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1.
Int J Mol Sci ; 25(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38255998

RESUMO

Cancer is defined as a group of diseases characterized by abnormal cell growth, expansion, and progression with metastasis. Various signaling pathways are involved in its development. Malignant tumors exhibit a high morbidity and mortality. Cancer research increased our knowledge about some of the underlying mechanisms, but to this day, our understanding of this disease is unclear. High throughput omics technology and bioinformatics were successful in detecting some of the unknown cancer mechanisms. However, novel groundbreaking research and ideas are necessary. A stay in orbit causes biochemical and molecular biological changes in human cancer cells which are first, and above all, due to microgravity (µg). The µg-environment provides conditions that are not reachable on Earth, which allow researchers to focus on signaling pathways controlling cell growth and metastasis. Cancer research in space already demonstrated how cancer cell-exposure to µg influenced several biological processes being involved in cancer. This novel approach has the potential to fight cancer and to develop future cancer strategies. Space research has been shown to impact biological processes in cancer cells like proliferation, apoptosis, cell survival, adhesion, migration, the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors, among others. This concise review focuses on publications related to genetic, transcriptional, epigenetic, proteomic, and metabolomic studies on tumor cells exposed to real space conditions or to simulated µg using simulation devices. We discuss all omics studies investigating different tumor cell types from the brain and hematological system, sarcomas, as well as thyroid, prostate, breast, gynecologic, gastrointestinal, and lung cancers, in order to gain new and innovative ideas for understanding the basic biology of cancer.


Assuntos
Neoplasias Pulmonares , Sarcoma , Ausência de Peso , Humanos , Masculino , Feminino , Proteômica , Citoesqueleto
2.
Front Immunol ; 14: 1223264, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575263

RESUMO

Introduction: Lipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far. Methods: SAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies. Results: Lipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype. Conclusions: In summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.


Assuntos
Lipedema , Humanos , Lipedema/metabolismo , Lipedema/patologia , Gordura Subcutânea/patologia , Adipócitos/metabolismo , Inflamação/metabolismo , Fibrose , Hipertrofia/metabolismo
3.
Cells ; 12(7)2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-37048115

RESUMO

Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism's ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.


Assuntos
MicroRNAs , Voo Espacial , Ausência de Peso , Animais , Humanos , Regulação da Expressão Gênica , Diferenciação Celular , MicroRNAs/genética
4.
Int J Mol Sci ; 24(3)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36768635

RESUMO

This manuscript investigates cabozantinib, vandetanib, pralsetinib, and selpercatinib, four tyrosine kinase inhibitors (TKIs), which are used to treat advanced and/or metastatic medullary thyroid cancer (MTC). Data on efficacy and safety are presented with the main focus on treatment-related hypertension, a well-known adverse effect (AE) of these TKIs. Taken together, TKI-induced hypertension is rarely a dose-limiting side effect. However, with increasing survival times of patients under treatment, hypertension-associated complications can be expected to be on the rise without proper medication.


Assuntos
Carcinoma Neuroendócrino , Hipertensão , Neoplasias da Glândula Tireoide , Humanos , Inibidores de Proteínas Quinases/efeitos adversos , Piperidinas/efeitos adversos , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Hipertensão/tratamento farmacológico , Hipertensão/induzido quimicamente
5.
J Reconstr Microsurg ; 39(8): 601-615, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36693394

RESUMO

BACKGROUND: Adequate treatment of deep sternal wound infections (DSWIs) after open thoracic surgery still presents a major challenge. This study retrospectively analyzes the results of a single center's 12-year experience in treating DSWI, with special emphasis on free flap reconstruction. METHODS: In this single-center, retrospective study, all patients admitted with the diagnosis of DSWI after open thoracic surgery between 2009 and 2020 were included. A comparative analysis was performed between: (1) pedicled versus free flaps, (2) the center's two workhorse flaps-the pedicled latissimus dorsi (pLD) versus free anterolateral thigh (fALT) flaps, as well as (3) myocutaneous (MC) versus fasciocutaneous (FC) flaps. Primary endpoints were length of hospital stay (LOS) after reconstruction and in-hospital mortality. RESULTS: Of a total of 165 patients included, 152 underwent DSWI defect reconstruction with a total of 12 different reconstruction methods. Although the defect size was larger in patients who underwent free flap coverage, and the risk profile in the fALT and FC flap groups was higher, the LOS after reconstruction (in days) did not differ significantly between the groups (pedicled vs. free flaps: 23 vs. 28, p > 0.05; pLD vs. fALT: 24.5 vs. 26, p > 0.05; MC vs. FC flaps: 23 vs. 26, p > 0.05). Also, no significant differences were found in terms of in-hospital mortality when comparing the groups (pedicled vs. free flaps: 11.2 vs. 17.4%, p > 0.05; pLD vs. fALT: 11.5 vs. 12.5%, p > 0.05; MC vs. FC flaps: 12.9 vs. 12.5%, p > 0.05). CONCLUSION: With proper patient selection, free tissue transfer is a valuable alternative in the treatment of sternal dehiscence after a DSWI. Furthermore, our data demonstrate that MC flaps are not necessarily superior to FC flaps in the reconstruction of sternal osteomyelitis defects.


Assuntos
Retalhos de Tecido Biológico , Osteomielite , Procedimentos de Cirurgia Plástica , Humanos , Esternotomia/efeitos adversos , Esternotomia/métodos , Retalhos de Tecido Biológico/cirurgia , Estudos Retrospectivos , Osteomielite/cirurgia
6.
Int J Low Extrem Wounds ; 22(3): 524-530, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34180745

RESUMO

Autologous fat transfer may offer a simple and effective treatment option for chronic wound patients, delivering adipose-derived stem cells, with potent regenerative attributes. Nevertheless, the clinical benefit has not yet been sufficiently demonstrated. A total of 39 wound patients were treated with autologous fat transfer (AFT) and matched with a control group, according to the identified confounding variables "gender" and "method of defect closure." All data were acquired retrospectively. Primary outcome was "wound closure" and "reduction of wound size."After a follow-up of 48 weeks, there was no significant difference in primary outcome (wound closure P = .54) between both groups. The relative wound reduction after fat transfer was 69.9% ± 42.7% compared to 53.4% ± 106.8% in the control group (P = .91). Subgroup analysis of all patients, healed by secondary intention, revealed an increased wound size reduction (P = .03) and wound closure rate (P = .20) in the case group after 12 weeks. No adverse events were recorded. Fat grafting can reduce the wound size if left to secondary healing and may be considered individually for reconstructive purposes. A repeated application of autologous fat might be beneficial due to a temporary effect.


Assuntos
Tecido Adiposo , Procedimentos de Cirurgia Plástica , Cicatrização , Humanos , Extremidade Inferior/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Tecido Adiposo/transplante
7.
Int J Mol Sci ; 23(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36555738

RESUMO

Breast cancer is the leading cause of cancer incidence worldwide and among the five leading causes of cancer mortality. Despite major improvements in early detection and new treatment approaches, the need for better outcomes and quality of life for patients is still high. Extracellular vesicles play an important role in tumor biology, as they are able to transfer information between cells of different origins and locations. Their potential value as biomarkers or for targeted tumor therapy is apparent. In this study, we analyzed the supernatants of MCF-7 breast cancer cells, which were harvested following 5 or 10 days of simulated microgravity on a Random Positioning Machine (RPM). The primary results showed a substantial increase in released vesicles following incubation under simulated microgravity at both time points. The distribution of subpopulations regarding their surface protein expression is also altered; the minimal changes between the time points hint at an early adaption. This is the first step in gaining further insight into the mechanisms of tumor progression, metastasis, the education of the tumor microenvironments, and preparation of the metastatic niche. Additionally, this may lighten up the processes of the rapid cellular adaptions in the organisms of space travelers during spaceflights.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Voo Espacial , Ausência de Peso , Humanos , Feminino , Qualidade de Vida , Simulação de Ausência de Peso , Microambiente Tumoral
8.
Int J Mol Sci ; 23(15)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35955775

RESUMO

Space travelers are exposed to microgravity (µg), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on treadmills or resistive apparatus. The objective of this systematic review is to provide a current overview of the state of the art of the field of bone loss in space and possible treatment options thereof. A total of 482 unique studies were searched through PubMed and Scopus, and 37 studies met the eligibility criteria. The studies showed that, despite increased bone formation during µg, the increase in bone resorption was greater. Different types of exercise and pharmacological treatments with bisphosphonates, RANKL antibody (receptor activator of nuclear factor κß ligand antibody), proteasome inhibitor, pan-caspase inhibitor, and interleukin-6 monoclonal antibody decrease bone resorption and promote bone formation. Additionally, recombinant irisin, cell-free fat extract, cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes, and strontium-containing hydroxyapatite nanoparticles also show some positive effects on bone loss.


Assuntos
Doenças Ósseas Metabólicas , Reabsorção Óssea , Voo Espacial , Ausência de Peso , Densidade Óssea , Osso e Ossos , Humanos , Receptor Ativador de Fator Nuclear kappa-B , Ausência de Peso/efeitos adversos
9.
Int J Mol Sci ; 23(14)2022 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-35887223

RESUMO

The high mortality in men with metastatic prostate cancer (PC) establishes the need for diagnostic optimization by new biomarkers. Mindful of the effect of real microgravity on metabolic pathways of carcinogenesis, we attended a parabolic flight (PF) mission to perform an experiment with the PC cell line PC-3, and submitted the resulting RNA to next generation sequencing (NGS) and quantitative real-time PCR (qPCR). After the first parabola, alterations of the F-actin cytoskeleton-like stress fibers and pseudopodia are visible. Moreover, numerous significant transcriptional changes are evident. We were able to identify a network of relevant PC cytokines and chemokines showing differential expression due to gravitational changes, particularly during the early flight phases. Together with differentially expressed regulatory lncRNAs and micro RNAs, we present a portfolio of 298 potential biomarkers. Via qPCR we identified IL6 and PIK3CB to be sensitive to vibration effects and hypergravity, respectively. Per NGS we detected five upregulated cytokines (CCL2, CXCL1, IL6, CXCL2, CCL20), one zink finger protein (TNFAIP3) and one glycoprotein (ICAM1) related to c-REL signaling and thus relevant for carcinogenesis as well as inflammatory aspects. We found regulated miR-221 and the co-localized lncRNA MIR222HG induced by PF maneuvers. miR-221 is related to the PC-3 growth rate and MIR222HG is a known risk factor for glioma susceptibility. These findings in real microgravity may further improve our understanding of PC and contribute to the development of new diagnostic tools.


Assuntos
MicroRNAs , Neoplasias da Próstata , Voo Espacial , Ausência de Peso , Carcinogênese , Citocinas/genética , Humanos , Interleucina-6 , Masculino , MicroRNAs/genética , Neoplasias da Próstata/genética
10.
Int J Mol Sci ; 23(6)2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35328492

RESUMO

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.


Assuntos
Neoplasias , Ausência de Peso , Humanos , Masculino , Organoides , Esferoides Celulares , Simulação de Ausência de Peso
11.
Front Cell Dev Biol ; 10: 841017, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252204

RESUMO

Prostate cancer metastasis has an enormous impact on the mortality of cancer patients. Factors involved in cancer progression and metastasis are known to be key players in microgravity (µg)-driven three-dimensional (3D) cancer spheroid formation. We investigated PC-3 prostate cancer cells for 30 min, 2, 4 and 24 h on the random positioning machine (RPM), a device simulating µg on Earth. After a 24 h RPM-exposure, the cells could be divided into two groups: one grew as 3D multicellular spheroids (MCS), the other one as adherent monolayer (AD). No signs of apoptosis were visible. Among others, we focused on cytokines involved in the events of metastasis and MCS formation. After 24 h of exposure, in the MCS group we measured an increase in ACTB, MSN, COL1A1, LAMA3, FN1, TIMP1, FLT1, EGFR1, IL1A, IL6, CXCL8, and HIF1A mRNA expression, and in the AD group an elevation of LAMA3, COL1A1, FN1, MMP9, VEGFA, IL6, and CXCL8 mRNAs compared to samples subjected to 1 g conditions. Significant downregulations in AD cells were detected in the mRNA levels of TUBB, KRT8, IL1B, IL7, PIK3CB, AKT1 and MTOR after 24 h. The release of collagen-1α1 and fibronectin protein in the supernatant was decreased, whereas the secretion of IL-6 was elevated in 24 h RPM samples. The secretion of IL-1α, IL-1ß, IL-7, IL-2, IL-8, IL-17, TNF-α, laminin, MMP-2, TIMP-1, osteopontin and EGF was not significantly altered after 24 h compared to 1 g conditions. The release of soluble factors was significantly reduced after 2 h (IL-1α, IL-2, IL-7, IL-8, IL-17, TNF-α, collagen-1α1, MMP-2, osteopontin) and elevated after 4 h (IL-1ß, IL-2, IL-6, IL-7, IL-8, TNF-α, laminin) in RPM samples. Taken together, simulated µg induced 3D growth of PC-3 cancer cells combined with a differential expression of the cytokines IL-1α, IL-1ß, IL-6 and IL-8, supporting their involvement in growth and progression of prostate cancer cells.

12.
Plast Reconstr Surg ; 149(3): 529e-541e, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35089257

RESUMO

BACKGROUND: Despite an increasing demand for surgical treatment of lipedema, the evidence for liposuction is still limited. Little is known about the influence of disease stage, patient age, body mass index, or existing comorbidities on clinical outcomes. It was hypothesized that younger patients with lower body mass index and stage would report better results. METHODS: This retrospective, single-center, noncomparative study included lipedema patients who underwent liposuction between July of 2009 and July of 2019. After a minimum of 6 months since the last surgery, all patients completed a disease-related questionnaire. The primary endpoint was the need for complex decongestive therapy based on a composite score. Secondary endpoints were the severity of disease-related complaints measured on a visual analogue scale. RESULTS: One hundred six patients underwent a total of 298 large-volume liposuctions (mean lipoaspirate, 6355 ± 2797 ml). After a median follow-up of 20 months, a median complex decongestive therapy score reduction of 37.5 percent (interquartile range, 0 to 88.8 percent; p < 0.0001) was observed. An improvement in lipedema-associated symptoms was also observed (p < 0.0001). The percentage reduction in complex decongestive therapy scores was greater in patients with a body mass index less than or equal to 35 kg/m2 (p < 0.0001) and in stage I and II patients (p = 0.0019). CONCLUSION: Liposuction reduces the severity of symptoms and the need for conservative treatment in lipedema patients, especially if it is performed in patients with a body mass index below 35 kg/m2 at an early stage of the disease. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Lipectomia/métodos , Lipedema/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Lipedema/diagnóstico , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Medidas de Resultados Relatados pelo Paciente , Estudos Retrospectivos
13.
Int J Mol Sci ; 22(23)2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34884646

RESUMO

As much as space travel and exploration have been a goal since humankind looked up to the stars, the challenges coming with it are manifold and difficult to overcome. Therefore, researching the changes the human organism undergoes following exposure to weightlessness, on a cellular or a physiological level, is imperative to reach the goal of exploring space and new planets. Building on the results of our CellBox-1 experiment, where thyroid cancer cells were flown to the International Space Station, we are now taking advantage of the newest technological opportunities to gain more insight into the changes in cell-cell communication of these cells. Analyzing the exosomal microRNA composition after several days of microgravity might elucidate some of the proteomic changes we have reported earlier. An array scan of a total of 754 miRNA targets revealed more than 100 differentially expressed miRNAs in our samples, many of which have been implicated in thyroid disease in other studies.


Assuntos
Exossomos/genética , Meio Ambiente Extraterreno , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/genética , Ausência de Peso , Linhagem Celular Tumoral , Exossomos/metabolismo , Humanos , MicroRNAs/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
14.
Int J Mol Sci ; 22(22)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34830100

RESUMO

Differentiated thyroid cancer (DTC) usually has a good prognosis when treated conventionally with thyroidectomy, radioactive iodine (RAI) and thyroid-stimulating hormone suppression, but some tumors develop a resistance to RAI therapy, requiring alternative treatments. Sorafenib, lenvatinib and cabozantinib are multikinase inhibitors (MKIs) approved for the treatment of RAI-refractory DTC. The drugs have been shown to improve progression-free survival (PFS) and overall survival (OS) via the inhibition of different receptor tyrosine kinases (RTKs) that are involved in tumorigenesis and angiogenesis. Both sorafenib and lenvatinib have been approved irrespective of the line of therapy for the treatment of RAI-refractory DTC, whereas cabozantinib has only been approved as a second-line treatment. Adverse effects (AEs) such as hypertension are often seen with MKI treatment, but are generally well manageable. In this review, current clinical studies will be discussed, and the toxicity and safety of sorafenib, lenvatinib and cabozantinib treatment will be evaluated, with a focus on AE hypertension and its treatment options. In short, treatment-emergent hypertension (TE-HTN) occurs with all three drugs, but is usually well manageable and leads only to a few dose modifications or even discontinuations. This is emphasized by the fact that lenvatinib is widely considered the first-line drug of choice, despite its higher rate of TE-HTN.


Assuntos
Antineoplásicos/uso terapêutico , Hipertensão , Radioisótopos do Iodo/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide , Humanos , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipertensão/terapia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/fisiopatologia
15.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445479

RESUMO

A spaceflight to the International Space Station (ISS) is a dream of many researchers. We had the chance to investigate the effect of real microgravity (CellBox-2 Space mission) on the transcriptome and proteome of FTC-133 human follicular thyroid cancer cells (TCC). The cells had been sent to the ISS by a Falcon 9 rocket of SpaceX CRS-13 from Cape Canaveral (United States) and cultured in six automated hardware units on the ISS before they were fixed and returned to Earth. Multicellular spheroids (MCS) were detectable in all spaceflight hardware units. The VCL, PXN, ITGB1, RELA, ERK1 and ERK2 mRNA levels were significantly downregulated after 5 days in space in adherently growing cells (AD) and MCS compared with ground controls (1g), whereas the MIK67 and SRC mRNA levels were both suppressed in MCS. By contrast, the ICAM1, COL1A1 and IL6 mRNA levels were significantly upregulated in AD cells compared with 1g and MCS. The protein secretion measured by multianalyte profiling technology and enzyme-linked immunosorbent assay (AngiogenesisMAP®, extracellular matrix proteins) was not significantly altered, with the exception of elevated angiopoietin 2. TCC in space formed MCS, and the response to microgravity was mainly anti-proliferative. We identified ERK/RELA as a major microgravity regulatory pathway.


Assuntos
Adenocarcinoma Folicular/patologia , Biomarcadores Tumorais/metabolismo , Proteoma/metabolismo , Esferoides Celulares/patologia , Neoplasias da Glândula Tireoide/patologia , Transcriptoma , Ausência de Peso , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/metabolismo , Biomarcadores Tumorais/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteoma/análise , Voo Espacial , Esferoides Celulares/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas
16.
Front Bioeng Biotechnol ; 9: 679650, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222218

RESUMO

Functioning as the outermost self-renewing protective layer of the human organism, skin protects against a multitude of harmful biological and physical stimuli. Consisting of ectodermal, mesenchymal, and neural crest-derived cell lineages, tissue homeostasis, and signal transduction are finely tuned through the interplay of various pathways. A health problem of astronauts in space is skin deterioration. Until today, wound healing has not been considered as a severe health concern for crew members. This can change with deep space exploration missions and commercial spaceflights together with space tourism. Albeit the molecular process of wound healing is not fully elucidated yet, there have been established significant conceptual gains and new scientific methods. Apoptosis, e.g., programmed cell death, enables orchestrated development and cell removal in wounded or infected tissue. Experimental designs utilizing microgravity allow new insights into the role of apoptosis in wound healing. Furthermore, impaired wound healing in unloading conditions would depict a significant challenge in human-crewed exploration space missions. In this review, we provide an overview of alterations in the behavior of cutaneous cell lineages under microgravity in regard to the impact of apoptosis in wound healing. We discuss the current knowledge about wound healing in space and simulated microgravity with respect to apoptosis and available therapeutic strategies.

17.
Front Cell Dev Biol ; 9: 672098, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277614

RESUMO

In this study, we evaluated changes in focal adhesions (FAs) in two types of breast cancer cell (BCC) lines (differentiated MCF-7 and the triple-negative MDA-MB-231 cell line) exposed to simulated microgravity (s-µg) created by a random positioning machine (RPM) for 24 h. After exposure, the BCC changed their growth behavior and exhibited two phenotypes in RPM samples: one portion of the cells grew as a normal two-dimensional monolayer [adherent (AD) BCC], while the other portion formed three-dimensional (3D) multicellular spheroids (MCS). After 1 h and 30 min (MDA-MB-231) and 1 h 40 min (MCF-7), the MCS adhered completely to the slide flask bottom. After 2 h, MDA-MB-231 MCS cells started to migrate, and after 6 h, a large number of the cells had left the MCS and continued to grow in a scattered pattern, whereas MCF-7 cells were growing as a confluent monolayer after 6 h and 24 h. We investigated the genes associated with the cytoskeleton, the extracellular matrix and FAs. ACTB, TUBB, FN1, FAK1, and PXN gene expression patterns were not significantly changed in MDA-MB-231 cells, but we observed a down-regulation of LAMA3, ITGB1 mRNAs in AD cells and of ITGB1, TLN1 and VCL mRNAs in MDA-MB-231 MCS. RPM-exposed MCF-7 cells revealed a down-regulation in the gene expression of FAK1, PXN, TLN1, VCL and CDH1 in AD cells and PXN, TLN and CDH1 in MCS. An interaction analysis of the examined genes involved in 3D growth and adhesion indicated a central role of fibronectin, vinculin, and E-cadherin. Live cell imaging of eGFP-vinculin in MCF-7 cells confirmed these findings. ß-catenin-transfected MCF-7 cells revealed a nuclear expression in 1g and RPM-AD cells. The target genes BCL9, MYC and JUN of the Wnt/ß-catenin signaling pathway were differentially expressed in RPM-exposed MCF-7 cells. These findings suggest that vinculin and ß-catenin are key mediators of BCC to form MCS during 24 h of RPM-exposure.

18.
Physiol Rep ; 9(11): e14800, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34121359

RESUMO

The objective of this review is to give an overview of the pathophysiological effects of the Coronavirus Disease 2019 (COVID-19) in relation to hypertension (HT), with a focus on the Renin-Angiotensin-Aldosterone System (RAAS) and the MAS receptor. HT is a multifactorial disease and a public health burden, as it is a risk factor for diseases like stroke, coronary artery disease, and heart failure, leading to 10.4 million deaths yearly. Blood pressure is regulated by the RAAS. The system consists of two counter-regulatory axes: ACE/ANG-II/AT1 R and ACE2/ANG-(1-7)/MAS. The main regulatory protein in balancing the RAAS is angiotensin-converting enzyme 2 (ACE2). The protein also functions as the main mediator of endocytosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. SARS-CoV-2 is the cause of COVID-19 and has caused a worldwide pandemic; however, the treatment and prophylaxis of COVID-19 are limited. Several drugs and vaccines are currently being tested in clinical trials with a few already approved by EMA and FDA. HT is a major risk factor regarding the severity and fatality of COVID-19, and the RAAS plays an important role in COVID-19 infection since SARS-CoV-2 can lead to a dysregulation of the system by reducing the ACE2 expression. The exact mechanisms of HT in relation to COVID-19 remain uncertain, and more research is needed for further elucidation.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/fisiopatologia , Hipertensão/virologia , Sistema Renina-Angiotensina/fisiologia , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Hipertensão/fisiopatologia , Pandemias , Fatores de Risco , SARS-CoV-2/isolamento & purificação
19.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669062

RESUMO

Obstructive sleep apnea (OSA) is a common disease, with approximately 3-7% of men and 2-5% of women worldwide suffering from symptomatic OSA. If OSA is left untreated, hypoxia, microarousals and increased chemoreceptor stimulation can lead to complications like hypertension (HT). Continuous positive airway pressure (CPAP) is the most common treatment for OSA, and it works by generating airway patency, which will counteract the apnea or hypopnea. More than one billion people in the world suffer from HT, and the usual treatment is pharmacological with antihypertensive medication (AHM). The focus of this review will be to investigate whether the CPAP therapy for OSA affects HT.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Hipertensão/complicações , Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Apneia Obstrutiva do Sono/complicações
20.
Int J Mol Sci ; 22(4)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33669943

RESUMO

Space travel has always been the man's ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in cell growth, gene, and protein expression have been described in different models on Earth and in space. Extracellular vesicles, and in particular exosomes, are important cell-cell communicators, being secreted from almost all the cells and therefore, are a perfect target to further investigate the underlying reasons of the organism's adaptations to microgravity. Here, we studied supernatants harvested from the CellBox-1 experiment, which featured human thyroid cancer cells flown to the International Space Station during the SpaceX CRS-3 cargo mission. The initial results show differences in the number of secreted exosomes, as well as in the distribution of subpopulations in regards to their surface protein expression. Notably, alteration of their population regarding the tetraspanin surface expression was observed. This is a promising step into a new area of microgravity research and will potentially lead to the discovery of new biomarkers and pathways of cellular cross-talk.


Assuntos
Exossomos/metabolismo , Voo Espacial , Neoplasias da Glândula Tireoide/metabolismo , Ausência de Peso , Antígenos CD/metabolismo , Linhagem Celular Tumoral , Fluorescência , Humanos , Interferometria , Tamanho da Partícula
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