC target, and that NF-κB/COX2 signaling was involved in this process. Moreover, TFF3 treatment or transfer of TFF3-derived PMN-MDSCs (TFF3-MDSCs) to experimental necrotizing enterocolitis (NEC) mice caused PMN-MDSC accumulation in the lamina propria (LP), which was associated with decreased intestinal inflammation, permeability, bacterial loading, and prolonged survival. Interestingly, no NEC severity remission was observed in Rag1 KO mice that were given TFF3-MDSCs, but coinjection with CD4+ T cells significantly relieved NEC inflammation. Overall, TFF3 mediates the NF-κB/COX2 pathway to regulate PMN-MDSC activation and attenuates NEC in a T-cell-dependent manner, which suggests a novel mechanism in preventing NEC occurrence.

6.
Anal Chem ; 93(4): 2200-2206, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33406817

RESUMO

The predicted liquid chromatographic retention times (RTs) of small molecules are not accurate enough for wide adoption in structural identification. In this study, we used the graph neural network to predict the retention time (GNN-RT) from structures of small molecules directly without the requirement of molecular descriptors. The predicted accuracy of GNN-RT was compared with random forests (RFs), Bayesian ridge regression, convolutional neural network (CNN), and a deep-learning regression model (DLM) on a METLIN small molecule retention time (SMRT) dataset. GNN-RT achieved the highest predicting accuracy with a mean relative error of 4.9% and a median relative error of 3.2%. Furthermore, the SMRT-trained GNN-RT model can be transferred to the same type of chromatographic systems easily. The predicted RT is valuable for structural identification in complementary to tandem mass spectra and can be used to assist in the identification of compounds. The results indicate that GNN-RT is a promising method to predict the RT for liquid chromatography and improve the accuracy of structural identification for small molecules.

7.
Bull Environ Contam Toxicol ; 106(1): 146-152, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33388833

RESUMO

Zinc (Zn) is enriched in carbonate area related to geological genesis. To ensure safety of rice, soil threshold values of Zn in soil-rice systems were assessed based on analysis of soil-rice Zn concentration in relation to human health risk. Models for the prediction of Zn concentration of early-season and late-season rice grain were accurately established on the basis of significant partial correlations between log10 (BAFs) and log10 (soil properties). The rice threshold value ranged from 10.67 to 37.90 mg/kg, which might not suitable for male and urban residents. The soil safety threshold of early-season rice and late-season rice in carbonate area ranged from 148-200 mg/kg, 119-200 mg/kg with pH below 6.5, 148-250 mg/kg, 119-250 mg/kg with pH ranging from 6.5 to 7.5; 148-300 mg/kg, 119-300 mg/kg with pH above 7.5, respectively.


Assuntos
Oryza , Poluentes do Solo , Cádmio/análise , Carbonatos , China , Humanos , Medição de Risco , Solo , Poluentes do Solo/análise , Zinco/análise
8.
Mol Ecol ; 30(5): 1174-1189, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33421231

RESUMO

Population genomic approaches can characterize dispersal across a single generation through to many generations in the past, bridging the gap between individual movement and intergenerational gene flow. These approaches are particularly useful when investigating dispersal in recently altered systems, where they provide a way of inferring long-distance dispersal between newly established populations and their interactions with existing populations. Human-mediated biological invasions represent such altered systems which can be investigated with appropriate study designs and analyses. Here we apply temporally restricted sampling and a range of population genomic approaches to investigate dispersal in a 2004 invasion of Aedes albopictus (the Asian tiger mosquito) in the Torres Strait Islands (TSI) of Australia. We sampled mosquitoes from 13 TSI villages simultaneously and genotyped 373 mosquitoes at genome-wide single nucleotide polymorphisms (SNPs): 331 from the TSI, 36 from Papua New Guinea (PNG) and four incursive mosquitoes detected in uninvaded regions. Within villages, spatial genetic structure varied substantially but overall displayed isolation by distance and a neighbourhood size of 232-577. Close kin dyads revealed recent movement between islands 31-203 km apart, and deep learning inferences showed incursive Ae. albopictus had travelled to uninvaded regions from both adjacent and nonadjacent islands. Private alleles and a co-ancestry matrix indicated direct gene flow from PNG into nearby islands. Outlier analyses also detected four linked alleles introgressed from PNG, with the alleles surrounding 12 resistance-associated cytochrome P450 genes. By treating dispersal as both an intergenerational process and a set of discrete events, we describe a highly interconnected invasive system.

9.
Food Chem ; 337: 127784, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795860

RESUMO

Variation in salt content and in pH are common in starch-based foods and can affect starch properties and final product texture. Fifteen accessions of proso millet starch with diverse amylose content were selected to investigate single factor and interaction effects of pH and NaCl on thermal, pasting, and textural properties. Pasting properties and gelatinization temperatures were markedly altered by salt addition. Changes in pH only had substantial effects on ΔH, but other properties were generally stable under different pH conditions. From two-way ANOVA, interactive effects of salt and pH were found to affect ΔH. The response of starch of different genotypes in terms of thermal and pasting properties differed under the same pH and salinity conditions. The reason is likely that ions in the starch-water system performed the roles of both reducing water activity and building of hydrogen bonds, which will have opposite effects on starch gelatinization.


Assuntos
Genótipo , Panicum/química , Amido/química , Amilose/análise , Amilose/química , Amilose/genética , Concentração de Íons de Hidrogênio , Panicum/genética , Cloreto de Sódio , Temperatura
10.
Food Chem ; 338: 128071, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33092005

RESUMO

This study was proposed to investigate the possibility of co-delivering essential oils and lipophilic nutrients via lecithin stabilized emulsions. Emulsions with different droplet sizes (62.5-105 nm), zeta potentials (-33.7 to -58.6 mV), and PdI values (0.155-0.275) were successfully prepared. Incorporation of curcumin into emulsions significantly improved its water solubility (1700-fold), thermal and photochemical stability. The droplet size of curcumin-loaded emulsions did not change over 30 days of storage at 4 °C. Gastrointestinal tract (GIT) digestion caused significant changes in the droplet size and interfacial properties of curcumin-loaded emulsions. The bioaccessibility of encapsulated curcumin was 4.79-10.6-fold higher than that of free molecule. This is mainly attributed to the different solubility of curcumin in essential oils, which also showed different bioaccessibility. The findings suggested that emulsions can be novel carriers for co-delivering essential oils and lipophilic nutrients with increased stability and bioaccessibility.


Assuntos
Emulsões/química , Lecitinas/química , Nutrientes/metabolismo , Óleos Voláteis/química , Soja/química , Água/química , Temperatura Baixa , Curcumina/química , Nutrientes/análise , Reologia , Solubilidade , Soja/metabolismo
11.
J Am Heart Assoc ; 10(1): e018020, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33372532

RESUMO

Background Proteomic biomarkers related to cardiovascular disease risk factors may offer insights into the pathogenesis of cardiovascular disease. We investigated whether modifiable lifestyle risk factors for cardiovascular disease are associated with distinctive proteomic signatures. Methods and Results We analyzed 1305 circulating plasma proteomic biomarkers (assayed using the SomaLogic platform) in 897 FHS (Framingham Heart Study) Generation 3 participants (mean age 46±8 years; 56% women; discovery sample) and 1121 FOS (Framingham Offspring Study) participants (mean age 52 years; 54% women; validation sample). Participants were free of hypertension, diabetes mellitus, and clinical cardiovascular disease. We used linear mixed effects models (adjusting for age, sex, body mass index, and family structure) to relate levels of each inverse-log transformed protein to 3 lifestyle factors (ie, smoking, alcohol consumption, and physical activity). A Bonferroni-adjusted P value indicated statistical significance (based on number of proteins and traits tested, P<4.2×10-6 in the discovery sample; P<6.85×10-4 in the validation sample). We observed statistically significant associations of 60 proteins with smoking (37/40 top proteins validated in FOS), 30 proteins with alcohol consumption (23/30 proteins validated), and 5 proteins with physical activity (2/3 proteins associated with the physical activity index validated). We assessed the associations of protein concentrations with previously identified genetic variants (protein quantitative trait loci) linked to lifestyle-related disease traits in the genome-wide-association study catalogue. The protein quantitative trait loci were associated with coronary artery disease, inflammation, and age-related mortality. Conclusions Our cross-sectional study from a community-based sample elucidated distinctive sets of proteins associated with 3 key lifestyle factors.

12.
Pharmacol Res ; : 105355, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285230

RESUMO

Adaptive responses to stress are critical to enhance physical and mental well-being, but excessive or prolonged stress may cause inadaptability and increase the risks of psychiatric disorders, such as depression. GABABR signaling is fundamental to brain function and has been identified in neuropsychiatric disorders. KCTD12 is a critical auxiliary subunit in GABABR signaling, but its role in mental disorders, such as depression is unclear. In the present study, we used a well-validated mice model, chronic social defeat stress (CSDS) to investigate behavioral responses to stress and explore the role of Kctd12 in stress response, as well as the relevant mechanisms. We found that CSDS increased the expression of Kctd12 in the dentate gyrus (DG), a subregion of hippocampus. Overexpression of Kctd12 in DG induced higher responsiveness to acute stress and increased vulnerability to social stress in mice, whereas knock-down of Kctd12 in DG prevented the social avoidance. Furthermore, an increased expression of GABAB receptor 2 (GB2) in the DG of CSDS-treated mice was observed, and CGP35348, an antagonist of GABABR, improved the stress-induced behavior responses along with suppressing the excess expression of Kctd12. In addition, Kctd12 regulated the excitability of granule cell in DG, and the stimulation of neuronal activity by silencing Kctd12 contributed to the antidepressant-like effect of fluoxetine. These findings identify that the Kctd12 in DG works as a critical mediator of stress responses, providing a promising therapeutic target in stress-related psychiatric disorders, including depression.

13.
Neurology ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268560

RESUMO

OBJECTIVE: To conduct a comprehensive analysis of circulating metabolites and incident stroke in large prospective population-based settings. METHODS: We investigated the association of metabolites with risk of stroke in seven prospective cohort studies including 1,791 incident stroke events among 38,797 participants in whom circulating metabolites were measured by Nuclear Magnetic Resonance (1H-NMR) technology. The relationship between metabolites and stroke was assessed using Cox proportional hazards regression models. The analyses were performed considering all incident stroke events and ischemic and hemorrhagic events separately. RESULTS: The analyses revealed ten significant metabolite associations. Amino acid histidine (hazard ratio (HR) per standard deviation (SD) = 0.90, 95% confidence interval (CI): 0.85, 0.94; P = 4.45×10-5), glycolysis-related metabolite pyruvate (HR per SD = 1.09, 95% CI: 1.04, 1.14; P = 7.45×10-4), acute phase reaction marker glycoprotein acetyls (HR per SD = 1.09, 95% CI: 1.03, 1.15; P = 1.27×10-3), cholesterol in high-density lipoprotein (HDL) 2 and several other lipoprotein particles were associated with risk of stroke. When focusing on incident ischemic stroke, a significant association was observed with phenylalanine (HR per SD = 1.12, 95% CI: 1.05, 1.19; P = 4.13×10-4) and total and free cholesterol in large HDL particles. CONCLUSIONS: We found association of amino acids, glycolysis-related metabolites, acute phase reaction markers, and several lipoprotein subfractions with the risk of stroke. These findings support the potential of metabolomics to provide new insights into the metabolic changes preceding stroke.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33225381

RESUMO

7α-Hydroxysteroid dehydrogenase (7α-HSDH) is one of the key enzymes in the catalytic reaction of taurochenodeoxycholic acid (TCDCA). To improve the activity of immobilized 7α-HSDH, the microenvironment of immobilized 7α-HSDH was modified with epoxy resin and ethanediamine (EDA). The amino-epoxy support was characterized by Fourier transform infrared (FTIR), Spectrometer elemental analysis (EA), scanning electron microscopy (SEM), contact angle (CA), and Zetasizer. The effects of the immobilization of 7α-HSDH on the amino-epoxy resin and epoxy resin were studied. The results indicated that the relative activity of immobilized 7α-HSDH on the amino-epoxy resin increased by approximately 80%. Meanwhile, the immobilized 7α-HSDH showed favorable thermal stability and operational stability. The thermal stability of immobilized 7α-HSDH increased at temperatures ranging from 15 to 35 °C, while the relative activities of 7α-HSDH immobilized on the amino-epoxy resin and epoxy resin retained 56.4% and 61.0%. After 6 cycles, the residual activities of the 7α-HSDH immobilized on the amino-epoxy resin and epoxy resin were 81.4% and 89.5%, respectively.

15.
Pest Manag Sci ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200882

RESUMO

BACKGROUND: The diamondback moth (DBM), Plutella xylostella (Lepidoptera: Plutellidae), is a notorious pest of cruciferous plants. In temperate areas, annual populations of DBM originate from adult migrants. However, the source populations and migration trajectories of immigrants remain unclear. Here, we investigated migration trajectories of DBM in China using genome-wide single nucleotide polymorphisms (SNPs) genotyped using double-digest RAD (ddRAD) sequencing. We first analyzed patterns of spatial and temporal genetic structure among southern source and northern recipient populations, then inferred migration trajectories into northern regions using discriminant analysis of principal components (DAPC), assignment tests, and spatial kinship patterns. RESULTS: Temporal genetic differentiation among populations was low, indicating that sources of recipient populations and migration trajectories are stable. Spatial genetic structure indicated three genetic clusters in the southern source populations. Assignment tests linked northern populations to the Sichuan cluster, and central-eastern populations to the southern and Yunnan clusters, indicating that Sichuan populations are sources of northern immigrants and southern and Yunnan populations are sources of central-eastern populations. First-order (full-sib) and second-order (half-sib) kin pairs were always found within populations, but ~ 35-40% of third-order (cousin) pairs were found in different populations. Closely related individuals in different populations were found at distances of 900-1500 km in ~ 35-40% of cases, while some were separated by > 2000 km. CONCLUSION: This study unravels seasonal migration patterns in the DBM. We demonstrate how careful sampling and population genomic analyses can be combined to help understand cryptic migration patterns in insects.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33219745

RESUMO

Constructing synthetic cells has recently become an appealing area of research. Decades of research in biochemistry and cell biology have amassed detailed part lists of components involved in various cellular processes. Nevertheless, recreating any cellular process in vitro in cell-sized compartments remains ambitious and challenging. Two broad features or principles are key to the development of synthetic cells-compartmentalization and self-organization/spatiotemporal dynamics. In this review article, we discuss the current state of the art and research trends in the engineering of synthetic cell membranes, development of internal compartmentalization, reconstitution of self-organizing dynamics, and integration of activities across scales of space and time. We also identify some research areas that could play a major role in advancing the impact and utility of engineered synthetic cells. This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

17.
Thorac Cancer ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33142039

RESUMO

BACKGROUND: Data on clinical, laboratory, and radiographic characteristics and risk factors for in-hospital mortality of lung cancer patients with COVID-19 are scarce. Here, we aimed to characterize the early clinical features of lung cancer patients with COVID-19 and identify risk factors associated with in-hospital mortality. METHODS: All consecutive lung cancer patients with laboratory-confirmed COVID-19 admitted to 12 hospitals in Hubei province, China, from 3 January to 6 May 2020 were included in the study. Patients without definite clinical outcomes during the period were excluded. Data on initial clinical, laboratory and radiographic findings were compared between survivors and nonsurvivors. Univariable and multivariable logistic regression analyses were used to explore the risk factors associated with in-hospital mortality. RESULTS: Of the 45 lung cancer patients (median [interquartile range] age, 66 [58-74] years; 68.9% males) included, 34 (75.6%) discharged and 11 (24.4%) died. Fever (73.3%) and cough (53.3%) were the dominant initial symptoms, and respiratory symptoms were common. Lung cancer patients also presented atypical appearances of COVID-19. In the multivariable analysis, prolonged prolongation prothrombin time (PT) (OR = 2.1, 95% CI: 1.00-4.41, P = 0.0497) and elevated high sensitivity cardiac troponin I (hs-TNI) (OR = 7.65, 95% CI: 1.24-47.39, P = 0.0287) were associated with an increased risk of in-hospital mortality. CONCLUSIONS: Lung cancer patients with COVID-19 have high in-hospital mortality. Prolonged PT and elevated hs-TNI are independent risk factors for in-hospital mortality of lung cancer patients with COVID-19. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Lung cancer patients with COVID-19 have atypical early symptoms and imaging features. The prolonged prothrombin time and elevated high sensitivity cardiac troponin I are independent risk factors for in-hospital mortality of lung cancer patients with COVID-19. WHAT THIS STUDY ADDS: This study characterizes the early clinical features of lung cancer patients with COVID-19 in China, and identifies the risk factors associated with in-hospital mortality of lung cancer patients with COVID-19.

18.
Crit Rev Food Sci Nutr ; : 1-28, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054344

RESUMO

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

19.
Mol Ecol ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108010

RESUMO

Dispersal is a key biological process serving several functions including connectivity among populations. Habitat fragmentation caused by natural or anthropogenic structures may hamper dispersal, thereby disrupting genetic connectivity. Investigating factors affecting dispersal and gene flow is important in the current era of anthropogenic global change, as dispersal comprises a vital part of a species' resilience to environmental change. Using finescale landscape genomics, we investigated gene flow and genetic structure of the Sooty Copper butterfly (Lycaena tityrus) in the Alpine Ötz valley system in Austria. We found surprisingly high levels of gene flow in L. tityrus across the region. Nevertheless, ravines, forests, and roads had effects on genetic structure, while rivers did not. The latter is surprising as roads and rivers have a similar width and run largely in parallel in our study area, pointing towards a higher impact of anthropogenic compared with natural linear structures. Additionally, we detected eleven loci potentially under thermal selection, including ones related to membranes, metabolism, and immune function. This study demonstrates the usefulness of molecular approaches in obtaining estimates of dispersal and population processes in the wild. Our results suggest that, despite high gene flow in the Alpine valley system investigated, L. tityrus nevertheless seems to be vulnerable to anthropogenically-driven habitat fragmentation. With anthropogenic rather than natural linear structures affecting gene flow, this may have important consequences for the persistence of species such as the butterfly studied here in altered landscapes.

20.
Oncol Lett ; 20(6): 312, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33093921

RESUMO

M2 isomer of pyruvate kinase (PKM2), a key enzyme in aerobic glycolysis, is closely related to cancer development and progression. Suppression of PKM2 exhibits synergistic effects with docetaxel in lung cancer, but the therapeutic potential in colorectal cancer (CRC) is unclear. The aim of the present study was to explore the synergic effects and mechanism of knocking down PKM2 combined with oxaliplatin (a chemosensitizer) treatment in two CRC cell lines (HCT116 and DLD1). The PKM2 gene was initially knocked down using small interfering (si)RNAs (si155 and si156). Subsequently, the effects of PKM2-siRNAs and oxaliplatin, on CRC cells were determined using MTS, cell cycle analysis and apoptosis assays. The mechanism of targeting PKM2 was explored by detecting glucose uptake, lactate secretion fluxes, and the levels of glucose-6-phosphate dehydrogenase (G6PD) mRNA, glutathione (GSH) and reactive oxygen species (ROS). Cell viability in the experimental groups (PKM2-siRNAs, oxaliplatin, PKM2-siRNAs + oxaliplatin) was significantly reduced compared with the control group, and combination treatments (PKM2-siRNAs + oxaliplatin) were more effective than single treatments (PKM2-siRNAs and oxaliplatin only groups). Similar results were observed with the apoptosis assay. The combination groups showed synergistic effects compared with both single treatment groups. Furthermore, glucose uptake and lactate secretion and mRNA levels of G6PD and PKM2 were decreased after PKM2 knockdown in the PKM2-siRNAs and PKM2-siRNAs + oxaliplatin groups. The GSH levels in the PKM2-siRNAs group was significantly lower compared with the negative control group. The ROS levels in the PKM2-siRNAs groups were also significantly increased. The combination of PKM2-siRNAs and oxaliplatin had synergistic effects on CRC cells (HCT116 and DLD1). PKM2 silencing may alter energy metabolism in cancer cells and initiate ROS-induced apoptosis after downregulation of the pentose phosphate pathway by PKM2-siRNAs.

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