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1.
Clin Oral Investig ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596771

RESUMO

OBJECTIVES: To query the experience of oral surgeons concerning referral routines and preferences for radiographic imaging modality before surgical removal of mandibular third molars and investigate factors that influence imaging modality preferences. MATERIALS AND METHODS: Members of the Swedish Association of Oral and Maxillofacial Surgeons (n = 280) were invited to participate in a web-based digital survey concerning their experiences and use of three imaging modalities in pre-surgical assessment of mandibular third molar removal. The survey comprised multiple-choice questions and four cases depicted in images; respondents reported whether they would supplement the cases with other images and, if so, from which modality. RESULTS: The response rate was 64%. Panoramic radiographs were most commonly used in pre-surgical planning (response options: always or often), significant difference between professions (p = 0.039), and considered to facilitate treatment planning (87%), as was CBCT (82%); for 51%, CBCT reduced post-operative complications. Preferred modality for localizing the mandibular canal was fairly evenly distributed and for non-complex case, significant difference between subgroups of OMFS surgeons was found (p = 0.003) as to preference for intraoral radiographs. CONCLUSIONS: A majority of respondents received a report within 2 weeks of their referral for CBCT and would read the report and view the images before surgery. Image modality preference differed depending on case complexity, with a greater perceived need for CBCT. Profession and practical experience affected choice. CLINICAL RELEVANCE: Choice of imaging modality in mandibular third molar assessment is also important from dose delivery and social economy standpoints.

2.
Transl Vis Sci Technol ; 10(5): 11, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-34550310

RESUMO

Purpose: The purpose of this study was to evaluate if corneal collagen cross-linking (CXL) pretreatment dampens suture-induced hemangiogenesis and lymphangiogenesis driven by inflammation. Methods: Four weeks after CXL pretreatment, suture emplacement was performed in rats. The time dependent effects were compared of this procedure in three groups: (1) suture-induced neovascularization (SNV group); (2) CXL treatment prior to suture-induced neovascularization (CXL + SNV group); (3) Normal control (NC group). Serial morphometric measurements evaluated suture-induced hemangiogenesis and lymphangiogenesis. CD45 and CD68 immunofluorescent staining pattern changes determined immune cell activation, stromal leucocyte, and macrophage infiltration. The real-time quantitative polymerase chain reaction (RT-qPCR) determined angiogenic and lymphangiogenic gene expression level changes. Western blots evaluated protein expression levels of vascular endothelial cell CD31 and lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Results: On days 7 and 14 after suture emplacement, the rises in angiogenesis, lymphangiogenesis, CD45+ and CD68+ cell infiltration were less in the CXL pretreated (CXL + SNV) group than in the untreated (SNV) group. Angiogenic and lymphangiogenic mRNA levels and CD31 and LYVE-1 protein and proinflammatory cytokines were also suppressed, confirming that CXL pretreatment improved the wound healing response. Conclusions: CXL pretreatment inhibits injury-induced angiogenesis and lymphangiogenesis. These reductions suggest that prior CXL therapy decrease ocular inflammation reactivated by secondary trauma. Translational Relevance: CXL pretreatment induces increases in stromal stiffness which in turn reduces trauma or microbial driven increases in inflammation, angiogenesis, and lymphangiogenesis. These beneficial effects suggest that this novel procedure may improve therapeutic management of trauma-induced corneal disease in a clinical setting.


Assuntos
Neovascularização da Córnea , Linfangiogênese , Animais , Colágeno , Neovascularização da Córnea/tratamento farmacológico , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Ratos
4.
Molecules ; 26(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34577017

RESUMO

Flavonoids are key secondary metabolites that are biologically active and perform diverse functions in plants such as stress defense against abiotic and biotic stress. In addition to its importance, no comprehensive information has been available about the secondary metabolic response of Populus tree, especially the genes that encode key enzymes involved in flavonoid biosynthesis under drought stress. In this study, the quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that the expression of flavonoid biosynthesis genes (PtPAL, Pt4-CL, PtCHS, PtFLS-1, PtF3H, PtDFR, and PtANS) gradually increased in the leaves of hybrid poplar (P. tremula × P. alba), corresponding to the drought stress duration. In addition, the activity and capacity of antioxidants have also increased, which is positively correlated with the increment of phenolic, flavonoid, anthocyanin, and carotenoid compounds under drought stress. As the drought stress prolonged, the level of reactive oxygen species such as hydrogen peroxide (H2O2) and singlet oxygen (O2-) too increased. The concentration of phytohormone salicylic acid (SA) also increased significantly in the stressed poplar leaves. Our research concluded that drought stress significantly induced the expression of flavonoid biosynthesis genes in hybrid poplar plants and enhanced the accumulation of phenolic and flavonoid compounds with resilient antioxidant activity.

5.
Cell Res ; 31(10): 1047-1060, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34465913

RESUMO

The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike's S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Mechanistically, such mechano-activation is fulfilled by force-induced opening and rotation of spike's receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding, up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application, and subsequently by force-accelerated S1/S2 detachment which is up to ~103 times faster than that in the no-force condition. Interestingly, the SARS2-S D614G mutant, a more infectious variant, shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment. We also reveal that an anti-S1/S2 non-RBD-blocking antibody that was derived from convalescent COVID-19 patients with potent neutralizing capability can reduce S1/S2 detachment by 3 × 106 times under force. Our study sheds light on the mechano-chemistry of spike activation and on developing a non-RBD-blocking but S1/S2-locking therapeutic strategy to prevent SARS2 invasion.


Assuntos
COVID-19/diagnóstico , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Resistência à Tração , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , COVID-19/terapia , COVID-19/virologia , Humanos , Concentração de Íons de Hidrogênio , Imunização Passiva , Simulação de Dinâmica Molecular , Ligação Proteica , Domínios Proteicos/imunologia , Subunidades Proteicas/química , Subunidades Proteicas/imunologia , Subunidades Proteicas/metabolismo , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Internalização do Vírus
6.
Phytochem Anal ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34431563

RESUMO

INTRODUCTION: Codonopsis Radix (CR) is an edible food and traditional Chinese herb medicine that is widely used in China and Southeast Asia. Saccharides, including fructo-oligosaccharides (FOS) and polysaccharides, are among the most important active substances in CR. However, a quality evaluation of CR based on oligosaccharides has not been conducted. OBJECTIVE: This study aimed to establish a high-performance liquid chromatography coupled with charged aerosol detector method (HPLC-CAD) for the quality evaluation of CR and processed products based on analysis of monosaccharides and oligosaccharides. METHOD: A sensitive and rapid HPLC-CAD method for the simultaneous determination of two monosaccharides (D-fructose and D-glucose), sucrose, and FOS (GF2-GF6) was established to evaluate the quality of CR for the first time. In the present study, 65 batches of CR from three species of the genus Codonopsis were analysed using multivariate statistical techniques. Furthermore, the effects of cultivation management measures (plant growth retardants supply, harvesting time, and growth period) and primary process (drying methods) in the production areas on the target compounds were studied by analysing 34 batches of processed samples. RESULTS: Different varieties of CR resulted in considerably different saccharide contents. Cultivation management measures and processing method remarkably affected the quality of CR. Low concentration of plant growth retardants was recommended. The best harvest time is in October after 4 years of growth. Dryer-drying was suggested to meet the requirement for large-scale processing. CONCLUSION: This method would provide an efficient analytical tool for monosaccharides and oligosaccharides of CR and contribute to the improvement of CR quality.

7.
Plant Cell ; 33(10): 3235-3249, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34338800

RESUMO

Protein S-acylation is an important post-translational modification in eukaryotes, regulating the subcellular localization, trafficking, stability, and activity of substrate proteins. The dynamic regulation of this reversible modification is mediated inversely by protein S-acyltransferases and de-S-acylation enzymes, but the de-S-acylation mechanism remains unclear in plant cells. Here, we characterized a group of putative protein de-S-acylation enzymes in Arabidopsis thaliana, including 11 members of Alpha/Beta Hydrolase Domain-containing Protein 17-like acyl protein thioesterases (ABAPTs). A robust system was then established for the screening of de-S-acylation enzymes of protein substrates in plant cells, based on the effects of substrate localization and confirmed via the protein S-acylation levels. Using this system, the ABAPTs, which specifically reduced the S-acylation levels and disrupted the plasma membrane localization of five immunity-related proteins, were identified respectively in Arabidopsis. Further results indicated that the de-S-acylation of RPM1-Interacting Protein 4, which was mediated by ABAPT8, resulted in an increase of cell death in Arabidopsis and Nicotiana benthamiana, supporting the physiological role of the ABAPTs in plants. Collectively, our current work provides a powerful and reliable system to identify the pairs of plant protein substrates and de-S-acylation enzymes for further studies on the dynamic regulation of plant protein S-acylation.

8.
Front Immunol ; 12: 695278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367155

RESUMO

Tuberculosis (TB) is one of the communicable diseases caused by Mycobacterium tuberculosis (Mtb) infection, affecting nearly one-third of the world's population. However, because the pathogenesis of TB is still not fully understood and the development of anti-TB drug is slow, TB remains a global public health problem. In recent years, with the gradual discovery and confirmation of the immunomodulatory properties of mesenchymal stem cells (MSCs), more and more studies, including our team's research, have shown that MSCs seem to be closely related to the growth status of Mtb and the occurrence and development of TB, which is expected to bring new hope for the clinical treatment of TB. This article reviews the relationship between MSCs and the occurrence and development of TB and the potential application of MSCs in the treatment of TB.

9.
BMC Med Imaging ; 21(1): 127, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425762

RESUMO

BACKGROUND: Adenoid hypertrophy among orthodontic patients may be detected in lateral cephalograms. The study investigates the aerodynamic characteristics within the upper airway (UA) by means of computational fluid dynamics (CFD) simulation. Furthermore, airflow features are compared between subgroups according to the adenoidal nasopharyngeal (AN) ratios. METHODS: This retrospective study included thirty-five patients aged 9-15 years having both lateral cephalogram and cone beam computed tomography (CBCT) imaging that covered the UA region. The cases were divided into two subgroups according to the AN ratios measured on the lateral cephalograms: Group 1 with an AN ratio < 0.6 and Group 2 with an AN ratio ≥ 0.6. Based on the CBCT images, segmented UA models were created and the aerodynamic characteristics at inspiration and expiration were simulated by the CFD method for the two groups. The studied aerodynamic parameters were pressure drop (ΔP), maximum midsagittal velocity (Vms), maximum wall shear stress (Pws), and minimum wall static pressure (Pw). RESULTS: The maximum Vms exhibits nearly 30% increases in Group 2 at both inspiration (p = 0.013) and expiration (p = 0.045) compared to Group 1. For the other aerodynamic parameters such as ΔP, the maximum Pws, and minimum Pw, no significant difference is found between the two groups. CONCLUSIONS: The maximum Vms seems to be the most sensitive aerodynamic parameter for the groups of cases. An AN ratio of more than 0.6 measured on a lateral cephalogram may associate with a noticeably increased maximum Vms, which could assist clinicians in estimating the airflow features in the UA.

10.
BMC Oral Health ; 21(1): 417, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433437

RESUMO

BACKGROUND: Optimal utilization of dental caries data is crucial in epidemiological research of individuals with juvenile idiopathic arthritis (JIA). The aims were to: explore whether caries is more prevalent among children and adolescents with JIA compared to controls; examine presence of caries according to JIA group, socio-behavioral and intraoral characteristics, and the extent to which surface-specific caries varies between and within individuals; assess whether surface-specific caries varies according to JIA group and dentition; and investigate whether disease-specific clinical features of JIA are associated with presence of caries. METHODS: In this comparative cross-sectional study, calibrated dentists examined index teeth (primary 2. molars, 1. permanent molars) of 4-16-year-olds with JIA (n = 219) and matched controls (n = 224), using a detailed caries diagnosis system (including enamel caries). JIA-specific characteristics were assessed by pediatric rheumatologists and socio-behavioral information collected by questionnaires. Multilevel mixed-effect logistic regressions reporting odds ratios (OR) with 95% confidence interval (CI) were applied (caries at surface level as outcome variable). Potential confounders were adjusted for, and the effect of dependency of surface-specific caries data was estimated by calculating intra-class correlation coefficients (ICC). RESULTS: At individual level, no significant difference in caries prevalence was found between individuals with JIA and controls, regardless of inclusion of enamel caries. Proportion of enamel lesions exceeded dentine lesions. JIA was not associated with presence of caries, but in both groups, low maternal educational level was associated with presence of caries (OR: 2.07, 95% CI: 1.24-3.46). Occlusal and mesial surfaces, compared to buccal surfaces, had generally higher OR according to presence of caries than distal and lingual surfaces (ICC = 0.56). Surface-specific caries in the permanent dentition differed significantly according to group affiliation. Some JIA disease-specific variables were suggested to associate with presence of caries. CONCLUSIONS: No overall difference in caries prevalence between individuals with JIA and controls was observed, but for both groups, low maternal educational level and tooth surface associated with presence of caries. Associations between JIA disease-specific variables and presence of caries cannot be excluded. Due to predominance of enamel lesions, the potential of preventative dental strategies is considerable.


Assuntos
Artrite Juvenil , Cárie Dentária , Adolescente , Artrite Juvenil/complicações , Artrite Juvenil/epidemiologia , Criança , Estudos Transversais , Cárie Dentária/epidemiologia , Cárie Dentária/etiologia , Dentição Permanente , Humanos , Análise Multinível , Dente Decíduo
12.
Dentomaxillofac Radiol ; : 20210165, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34324382

RESUMO

OBJECTIVES: This retrospective observational study aimed to evaluate the diagnostic accuracy of two-dimensional radiographs on canine-induced root resorption (CIRR) in lateral incisors and identify predictors of CIRR in patients with impacted maxillary canines (IMC). METHODS: Ninety-nine patients aged 9-17 years, with 156 IMCs, were included in the study. All had CBCT-volumes and two-dimensional radiographs consisting of at least one panoramic radiograph. Two radiologists jointly viewed all cases twice. First, radiographic features related to the IMC and possible CIRR were recorded from two-dimensional radiographs. Then, CIRR was determined from CBCT and according to position and extension classified as mild, moderate and severe. RESULTS: CIRRs was detected in 80% of lateral incisors (mild: 45%; moderate: 44%; severe: 11%). The sensitivity was generally low at mild and moderate cut-offs (29 and 29%), and somewhat higher for severe (50%). Corresponding specificities were 48%, 63% and 68%. Canine cusp-tip superimposing the lateral incisor's middle third and root/crown ratio >1 was positively associated with mild CIRR, with an odds ratio (OR) of 3.8 and 6.7, respectively. In addition, the root development stage was positively associated with moderate/severe CIRR when the canine root was nearly or fully developed (OR = 3.1). CONCLUSIONS: The diagnostic accuracy of two-dimensional radiographs was inadequate for detecting CIRR amongst patients referred for CBCT examinations. Based on our results, none of the suggested two-dimensional radiographic features could predict moderate/severe CIRR except for root development stage. IMC in a later stage of root development seems to be associated with a higher risk of moderate/severe CIRR.

13.
Nucleic Acids Res ; 49(13): 7361-7374, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34181729

RESUMO

N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the RNA m6A levels at specific transcriptomic loci empower interrogation of biological functions of epitranscriptomic modifications. Here, we developed a bidirectional dCasRx epitranscriptome editing platform composed of a nuclear-localized dCasRx conjugated with either a methyltransferase, METTL3, or a demethylase, ALKBH5, to manipulate methylation events at targeted m6A sites. Leveraging this platform, we specifically and efficiently edited m6A modifications at targeted sites, reflected in gene expression and cell proliferation. We employed the dCasRx epitranscriptomic editor system to elucidate the molecular function of m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our dCasRx epitranscriptome perturbation platform permits site-specific m6A editing for delineating of functional roles of individual m6A modifications in the mammalian epitranscriptome.


Assuntos
Adenosina/análogos & derivados , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Metiltransferases/metabolismo , RNA Mensageiro/metabolismo , Adenosina/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Proteínas Associadas a CRISPR/genética , Proliferação de Células , Células Cultivadas , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Metiltransferases/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mensageiro/química , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Transcriptoma
14.
Environ Res ; 200: 111459, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34126051

RESUMO

BACKGROUND: Bisphenol A (BPA) and its alternatives, including BPF and BPS, exhibit endocrine disruption activities. However, the effects of bisphenols on fetal growth in twins remain unclear. OBJECTIVE: To explore the associations of prenatal BPA, BPF, and BPS exposure with birth outcome differences in twins. METHODS: We recruited 289 twin pregnant women who visited the hospital for prenatal examination during the first trimester from 2013 to 2016. Urinary bisphenol levels were determined during the first, second, and third trimesters. The associations of maternal exposure to bisphenols with birth outcome differences in twins were analyzed after stratification by different trimesters. We applied the multiple informant model to estimate trimester-specific associations between urinary bisphenol concentrations and birth outcome differences in twins. RESULTS: We found low reproducibility (ICC<0.40) for maternal urinary BPA and moderate reproducibility (0.40 < ICC<0.75) for BPF and BPS. Urinary BPA concentrations were positively associated with within-pair twin birth weight difference when comparing the third vs. the first tertile in each of the three trimesters (i.e., 133.06 g, 95% CI: 68.19, 197.94; 144.5 g, 95%CI: 81.82-207.18 g; and 135.04 g, 95%CI: 71.37-198.71 g for the 1st, 2nd, and 3rd trimester, respectively). The effect of urinary BPA concentration on increased birth length difference within-pair twins were also observed across different trimesters (All P for trends < 0.05). Urinary BPA levels were positively associated with the within-pair birth weight and birth length differences across pregnancy trimesters (All of Type 3 P for values < 0.05). CONCLUSION: Maternal BPA exposure appeared to influence birth wight and birth length differences in twins. Our results warrant further confirmation.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/toxicidade , Estudos de Coortes , Feminino , Humanos , Exposição Materna/efeitos adversos , Fenóis , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Reprodutibilidade dos Testes
15.
J Affect Disord ; 292: 295-304, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34134028

RESUMO

BACKGROUND: Suicidality is common in people living with HIV/AIDS. However, the prevalence estimates of the suicidality vary between studies. Here, we performed a systematic review and estimated the prevalence of suicidal behavior in this population. METHODS: Systematic search of PubMed, Embase, Web of Science, CINAHL, Scopus and PsycINFO for relevant studies published before August 29, 2020. A random-effects model was used to pool the estimates of the prevalence of suicidal ideation, attempts and plans, which were also stratified by continent or region and screening instrument from the studies included in this meta-analysis. RESULTS: Suicide prevalence data were extracted from 36 studies(n=32,818) from 15 countries. The overall pooled crude prevalence estimates of suicidal ideation, plans, and attempts were 20.9% [95% confidence interval (CI) 16.5-21.6%],8.1% (95% CI 5.4-11.3%), and 7.5% (95% CI 5.7-9.5%), respectively. For lifetime suicidal ideation and attempts prevalence, this was 22.4% (95% CI 15.9-29.8%), and 12.0% (95% CI 6.9- 18.1%), respectively. Summary prevalence estimates ranged across assessment modalities from 6.5% to 33.7%. Pooled estimates were generally higher for females, as compared with males (risk ratios in the range 1.48-1.85). The leave-one-out analysis showed that no single study significantly affected the final pooled results.


Assuntos
Infecções por HIV , Ideação Suicida , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Razão de Chances , Prevalência , Tentativa de Suicídio
16.
J Clin Pediatr Dent ; 45(3): 208-215, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34192749

RESUMO

Objectives The present study evaluated the effect of rapid maxillary expansion (RME) on the morphology of the upper airway (UA) by calculating cross-sectional areas and volumes and comparing the effect in patients with a normal-sized adenoid with the effect in patients with an enlarged adenoid. Study design: Seventeen patients met the inclusion criteria. We constructed 3D models of the UA on cone-beam computed tomography images to calculate cross-sectional areas and volumes at the levels of the nasopharyngeal, retropalatal, and retroglossal airways. Patients were divided into two groups: group 1 was comprised of patients with an adenoidal nasopharyngeal (AN) ratio < 0.6 and group 2 with an AN ratio ≥ 0.6. Paired samples t-tests assessed any area and volumetric changes of the UA after RME. Changes in degree of nasal obstruction, calculated as the AN ratio, was then compared for the two groups. An independent samples t-test compared volumetric changes in the nasopharynx between the two groups before and after RME. Results Changes in cross-sectional areas and volumes of the UA due to RME were not significant. The effects of RME on AN ratio (11 % vs 0 %) and nasopharyngeal volume (36.8 % vs 5.97%) were somewhat larger in group 2 patients who had adenoid-associated nasal obstruction compared with group 1 patients with a normal-sized adenoid; however, the differences were not significant. Conclusions After RME, the patients with an enlarged adenoid had more increases in nasopharyngeal volume compared with those with normal adenoid, despite there was no significant difference.


Assuntos
Tonsila Faríngea , Técnica de Expansão Palatina , Tonsila Faríngea/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Humanos , Maxila , Nariz/diagnóstico por imagem , Estudos Retrospectivos
17.
Gynecol Endocrinol ; 37(7): 629-634, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34008465

RESUMO

AIM: PCOS often showed abnormal follicular development. Previous studies have found that the increased apoptosis of granulosa cells (GCs) is one of the key factors leading to follicular dysplasia. It has been found that the decrease or deletion of PATL2 function can significantly inhibit the development and maturation of human oocytes. We found that PATL2 was also expressed in human ovarian GCs, suggesting that PATL2 may be involved in the regulation of related biological events in GCs. This study aims to explore the function of PATL2 on regulation of GCs apoptosis, and the potential role of PATL2 in the development of PCOS-related abnormal follicles. MATERIALS AND METHODS: The follicular GCs of PCOS patients and normal ovulating female patients were collected. Moreover, human granular cell line (KGN) was used for in vitro experiments. RESULTS: (1) The maturation rate and fertilization rate of oocytes in the PCOS group were significantly lower than those in the normal control group (p<0.05). (2) Flow cytometry and TUNEL staining showed that the apoptosis level of GCs in the PCOS group was significantly increased. (3) Immunofluorescence and Western Blot showed that the PATL2 expression level of GCs in the PCOS group was significantly reduced. (4) Knocking down the expression of PATL2 by siRNA significantly prevented the apoptosis of GCs. CONCLUSIONS: Reduced PATL2 could resulted in the increased apoptosis level of ovarian GCs, which might be closely related to the occurrence and development of abnormal follicles in PCOS.

18.
Plant Cell ; 33(8): 2883-2898, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34015125

RESUMO

Endoplasmic reticulum-associated degradation (ERAD) is known to regulate plant responses to diverse stresses, yet its underlying molecular mechanisms and links to various stress signaling pathways are poorly understood. Here, we show that the ERAD component ubiquitin-conjugating enzyme UBC32 positively regulates drought tolerance in Arabidopsis thaliana by targeting the aquaporins PIP2;1 and PIP2;2 for degradation. Furthermore, we demonstrate that the RING-type ligase Rma1 acts together with UBC32 and that the E2 activity of UBC32 is essential for the ubiquitination of Rma1. This complex ubiquitinates a phosphorylated form of PIP2;1 at Lys276 to promote its degradation, thereby enhancing plant drought tolerance. Extending these molecular insights into crops, we show that overexpression of Arabidopsis UBC32 also improves drought tolerance in rice (Oryza sativa). Thus, beyond uncovering the molecular basis of an ERAD-regulated stress response, our study suggests multiple potential strategies for engineering crops with improved drought tolerance.

19.
J Biol Chem ; 297(1): 100811, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023381

RESUMO

A20 is a potent anti-inflammatory protein that mediates both inflammation and ubiquitination in mammals, but the related mechanisms are not clear. In this study, we performed mass spectrometry (MS) screening, gene ontology (GO) analysis, and coimmunoprecipitation (co-IP) in a lipopolysaccharide (LPS)-induced inflammatory cell model to identify novel A20-interacting proteins. We confirmed that the E3 ubiquitin ligase Nrdp1, also known as ring finger protein 41 (RNF41), interacted with A20 in LPS-stimulated cells. Further co-IP analysis demonstrated that when A20 was knocked out, degradation-inducing K48-linked ubiquitination of inflammatory effector MyD88 was decreased, but protein interaction-mediating K63-linked ubiquitination of another inflammatory effector TBK1 was increased. Moreover, western blot experiments showed that A20 inhibition induced an increase in levels of MyD88 and phosphorylation of downstream effector proteins as well as of TBK1 and a downstream effector, while Nrdp1 inhibition induced an increase in MyD88 but a decrease in TBK1 levels. When A20 and Nrdp1 were coinhibited, no further change in MyD88 was observed, but TBK1 levels were significantly decreased compared with those upon A20 inhibition alone. Gain- and loss-of-function analyses revealed that the ZnF4 domain of A20 is required for Nrdp1 polyubiquitination. Upon LPS stimulation, the inhibition of Nrdp1 alone increased the secretion of IL-6 and TNF-α but decreased IFN-ß secretion, as observed in other studies, suggesting that Nrdp1 preferentially promotes the production of IFN-ß. Taken together, these results demonstrated that A20/Nrdp1 interaction is important for A20 anti-inflammation, thus revealing a novel mechanism for the anti-inflammatory effects of A20.


Assuntos
Inflamação/metabolismo , Lisina/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Poliubiquitina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Animais , Ativação Enzimática , Inflamação/patologia , Interferons/metabolismo , Macrófagos/metabolismo , Camundongos , Modelos Biológicos , Ligação Proteica , Domínios Proteicos , Proteólise , Células RAW 264.7 , Transdução de Sinais , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/química
20.
Plant Commun ; 2(3): 100186, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34027397

RESUMO

Accumulating evidence has revealed that the ubiquitin proteasome system plays fundamental roles in the regulation of diverse cellular activities in eukaryotes. The ubiquitin protein ligases (E3s) are central to the proteasome system because of their ability to determine its substrate specificity. Several studies have demonstrated the essential role of a group of ER (endoplasmic reticulum)-localized E3s in the positive or negative regulation of cell homeostasis. Most ER-related E3s are conserved between plants and mammals, and a few plant-specific components have been reported. In this review, we summarize the functions of ER-related E3s in plant growth, ER-associated protein degradation and ER-phagy, abiotic and biotic stress responses, and hormone signaling. Furthermore, we highlight several questions that remain to be addressed and suggest directions for further research on ER-related E3 ubiquitin ligases.

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