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1.
Biosci Trends ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34732614

RESUMO

In the context of an aging global population, the aging of patients with HIV is an issue that society will have to face. Data indicate that between 2011 and 2019, the proportion of patients age 60 and over who were newly diagnosed with HIV in China increased from 12% to 25%. In contrast to younger groups, the special characteristics of older patients pose major challenges to the management of their disease. The current study examined the clinical outcomes and psychological status of patients age 50 and over who were diagnosed with HIV. Out of a total of 566 older patients from eastern China, viral suppression was achieved in 446 (78.8%), treatment was immunologically effective in 410 (72.4%), and treatment was effective in 324 (57.2%). Thirty-nine patients (6.9%) had significant anxiety and 143 (25.3%) exhibited depressive tendencies. Level of education and the time from diagnosis to treatment were associated with the effectiveness of treatment. Age, sleep quality, chronic illness, exercise, and travel time to medical appointments were associated with depressive symptoms. These findings suggest that the burden of HIV among the older population remains high in more economically developed areas. The urgent need for HIV education and screening programs, as well as follow-up visits and early initiation of treatment in older patients, is called for.

2.
Nat Sci Sleep ; 13: 2019-2028, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785966

RESUMO

Objective: Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) have impaired dynamic cerebral autoregulation (dCA). This study aimed to explore whether serum levels of apolipoprotein B-100 (ApoB-100), fibronectin (FN), and ceruloplasmin (CP) were related to impaired dCA in OSAHS. Methods: A total of 90 patients with OSAHS from our database management system were enrolled and further divided into three subgroups according to the apnea-hypopnea index (AHI) using polysomnography results: mild (5 ≤ AHI ≤ 15), moderate (15 < AHI ≤ 30), and severe OSAHS (AHI > 30), with 30 patients in each group. Thirty sex- and age-matched healthy controls were recruited for this study. The serum levels of ApoB-100, FN, and CP were measured by enzyme-linked immunosorbent assays. dCA was assessed by analyzing the phase difference (PD) using transfer function analysis. Results: Serum levels of ApoB-100, FN, and CP were significantly higher in the mild, moderate, and severe OSAHS groups than that in the control group (P<0.001, respectively). The average PD of the moderate and severe OSAHS groups was lower than that of the control group (P=0.001 and P<0.001, respectively). Receiver operating curve analysis revealed that ApoB-100, FN, and CP might be able to distinguish patients with OSAHS from healthy individuals (area under the curve = 0.959 [95% CI 0.92-1.00], 0.987 [95% CI 0.96-1.01], 0.982 [95% CI 0.96-1.00]), respectively, P<0.001). The average PD was linearly correlated with the serum levels of ApoB-100, FN, and CP in patients with OSAHS. Multivariable analysis showed that FN and arousal index in polysomnography were associated with impaired average PD (P<0.001 and P=0.025, respectively). Conclusion: Serum levels of ApoB-100, FN, and CP increased in patients with OSAHS. dCA was compromised in patients with OSAHS and was positively correlated with ApoB-100, FN, and CP serum levels, and FN serum levels and arousal index in polysomnography were independently associated with impaired dCA.

3.
Int J Pharm ; : 121291, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34780929

RESUMO

Reducing post-surgical pain can promote recovery of mobility, improve patient satisfaction, and reduce the risk of chronic pain syndrome. When managing post-surgical pain, single-injection local anesthesia is more convenient and involves lower risk to the patient than multi-injection regimes, but the effects are not long-lasting. Here we developed a system that can prolong local anesthesia after a single injection. In this system, ropivacaine (Ro) is encapsulated into liposomes, which are then loaded into Poloxamer 407-based thermosensitive hydrogels. The Ro-loaded liposome-in-gel system (Ro-Lip-Gel) is in a sol state before injection, and immediately after subcutaneous injection, it forms a gel in situ. We show through in vitro release and in vivo pharmacokinetics studies that this gel acts as a drug release depot. In rats, the initial burst release of Ro was smaller from Ro-Lip-Gel than from Ro solution or Ro-Gel, and Ro-Lip-Gel caused nerve blockade lasting four times longer than Ro solution. Ro-Lip-Gel degraded in vivo and showed good biocompatibility. Our results suggest that a liposome-in-gel system can show small initial burst release, long-term nerve blockade and good biocompatibility in vitro and in vivo. Therefore, such a system may be useful for sustained local anesthesia without systemic toxicity.

4.
Nat Metab ; 3(11): 1536-1551, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34782792

RESUMO

Beiging of white adipose tissue (WAT) is associated with an increase of anti-inflammatory M2-like macrophages in WAT. However, mechanisms through which M2-like macrophages affect beiging are incompletely understood. Here, we show that the macrophage cytokine Slit3 is secreted by adipose tissue macrophages and promotes cold adaptation by stimulating sympathetic innervation and thermogenesis in mice. Analysing the transcriptome of M2-like macrophages in murine inguinal WAT (iWAT) after cold exposure, we identify Slit3 as a secreted cytokine. Slit3 binds to the ROBO1 receptor on sympathetic neurons to stimulate Ca2+/calmodulin-dependent protein kinase II signalling and norepinephrine release, which enhances adipocyte thermogenesis. Adoptive transfer of Slit3-overexpressing M2 macrophages to iWAT promotes beiging and thermogenesis, whereas mice that lack Slit3 in myeloid cells are cold-intolerant and gain more weight. Our findings shed new light on the integral role of M2-like macrophages for adipose tissue homeostasis and uncover the macrophage-Slit3-sympathetic neuron-adipocyte signalling axis as a regulator of long-term cold adaptation.

5.
J Inorg Biochem ; 226: 111656, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34798307

RESUMO

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.

6.
Front Cell Dev Biol ; 9: 688238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733837

RESUMO

This study aimed to investigate the role and mechanisms of Receptor interacting protein kinase 2 (RIP2) in pressure overload-induced cardiac remodeling. Human failing or healthy donor hearts were collected for detecting RIP2 expression. RIP2 cardiomyocyte-specific overexpression, RIP2 global knockout, or wild-type mice were subjected to sham or aortic banding (AB) surgery to establish pressure overload-induced cardiac remodeling in vivo. Phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) were used for further investigation in vitro. The expression of RIP2 was significantly upregulated in failing human heart, mouse remodeling heart, and Ang II-treated NRCMs. RIP2 overexpression obviously aggravated pressure overload-induced cardiac remodeling. Mechanistically, RIP2 overexpression significantly increased the phosphorylation of TAK1, P38, and JNK1/2 and enhanced IκBα/p65 signaling pathway. Inhibiting TAK1 activity by specific inhibitor completely prevented cardiac remodeling induced by RIP2 overexpression. This study further confirmed that RIP2 overexpression in NRCM could exacerbate PE-induced NRCM hypertrophy and TAK1 silence by specific siRNA could completely rescue RIP2 overexpression-mediated cardiomyocyte hypertrophy. Moreover, this study showed that RIP2 could bind to TAK1 in HEK293 cells, and PE could promote their interaction in NRCM. Surprisingly, we found that RIP2 overexpression caused spontaneous cardiac remodeling at the age of 12 and 18 months, which confirmed the powerful deterioration of RIP2 overexpression. Finally, we indicated that RIP2 global knockout attenuated pressure overload-induced cardiac remodeling via reducing TAK1/JNK1/2/P38 and IκBα/p65 signaling pathways. Taken together, RIP2-mediated activation of TAK1/P38/JNK1/2 and IκBα/p65 signaling pathways played a pivotal role in pressure overload-induced cardiac remodeling and spontaneous cardiac remodeling induced by RIP2 overexpression, and RIP2 inhibition might be a potential strategy for preventing cardiac remodeling.

7.
Brief Bioinform ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643232

RESUMO

Cancer is thought to be caused by the accumulation of driver genetic mutations. Therefore, identifying cancer driver genes plays a crucial role in understanding the molecular mechanism of cancer and developing precision therapies and biomarkers. In this work, we propose a Multi-Task learning method, called MTGCN, based on the Graph Convolutional Network to identify cancer driver genes. First, we augment gene features by introducing their features on the protein-protein interaction (PPI) network. After that, the multi-task learning framework propagates and aggregates nodes and graph features from input to next layer to learn node embedding features, simultaneously optimizing the node prediction task and the link prediction task. Finally, we use a Bayesian task weight learner to balance the two tasks automatically. The outputs of MTGCN assign each gene a probability of being a cancer driver gene. Our method and the other four existing methods are applied to predict cancer drivers for pan-cancer and some single cancer types. The experimental results show that our model shows outstanding performance compared with the state-of-the-art methods in terms of the area under the Receiver Operating Characteristic (ROC) curves and the area under the precision-recall curves. The MTGCN is freely available via https://github.com/weiba/MTGCN.

8.
Front Plant Sci ; 12: 754325, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659323

RESUMO

Blueberries (Vaccinium corymbosum) contain large amounts of flavonoids, which play important roles in the plant's ability to resist stress and can also have beneficial effects on human health when the fruits are eaten. However, the molecular mechanisms that regulate flavonoid synthesis in blueberries are still unclear. In this study, we combined two different transcriptome sequencing platforms, single-molecule real-time (SMRT) and Illumina sequencing, to elucidate the flavonoid synthetic pathways in blueberries. We analyzed transcript quantity, length, and the number of annotated genes. We mined genes associated with flavonoid synthesis (such as anthocyanins, flavonols, and proanthocyanidins) and employed fluorescence quantitative PCR to analyze the expression of these genes and their correlation with flavonoid synthesis. We discovered one R2R3 MYB transcription factor from the sequencing library, VcMYB1, that can positively regulate anthocyanin synthesis in blueberries. VcMYB1 is mainly expressed in colored (mature) fruits. Experiments showed that overexpression and transient expression of VcMYB1 promoted anthocyanin synthesis in Arabidopsis, tobacco (Nicotiana benthamiana) plants and green blueberry fruits. Yeast one-hybrid (Y1H) assay, electrophoretic mobility shift assay, and transient expression experiments showed that VcMYB1 binds to the MYB binding site on the promoter of the structural gene for anthocyanin synthesis, VcMYB1 to positively regulate the transcription of VcDFR, thereby promoting anthocyanin synthesis. We also performed an in-depth investigation of transcriptional regulation of anthocyanin synthesis. This study provides background information and data for studying the synthetic pathways of flavonoids and other secondary metabolites in blueberries.

9.
J Healthc Eng ; 2021: 5754160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676062

RESUMO

Objectives: This study aimed to investigate whether soluble dietary fibers (SDFs) could protect against obesity by influencing weight, body mass index (BMI), body fat rate (BFR), visceral fat rate (VFR), or waistline. Methods: We examined obese adult patients from western China at 0 and 3 weeks after an SDF diet. Index assessments of obesity including height, weight, BMI, BFR, VFR, and waistline were carried out. We used the Mann-Whitney U test to examine the difference between the usual diet and the SDF group. Results: Weight, BMI, BFR, and waistline were reduced in both the control group and the SDF group (P < 0.001). The reduction of the four indices in the SDF group was significantly higher than in the control group (P < 0.001). Higher intake of various SDFs has significantly reduced the weight, BMI, BFR, and waistline than the usual diet group in obesity. Conclusion: Our results indicated that increased intake of SDFs in the diet of obese patients would protect against obesity in the first 3 weeks.

10.
Front Pharmacol ; 12: 706617, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690754

RESUMO

Background: Astragalus polysaccharide extract (APS) has been shown to exhibit antioxidant and anti-inflammatory potential in the treatment of several diseases. However, whether APS could protect against renal damage in hypertensive mice is unknown. Methods: Hematoxylin and eosin staining, immunohistochemistry, real-time polymerase chain reaction, and Western blotting were used to investigate the effect of APS on the renal damage in deoxycorticosterone acetate- (DOCA) salt- and angiotensin II- (Ang II-) induced hypertensive mice and to elucidate the underlying mechanisms. Results: Our data demonstrated that APS significantly reduced blood pressure in DOCA-salt- and Ang II-treated mice. Furthermore, APS reduced the inflammatory response and renal fibrosis, thereby improving renal function. Furthermore, the levels of serum creatinine, urea nitrogen, and uric acid increased in DOCA-salt-treated mice, alleviated by APS administration. At the molecular level, DOCA-salt and Ang II increased the mRNA levels of IL-1ß, IL-6, α-SMA, collagen I, and collagen III, while APS significantly inhibited these effects. APS inhibited the TGF-ß1/ILK signaling pathway, which was activated in hypertensive mice due to the administration of DOCA-salt. Conclusion: Our results suggest that APS plays a beneficial role in improving renal dysfunction in hypertensive mice.

11.
Front Nutr ; 8: 748031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631774

RESUMO

Origanum majorana L. is an aromatic herb that has been grown in several Mediterranean countries since ancient times, but became popular during the Middle Ages as a medicinal plant and seasoning ingredient. O. majorana has many pharmacological effects, but its immunoreactive components and mechanisms are still unclear. In this study, four compounds were isolated and identified from O. majorana by a spectral analysis, including 1H and 13C-NMR. They were 1H-indole-2-carboxylic acid (1), (+)-laricresol (2), (+)-isolaricresol (3), and procumboside B (4, pB), which were isolated for the first time in O. majorana. The immunomodulatory effects of the four compounds were screened, and pB had good immunomodulatory activity on RAW 264.7 cells. The immunomodulatory mechanism of pB was proved, in which pB could increase the secretion of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) and simultaneously upregulate the expression of CD80 and CD86 on the cell surface. These results suggested that the mechanism of pB may be related to the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs)-signaling pathways. O. majorana is rich in nutrients and is commonly used in diets, so it can be used as a nutritional supplement with immunomodulatory effects.

12.
EMBO J ; : e108069, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34704268

RESUMO

Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine-fed mice showed better cold tolerance. In mice with diet-induced obesity, the asparagine-fed group was more responsive to ß3-adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and 13 C-glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis.

13.
14.
Int J Nanomedicine ; 16: 6681-6692, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616151

RESUMO

Purpose: Extracellular vesicles (EVs) are membrane-encapsulated nanoparticles that function as carriers and play a role in intercellular communication. There are a large number of EVs in the blood and serve as an indicator of pathophysiological conditions. Studies on the basics and application of EVs are hampered by the limitations of current protocols to isolate EVs from blood. However, current isolation methods are difficult to achieve a balance between yield and purity. Methods: Firstly, we use Sepharose-4B to build a self-made size exclusion chromatography (SEC) column and perform separation and characteristics. Then, we use the SEC column to systematically compare the efficiency with the most common EV isolation methods: Ultracentrifugation (UC) and total exosomes isolation commercial kit (TEI). The EVs isolated through different methods were characterized the yield and size of EVs, analyzed their protein profiles, the morphology and purity were observed under the transmission electron microscope. To further improve the quality and purity, we combined SEC and UC methods and established a two-steps method to isolated EVs from serum. Results: Self-made SEC column can well separate EVs from complex serum protein, and EVs enriched in the 8-13 fractions with good morphology and yield. By systematically compare SEC with the commonly used UC and TEI kit, SEC is outstanding in all aspects and balances both isolation purity and yield. However, using the SEC method alone still has certain limitations and residual impurities. The SEC+UC combined method can cleverly solve the shortcomings of SEC and optimize the quality and purity of EVs from serum, which is much better than using one method alone. Conclusion: Our study presents the combination of size-exclusion chromatography and ultracentrifugation as a feasible and time-saving method to isolate high-quality and purity extracellular vesicles from serum.


Assuntos
Exossomos , Vesículas Extracelulares , Proteínas Sanguíneas , Cromatografia em Gel , Ultracentrifugação
15.
16.
ACS Omega ; 6(36): 23447-23459, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34549143

RESUMO

Human health is being threatened by cationic pollutants in wastewater, for example, methylene blue (MB) and Cu(II). Our research team successfully fabricated biofoam adsorbents from recycled bamboo waste that removed cationic pollutants via introducing bamboo fiber sources, i.e., bamboo fiber, bamboo α-cellulose fiber, and bamboo nanocellulose fiber, into a polyurethane (PU) foam matrix. The biofoam adsorbent with 1 g of nanocellulose (PUN1) presented high removal efficiencies for MB (95.52%) and Cu(II) (100%) in low cationic pollutant concentration aqueous solutions. The biofoam adsorbent with 1 g of bamboo fiber (PUB1) also displayed excellent removal efficiency for MB (98.61%) at pH 11. Meanwhile, 100% removal of Cu(II) was obtained by PUB1 at pH 7 (initial content = 15 mg/L). Furthermore, the PUN1 sample had excellent reusability, evidenced by 61.25% removal of MB after five adsorption-desorption cycles, suggesting that PUN1 is a promising renewable adsorbent for cationic pollutants. In addition, PUB1 is a low-cost adsorbent with good adsorption efficiencies for MB in weak alkaline solutions and Cu(II) in neutral aqueous solutions.

17.
Front Cell Dev Biol ; 9: 666422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513822

RESUMO

High-mobility group A1 (HMGA1) acts as a transcription factor in several cardiovascular diseases. However, the implications of HMGA1 in cardiac fibrosis remain unknown. Here, we investigated the impact of HMGA1 on cardiac fibrosis. A mouse cardiac fibrosis model was constructed via subcutaneous injection of isoproterenol (ISO) or angiotensin II (Ang II) infusion. Adult mouse cardiac fibroblasts (CFs) were isolated and cultured. CFs were stimulated with transforming growth factor-ß1 (TGF-ß1) for 24 h. As a result, HMGA1 was upregulated in fibrotic hearts, as well as TGF-ß-stimulated CFs. Overexpression of HMGA1 in CFs aggravated TGF-ß1-induced cell activation, proliferation, and collagen synthesis. Overexpression of HMGA1 in fibroblasts, by an adeno-associated virus 9 dilution system with a periostin promoter, accelerated cardiac fibrosis and cardiac dysfunction. Moreover, HMGA1 knockdown in CFs inhibited TGF-ß1-induced cell activation, proliferation, and collagen synthesis. Mechanistically, we found that HMGA1 increased the transcription of FOXO1. The FOXO1 inhibitor AS1842856 counteracted the adverse effects of HMGA1 overexpression in vitro. HMGA1 silencing in mouse hearts alleviated Ang II-induced cardiac fibrosis and dysfunction. However, FOXO1 knockdown in mouse hearts abolished the deteriorating effects of HMGA1 overexpression in mice. Collectively, our data demonstrated that HMGA1 plays a critical role in the development of cardiac fibrosis by regulating FOXO1 transcription.

18.
Huan Jing Ke Xue ; 42(10): 4880-4888, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581131

RESUMO

To understand surface soil heavy metal pollution characteristics, and the spatial distribution and sources of pollution in the main sedimentary features of the Qaidam Basin, a total of 129 topsoil samples(0-10 cm) were collected within a 25 km radius. The concentrations of As, Ba, Cr, Mn, Nb, Ni, Pb, Ti, Zn, Zr, and ten kinds of heavy metals were determined, the degree of contamination and potential sources quantitatively analyzed based on enrichment factors(EFs), the ground accumulation index(Igeo), and the absolute principal component-multiple linear regression(APCS-MLR) receptor model. The results showed that the surface soils of the Qaidam Basin have experienced pollution from ten kinds of heavy metals since the 1960s, with varying degrees of enrichment. As and Pb represent probable point source pollutants, and the basin as a whole shows negligible to low levels of pollution. The APCS-MLR analysis showed that heavy metal pollution derives from two sources, natural factors and anthropogenic(transportation) sources. Specifically, As, Cr, Mn, Nb, Ni, Ti, Zn, and Zr are associated with natural sources, while Ba and Pb are associated with both natural and anthropogenic sources.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Poluição Ambiental , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
19.
Nat Commun ; 12(1): 5328, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493725

RESUMO

Aliphatic esters are essential constituents of biologically active compounds and versatile chemical intermediates for the synthesis of drugs. However, their preparation from readily available olefins remains challenging. Here, we report a strategy to access aliphatic esters from olefins through a photocatalyzed alkoxycarbonylation reaction. Alkyloxalyl chlorides, generated in situ from the corresponding alcohols and oxalyl chloride, are engaged as alkoxycarbonyl radical fragments under photoredox catalysis. This transformation tolerates a broad scope of electron-rich and electron-deficient olefins and provides the corresponding ß-chloro esters in good yields. Additionally, a formal ß-selective alkene alkoxycarbonylation is developed. Moreover, a variety of oxindole-3-acetates and furoindolines are prepared in good to excellent yields. A more concise formal synthesis of (±)-physovenine is accomplished as well. With these strategies, a wide range of natural-product-derived olefins and alkyloxalyl chlorides are also successfully employed.


Assuntos
Alcenos/química , Técnicas de Química Sintética , Ésteres/química , Indóis/síntese química , Oxindóis/síntese química , Álcoois/química , Catálise , Cloretos/química , Humanos , Estrutura Molecular , Oxalatos/química , Oxirredução , Processos Fotoquímicos , Fisostigmina/análogos & derivados , Fisostigmina/síntese química , Estereoisomerismo
20.
Molecules ; 26(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34500720

RESUMO

Mutation patterns of DNA adducts, such as mutational spectra and signatures, are useful tools for diagnostic and prognostic purposes. Mutational spectra of carcinogens derive from three sources: adduct formation, replication bypass, and repair. Here, we consider the repair aspect of 1,N6-ethenoadenine (εA) by the 2-oxoglutarate/Fe(II)-dependent AlkB family enzymes. Specifically, we investigated εA repair across 16 possible sequence contexts (5'/3' flanking base to εA varied as G/A/T/C). The results revealed that repair efficiency is altered according to sequence, enzyme, and strand context (ss- versus ds-DNA). The methods can be used to study other aspects of mutational spectra or other pathways of repair.

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