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1.
Front Immunol ; 15: 1303589, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455056

RESUMO

Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting the world with a surge in cases. A variety of autoimmune diseases occur after SARS-CoV-2 infection or vaccination, of which IgG4-related disease (IgG4-RD) is an important type. IgG4-RD can involve multiple organs of the body. The ocular manifestation of IgG4-RD is called IgG4-related ophthalmic disease (IgG4-ROD). We herein report a patient diagnosed with IgG4-ROD. The patient developed ptosis and vision loss after SARS-CoV-2 vaccination, and the symptoms worsened after SARS-CoV-2 infection. After excluding other diseases like myasthenia gravis and Eaton-Lambert syndrome that may cause ptosis, the diagnosis of IgG4-ROD was confirmed by pathological examination. We discussed the predisposing factors, diagnosis and treatment of this patient to provide a more empirical and theoretical basis for clinical diagnosis and treatment. We conducted a literature review of previously reported cases of IgG4-RD following SARS-CoV-2 infection or vaccination. We retrieved a total of 9 cases, of which 5 developed symptoms after vaccination and 4 after infection. Demographic and clinical characteristics were summarized. In conclusion, our case represents the first case of proven IgG4-ROD after COVID-19 vaccination. We believe that IgG4-ROD and SARS-CoV-2 infection or vaccination are closely related, and the immune system disorder caused by SARS-CoV-2 infection or vaccination may be a key factor in the pathogenesis of IgG4-RD. But for now, there is no direct evidence that there is a causal relationship between SARS-CoV-2 infection or vaccination and IgG4-ROD, which still needs more research and exploration to confirm.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Oftalmopatias , Doença Relacionada a Imunoglobulina G4 , Humanos , Vacinas contra COVID-19/efeitos adversos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/induzido quimicamente , Vacinação , Oftalmopatias/induzido quimicamente
2.
Aesthet Surg J ; 44(5): NP337-NP346, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38299361

RESUMO

BACKGROUND: Intravascular injection represents the most severe complication in fat transplantation procedures. Currently, the prognosis for patients who suffer from blindness due to fat transplantation-induced ocular vascular occlusion is far from optimistic. OBJECTIVES: The aim of this study was to explore and evaluate the efficacy and safety of arterial thrombolysis in the treatment of ocular vascular occlusion caused by fat transplantation. METHODS: We analyzed the data of 12 patients who underwent intraarterial thrombolysis and conservative treatments for facial autologous fat grafting-associated ocular vascular occlusion. Among the cases, there were 6 instances of ophthalmic artery embolism and 6 cases of central retinal artery occlusion. All patients suffered with sudden blindness, sometimes accompanied by eye pain, ptosis, strabismus, skin necrosis at the injection site, or cerebral microinfarction. They received symptomatic conservative treatments and intraarterial thrombolysis, encompassing mechanical vessel recanalization, vessel dilation, and dissolution of thrombus constituents. RESULTS: Following intraarterial thrombolysis, a noteworthy improvement in the blood flow of both the main trunk and peripheral branches of the ophthalmic artery was observed in the majority of patients when contrasted with their pretreatment status. One patient experienced a headache intraoperatively, while no significant discomfort was reported by the remaining patients. After conservative treatments and intraarterial thrombolysis, all patients experienced improvement in ocular symptoms, skin necrosis, and cerebral infarction. Three patients demonstrated improvement in visual acuity. These patients had surpassed the recommended time window for treatment, yet the occlusion of the ophthalmic artery was not complete. CONCLUSIONS: Intraarterial thrombolysis combined with conservative treatments achieves early perfusion and is expected to promote visual recovery. Hospitals that possess the necessary treatment capabilities are encouraged to establish this therapeutic pathway.


Assuntos
Oclusão da Artéria Retiniana , Doenças Vasculares , Humanos , Cegueira/etiologia , Cegueira/terapia , Oclusão da Artéria Retiniana/etiologia , Oclusão da Artéria Retiniana/terapia , Prognóstico , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Necrose
3.
Aesthetic Plast Surg ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302710

RESUMO

BACKGROUND: Aesthetic injections have become increasingly popular for maintaining a youthful appearance. However, with the rise of SARS-CoV-2, there have been concerns about potential complications. This study aims to summarize and understand the complications that occur in individuals who have received cosmetic injections after SARS-CoV-2 infection or vaccination. By doing so, we hope to provide recommendations to minimize these complications and ensure the safety of aesthetic treatments in the current COVID-19 era. METHODS: The PRISMA guidelines, the Preferred Reporting Program for Systematic Reviews and Meta-Analyses, were used for this review. Databases including PubMed, EMBASE, Medline, Web of Science and ScienceDirect were searched. The last search time of each database was May 10, 2023. In addition, relevant references were manually searched. RESULTS: A total of 26 studies containing 139 patients were searched. The complication with the highest percentage of reported patients was delayed inflammatory response (DIR) (n = 68; 48.92%), followed by diminished efficacy (n = 45; 32.37%) and filler reaction (n = 12; 8.63%). The remaining complications include hypersensitivity reactions, symptomatic hypercalcemia, sub-acute hypersensitive reactions, hyperalgesia, infection, fat necrosis and granulomatous reaction. CONCLUSIONS: Cosmetic injectable procedures are generally safe but may have adverse effects, particularly during the pandemic. It is important for individuals to fully understand these risks beforehand. Clinicians should be knowledgeable about adverse event mechanisms and management to prevent issues. Industry leaders should strengthen risk management efforts to ensure safe and steady development of cosmetic injections. Overall, a comprehensive understanding, effective communication and risk management are crucial for the safe use of cosmetic injectable procedures. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266 .

4.
Aesthetic Plast Surg ; 47(5): 2159-2174, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37648929

RESUMO

BACKGROUND: At present, there are many kinds of hypertrophic scar treatment methods, among which pressure therapy and silicone therapy are very common and standard therapies, but whether they are used alone or in combination is still controversial. Therefore, the purpose of this systematic review was to compare the efficacy and safety of the combination of pressure therapy and silicone therapy (PTS) with pressure therapy alone (PT) in the treatment of hypertrophic scars to provide clinicians with information so that they can make better decisions. METHODS: Relevant randomized controlled trials (RCTs) were collected by searching PubMed, Ovid MEDLINE, Embase, ScienceDirect, Web of Science, The Cochrane Library, Scopus, and Google Scholar databases to assess scar scores (The Vancouver Scar Scale, VSS; Visual Analog Scale, VAS) and adverse effects. RESULTS: We screened 1270 articles and included 6 RCTs including 228 patients. We found that height (MD = 0.15, 95%CI 0.10-0.21, p < 0.01) and pliability (MD = 0.35, 95%CI 0.25-0.46, p <0.01) had a significant difference, these two measures showed that the PTS group was superior to the PT group. Results in other aspects, such as VSS, vascularity, pigmentation, VAS, and adverse effects were similar between the two groups. CONCLUSIONS: There was no significant difference between PTS and PT in the overall treatment efficacy of hypertrophic scars with similar VSS and adverse effects, but PTS might have potential benefits for height and pliability. Additional studies with larger sample size and sound methodological quality are needed to confirm our conclusions. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Cicatriz Hipertrófica , Humanos , Cicatriz Hipertrófica/prevenção & controle , Cicatriz Hipertrófica/patologia , Silicones , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Front Oncol ; 13: 1151871, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342181

RESUMO

Background: In the last decades, growing attention has been focused on identifying effective therapeutic strategies in the orphan clinical setting of women with platinum-resistant ovarian cancer (PROC), generating thousands of original articles. However, the literature involving bibliometric analysis of PROC has not been published yet. Objective: This study hopes to gain a better understanding of the hot spots and trends in PROC by conducting a bibliometric analysis, as well as identify potential new research directions. Methods: We searched the Web of Science Core Collection (WOSCC) for PROC-related articles published between 1990 and 2022. CiteSpace 6.1.R2 and VOS viewer 1.6.18.0 were primarily utilized to evaluate the contribution and co-occurrence relationships of various countries and regions, institutes, and journals and to identify research hotspots and promising future trends in this research field. Results: A total of 3,462 Web of Science publications were retrieved that were published in 671 academic journals by 1135 authors from 844 organizations in 75 countries and regions. The United States was the leading contributor in this field, and the University of Texas MD Anderson Cancer Center was the most productive institution. Gynecologic Oncology was the most productive journal, while the Journal of Clinical Oncology was the most cited and influential. Co-citation cluster labels revealed the characteristics of seven major clusters, including synthetic lethality, salvage treatment, human ovarian-carcinoma cell line, PARP inhibitor resistance, antitumor complexes, folate receptor, and targeting platinum-resistant disease. Keywords and references burst detection indicated that biomarkers, genetic and phenotypic changes, immunotherapy, and targeted therapy were the most recent and most significant aspects of PROC research. Conclusion: This study conducted a comprehensive review of PROC research using bibliometric and visual techniques. Understanding the immunological landscape of PROC and identifying the population that can benefit from immunotherapy, especially in combination with other therapeutic options (such as chemotherapy and targeted therapy), will continue to be the focal point of research.

6.
Appl Opt ; 62(13): 3338-3346, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132834

RESUMO

Most of the existing schemes for extracting the Brillouin frequency shift (BFS) are based on the line shape of the Brillouin gain spectrum (BGS) curve. However, in some circumstances, such as in this paper, there is a cyclic shift in the BGS curve, causing difficulty in obtaining the BFS accurately with traditional methods. To solve this problem, we propose a method for extracting Brillouin optical time domain analyzer sensing information in the transform domain-the fast Fourier Lorentz curve fitting method. It shows better performance especially when the cyclic start frequency is near the BGS central frequency position or when the full width at half maximum is large. The results show that our method can obtain BGS parameters more accurately in most cases than the Lorenz curve fitting method.

7.
Surg Endosc ; 37(8): 6333-6342, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37208483

RESUMO

BACKGROUND: Robotic gastrectomy (RG) has been reported to be technically feasible and safe for patients with gastric cancer. However, 5-year long-term survival and recurrence outcomes for advanced gastric cancer have rarely been reported. This study aimed to compare the long-term oncologic outcomes between RG and laparoscopic gastrectomy (LG) for gastric cancer. METHODS: The general clinicopathological data of 1905 consecutive patients who underwent RG and LG were retrospectively collected at the Chinese People's Liberation Army General Hospital between November 2011 and October 2017. Propensity score matching (PSM) was used to match groups. The primary endpoints were 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: After PSM, a well-balanced cohort of 283 patients in the RG group and 701 patients in the LG group were included in the analysis. The 5-year cumulative DFS rates were 67.28% in the robotic group and 70.41% in the laparoscopic group. The 5-year OS rate was 69.01% in the robotic group and 69.58% in the laparoscopic group. No significant differences in Kaplan-Meier survival curves for DFS (HR = 1.08, 95% CI 0.83-1.39, Log-rank P = 0.557) and OS (HR = 1.02, 95% CI 0.78-1.34, Log-rank P = 0.850) were observed between the 2 groups. In the subgroup analyses for potential confounding variables, there were no significant differences in 5-year DFS and 5-year OS survival between the 2 groups (P > 0.05), except for patients with pathological stage III and pathological stage N3 (P < 0.05). CONCLUSION: For patients with early gastric cancer, robotic and laparoscopic approaches have similar long-term survival. For patients with advanced gastric cancer, further studies need to be conducted to assess the long-term survival outcomes of RG.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Estudos de Coortes , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Gastrectomia , Pontuação de Propensão , Resultado do Tratamento
8.
Nanomicro Lett ; 15(1): 109, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37071340

RESUMO

Realizing real-time monitoring of physiological signals is vital for preventing and treating chronic diseases in elderly individuals. However, wearable sensors with low power consumption and high sensitivity to both weak physiological signals and large mechanical stimuli remain challenges. Here, a flexible triboelectric patch (FTEP) based on porous-reinforcement microstructures for remote health monitoring has been reported. The porous-reinforcement microstructure is constructed by the self-assembly of silicone rubber adhering to the porous framework of the PU sponge. The mechanical properties of the FTEP can be regulated by the concentrations of silicone rubber dilution. For pressure sensing, its sensitivity can be effectively improved fivefold compared to the device with a solid dielectric layer, reaching 5.93 kPa-1 under a pressure range of 0-5 kPa. In addition, the FTEP has a wide detection range up to 50 kPa with a sensitivity of 0.21 kPa-1. The porous microstructure makes the FTEP ultra-sensitive to external pressure, and the reinforcements endow the device with a greater deformation limit in a wide detection range. Finally, a novel concept of the wearable Internet of Healthcare (IoH) system for real-time physiological signal monitoring has been proposed, which could provide real-time physiological information for ambulatory personalized healthcare monitoring.

9.
IEEE J Biomed Health Inform ; 27(7): 3645-3656, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37115836

RESUMO

The increasing reliance on online communities for healthcare information by patients and caregivers has led to the increase in the spread of misinformation, or subjective, anecdotal and inaccurate or non-specific recommendations, which, if acted on, could cause serious harm to the patients. Hence, there is an urgent need to connect users with accurate and tailored health information in a timely manner to prevent such harm. This article proposes an innovative approach to suggesting reliable information to participants in online communities as they move through different stages in their disease or treatment. We hypothesize that patients with similar histories of disease progression or course of treatment would have similar information needs at comparable stages. Specifically, we pose the problem of predicting topic tags or keywords that describe the future information needs of users based on their profiles, traces of their online interactions within the community (past posts, replies) and the profiles and traces of online interactions of other users with similar profiles and similar traces of past interaction with the target users. The result is a variant of the collaborative information filtering or recommendation system tailored to the needs of users of online health communities. We report results of our experiments on two unique datasets from two different social media platforms which demonstrates the superiority of the proposed approach over the state of the art baselines with respect to accurate and timely prediction of topic tags (and hence information sources of interest).


Assuntos
Informação de Saúde ao Consumidor , Mídias Sociais , Humanos
10.
Heliyon ; 8(12): e11979, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36578422

RESUMO

Embryonic stem cells (ESCs) exhibit an unusual cell cycle profile containing a short G1 phase. Whether this feature is required to maintain pluripotency is a matter of debate. Here, we report that the short G1 phase is a consequence of MEK1/2 kinase-mediated promotion of G1/S transition, but not necessarily coupled with pluripotency maintenance. We find that compared to primed ESCs, naïve ESCs exhibit a significantly longer G1 phase due to the inhibition of MEK1/2 kinases. MEK1/2 inhibition increases intracellular level of reactive oxygen species (ROS), leading to the stabilization of p53 protein. The genetic ablation of p53 largely converts the cell cycle profile of naïve ESCs to that of primed ESCs. These results demonstrate that pluripotency and proliferation are separable cellular events, and the short G1 phase of primed ESCs is a manifestation of the intricate interplay between classical oncogenes MEK1/2 and tumor suppressor gene TP53 to promote G1/S transition.

11.
iScience ; 25(9): 104844, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36034227

RESUMO

Testicular germ cell tumors and closely related embryonal stem cells are exquisitely sensitive to cisplatin, a feature thought to be linked to their pluripotent state and p53 status. It remains unclear whether and how cellular state is coordinated with p53 to confer cisplatin sensitivity. Here, we report that positive transcription elongation factor b (P-TEFb) determines cell fate upon DNA damage. We find that cisplatin rapidly activates P-TEFb by releasing it from inhibitory 7SK small nuclear ribonucleoprotein complex. P-TEFb directly phosphorylates pluripotency factor estrogen-related receptor beta (ESRRB), and induces its proteasomal degradation to enhance pro-survival glycolysis. On the other hand, P-TEFb is required for the transcription of a substantial portion of p53 target genes, triggering cell death during prolonged cisplatin treatment. These results reveal previously underappreciated roles of P-TEFb to coordinate the DNA damage response. We discuss the implications for using P-TEFb inhibitors to treat cancer and ameliorate cisplatin-induced ototoxicity.

12.
Chemosphere ; 297: 134230, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35257700

RESUMO

Short-chain (SC) and medium-chain (MC) chlorinated paraffins (CPs) are found widely in the environment. Little research into air-soil exchange of SCCPs and MCCPs has been performed. In this study, CP concentrations, congener group profiles, and air-soil exchange in a typical contaminated area were investigated. A total of 10 soil samples and 10 air samples were collected from Zhoushan, an island in China. The samples were analyzed by two-dimensional gas chromatography electron capture negative ionization mass spectrometry. The SCCP and MCCP concentrations in the soil samples were 72-3842 and 117-8819 ng/g, respectively, and the SCCP and MCCP concentrations in the air samples were 57-208 and 1.8-25 ng/m3, respectively. The highest CP concentrations in both soil and air were found in samples from near shipyards, possibly because of CPs being emitted from metal cutting fluids and marine paints used at the shipyards. C14-15Cl7-9 were the dominant CP congener groups in the soil samples. C10Cl6-7 were the dominant CP congener groups in the air samples. Chlorinated decane and undecane and penta-, hexa-, and hepta-chlorinated CPs were enriched in the air relative to the soil. These congeners may have been released from the commercial CP-42 and CP-52. The fugacity fractions (ffs) of 48 homologs decreased as Koa increased. The ffs indicated that SCCPs and MCCPs dominated deposition. The net air-soil exchange fluxes of CPs were 201-769 ng/(m2·h). A preliminary risk assessment indicated that CPs pose low ecological risk except at sampling site S7 and do not pose significant health risks.


Assuntos
Hidrocarbonetos Clorados , Solo , China , Meios de Cultura , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas , Hidrocarbonetos Clorados/análise , Parafina/análise
13.
Opt Express ; 30(3): 4231-4248, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35209664

RESUMO

We propose the asynchronous control of anisotropic diffusion (AD) algorithm, and such asynchronous anisotropic diffusion (AAD) algorithm is demonstrated experimentally to reduce noise from the sensing signals obtained from Brillouin distributed optical fiber sensors. The performance of the proposed AAD algorithm is analyzed in detail for different experimental conditions and compared with that of block-matching and 3D filtering, two-dimensional wavelet denoising, AD, and non-local means algorithms. Some key factors of the proposed algorithm, such as the impact of convolution kernel size on the performance of AD algorithms, the influence of low sampling point number (SPN) on the quality of Brillouin frequency shift and the selection of diffusion thresholds are analyzed and discussed with experimental results. The experimental results validate that the AAD algorithm can provide better root-mean-square error (RMSE) and spatial resolution (SR) than the other four algorithms, especially for higher signal-to-noise ratio (SNR) improvement and higher SPNs. For lower SPNs, the performance of AAD is also not inferior to the RMSE performance of NLM and AD. The runtime of the AAD algorithm is also quite low. Moreover, the proposed algorithm offers the best SR performance as compared to other noise reduction algorithms investigated in this study. Thus, the proposed AAD algorithm can be an effective candidate to improve the measurement accuracy of Brillouin distributed optical fiber sensors.

14.
Environ Pollut ; 293: 118456, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34740736

RESUMO

Chlorinated paraffins (CPs) are used as additives in metal processing in the metal smelting industry. Data on CPs in the environment near metal smelting plants are limited. The objectives of this study were to investigate the concentrations and congener profiles of CPs in soil around factories in a non-ferrous metal recycling park located in Hebei, China, and to investigate human exposure to CPs in the soil. The concentrations of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) were determined by two-dimensional gas chromatography with electron capture negative ionization mass spectrometry. The SCCP and MCCP concentrations in the soil samples were 121-5159 ng/g and 47-6079 ng/g, respectively. Generally, the CP concentrations in soils around the factories were relatively high compared with those near other contaminated sites and in rural and urban areas. There were significant correlations between the MCCP concentrations, some SCCP carbon homologs, and the total organic carbon content (p < 0.05). The major SCCP and MCCP congener groups were C10Cl6-7 and C15-16Cl5, respectively. Hierarchical cluster analysis and principal component analysis indicated that SCCPs and MCCPs in the soil might originate from extreme pressure additives containing CP-42 and CP-52 and CP-containing waste material from the factories. The concentrations in two samples collected near a metal recycling factory posed a moderate risk according to a risk assessment conducted using risk quotients. Further risk assessment showed that the CPs concentrations in soil did not pose significant health risks to either children or adults.


Assuntos
Hidrocarbonetos Clorados , Parafina , Adulto , Criança , China , Monitoramento Ambiental , Humanos , Hidrocarbonetos Clorados/análise , Parafina/análise , Medição de Risco , Solo
15.
Huan Jing Ke Xue ; 42(3): 1131-1140, 2021 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742909

RESUMO

Short-chain chlorinated paraffins are persistent organic pollutants, and chlorinated paraffins were widely used as sizing agent in the paper industry. In order to investigate the levels and risk assessment of short-chain and medium-chain chlorinated paraffins in the paper mill plant, the surface soil and soil of different depths were collected.The concentrations, congener group profiles of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in soil were determined by two-dimensional gas chromatography coupled with electron capture-negative ion mass spectrometry. The SCCPs and MCCPs concentrations were 42-3853 ng·g-1 and 34-2091 ng·g-1. The chlorine contents were 59.9%-61.9% and 48.7%-52.8%. The concentrations of SCCPs and MCCPs were different in the soil collected in different sampling site. The concentration of SCCPs and MCCPs were relatively higher in soil of sewage treatment area and coating area. The CP levels in soil from the paper mill plant were at a high level compared with those in other regions. C10Cl6-7 and C14-15Cl5 were the main congener groups in most soil samples. The results of principal component analysis showed that the CP52 commercial products may be sources of SCCPs and MCCPs in the soil. The risk quotient (RQ) for SCCPs and MCCPs were assessed in soil of paper mill plant. The results showed that the RQ values for SCCPs in soil ranged from 0.01 to 0.73 which are the medium risk, and the RQ values for MCCPs in soil ranged from 0 to 0.07, which are the low risk. The human exposure values of children and adults are lower than TDI[10 µg·(kg·d)-1] in both cases. The health risks caused by non-dietary exposure under paper mill area are low.


Assuntos
Hidrocarbonetos Clorados , Parafina , Criança , China , Monitoramento Ambiental , Humanos , Hidrocarbonetos Clorados/análise , Parafina/análise , Medição de Risco , Solo
16.
Nat Commun ; 9(1): 1876, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29760377

RESUMO

The assembly of prereplicative complex (pre-RC) during G1 phase must be tightly controlled to sustain cell proliferation and maintain genomic stability. Mechanisms to prevent pre-RC formation in G2/M and S phases are well appreciated, whereas how cells ensure efficient pre-RC assembly during G1 is less clear. Here we report that cyclin K regulates pre-RC formation. We find that cyclin K expression positively correlates with cell proliferation, and knockdown of cyclin K or its cognate kinase CDK12 prevents the assembly of pre-RC in G1 phase. Mechanistically we uncover that cyclin K promotes pre-RC assembly by restricting cyclin E1 activity in G1. We identify a cyclin K-dependent, novel phosphorylation site in cyclin E1 that disrupts its interaction with CDK2. Importantly, this antagonistic relationship is largely recapitulated in cyclin E1-overexpressing tumors. We discuss the implications of our findings in light of recent reports linking cyclin K and CDK12 to human tumorigenesis.


Assuntos
Neoplasias da Mama/genética , Carcinogênese/genética , Quinases Ciclina-Dependentes/genética , Ciclinas/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Proliferação de Células , Ciclina E/genética , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/antagonistas & inibidores , Ciclinas/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Instabilidade Genômica , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/genética
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