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1.
Anticancer Res ; 41(7): 3253-3260, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230119

RESUMO

Epithelial ovarian cancer is the second most common malignancy of the female genital tract, with approximately 7,400 new cases annually in Germany. With 5,500 deaths per year, ovarian cancer is the leading gynecologic cause of death. Epithelial ovarian cancer is characterized by morphologic heterogeneity with 4 molecular biological subtypes (immunoreactive-like, differentiated-like, proliferative-like, mesenchymal-like) with different prognosis. Significantly improved survival is achieved by optimal debulking with no residual disease (R0). Systematic lymphonodectomy of clinical negative lymph nodes has no effect on overall survival in advanced ovarian cancer. Interval debulking in advanced ovarian cancer after three cycles of neoadjuvant chemotherapy with carboplatin/paclitaxel is controversial. Standard chemotherapy for advanced ovarian cancer consists of six cycles of carboplatin AUC5 and paclitaxel 175 mg/m2, in a three-week cycle. Intraperitoneal chemotherapy is not a standard therapy. Anti-hormonal therapy with an aromatase inhibitor plays a minor role in therapy of both low grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC). A major achievement in ovarian cancer therapy has been the results of the SOLO-1 trial, in which olaparib as a first line maintenance monotherapy resulted in an overall 70% lower risk of disease progression in patients with advanced Breast Cancer Gene (BRCA)-mutated ovarian cancer.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/métodos , Feminino , Alemanha , Humanos , Terapia Neoadjuvante/métodos
2.
Spine (Phila Pa 1976) ; 46(13): E743-E749, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34100842

RESUMO

STUDY DESIGN: Case report and literature review. OBJECTIVE: We present a case of a pathologic unstable fracture of the odontoid process due to vertebral osseous sarcoidosis. The surgical management of this unreported pathology is described and a review of the literature is given. SUMMARY OF BACKGROUND DATA: Sarcoidosis is a chronic inflammatory systemic disease of unknown etiology, characterized by multiorgan noncaseating granulomatous infiltrations. It affects primarily the lungs, lymphatic system, eyes, skin, heart, and nervous system. Osseous sarcoidosis is usually clinically asymptomatic and therefore frequently under-diagnosed. When it does affect the skull or vertebral column, specific surgical therapy is only necessary in cases with nonmanageable pain or where structural integrity is threatened. METHODS: Our patient underwent a so-called semiconservative approach, consisting of a minimally invasive transoral-transpharyngeal approach, surgical debridement of the lytic bony lesion, transplantation of cancellous homologous bone, and carbon chest halo-immobilization. Halo-immobilization was left for 8 weeks, followed by a further 6 weeks with a hard cervical collar. RESULTS: Routine computed tomography scans 3 days, 6, 12, 18 weeks, and 1 year after surgery showed good filling of the original defect with cancellous bone, correct alignment of the upper cervical spine, and progressive fracture consolidation and stability. Surgical site infection (SSI) was not observed. The patient had no neurological postoperative deficits. After initial dysphagia, swallowing was not permanently impaired. CONCLUSION: Sarcoidosis-induced odontoid fractures can be managed successfully using a semiconservative approach, consisting of transoral-transmucosal, minimally invasive surgical procedure for debridement of the lesion and transplantation of cancellous bone with additional halo-immobilization. Permanent fusion of C1-2 with loss of the cervical range of motion is avoided. Despite performing bone surgery in a potentially markedly contaminated site, bacterial infection was not an issue, possibly supported by the temporary discontinuation of immunosuppressive agents and the prudent use of antibiotics.Level of Evidence: 4.


Assuntos
Processo Odontoide , Sarcoidose , Fraturas da Coluna Vertebral , Humanos , Pescoço/diagnóstico por imagem , Processo Odontoide/diagnóstico por imagem , Processo Odontoide/lesões , Amplitude de Movimento Articular/fisiologia , Sarcoidose/complicações , Sarcoidose/diagnóstico por imagem , Sarcoidose/fisiopatologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Fraturas da Coluna Vertebral/terapia , Tomografia Computadorizada por Raios X
3.
ISME J ; 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155335

RESUMO

Permanently cold marine sediments are heavily influenced by increased input of iron as a result of accelerated glacial melt, weathering, and erosion. The impact of such environmental changes on microbial communities in coastal sediments is poorly understood. We investigated geochemical parameters that shape microbial community compositions in anoxic surface sediments of four geochemically differing sites (Annenkov Trough, Church Trough, Cumberland Bay, Drygalski Trough) around South Georgia, Southern Ocean. Sulfate reduction prevails in Church Trough and iron reduction at the other sites, correlating with differing local microbial communities. Within the order Desulfuromonadales, the family Sva1033, not previously recognized for being capable of dissimilatory iron reduction, was detected at rather high relative abundances (up to 5%) while other members of Desulfuromonadales were less abundant (<0.6%). We propose that Sva1033 is capable of performing dissimilatory iron reduction in sediment incubations based on RNA stable isotope probing. Sulfate reducers, who maintain a high relative abundance of up to 30% of bacterial 16S rRNA genes at the iron reduction sites, were also active during iron reduction in the incubations. Thus, concurrent sulfate reduction is possibly masked by cryptic sulfur cycling, i.e., reoxidation or precipitation of produced sulfide at a small or undetectable pool size. Our results show the importance of iron and sulfate reduction, indicated by ferrous iron and sulfide, as processes that shape microbial communities and provide evidence for one of Sva1033's metabolic capabilities in permanently cold marine sediments.

4.
Exp Eye Res ; 209: 108679, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34147508

RESUMO

Although protein crosslinking is often linked with aging as well as some age-related diseases, very few molecular details are available on the nature of the amino acids involved, or mechanisms that are responsible for crosslinking. Recent research has shown that several amino acids are able to generate reactive intermediates that ultimately lead to covalent crosslinking through multiple non-enzymatic mechanisms. This information has been derived from proteomic investigations on aged human lenses and the mechanisms of crosslinking, in each case, have been elucidated using model peptides. Residues involved in spontaneous protein-protein crosslinking include aspartic acid, asparagine, cysteine, lysine, phosphoserine, phosphothreonine, glutamic acid and glutamine. It has become clear, therefore, that several amino acids can act as potential sites for crosslinking in the long-lived proteins that are present in aged individuals. Moreover, the lens has been an invaluable model tissue and source of crosslinked proteins from which to determine crosslinking mechanisms that may lead to crosslinking in other human tissues.

5.
J Cancer Surviv ; 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118000

RESUMO

PURPOSE: Although young adults represent a significant portion of the working population, little is known about the work ability and cognitive impairments in adolescent and young adult (AYA) cancer patients (including the long-term course) following cancer treatment. METHODS: As part of the AYA-Leipzig study, we surveyed AYA cancer survivors (aged 18-39 years at diagnosis; time since diagnosis ≤ 4 years, including all cancer diagnoses) at two time points (t2 = 12 months after t1). Work ability (Work Ability Index, WAI-r) and cognitive impairments (Copenhagen Psychosocial Questionnaire, COPSOQ) were compared at both time points. We analysed predictors for work ability at, on average, 2 years post cancer diagnosis (t2) by using multivariate regression analyses. RESULTS: A total of 502 patients (74.7% women) participated in both measurements. Mean work ability increased significantly from t1 (6.0; SD = 2.3) to t2 (6.8; SD = 2.2) (t = -9.3; p < 0.001). As many as 380 (76%) AYA cancer survivors reported reduced work ability at t1; 1 year later, this still applied to 287 (57%) of them. Decreased work ability (t2) was associated with more cognitive impairment, higher effort coping with the disease, comorbidities, sick leave > 6 months (since diagnosis), and having children (adj R2 = .48). Cognitive impairments occurred in approximately every fifth patient at both surveys. CONCLUSIONS: Achieving maximum work ability is a major challenge for AYAs. Our results show the need for multimodal cancer survivorship and rehabilitation programmes with a special focus on improving cognitive and psychosocial functioning. IMPLICATIONS FOR CANCER SURVIVORS: AYAs with cancer should receive targeted occupational counselling early in the course of the disease.

6.
Health Qual Life Outcomes ; 19(1): 147, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001165

RESUMO

PURPOSE: The assessment of patient satisfaction during treatment is essential to provide patient-centered high-quality cancer care. Nevertheless, no German instrument assesses patient satisfaction with comprehensive cancer care, which not only includes oncological treatment, but also interpersonal quality of care as well as psychosocial support services. Based on the French REPERES-60, we developed the German Patient Satisfaction with Comprehensive Cancer Care (SCCC) questionnaire. METHODS: The REPERES-60 was translated and the items were adapted to make it applicable to the German healthcare system and across different tumor entities. Scales of the resulting instrument were extracted via principal axis factoring (PAF). Subsequently, we investigated the reliability (Cronbach's Alpha, CA), discriminatory power (corrected item-scale correlations) and convergent validity (pre-specified correlations of the SCCC with different outcomes). RESULTS: The SCCC consisted of 32 items which were subsequently tested among a sample of 333 patients across different tumor entities (response rate: 47%). Average age was 59 years (standard deviation: 14), 63% were male. PAF revealed four multi-item scales named Competence, Information, Access and Support accounting for 71% of the variance. Two single-items scales assess global satisfaction with medical and psychosocial care, respectively. CA across the multi-item scales ranged from .84 to .96. Discriminatory power was sufficiently high, with all r ≥ .5. Convergent validity was largely verified by negative associations of the four multi-item scales with depressive/anxious symptomatology (r ≥ - .18, p < .01) and fatigue/overall symptom burden (r ≥ - .14, p < .01). CONCLUSION: We developed a tool to assess patient satisfaction with comprehensive cancer care in Germany. The SCCC showed satisfactory psychometric properties. Further studies are needed to verify these preliminary findings.


Assuntos
Neoplasias/terapia , Satisfação do Paciente/estatística & dados numéricos , Satisfação Pessoal , Psicometria/normas , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , França , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Traduções , Adulto Jovem
7.
Environ Int ; 156: 106602, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34051435

RESUMO

Colonization of newly ice-free areas by marine benthic organisms intensifies burial of macroalgae detritus in Potter Cove coastal surface sediments (Western Antarctic Peninsula). Thus, fresh and labile macroalgal detritus serves as primary organic matter (OM) source for microbial degradation. Here, we investigated the effects on post-depositional microbial iron reduction in Potter Cove using sediment incubations amended with pulverized macroalgal detritus as OM source, acetate as primary product of OM degradation and lepidocrocite as reactive iron oxide to mimic in situ conditions. Humic substances analogue anthraquinone-2,6-disulfonic acid (AQDS) was also added to some treatments to simulate potential for electron shuttling. Microbial iron reduction was promoted by macroalgae and further enhanced by up to 30-folds with AQDS. Notably, while acetate amendment alone did not stimulate iron reduction, adding macroalgae alone did. Acetate, formate, lactate, butyrate and propionate were detected as fermentation products from macroalgae degradation. By combining 16S rRNA gene sequencing and RNA stable isotope probing, we reconstructed the potential microbial food chain from macroalgae degraders to iron reducers. Psychromonas, Marinifilum, Moritella, and Colwellia were detected as potential fermenters of macroalgae and fermentation products such as lactate. Members of class deltaproteobacteria including Sva1033, Desulfuromonas, and Desulfuromusa together with Arcobacter (former phylum Epsilonbacteraeota, now Campylobacterota) acted as dissimilatory iron reducers. Our findings demonstrate that increasing burial of macroalgal detritus in an Antarctic fjord affected by glacier retreat intensifies early diagenetic processes such as iron reduction. Under scenarios of global warming, the active microbial populations identified above will expand their environmental function, facilitate OM remineralisation, and contribute to an increased release of iron and CO2 from sediments. Such indirect consequences of glacial retreat are often overlooked but might, on a regional scale, be relevant for the assessment of future nutrient and carbon fluxes.


Assuntos
Alga Marinha , Regiões Antárticas , Elétrons , Sedimentos Geológicos , Ferro , RNA Ribossômico 16S/genética
8.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805376

RESUMO

The truncation of Tau is thought to be important in promoting aggregation, with this feature characterising the pathology of dementias such as Alzheimer disease. Antibodies to the C-terminal and N-terminal regions of Tau were employed to examine Tau cleavage in five human brain regions: the entorhinal cortex, prefrontal cortex, motor cortex, hippocampus, and cerebellum. These were obtained from normal subjects ranging in age from 18 to 104 years. Tau fragments of approximately 40 kDa and 45 kDa with an intact N-terminus retained were found in soluble and insoluble brain fractions. In addition, smaller C-terminal Tau fragments ranging in mass from 17 kDa to 25 kDa were also detected. These findings are consistent with significant Tau cleavage taking place in brain regions from 18 years onwards. It appears that site-specific cleavage of Tau is widespread in the normal human brain, and that large Tau fragments that contain the N-terminus, as well as shorter C-terminal Tau fragments, are present in brain cells across the age range.


Assuntos
Envelhecimento , Encéfalo/metabolismo , Proteínas tau/análise , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Encéfalo/fisiopatologia , Cerebelo/metabolismo , Cerebelo/fisiopatologia , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Pessoa de Meia-Idade , Desdobramento de Proteína , Proteólise , Adulto Jovem , Proteínas tau/metabolismo
9.
Psychooncology ; 30(8): 1311-1321, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33739567

RESUMO

AIM: This study systematically assesses the awareness of, utilisation of and satisfaction with psychosocial care for adolescents and young adult (AYA) cancer survivors in aftercare. METHODS: Survivors between 18 and 39 years were surveyed in aftercare. Awareness of, utilisation of and satisfaction with psychological counselling (PC), social-legal counselling (SLC) and other psychosocial care (OPC) were measured using self-developed questionnaires. Multivariate analyses were conducted to determine factors correlated with awareness and use of psychosocial care. RESULTS: Five hundred and fourteen survivors participated; the mean age at diagnosis was 29.6 years (SD = 6.14). 54% of cancer survivors were aware of PC, 45% of SLC and 24% of OPC. Those who possessed knowledge about these services used it to a considerable extent (63%-74%), and the majority (66%-75%) was highly satisfied. No common factors could be found that increase the likelihood of being aware of these three services (R2  = 0.028-0.138). Female gender (OR = 2.08-2.18) and high anxiety (OR = 1.19-1.38) were identified as common factors that increase the likelihood of utilising psychosocial services (R2  = 0.160-0.395). CONCLUSION: AYA who are aware of psychosocial services in aftercare are motivated to use them and express high satisfaction with use. For the utilisation of psychosocial services, anxiety and female gender can be identified as common factors. The visibility of psychosocial services for aftercare should be increased given the high number of unaware AYA survivors. The active and repeated addressing of psychosocial issues and regular provision of information (e.g., written guides on survivorship) by caregivers should be made a standard of care for AYA cancer survivors.

10.
Head Neck ; 43(4): 1229-1241, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33615608

RESUMO

BACKGROUND: Compared with other malignancies, head and neck cancer (HNC) increases the risk of not returning to work (RTW). METHODS: Within a cross-sectional study, patients with HNC filled out the OncoFunction questionnaire, a version of the International Classification of Functioning Core Sets for HNC. In 231 patients below 65 years of age, associations of sociodemographic, clinical, functional, and psychological factors with employment and participation in rehabilitation program were explored. RESULTS: Unemployed patients reported more swallowing difficulties and speaking problems. Being unemployed was associated with higher levels of depressive and anxiety symptoms, fatigue, and lower global health. Rehabilitation participation was not significantly associated with any of the assessed factors except for smoking. CONCLUSIONS: Unemployed patients with HNC are more burdened than employed patients with HNC regarding clinical, psychological, and functional factors. These differences are more evident later in recovery. Rehabilitation participation was not associated with psychological and functional burden which indicates the need for tailored HNC rehabilitation programs.


Assuntos
Neoplasias de Cabeça e Pescoço , Ansiedade/epidemiologia , Estudos Transversais , Emprego , Humanos , Retorno ao Trabalho
11.
Eur J Cancer Care (Engl) ; 30(3): e13400, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33459435

RESUMO

OBJECTIVES: Fear of progression (FoP) among cancer survivors can adversely affect all areas of life. Existing instruments are too long for implementation in routine care. Therefore, we developed and tested a rapid screener for FoP (FoP-Q-RS). METHODS: Data were derived from a register-based study among cancer survivors. The 12-item short form of the Fear-of-Progression Questionnaire (FoP-Q-SF) served as item-pool. Confirmatory factor analysis (CFA) was applied to determine (a) fit indices including comparative fit index (CFI) and standardised root mean square residual (SRMR) and (b) measures of reliability including composite reliability (CR). Fit indices were compared to the FoP-Q-SF. Sensitivity and specificity were calculated to recommend a cut-off (criterion: GAD-7 score ≥10). RESULTS: One thousand two cancer survivors participated (response rate: 53%). We selected five items for the FoP-Q-RS. CFA indicated acceptable fit (CFI = 0.936; SRMR = 0.048) and reliability (CR = 0.793). Fit indices were better than for the FoP-Q-SF. The cut-off ≥12 showed optimal balance between sensitivity (72%) and specificity (70%), the cut-off ≥10 revealed higher sensitivity (86%) with still tolerable specificity (52%). CONCLUSION: The FoP-Q-RS shows good psychometric properties and may be applied in routine care. Further studies on preferable cut-offs and other populations are needed.


Assuntos
Sobreviventes de Câncer , Progressão da Doença , Medo , Neoplasias , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
12.
Sci Total Environ ; 758: 143581, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33223169

RESUMO

Asgard is a newly proposed archaeal superphylum, which has been suggested to hold the key to decipher the origin of Eukaryotes. However, their ecology remains largely unknown. Here, we conducted a meta-analysis of publicly available Asgard-associated 16S rRNA gene fragments, and found that just three previously proposed clades (Lokiarchaeota, Thorarchaeota, and Asgard clade 4) are widely distributed, whereas the other seven clades (phylum or class level) are restricted to the sediment biosphere. Asgard archaea, especially Loki- and Thorarchaeota, seem to adapt to marine sediments, and water depth (the depth of the sediment below water surface) and salinity might be crucial factors for the proportion of these microorganisms as revealed by multivariate regression analyses. However, the abundance of Asgard archaea exhibited distinct environmental drivers at the clade-level; for instance, the proportion of Asgard clade 4 was higher in less saline environments (salinity <6.35 psu), while higher for Heimdallarchaeota-AAG and Asgard clade 2 in more saline environment (salinity ≥35 psu). Furthermore, co-occurrence analysis allowed us to find a significant non-random association of different Asgard clades with other groups (e.g., Lokiarchaeota with Deltaproteobacteria and Anaerolineae; Odinarchaeota with Bathyarchaeota), suggesting different interaction potentials among these clades. Overall, these findings reveal Asgard archaea as a ubiquitous group worldwide and provide initial insights into their ecological features on a global scale.


Assuntos
Archaea , Eucariotos , Archaea/genética , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S/genética , Salinidade
13.
J Adolesc Young Adult Oncol ; 10(2): 226-233, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32746763

RESUMO

Purpose: Although cancer often impacts work issues in patients, little is known about changes in the employment situation of adolescent and young adult (AYA) cancer survivors. Materials and Methods: We surveyed AYA cancer patients (18-39 years at diagnosis, diagnosis ≤4 years) using as set of validated self-report measures. By using multivariate and regression analyses, we analyzed employment status prediagnosis (in retrospect) and return to work (RTW) rate about 2 years postcancer diagnosis and related predictors. We compared work-related characteristics (occupational position, weekly working hours, and type of employment contract) at both time points. Cancer-related financial distress (European Organization for Research Treatment of Cancer-Quality of Life Questionnaire [EORTC QLQ-C30]) was assessed. Results: A total of 505 AYAs (mean age at diagnosis 29.7 years) completed the questionnaire. After an average of 2 years postcancer diagnosis, 83.4% among those being employed at the time of diagnosis (n = 355) had returned to work, 2.8% were on vocational training, 4.5% were unemployed, 4.2% were disabled due to reduced work capacity, and 5.1% were not employed for other reasons. For 158 of 505 AYAs (31.3%), employment status had changed since diagnosis. Significant changes of work-related characteristics were found for the weekly working hours (Matdiagnosis = 35.8; standard deviation [SD] = 7.4; Mt2 = 34.7; SD = 8.2; p = 0.004). Twenty-four percent of the RTW patients and 68% of patients not RTW reported cancer-related financial distress. Patients with comorbid diseases, having hematological cancer or sarcoma, were less likely to RTW. Conclusion: Most AYAs returned to work in the medium term, often by reducing weekly working hours. Since AYAs state significant cancer-related financial distress, even after RTW, it seems particularly relevant to provide financial support and occupational counseling.

14.
ISME J ; 15(3): 848-861, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33149207

RESUMO

Asgard is a recently discovered archaeal superphylum, closely linked to the emergence of eukaryotes. Among Asgard archaea, Lokiarchaeota are abundant in marine sediments, but their in situ activities are largely unknown except for Candidatus 'Prometheoarchaeum syntrophicum'. Here, we tracked the activity of Lokiarchaeota in incubations with Helgoland mud area sediments (North Sea) by stable isotope probing (SIP) with organic polymers, 13C-labelled inorganic carbon, fermentation intermediates and proteins. Within the active archaea, we detected members of the Lokiarchaeota class Loki-3, which appeared to mixotrophically participate in the degradation of lignin and humic acids while assimilating CO2, or heterotrophically used lactate. In contrast, members of the Lokiarchaeota class Loki-2 utilized protein and inorganic carbon, and degraded bacterial biomass formed in incubations. Metagenomic analysis revealed pathways for lactate degradation, and involvement in aromatic compound degradation in Loki-3, while the less globally distributed Loki-2 instead rely on protein degradation. We conclude that Lokiarchaeotal subgroups vary in their metabolic capabilities despite overlaps in their genomic equipment, and suggest that these subgroups occupy different ecologic niches in marine sediments.


Assuntos
Archaea , Sedimentos Geológicos , Archaea/genética , Metagenoma , Mar do Norte , Filogenia
15.
ISME J ; 15(4): 965-980, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33154547

RESUMO

Elevated dissolved iron concentrations in the methanic zone are typical geochemical signatures of rapidly accumulating marine sediments. These sediments are often characterized by co-burial of iron oxides with recalcitrant aromatic organic matter of terrigenous origin. Thus far, iron oxides are predicted to either impede organic matter degradation, aiding its preservation, or identified to enhance organic carbon oxidation via direct electron transfer. Here, we investigated the effect of various iron oxide phases with differing crystallinity (magnetite, hematite, and lepidocrocite) during microbial degradation of the aromatic model compound benzoate in methanic sediments. In slurry incubations with magnetite or hematite, concurrent iron reduction, and methanogenesis were stimulated during accelerated benzoate degradation with methanogenesis as the dominant electron sink. In contrast, with lepidocrocite, benzoate degradation, and methanogenesis were inhibited. These observations were reproducible in sediment-free enrichments, even after five successive transfers. Genes involved in the complete degradation of benzoate were identified in multiple metagenome assembled genomes. Four previously unknown benzoate degraders of the genera Thermincola (Peptococcaceae, Firmicutes), Dethiobacter (Syntrophomonadaceae, Firmicutes), Deltaproteobacteria bacteria SG8_13 (Desulfosarcinaceae, Deltaproteobacteria), and Melioribacter (Melioribacteraceae, Chlorobi) were identified from the marine sediment-derived enrichments. Scanning electron microscopy (SEM) and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) images showed the ability of microorganisms to colonize and concurrently reduce magnetite likely stimulated by the observed methanogenic benzoate degradation. These findings explain the possible contribution of organoclastic reduction of iron oxides to the elevated dissolved Fe2+ pool typically observed in methanic zones of rapidly accumulating coastal and continental margin sediments.


Assuntos
Sedimentos Geológicos , Ferro , Benzoatos , Compostos Férricos , Hibridização in Situ Fluorescente , Oxirredução , Óxidos
16.
Biochem J ; 478(2): 327-339, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33345277

RESUMO

Long-lived proteins (LLPs) are susceptible to the accumulation of both enzymatic and spontaneous post-translational modifications (PTMs). A prominent PTM observed in LLPs is covalent protein-protein crosslinking. In this study, we examined aged human lenses and found several proteins to be crosslinked at Glu and Gln residues. This new covalent bond involves the amino group of Lys or an α-amino group. A number of these crosslinks were found in intermediate filament proteins. Such crosslinks could be reproduced experimentally by incubation of Glu- or Gln-containing peptides and their formation was consistent with an amino group attacking a glutarimide intermediate. These findings show that both Gln and Glu residues can act as sites for spontaneous covalent crosslinking in LLPs and they provide a mechanistic explanation for an otherwise puzzling observation, that a major fraction of Aß in the human brain is crosslinked via Glu 22 and the N-terminal amino group.


Assuntos
Proteínas do Olho/química , Proteínas do Olho/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Cristalino/química , Catarata/metabolismo , Ácido Glutâmico/química , Glutamina/química , Humanos , Cristalino/metabolismo , Lisina/química , Lisina/metabolismo , Pessoa de Meia-Idade , Piperidonas/química , Domínios e Motivos de Interação entre Proteínas/fisiologia , Processamento de Proteína Pós-Traducional , Adulto Jovem
17.
J Orthop Surg (Hong Kong) ; 29(1): 2309499020968296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33377405

RESUMO

PURPOSE: C-reactive protein (CRP) and white blood cell (WBC) count are routine blood chemistry parameters in monitoring infection. Little is known about the natural history of their serum levels in conservative and operative spondylodiscitis treatment. METHODS: Pre- and postoperative serum levels of CRP and WBC count in 145 patients with spondylodiscitis were retrospectively assessed. One hundred and four patients were treated by debridement, spondylodesis, and an antibiotic regime, 41 only with a brace and antibiotics. The results of the surgical group were compared to 156 patients fused for degenerative disc disease (DDD). RESULTS: Surgery had a significant effect on peak postoperative CRP levels. In surgically managed patients, CRP peaked at 2-3 days after surgery (spondylodiscitis: pre-OP: 90 mg/dl vs. post-OP days 2-3: 146 mg/dl; DDD: 9 mg/dl vs. 141 mg/dl; p < 0.001), followed by a sharp decline. Although values were higher for spondylodiscitis patients, dynamics of CRP values were similar in both groups. Nonoperative treatment showed a slower decline. Surgically managed spondylodiscitis showed a higher success rate in identifying bacteria. Specific antibiotic treatment led to a more predictable decline of CRP values. WBC did not show an interpretable profile. CONCLUSION: CRP is a predictable serum parameter in patients with spondylodiscitis. WBC count is unspecific. Initial CRP increase after surgery is of little value in monitoring infection. A preoperative CRP value, and control once during the first 3 days after surgery is sufficient. Closer monitoring should then be continued. Should a decline not be observed, therapy needs to be scrutinized, antibiotic treatment reassessed, and concomitant infection contemplated.


Assuntos
Proteína C-Reativa/análise , Discite/sangue , Contagem de Leucócitos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Discite/tratamento farmacológico , Discite/microbiologia , Discite/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/métodos , Adulto Jovem
18.
J Transl Med ; 18(1): 371, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993793

RESUMO

BACKGROUND: The non-classical human leukocyte antigen (HLA)-G is a strong immunomodulatory molecule. Under physiological conditions, HLA-G induces immunological tolerance in immune privileged tissues, while under pathophysiological situations it contributes to immune escape mechanisms. Therefore, HLA-G could act as a potential immune checkpoint for future anti-cancer immunotherapies. Recent data suggest an aberrant expression of the cAMP response element binding protein (CREB) in clear cell renal cell carcinoma (ccRCC), which is correlated with tumor grade and stage. Furthermore, preliminary reports demonstrated a connection of CREB as a control variable of HLA-G transcription due to CREB binding sites in the HLA-G promoter region. This study investigates the interaction between CREB and HLA-G in different renal cell carcinoma (RCC) subtypes and its correlation to clinical parameters. METHODS: The direct interaction of CREB with the HLA-G promoter was investigated by chromatin immunoprecipitation in RCC cell systems. Furthermore, the expression of CREB and HLA-G was determined by immunohistochemistry using a tissue microarray (TMA) consisting of 453 RCC samples of distinct subtypes. Staining results were assessed for correlations to clinical parameters as well as to the composition of the immune cell infiltrate. RESULTS: There exists a distinct expression pattern of HLA-G and CREB in the three main RCC subtypes. HLA-G and CREB expression were the lowest in chromophobe RCC lesions. However, the clinical relevance of CREB and HLA-G expression differed. Unlike HLA-G, high levels of CREB expression were positively associated to the overall survival of RCC patients. A slightly, but significantly elevated number of tumor infiltrating regulatory T cells was observed in tumors of high CREB expression. Whether this small increase is of clinical relevance has to be further investigated. CONCLUSIONS: An interaction of CREB with the HLA-G promoter could be validated in RCC cell lines. Thus, for the first time the expression of CREB and its interaction with the HLA-G in human RCCs has been shown, which might be of clinical relevance.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Antígenos HLA-G/genética , Humanos , Neoplasias Renais/genética , Regiões Promotoras Genéticas/genética
19.
Oncoimmunology ; 9(1): 1774323, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32923135

RESUMO

Tumor escape is often associated with abnormalities in the surface expression of the human leukocyte antigen class I (HLA-I) antigens thereby limiting CD8+ cytotoxic T cell responses. This impaired HLA-I surface expression can be mediated by deficient expression of components of the antigen processing and presentation machinery (APM) due to epigenetic, transcriptional and/or post-transcriptional processes. Since a discordant mRNA and protein expression pattern of APM components including the peptide transporter associated with antigen processing 1 (TAP1) has been frequently described in tumors of distinct origin, a post-transcriptional control of APM components caused by microRNAs (miR) was suggested. Using an in silico approach, miR-200a-5p has been identified as a candidate miR binding to the 3' untranslated region (UTR) of TAP1. Luciferase reporter assays demonstrated a specific binding of miR-200a-5p to the TAP1 3'-UTR. Furthermore, the miR-200a-5p expression is inversely correlated with the TAP1 protein expression in HEK293T cells and in a panel of melanoma cell lines as well as in primary melanoma lesions. High levels of miR-200a-5p expression were associated with a shorter overall survival of melanoma patients. Overexpression of miR-200a-5p reduced TAP1 levels, which was accompanied by a decreased HLA-I surface expression and an enhanced NK cell sensitivity of melanoma cells. These data show for the first time a miR-mediated control of the peptide transporter subunit TAP1 in melanoma thereby leading to a reduced HLA-I surface expression accompanied by an altered immune recognition and reduced patients' survival. Abbreviations: Ab: antibody; ACTB: ß-actin; APM: antigen processing and presentation machinery; ATCC: American tissue culture collection; ß2-m: ß2-microglobulin; BSA: bovine serum albumin; CTL: cytotoxic T lymphocyte; FCS: fetal calf serum; FFL: firefly luciferase; FFPE: formalin-fixed paraffin-embedded; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HC: heavy chain; HLA: human leukocyte antigen; HLA-I: HLA class I; HRP: horseradish peroxidase; IFN: interferon; im-miR: immune modulatory miRNA; LMP: low molecular weight protein; luc: luciferase; MFI: mean fluorescence intensity; MHC: major histocompatibility complex; miR: microRNA; NC: negative control; NK: natural killer; NSCLC: non-small cell lung carcinoma; OS: overall survival; PBMC: peripheral blood mononuclear cells; RBP: RNA-binding proteins; RL: Renilla; RLU: relative light units; TAP: transporter associated with antigen processing; tpn: tapasin; UTR: untranslated region.

20.
J Clin Med ; 9(9)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825219

RESUMO

The underlying molecular mechanisms of the aberrant expression of components of the HLA class I antigen processing and presentation machinery (APM) in tumors leading to evasion from T cell-mediated immune surveillance could be due to posttranscriptional regulation mediated by microRNAs (miRs). So far, some miRs controlling the expression of different APM components have been identified. Using in silico analysis and an miR enrichment protocol in combination with small RNA sequencing, miR-26b-5p and miR-21-3p were postulated to target the 3' untranslated region (UTR) of the peptide transporter TAP1, which was confirmed by high free binding energy and dual luciferase reporter assays. Overexpression of miR-26b-5p and miR-21-3p in melanoma cells downregulated the TAP1 protein and reduced expression of HLA class I cell surface antigens, which could be reverted by miR inhibitors. Moreover, miR-26b-5p overexpression induced a decreased T cell recognition. Furthermore, an inverse expression of miR-26b-5p and miR-21-3p with TAP1 was found in primary melanoma lesions, which was linked with the frequency of CD8+ T cell infiltration. Thus, miR-26-5p and miR-21-3p are involved in the HLA class I-mediated immune escape and might be used as biomarkers or therapeutic targets for HLA class Ilow melanoma cells.

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