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1.
Front Cardiovasc Med ; 8: 717128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621799

RESUMO

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients. Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity. Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 µmol/L; middle (SUA stable): ≥-32.6 µmol/L, <40.2 µmol/L; high (SUA increase substantially): ≥40.2 µmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially. Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

2.
Opt Lett ; 46(19): 5027-5030, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598261

RESUMO

Waveguide taper, a key component in the photonic integrated circuit (PIC), enables on-chip mode conversion, but large-footprint tapers are detrimental to the PIC, which desires compact and efficient devices. Polarization sensitivity also limits the tapers in the applications involving orthogonal modes. In this work, we design an efficient polarization-insensitive ultra-short MMI-based waveguide taper, through the mode spreading principle and the self-image principle. The proposed taper is 26.3 µm long, one order of magnitude shorter than the standard linear taper. We fabricate the taper, and experimentally demonstrate that it exhibits a high transmission efficiency of ∼70% and a wide 1 dB bandwidth of >54nm, for both TE and TM polarizations.

3.
Opt Express ; 29(16): 25859-25867, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34614905

RESUMO

Quantum key distribution (QKD) provides information theoretically secure key exchange requiring authentication of the classic data processing channel via pre-sharing of symmetric private keys to kick-start the process. In previous studies, the lattice-based post-quantum digital signature algorithm Aigis-Sig, combined with public-key infrastructure (PKI), was used to achieve high-efficiency quantum security authentication of QKD, and we have demonstrated its advantages in simplifying the MAN network structure and new user entry. This experiment further integrates the PQC algorithm into the commercial QKD system, the Jinan field metropolitan QKD network comprised of 14 user nodes and 5 optical switching nodes, and verifies the feasibility, effectiveness and stability of the post-quantum cryptography (PQC) algorithm and advantages of replacing trusted relays with optical switching brought by PQC authentication large-scale metropolitan area QKD network. QKD with PQC authentication has potential in quantum-secure communications, specifically in metropolitan QKD networks.

4.
Plant Physiol ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34599593

RESUMO

Plant TRANS-ACTING SIRNA3 (TAS3)-derived short interfering RNAs (siRNAs) include tasiR-AUXIN RESPONSE FACTORs (ARFs), which are functionally conserved in targeting ARF genes, and a set of non-tasiR-ARF siRNAs, which have rarely been studied. In this study, TAS3 siRNAs were systematically characterized in rice (Oryza sativa). Small RNA sequencing results showed that an overwhelming majority of TAS3 siRNAs belong to the non-tasiR-ARF group, while tasiR-ARFs occupy a diminutive fraction. Phylogenetic analysis of TAS3 genes across dicot and monocot plants revealed that the siRNA-generating regions were highly conserved in grass species, especially in the Oryzoideae. Target genes were identified for not only tasiR-ARFs but also non-tasiR-ARF siRNAs by analyzing rice Parallel Analysis of RNA Ends datasets, and some of these siRNA-target interactions were experimentally confirmed using tas3 mutants generated by genome editing. Consistent with the de-repression of target genes, phenotypic alterations were observed for mutants in three TAS3 loci in comparison to wild-type rice. The regulatory role of ribosomes in the TAS3 siRNA-target interactions was further revealed by the fact that TAS3 siRNA-mediated target cleavage, in particular tasiR-ARFs targeting ARF2/3/14/15, occurred extensively in rice polysome samples. Altogether, our study sheds light into TAS3 genes in plants and expands our knowledge about rice TAS3 siRNA-target interactions.

5.
Adv Mater ; : e2104139, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596293

RESUMO

Targeted oral delivery of a drug via the intestinal lymphatic system (ILS) has the advantages of protecting against hepatic first-pass metabolism of the drug and improving its pharmacokinetic performance. It is also a promising route for the oral delivery of vaccines and therapeutic agents to induce mucosal immune responses and treat lymphatic diseases, respectively. This article describes the anatomical structures and physiological characteristics of the ILS, with an emphasis on enterocytes and microfold (M) cells, which are the main gateways for the transport of particulate delivery vehicles across the intestinal epithelium into the lymphatics. A comprehensive overview of recent advances in the rational engineering of particulate vehicles, along with the challenges and opportunities that they present for improving ILS drug delivery, is provided, and the mechanisms by which such vehicles target and transport through enterocytes or M cells are discussed. The use of naturally sourced materials, such as yeast microcapsules and their derived polymeric ß-glucans, as novel ILS-targeting delivery vehicles is also reviewed. Such use is the focus of an emerging field of research. Their potential use in the oral delivery of nucleic acids, such as mRNA vaccines, is proposed.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1387-1393, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627415

RESUMO

OBJECTIVE: To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562. METHODS: CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC50 were calculated. The effects of ZL-n-91 to the cycle of L1210 and K562 cells was detected by PE single staining, and the effects of ZL-n-91 to the apoptosis of L1210 and K562 cells was detected by PE/7AA-D double staining. Western blot was used to detect the effect of ZL-n-91 to the expression levels of apoptosis related proteins. Subcutaneous tumor transplantation model of acute lymphoblastic leukemia L1210 was established in the nude mice, and the inhibitory effect of oral administration of ZL-n-91 to the xenograft was observed. RESULTS: ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05). CONCLUSION: The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.


Assuntos
Leucemia , Inibidores da Fosfodiesterase 4 , Animais , Proliferação de Células , Humanos , Células K562 , Camundongos , Camundongos Nus , Inibidores da Fosfodiesterase 4/farmacologia
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1504-1509, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627431

RESUMO

OBJECTIVE: To investigate the effect of arsenic disulfide (AS2S2) combined with itraconazole on the proliferation, apoptosis and hedgehog pathway of diffuse large B-cell lymphoma (DLBCL) cells. METHODS: The human DLBCL cell OCI-LY3 was treated with different concentrations of AS2S2 and itraconazole. Cell proliferation inhibition was detected by CCK-8, cell apoptosis rate was determined by flow cytometry. The expression levels of BCL-2, BAX, SMO and GLi1 were detected by Western blot. RESULTS: The DLBCL cell viability was decreased significantly at 24, 48 or 72 h as cultured with itraconazole. Along with the increasing of itraconazole concentration, the DLBCL cell viability was significantly reduced as compared with that in control group, and the results showed statistically significant(r=-0.690,r=-0.639, r=-0.833, r=-0.808, r=-0.578). The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and AS2S2(P<0.05). The protein levels of SMO and Glil were significantly down-regulated after treated by arsenic disulfide and itraconazole alone(P<0.01). The protein expression levels of SMO and Glil was down-regulated in the combined-treatment group(P<0.01). CONCLUSION: Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner. In addition, the combination of AS2S2 and itraconazole show a synergistic effects, which may be related with the down-regulated protein expression of SMO and Glil of Hedgehog signaling pathway.


Assuntos
Proteínas Hedgehog , Linfoma Difuso de Grandes Células B , Apoptose , Arsenicais , Humanos , Itraconazol/farmacologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Sulfetos
8.
Am J Cancer Res ; 11(9): 4515-4527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659902

RESUMO

TNBG-5602, a new synthesized derivative of tetrazanbigen, is a potential chemotherapeutic agent against cancer. However, its underlying mechanism is complex and still unknown. In this investigation, the anticancer effects of TNBG-5602 were determined in vitro and in vivo. Small RNA retroviral library plasmids that overexpress 19-bp fragments were used to generate TNBG-5602-resistant cells. After validation, the overexpressed 19-bp fragments were sequenced using next-generation sequencing (NGS) in the drug-resistant cells. Furthermore, the relationship of TNBG-5602, phosphatase and tensin homolog deleted on Chromosome 10 (PTEN), and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway was explored. The results showed that TNBG-5602 can effectively inhibit cancer cell proliferation and induce apoptosis in vitro and in vivo. Drug-resistant cells were screened using the small RNA library. Compared with naïve cells, drug-resistant cells were more resistant to TNBG-5602 in vitro and in vivo. NGS results revealed that the second highest overexpressed 19-bp fragment perfectly matched the PTEN gene, so the expression of PTEN in various cells and tissues was verified. Further research showed that exogenous overexpression of PTEN strengthened the anticancer effects of TNBG-5602 on p-Akt expression, whereas silencing of PTEN weakened these effects in naïve cells. Taken together, by using this library, we confirmed that PTEN is the target gene to the anticancer effects of TNBG-5602 via the PI3K/Akt pathway.

9.
Artigo em Russo | MEDLINE | ID: mdl-34665553

RESUMO

The purpose of the study is to determine therapeutic effectiveness of the pulsed high intensity optical irradiation device "Zarya" exemplified by treatment of model wounds in laboratory animals and to compare with traditional methods of wound treatment. The prototype of "Zarya" device was used whose operating principle was based on pulsed irradiation of affected areas with high intensity optical radiation in continuous spectrum generated by pulsed xenon lamp. The therapeutic effect of the "Zarya" device was compared with effectiveness of the certified medical ultraviolet irradiator based on low-pressure mercury lamp and also with known wound-healing and antibacterial medication Levomekol ointment. The mature male rats of Wistar line were used in the study. The animals were distributed to 4 groups: group 1 was irradiated by "Zarya" device, group 2 was irradiated by low-pressure mercury lamp, group 3 was treated with Levomekol ointment and group 4 was exposed to no exposure. The linear wound was modeled according to the standard method under ether anesthesia. The therapeutic procedures were applied daily during 7 days. The bactericidal effect was studied on the basis of smears from wound onto flora on the 2nd, 5th and 7th day. On the 8th day the animals were subjected to euthanasia. It was established that "Zarya" device application permits to reduce considerably both duration of therapeutic procedures and therapy course in general and also to achieve more pronounced bactericidal effect. The obtained data is supposed to be used for development of program of clinical trials.

10.
Membranes (Basel) ; 11(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34677524

RESUMO

By a sol-gel method, a BiFeO3 (BFO) capacitor is fabricated and connected with the control thin film transistor (TFT). Compared with a control thin-film transistor, the proposed BFO TFT achieves 56% drive current enhancement and 7-28% subthreshold swing (SS) reduction. Moreover, the effect of the proposed BiFeO3 capacitor on IDS-VGS hysteresis in the BFO TFT is 0.1-0.2 V. Because dVint/dVGS > 1 is obtained at a wide range of VGS, it reveals that the incomplete dipole flipping is a major mechanism to obtain improved SS and a small hysteresis effect in the BFO TFT. Experimental results indicate that sol-gel BFO TFT is a potential candidate for digital application.

11.
Int J Mol Sci ; 22(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34681763

RESUMO

MicroRNA156 (miR156) and miR529 have high sequence similarity and recognize overlapping sites in the same target genes, SQUAMOSA promoter binding protein-like (SPL or SBP box) genes, making it difficult to accurately distinguish their roles in regulatory networks that affect numerous biological functions. Here, we collected data about miR156 and miR529 family members from representative land plants and performed sequence comparisons, phylogenetic analysis, small RNA sequencing, and parallel analysis of RNA ends (PARE) analysis to dissect their evolutionary and functional differences. Although miR156 and miR529 are highly similar, there are differences in their mismatch-sensitive regions, which are essential for target recognition. In land plants, miR156 precursors are conserved mainly within the hairpin region, whereas miR529 precursors are conserved outside the hairpin region, including both the 5' and 3' arms. Phylogenetic analysis showed that MIR156 and MIR529 evolved independently, through divergent evolutionary patterns. The two genes also exhibit different expression patterns, with MIR529 preferentially expressed in reproductive tissues and MIR156 in other tissues. PARE analysis revealed that miR156 and miR529 possess specific targets in addition to common targets in maize, pointing to functional differences between them. Based on our findings, we developed a method for the rapid identification of miR529 and miR156 family members and uncovered the evolutionary divergence of these families, providing insights into their different regulatory roles in plant growth and development.

12.
Adv Mater ; : e2107211, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648207

RESUMO

Owing to their insufficient light absorption and charge transport, 2D Ruddlesden-Popper (RP) perovskites show relatively low efficiency. In this work, methylammonium (MA), formamidinum (FA), and FA/MA mixed 2D perovskite solar cells (PSCs) are fabricated. Incorporating FA cations extends the absorption range and enhances the light absorption. Optical spectroscopy shows that FA cations substantially increase the portion of 3D-like phase to 2D phases, and X-ray diffraction (XRD) studies reveal that FA-based 2D perovskite possesses an oblique crystal orientation. Nevertheless, the ultrafast interphase charge transfer results in an extremely long carrier-diffusion length (≈1.98 µm). Also, chloride additives effectively suppress the yellow δ-phase formation of pure FA-based 2D PSCs. As a result, both FA/MA mixed and pure FA-based 2D PSCs exhibit a greatly enhanced power conversion efficiency (PCE) over 20%. Specifically, the pure FA-based 2D PSCs achieve a record PCE of 21.07% (certified at 20%), which is the highest efficiency for low-dimensional PSCs (n ≤ 10) reported to date. Importantly, the FA-based 2D PSCs retain 97% of their initial efficiency at 85 °C persistent heating after 1500 h. The results unambiguously demonstrate that pure-FA-based 2D PSCs are promising for achieving comparable efficiency to 3D perovskites, along with a better device stability.

13.
Natl Sci Rev ; 8(9): nwab115, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34691744

RESUMO

This perspectives article surveys the most promising privacy-preserving cryptographic technologies including secure multiparty computation, zero-knowledge proofs and fully homomorphic encryption, and their various real-world applications.

14.
Natl Sci Rev ; 8(9): nwab154, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34691746
15.
J Drug Target ; : 1-13, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34668814

RESUMO

The review highlights the safety issues of drug delivery systems based on liposomes. Due to their small sizes (about 80-120 nm, sometimes even smaller), phospholipid nanoparticles interact intensively with living systems during parenteral administration. This interaction significantly affects both their transport role and safety; therefore, special attention is paid to these issues. The review summarises the data on the basic factors affecting the safety of nanoliposomes: composition, size, surface charge, stability, the release of an incorporated drug, penetration into tissues, interaction with the complement system. Attention is paid to the authors' own research of unique phospholipid nanoparticles with a diameter of 20-30 nm. The influence of technological processes of nanoliposome production on their properties is considered. The article also discusses the modern safety assessment criteria contained in the preliminary regulatory documents of the manufacturing countries for new nanoliposome-based drugs being developed or used in the clinic.

16.
Chemosphere ; : 132643, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34687685

RESUMO

Content, isotopes and budget of Pb in suspended particulate matter (SPM) in the Changjiang Estuary and adjacent East China Sea (ECS) were determined to investigate the biogeochemical cycling of particulate Pb in coastal sea. The content of particulate Pb ranged from 11.3 to 669.4 µg/g in February (winter) and from 20.1 to 79.4 µg/g in August (summer). Except in surface water, particulate Pb content in August is higher than that in February. In lower water, particulate Pb and Th and SPM all decreased gradually from the estuary towards the sea, indicating their lithogenic origin from the Changjiang River. Particulate Pb displayed abnormally high concentration in February surface water, resulting from the atmospheric deposition of anthropogenic Pb in winter. 208Pb/206Pb and 207Pb/206Pb in surface water north to the estuary were higher than background values, suggesting anthropogenic disturbance of Pb. Particulate Pb content in the Changjiang River and the estuary had increased by 77-78% from the 1980s to 2016 due to pollution. Pb was also scavenged by organic matter, leading to higher Pb content in waters with high productivity. Budget of particulate Pb in the northern ECS was established. The Changjiang River contributed 97.0% and 58.1% of particulate Pb input in summer and winter half year, respectively. 88.8% of particulate Pb was deposited in the estuary and adjacent coastal sea in summer but 88.7% was exported with southward coastal currents in winter.

17.
J Cutan Pathol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622970

RESUMO

Primary cutaneous anaplastic large cell lymphoma (pC-ALCL) is distinguished from systemic anaplastic large cell lymphoma (S-ALCL) with cutaneous involvement. Although pC-ALCL is a unique entity with different genetics, clinical characteristics, and prognosis, its causes are unknown. Herein, we report the case of a Chinese woman with a 4-month history of a gradually enlarged ulcerative mass in her right forearm following an unidentified insect bite. Biopsy revealed an extensive infiltrate with patches of large anaplastic lymphoid cells. These cells were immunohistochemically positive for CD45, CD30, and TIA-1 and negative for CD2, CD3, CD4, CD5, CD20, CD7, CD8, and ALK-1. DUSP22-IRF4 rearrangement was detected whereas TP63 rearrangement was not observed by fluorescence in situ hybridization (FISH). No Epstein-Barr virus-encoded small RNAs (EBERs) were detected by ISH. Rearrangement of monoclonal TCR gene was found using BIOMED-2 polymerase chain reaction. No abnormality was found on the subsequent positron emission tomography-computed tomography (PET-CT) scan. After five cycles of CHOP chemotherapy, the patient achieved complete remission. This is the first report of a unique pC-ALCL with DUSP22-IRF4 rearrangement following an insect bite other than S-ALCL involving the skin. This article is protected by copyright. All rights reserved.

18.
Epigenomics ; 13(17): 1385-1401, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34528447

RESUMO

Aims: Few circRNAs have been thoroughly explored in ulcerative colitis (UC). Materials & methods: Microarrays and qualitative real-time PCRs were used to detect and confirm dysregulated circRNAs associated with UC. Functional analysis was performed to explore the roles. Results: A total of 580 circRNAs and 87 miRNAs were simultaneously dysregulated in both inflamed and noninflamed UC colonic mucosa compared with healthy controls. Accordingly, hsa_circ_0001021 was significantly downregulated in patients with UC and was related to Mayo scores. Clinical samples and cell experiments revealed that hsa_circ_0001021 was expressed in epithelial cells and correlated with ZO-1, occludin and CLDN-2. Moreover, hsa_circ_0001021 sponged miR-224-5p to upregulate smad4 and increased ZO-1 and occludin. Conclusion: Hsa_circ_0001021 is related to UC severity and regulates epithelial barrier function via sponging miR-224-5p.

19.
Environ Int ; 157: 106870, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34534788

RESUMO

BACKGROUND: Previous studies have revealed a significant association of fine particulate matter (PM2.5) with emotional disorders. However, as a crucial component of PM2.5, little is known about the potential effect of exposure to black carbon (BC) on the symptoms of depression and anxiety. OBJECTIVES: To explore the associations of long-term exposure to BC during the past six years with the current symptoms of depression and anxiety in a group of incoming college students. METHODS: This was a retrospective cohort study of incoming students in five universities of China. Symptoms of depression and anxiety during the past two weeks were measured by the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder Scale-2 (GAD-2), respectively. Levels of BC and other environmental factors during 2013 âˆ¼ 2018 (six years prior to the recruitment) was obtained from public repositories and linked to individual data by home addresses. Averagely daily dose of BC exposure was estimated according to the respiratory rate. Demographic and behavioral variables were collected through a questionnaire. The associations of BC with symptoms of depression and anxiety were estimated by mixed linear models adjusting for socioeconomic and behavioral characteristics, and the principal components of multiple environmental exposures. Subgroup analysis was conducted to assess the effect modification by covariates. Overall effect of environmental mixture was evaluated by weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR). RESULTS: A total of 20,079 participants was included in the current study. After adjustment for covariates, long-term BC exposure was significantly associated with symptoms of depression (ß = 0.17, P < 0.001) but not anxiety (ß = 0.07, P = 0.125). Effect modification by sex and parental educational level: BC was correlated with depressive symptoms in women (ß = 0.23, P < 0.001) but not in men (ß = 0.04, P = 0.581), and higher educational level was associated with decreased effect sizes of BC. Sensitivity analysis showed that the acute and short-term effects of BC on depression was consistent with its long-term exposure (ß varied from 0.18 to 0.20). WQS identified BC as the primary pollutant in association with symptoms of depression but not anxiety. BKMR identified no significant interaction between BC and other exposures. CONCLUSION: Exposure to BC is associated with symptoms of depression but not anxiety in college students, and the relationship is modified by sex and education.


Assuntos
Poluentes Atmosféricos , Depressão , Poluentes Atmosféricos/análise , Teorema de Bayes , Carbono , Depressão/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Material Particulado/análise , Estudos Retrospectivos , Estudantes
20.
BMC Genomics ; 22(1): 696, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565328

RESUMO

BACKGROUND: Aging and inflammation are important components of Parkinson's disease (PD) pathogenesis and both are associated with changes in hematopoiesis and blood cell composition. DNA methylation (DNAm) presents a mechanism to investigate inflammation, aging, and hematopoiesis in PD, using epigenetic mitotic aging and aging clocks. Here, we aimed to define the influence of blood cell lineage on epigenetic mitotic age and then investigate mitotic age acceleration with PD, while considering epigenetic age acceleration biomarkers. RESULTS: We estimated epigenetic mitotic age using the "epiTOC" epigenetic mitotic clock in 10 different blood cell populations and in a population-based study of PD with whole-blood. Within subject analysis of the flow-sorted purified blood cell types DNAm showed a clear separation of epigenetic mitotic age by cell lineage, with the mitotic age significantly lower in myeloid versus lymphoid cells (p = 2.1e-11). PD status was strongly associated with accelerated epigenetic mitotic aging (AccelEpiTOC) after controlling for cell composition (OR = 2.11, 95 % CI = 1.56, 2.86, p = 1.6e-6). AccelEpiTOC was also positively correlated with extrinsic epigenetic age acceleration, a DNAm aging biomarker related to immune system aging (with cell composition adjustment: R = 0.27, p = 6.5e-14), and both were independently associated with PD. Among PD patients, AccelEpiTOC measured at baseline was also associated with longitudinal motor and cognitive symptom decline. CONCLUSIONS: The current study presents a first look at epigenetic mitotic aging in PD and our findings suggest accelerated hematopoietic cell mitosis, possibly reflecting immune pathway imbalances, in early PD that may also be related to motor and cognitive progression.


Assuntos
Envelhecimento , Doença de Parkinson , Envelhecimento/genética , Células Sanguíneas , Linhagem da Célula/genética , Metilação de DNA , Epigênese Genética , Humanos , Doença de Parkinson/genética
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