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Natural killer (NK) cells hold promise in cancer treatment due to their ability to spontaneously lyse cancer cells. For clinical use, high quantities of pure, functional NK cells are necessary. Combining adherence-based isolation with specialized media showed the unreliability of the isolation method, but demonstrated the superiority of the NK MACS® medium, particularly in suboptimal conditions. Neither human pooled serum, fetal calf serum (FCS), human platelet lysate, nor chemically defined serum replacement could substitute human AB serum. Interleukin (IL-)2, IL-15, IL-21, and combined CD2/NKp46 stimulation were assessed. IL-21 and CD2/NKp46 stimulation increased cytotoxicity, but reduced NK cell proliferation. IL-15 stimulation alone achieved the highest proliferation, but the more affordable IL-2 performed similarly. The RosetteSep™ human NK cell enrichment kit was effective for isolation, but the presence of peripheral blood mononuclear cells (PBMCs) in the culture enhanced NK cell proliferation, despite similar expression levels of CD16, NKp46, NKG2D, and ICAM-1. In line with this, purified NK cells cultured in NK MACS® medium with human AB serum and IL-2 demonstrated high cytotoxicity against primary glioblastoma stem cells.
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Proliferação de Células , Meios de Cultura , Células Matadoras Naturais , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Técnicas de Cultura de Células/métodos , Interleucina-2/metabolismo , Citotoxicidade Imunológica , Interleucina-15/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/citologia , Células-Tronco Neoplásicas/metabolismo , Glioblastoma/imunologia , Glioblastoma/patologia , Separação Celular/métodosRESUMO
(1) Background: Osteoarthritis (OA) is the most common joint disease in the world. It is chronic, systemic, progressive and disabling. Orthobiologics have the potential to positively alter the course of this disease. Therefore, the aim of this study is to evaluate the efficacy of SVF/ACP in the treatment of advanced osteoarthritis of the knee in an unfiltered patient population. We hypothesize that this therapy can improve the symptoms associated with osteoarthritis of the knee. We also hypothesize that there are patient-related factors that influence the efficacy of therapy. (2) Methods: Two hundred and thirteen patients with moderate to severe OA of the knee and SVF/ACP injection were recruited for this study. Patients were excluded if they did not provide informed consent or were not receiving SVF/ACP therapy. Pain, function, symptoms and quality of life were assessed using standardized scores (KOOS, WOMAC) before and after treatment. (3) Results: The VAS pain score was significantly reduced by at least 30% (p < 0.001). Knee function, as measured by the KOOS daily activity and sport scores, showed significant increases of 21% and 45%, respectively, at 6 months (p < 0.04). (4) Conclusions: Treatment of knee OA with SVF/ACP injection positively modifies the disease by significantly reducing pain and improving function.
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Cardiovascular diseases (CVDs) are often linked to ageing and are the major cause of death worldwide. The declined proliferation of adult stem cells in the heart often impedes its regenerative potential. Thus, an investigation of the proliferative potential of adult human cardiac stem cells (hCSCs) might be of great interest for improving cell-based treatments of cardiovascular diseases. The application of human blood serum was already shown to enhance hCSC proliferation and reduce senescence. Here, the underlying signalling pathways of serum-mediated hCSC proliferation were studied. We are the first to demonstrate the involvement of the transcription factor NF-κB in the serum-mediated proliferative response of hCSCs by utilizing the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). RNA-Sequencing (RNA-Seq) revealed ATF6B, COX5B, and TNFRSF14 as potential targets of NF-κB that are involved in serum-induced hCSC proliferation.
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Células-Tronco Adultas , Doenças Cardiovasculares , Adulto , Humanos , NF-kappa B , Soro , EnvelhecimentoRESUMO
Implant-related infections or inflammation are one of the main reasons for implant failure. Therefore, different concepts for prevention are needed, which strongly promote the development and validation of improved material designs. Besides modifying the implant surface by, for example, antibacterial coatings (also implying drugs) for deterring or eliminating harmful bacteria, it is a highly promising strategy to prevent such implant infections by antibacterial substrate materials. In this work, the inherent antibacterial behavior of the as-cast biodegradable Fe69Mn30C1 (FeMnC) alloy against Gram-negative Pseudomonas aeruginosa and Escherichia coli as well as Gram-positive Staphylococcus aureus is presented for the first time in comparison to the clinically applied, corrosion-resistant AISI 316L stainless steel. In the second step, 3.5 wt % Cu was added to the FeMnC reference alloy, and the microbial corrosion as well as the proliferation of the investigated bacterial strains is further strongly influenced. This leads for instance to enhanced antibacterial activity of the Cu-modified FeMnC-based alloy against the very aggressive, wild-type bacteria P. aeruginosa. For clarification of the bacterial test results, additional analyses were applied regarding the microstructure and elemental distribution as well as the initial corrosion behavior of the alloys. This was electrochemically investigated by a potentiodynamic polarization test. The initial degraded surface after immersion were analyzed by glow discharge optical emission spectrometry and transmission electron microscopy combined with energy-dispersive X-ray analysis, revealing an increase of degradation due to Cu alloying. Due to their antibacterial behavior, both investigated FeMnC-based alloys in this study are attractive as a temporary implant material.
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Ligas , Próteses e Implantes , Ligas/química , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
The ageing phenotype is strongly driven by the exhaustion of adult stem cells (ASCs) and the accumulation of senescent cells. Cardiovascular diseases (CVDs) and heart failure (HF) are strongly linked to the ageing phenotype and are the leading cause of death. As the human heart is considered as an organ with low regenerative capacity, treatments targeting the rejuvenation of human cardiac stem cells (hCSCs) are of great interest. In this study, the beneficial effects of human blood serum on proliferation and senescence of hCSCs have been investigated at the molecular level. We show the induction of a proliferation-related gene expression response by human blood serum at the mRNA level. The concurrent differential expression of the TGFß target and inhibitor genes indicates the participation of TGFß signalling in this context. Surprisingly, the application of TGFß1 as well as the inhibition of TGFß type I and type II receptor (TGFßRI/II) signalling strongly increased the proliferation of hCSCs. Likewise, both human blood serum and TGFß1 reduced the senescence in hCSCs. The protective effect of serum on senescence in hCSCs was enhanced by simultaneous TGFßRI/II inhibition. These results strongly indicate a dual role of TGFß signalling in terms of the serum-mediated effects on hCSCs. Further analysis via RNA sequencing (RNA-Seq) revealed the participation of Ras-inactivating genes wherefore a prevention of hyperproliferation upon serum-treatment in hCSCs via TGFß signalling and Ras-induced senescence is suggested. These insights may improve treatments of heart failure in the future.
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Células-Tronco Adultas , Insuficiência Cardíaca , Adulto , Humanos , Soro , Insuficiência Cardíaca/genética , Fator de Crescimento Transformador beta , Proliferação de Células , Proteína Smad2RESUMO
Sex-related differences are a current topic in contemporary science. In addition to hormonal regulation, cell-autonomous mechanisms are important in bone homeostasis and regeneration. In this study, human skeletal stem cells (SSCs) from female and male adults were cultured and analyzed with immunological assays and osteogenic differentiation assessments. Female SSCs exhibited a mean doubling time of 100.6 h, whereas male SSCs displayed a mean doubling time of 168.0 h. Immunophenotyping revealed the expression of the stem cell markers Nestin, CD133, and CD164, accompanied by the neural-crest marker SOX9. Furthermore, multiparameter flow cytometric analyses revealed a substantial population of multipotent SSCs, comprising up to 80% in both sexes. An analysis of the osteogenic differentiation potential demonstrated a strong mineralization in both male and female SSCs under physiological conditions. Recognizing the prevailing association of bone diseases with inflammatory processes, we also analyzed the osteogenic potential of SSCs from both sexes under pro-inflammatory conditions. Upon TNF-α and IL-1ß treatment, we observed no sexual dimorphism on osteogenesis. In summary, we demonstrated the successful isolation and characterization of SSCs capable of rapid osteogenic differentiation. Taken together, in vitro cultured SSCs might be a suitable model to study sexual dimorphisms and develop drugs for degenerative bone diseases.
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Doenças Ósseas , Células-Tronco Mesenquimais , Humanos , Masculino , Feminino , Osteogênese , Caracteres Sexuais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco , Doenças Ósseas/metabolismoRESUMO
BACKGROUND: Sexual differences in the biology of human stem cells are increasingly recognized to influence their proliferation, differentiation and maturation. Especially in neurodegenerative diseases such as Alzheimers disease (AD), Parkinson's disease (PD) or ischemic stroke, sex is a key player for disease progression and recovery of damaged tissue. Recently, the glycoprotein hormone erythropoietin (EPO) has been implicated as a regulator of neuronal differentiation and maturation in female rats. METHODS: In this study, we used adult human neural crest-derived stem cells (NCSCs) as a model system for exploring potential sex specific effects of EPO on human neuronal differentiation. We started with expression validation of the specific EPO receptor (EPOR) by performing PCR analysis in the NCSCs. Next, EPO mediated activation of nuclear factor-κB (NF-κB) via Immunocytochemistry (ICC) was performed, followed by investigating the sex-specific effects of EPO on neuronal differentiation by determining morphological changes in axonal growth and neurite formation accompanied by ICC. RESULTS: Undifferentiated male and female NCSCs showed a ubiquitous expression of the EPO receptor (EPOR). EPO treatment resulted in a statistically profound (male p = 0.0022, female p = 0.0012) nuclear translocation of NF-κB RELA in undifferentiated NCSCs of both sexes. But after one week of neuronal differentiation, we could show a highly significant (p = 0,0079) increase of nuclear NF-κB RELA in females only. In contrast, we observed a strong decrease (p = 0,0022) of RELA activation in male neuronal progenitors. Extending the view on the role of sex during human neuronal differentiation, here we demonstrate a significant increase of axon lengths in female NCSCs-derived neurons upon EPO-treatment (+ EPO: 167,73 (SD = 41,66) µm, w/o EPO: 77,68 (SD = 18,31) µm) compared to their male counterparts (+ EPO: 68,37 (SD = 11,97) µm, w/o EPO: 70,23 (SD = 12,89) µm). CONCLUSION: Our present findings therefore show for the first time an EPO-driven sexual dimorphism in neuronal differentiation of human neural-crest derived stem cells and emphasize sex-specific variability as a crucial parameter in stem cell biology and for treating neurodegenerative diseases.
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Eritropoetina , NF-kappa B , Humanos , Adulto , Feminino , Masculino , Animais , Ratos , Crista Neural , Eritropoetina/farmacologia , Caracteres Sexuais , Diferenciação CelularRESUMO
The performance of plastic components in water-bearing parts of industrial and household appliances, often in the presence of harsh environments and elevated temperatures, critically relies on the mechanical and thermal polymer stability. In this light, the precise knowledge of aging properties of polymers formulated with dedicated antiaging additive packages as well as various fillers is crucial for long-time device warranty. We investigated and analysed the time-dependent, polymer-liquid interface aging of different industrial performance polypropylene samples in aqueous detergent solution at high temperatures (95 °C). Special emphasis was put on the disadvantageous process of consecutive biofilm formation that often follows surface transformation and degradation. Atomic force microscopy, scanning electron microscopy, and infrared spectroscopy were used to monitor and analyse the surface aging process. Additionally, bacterial adhesion and biofilm formation was characterised by colony forming unit assays. One of the key findings is the observation of crystalline, fibre-like growth of ethylene bis stearamide (EBS) on the surface during the aging process. EBS is a widely used process aid and lubricant enabling the proper demoulding of injection moulding plastic parts. The aging-induced surface-covering EBS layers changed the surface morphology and promoted bacterial adhesion as well as biofilm formation of Pseudomonas aeruginosa.
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In household washing machines, opportunistic pathogens such as Pseudomonas aeruginosa are present, which represent the household as a possible reservoir for clinical pathogens. Here, four novel P. aeruginosa strains, isolated from different sites of household appliances, were investigated regarding their biofilm formation. Only two isolates showed strong surface-adhered biofilm formation. In consequence of these phenotypic differences, we performed whole genome sequencing using Oxford Nanopore Technology together with Illumina MiSeq. Whole genome data were screened for the prevalence of 285 virulence- and biofilm-associated genes as well as for prophages. Linking biofilm phenotypes and parallelly appearing gene compositions, we assume a relevancy of the las quorum sensing system and the phage-encoded bacteriophage control infection gene bci, which was found on integrated phi297 DNA in all biofilm-forming isolates. Additionally, only the isolates revealing strong biofilm formation harbored the ÏCTX-like prophage Dobby, implicating a role of this prophage on biofilm formation. Investigations on clinically relevant pathogens within household appliances emphasize their adaptability to harsh environments, with high concentrations of detergents, providing greater insights into pathogenicity and underlying mechanisms. This in turn opens the possibility to map and characterize potentially relevant strains even before they appear as pathogens in society.
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Microorganisms forming a biofilm might become multidrug-resistant by information exchange. Multi-resistant, biofilm-producing microorganisms are responsible for a major portion of hospital-acquired infections. Additionally, these microorganisms cause considerable damage in the industrial sector. Here, we screened several nanoparticles of transition metals for their antibacterial properties. The nanoparticles sizes of nickel (<300 nm) and nickel oxide (<50 nm) were analyzed with transmission electron microscopy. We could show that the antibacterial efficacy of nickel and nickel oxide nanoparticles on Pseudomonas aeruginosa isolated from household appliances and Staphylococcus aureus was the highest. Interestingly, only P. aeruginosa was able to survive at high concentrations (up to 50 mM) due to clustering toxic nanoparticles out of the medium by biofilm formation. This clustering served to make the medium nearly free of nanoparticles, allowing the bacteria to continue living without contact to the stressor. We observed these clusters by CLSM, SEM, and light microscopy. Moreover, we calculated the volume of NiO particles in the bacterial biofilms based on an estimated thickness of 5 nm from the TEM images as an average volume of 3.5 × 10−6 µm3. These results give us a new perspective on bacterial defense mechanisms and might be useful in industries such as water purification.
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Glioblastoma multiforme (GBM) is the most aggressive and most common malignant brain tumor with poor patient survival despite therapeutic intervention. On the cellular level, GBM comprises a rare population of glioblastoma stem cells (GSCs), driving therapeutic resistance, invasion, and recurrence. GSCs have thus come into the focus of therapeutic strategies, although their targeting remains challenging. In the present study, we took advantage of three GSCs-populations recently established in our lab to investigate key signaling pathways and subsequent therapeutic strategies targeting GSCs. We observed that NF-κB, a crucial transcription factor in GBM progression, was expressed in all CD44+/CD133+/Nestin+-GSC-populations. Exposure to TNFα led to activation of NF-κB-RELA and/or NF-κB-c-REL, depending on the GBM type. GSCs further expressed the proto-oncogene MYC family, with MYChigh GSCs being predominantly located in the tumor spheres ("GROW"-state) while NF-κB-RELAhigh GSCs were migrating out of the sphere ("GO"-state). We efficiently targeted GSCs by the pharmacologic inhibition of NF-κB using PTDC/Bortezomib or inhibition of MYC by KJ-Pyr-9, which significantly reduced GSC-viability, even in comparison to the standard chemotherapeutic drug temozolomide. As an additional cell-therapeutic strategy, we showed that NK cells could kill GSCs. Our findings offer new perspectives for developing efficient patient-specific chemo- and immunotherapy against GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/metabolismo , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Transdução de Sinais , Imunoterapia , Linhagem Celular TumoralRESUMO
In the light of the SARS-CoV-2 pandemic and growing numbers of bacteria with resistance to antibiotics, the development of antimicrobial coatings is rising worldwide. Inorganic coatings are attractive because of low environmental leakage and wear resistance. Examples for coatings are hot metal dipping or physical vapor deposition of nanometer coatings. Here, magnetron sputtering of various transition metals, such as gold, ruthenium and tantalum, was investigated. Metal films were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) and energy dispersive X-ray spectroscopy (EDX). We investigated the growth of Pseudomonas aeruginosa isolated from household appliances on different sputter-coated metal surfaces. The fine-grained nanometric structure of these metal coatings was between 14 nm (tantalum) and 26 nm (gold) and the roughness was in a range of 164 pm (ruthenium) to 246 pm (gold). Antibacterial efficacy of metal surfaces followed the order: gold > tantalum > ruthenium. Interestingly, gold had the strongest inhibitory effect on bacterial growth, as analyzed by LIVE/DEAD and CFU assay. High-magnification SEM images showed dead bacteria characterized by shrinkage induced by metal coatings. We conclude that sputtering might be a new application for the development of antimicrobial surfaces on household appliances and or surgical instruments.
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Tissue regeneration substantially relies on the functionality of tissue-resident endogenous adult stem cell populations. However, during aging, a progressive decline in organ function and regenerative capacities impedes endogenous repair processes. Especially the adult human heart is considered as an organ with generally low regenerative capacities. Interestingly, beneficial effects of systemic factors carried by young blood have been described in diverse organs including the heart, brain and skeletal muscle of the murine system. Thus, the interest in young blood or blood components as potential therapeutic agents to target age-associated malignancies led to a wide range of preclinical and clinical research. However, the translation of promising results from the murine to the human system remains difficult. Likewise, the establishment of adequate cellular models could help to study the effects of human blood plasma on the regeneration of human tissues and particularly the heart. Facing this challenge, this review describes the current knowledge of blood plasma-mediated protection and regeneration of aging tissues. The current status of preclinical and clinical research examining blood borne factors that act in stem cell-based tissue maintenance and regeneration is summarized. Further, examples of cellular model systems for a more detailed examination of selected regulatory pathways are presented.
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Células-Tronco Adultas , Células-Tronco , Idoso , Envelhecimento/fisiologia , Animais , Humanos , Camundongos , Músculo Esquelético/fisiologia , Células-Tronco/fisiologia , CicatrizaçãoRESUMO
The transcription factor NF-κB is commonly known to drive inflammation and cancer progression, but is also a crucial regulator of a broad range of cellular processes within the mammalian nervous system. In the present review, we provide an overview on the role of NF-κB in the nervous system particularly including its constitutive activity within cortical and hippocampal regions, neuroprotection as well as learning and memory. Our discussion further emphasizes the increasing role of human genetics in neurodegenerative disorders, namely, germline mutations leading to defects in NF-κB-signaling. In particular, we propose that loss of function mutations upstream of NF-κB such as ADAM17, SHARPIN, HOIL, or OTULIN affect NF-κB-activity in Alzheimer's disease (AD) patients, in turn driving anatomical defects such as shrinkage of entorhinal cortex and the limbic system in early AD. Similarly, E3 type ubiquitin ligase PARKIN is positively involved in NF-κB signaling. PARKIN loss of function mutations are most frequently observed in Parkinson's disease patients. In contrast to AD, relying on germline mutations of week alleles and a disease development over decades, somatic mutations affecting NF-κB activation are commonly observed in cells derived from glioblastoma multiforme (GBM), the most common malignant primary brain tumor. Here, our present review particularly sheds light on the mutual exclusion of either the deletion of NFKBIA or amplification of epidermal growth factor receptor (EGFR) in GBM, both resulting in constitutive NF-κB-activity driving tumorigenesis. We also discuss emerging roles of long non-coding RNAs such as HOTAIR in suppressing phosphorylation of IκBα in the context of GBM. In summary, the recent progress in the genetic analysis of patients, particularly those suffering from AD, harbors the potential to open up new vistas for research and therapy based on TNFα/NF-κB pathway and neuroprotection.
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Endometrial cancer is one of the most common malignant diseases in women worldwide, with an incidence of 5.9%. Thus, it is the most frequent cancer of the female genital tract, with more than 34,000 women dying, in Europe and North America alone. Endometrial Cancer Stem Cells (CSC) might be drivers of carcinogenesis as well as metastatic and recurrent disease. Therefore, targeting CSCs is of high interest to improve prognosis of patients suffering of advanced or recurrent endometrial cancer. This review describes the current evidence of molecular mechanisms in endometrial CSCs with special emphasis on MYC and NF-κB signaling as well as mitochondrial metabolism. Furthermore, the current status of immunotherapy targeting PD-1 and PD-L1 in endometrial cancer cells and CSCs is elucidated. The outlined findings encourage novel therapies that target signaling pathways in endometrial CSCs as well as immunotherapy as a promising therapeutic approach in the treatment of endometrial cancer to impede cancer progression and prevent recurrence.
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Neoplasias do Endométrio , Recidiva Local de Neoplasia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Feminino , Humanos , Imunoterapia , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/metabolismo , Transdução de SinaisRESUMO
Female sex is increasingly associated with a loss of bone mass during aging and an increased risk of developing nonunion fractures. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation in human adult neural crest-derived stem cells (NCSCs). Next to an elevated expression of pro-osteogenic regulators, global transcriptomics revealed Lysine Demethylase 5D (KDM5D) to be highly upregulated in differentiating male NCSCs. Loss of function by siRNA or pharmacological inhibition of KDM5D significantly reduced the osteogenic differentiation capacity of male NCSCs. In summary, we demonstrated craniofacial osteogenic differentiation to be sexually dimorphic with the expression of KDM5D as a prerequisite for accelerated male osteogenic differentiation, emphasizing the analysis of sex-specific differences as a crucial parameter for treating bone defects.
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Lisina , Osteogênese , Animais , Diferenciação Celular/genética , Feminino , Histona Desmetilases/genética , Humanos , Masculino , Antígenos de Histocompatibilidade Menor , RNA Interferente Pequeno/genética , Ratos , CrânioRESUMO
Cancer stem cells (CSCs) are a small subpopulation of tumor cells harboring properties that include self-renewal, multi-lineage differentiation, tumor reconstitution, drug resistance and invasiveness, making them key players in tumor relapse. In the present paper, we develop new CSC models and analyze the molecular pathways involved in survival to identify targets for the establishment of novel therapies. Endometrial carcinoma-derived stem-like cells (ECSCs) were isolated from carcinogenic gynecological tissue and analyzed regarding their expression of prominent CSC markers. Further, they were treated with the MYC-signaling inhibitor KJ-Pyr-9, chemotherapeutic agent carboplatin and type II diabetes medication metformin. ECSC populations express common CSC markers, such as Prominin-1 and CD44 antigen as well as epithelial-to-mesenchymal transition markers, Twist, Snail and Slug, and exhibit the ability to form free-floating spheres. The inhibition of MYC signaling and treatment with carboplatin as well as metformin significantly reduced the cell survival of ECSC-like cells. Further, treatment with metformin significantly decreased the mitochondrial membrane potential of ECSC-like cells, while the extracellular lactate concentration was increased. The established ECSC-like populations represent promising in vitro models to further study the contribution of ECSCs to endometrial carcinogenesis. Targeting MYC signaling as well as mitochondrial bioenergetics has shown promising results in the diminishment of ECSCs, although molecular signaling pathways need further investigations.
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Carboplatina/farmacologia , Neoplasias do Endométrio/metabolismo , Metformina/farmacologia , Mitocôndrias/metabolismo , Células-Tronco Neoplásicas/citologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Piridinas/farmacologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Among the cell populations existing within a tumor, cancer stem cells are responsible for metastasis formation and chemotherapeutic resistance. In the present review, we focus on the transcription factor NF-κB, which is present in every cell type including cancer stem cells. NF-κB is involved in pro-tumor inflammation by its target gene interleukin 1 (IL1) and can be activated by a feed-forward loop in an IL1-dependent manner. Here, we summarize current strategies targeting NF-κB by chemicals and biologicals within an integrated cancer therapy. Specifically, we start with a tyrosine kinase inhibitor targeting epidermal growth factor (EGF)-receptor-mediated phosphorylation. Furthermore, we summarize current strategies of multiple myeloma treatment involving lenalidomide, bortezomib, and dexamethasone as potential NF-κB inhibitors. Finally, we discuss programmed death-ligand 1 (PD-L1) as an NF-κB target gene and its role in checkpoint therapy. We conclude, that NF-κB inhibition by specific inhibitors of IκB kinase was of no clinical use but inhibition of upstream and downstream targets with drugs or biologicals might be a fruitful way to treat cancer stem cells.
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The COVID-19 Pandemic leads to an increased worldwide demand for personal protection equipment in the medical field, such as face masks. New approaches to satisfy this demand have been developed, and one example is the use of 3D printing face masks. The reusable 3D printed mask may also have a positive effect on the environment due to decreased littering. However, the microbial load on the 3D printed objects is often disregarded. Here we analyze the biofilm formation of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli on suspected antimicrobial Plactive™ PLA 3D printing filaments and non-antimicrobial Giantarm™ PLA. To characterize the biofilm-forming potential scanning electron microscopy (SEM), Confocal scanning electron microscopy (CLSM) and colony-forming unit assays (CFU) were performed. Attached cells could be observed on all tested 3D printing materials. Gram-negative strains P. aeruginosa and E. coli reveal a strong uniform growth independent of the tested 3D filament (for P. aeruginosa even with stressed induced growth reaction by Plactive™). Only Gram-positive S. aureus shows strong growth reduction on Plactive™. These results suggest that the postulated antimicrobial Plactive™ PLA does not affect Gram-negative bacteria species. These results indicate that reusable masks, while better for our environment, may pose another health risk.
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Neuroprotection from oxidative stress is critical during neuronal development and maintenance but also plays a major role in the pathogenesis and potential treatment of various neurological disorders and neurodegenerative diseases. Emerging evidence in the murine system suggests neuroprotective effects of blood plasma on the aged or diseased brain. However, little is known about plasma-mediated effects on human neurons. In the present study, we demonstrate the neuroprotective effect mediated by human plasma and the most abundant plasma-protein human serum albumin against oxidative stress in glutamatergic neurons differentiated from human neural crest-derived inferior turbinate stem cells. We observed a strong neuroprotective effect of human plasma and human serum albumin against oxidative stress-induced neuronal death on the single cell level, similar to the one mediated by tumor necrosis factor alpha. Moreover, we detected neuroprotection of plasma and human serum albumin against kainic acid-induced excitatory stress in ex vivo cultured mouse hippocampal tissue slices. The present study provides deeper insights into plasma-mediated neuroprotection ultimately resulting in the development of novel therapies for a variety of neurological and, in particular, neurodegenerative diseases.