Publications

The successful application of Saccharomyces eubayanus and Saccharomyces paradoxus in brewery fermentations has highlighted the potential of wild yeast for brewing, and prompted investigation into the application potential of other members of the genus. Here, we evaluate, for the first...

Despite Saccharomyces cerevisiae being a synonym for baker’s yeast, the species does not perform well in all baking-related conditions. In particular, dough fermentation, or proofing, is compromised by the species’ sensitivity to the low and freezing temperatures that are often...

Background aims: Cultured patient-specific keratinocyte sheets have been used clinically since the 1970s for the treatment of large severe burns. However, despite significant developments in recent years, successful and sustainable treatment is still a challenge. Reliable, high-quality grafts with faster...

Protocols for specifying human primordial germ cell-like cells (hPGCLCs) from human embryonic stem cells (hESCs) remain hindered by differences between hESC lines, their derivation methods, and maintenance culture conditions. This poses significant challenges for establishing reproducible in vitro models of...

The combination effect of co-exposed different types of nanomaterials is little known although humans are generally exposed to a mixture of nanomaterials from urban ultrafine particles or industrial nanomaterials. Herein, we evaluated the combined effect of nanoparticles (NPs) using three...

Background: Human induced pluripotent stem cells (hiPSCs) hold enormous promise in accelerating breakthroughs in understanding human development, drug screening, disease modeling, and cell and gene therapies. Their potential, however, has been bottlenecked in a mostly laboratory setting due to bioprocess...

Chondrocytes are the main cells responsible for the maintenance of cartilage homeostasis and integrity. During development, extracellular matrix (ECM) macromolecules are produced and deposited by chondrocyte precursors. Autophagy, a highly dynamic process aimed at degradation of dysfunctional or pathogenic proteins,...

The inflammatory response after traumatic brain injury (TBI) can lead to significant secondary brain injury and chronic inflammation within the central nervous system. Cell therapies, including mesenchymal stromal cells (MSC), have led to improvements in animal models of TBI and...

Live attenuated influenza vaccine (LAIV) is widely used to protect humans from seasonal influenza infection, particularly in children. In contrast to inactivated vaccines, the LAIV can induce both mucosal and cellular immune responses. Here we show that a single dose...

Anti-Leishmanial drug therapy faces significant challenges related to cytotoxicity and drug resistance. Thus, new and efficient anti-Leishmanial drugs need to be identified. Due to their broad-spectrum antimicrobial and also immunomodulatory activities, antimicrobial peptides (AMPs) have attracted considerable attention. In this...

In atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in...

Surgery followed by a chemotherapy agent is the first-line treatment for breast cancer patients. Nevertheless, new targets are required for women with triple-negative breast cancer (TNBC) in order to improve the treatment of this aggressive cancer subtype. Multiple pro-inflammatory molecules...

Background: In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or...

Adipose tissue is an abundant source of stem cells. However, liposuction cannot yield cell quantities sufficient for direct applications in regenerative medicine. Therefore, the development of GMP-compliant ex vivo expansion protocols is required to ensure the production of a “cell...

Measured variability of product within Cell and Gene Therapy (CGT) manufacturing arises from numerous sources across pre-analytical to post-analytical phases of testing. Operators are a function of the manufacturing process and are an important source of variability as a result...

Previous studies revealed that direct contact with graphene oxide (GO) induced cytotoxic effects, but the importance of involvement of metabolic pathways, in particular lipid metabolism pathways, might be overlooked. In this study, human umbilical vein endothelial cells (HUVECs) were exposed...

Oxidative stress has been implicated in the pathogenesis of Alzheimer’s disease (AD). Mitochondrial dysfunction is linked to oxidative stress and reactive oxygen species (ROS) in neurotoxicity during AD. Impaired mitochondrial metabolism has been associated with mitochondrial dysfunction in brain damage...

Titanium porous scaffolds comprising multimodal pore ranges (i.e., uni-, bi-, tri-modal and random) were studied to evaluate the effect of pore size on osteoblastogenesis. The scaffolds were manufactured using spaceholder-powder metallurgy, and porosity and pore size were kept independent. Their...

Tart cherry (Prunus cerasus L.), a medicinal food containing high concentrations of phytochemicals, has a variety of antioxidant activities and health benefits. Here, we investigate the functional effect of tart cherry during apoptotic cell death elicited by airborne particulate matter...

Fusion cages composed of titanium and its alloys are emerging as valuable alternative to standard polyetheretherketone (PEEK) ones routinely used in cervical and lumbar spine surgery. Aim of this study was to evaluate osteo-inductive and osteo-conductive ability of an innovative...

Morphology plays a vital role in determining the biological effects of silica nanoparticles (NPs), but its influence on the toxicity of silica NPs in endothelial cells (ECs) is still inconclusive. We synthesized five kinds of Santa Barbara 15 amorphous (SBA-15)...

Genetic studies have identified several epithelial-derived genes associated with airway diseases. However, techniques used to study gene function frequently exceed the proliferative potential of primary human bronchial epithelial cells (HBECs) isolated from patients. Increased expression of the polycomb group protein...

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of...

Epidemiological evidence has shown the association between exposure to ambient fine particulate matter (PM) and increased susceptibility to bacterial and viral respiratory infections. However, to date, the underlying mechanisms of immunomodulatory effects of PM remain unclear. Our objective was to...

Adipose-derived stromal/stem cells (ASCs) are being tested as a possible treatment for a wide range of diseases to exploit the immunomodulatory and regenerative potential demonstrated in vitro. Pooled human platelet lysate (pHPL) has replaced fetal bovine serum (FBS) as the...

Purpose: Prognosis for acute myeloid leukemia (AML) patients is poor, particularly in TP53 mutated AML, secondary, relapsed, and refractory AML, and in patients unfit for intensive treatment, thus highlighting an unmet need for novel therapeutic approaches. The combined use of...

Spitzoid melanoma is a rare malignancy with histological characteristics similar to Spitz nevus. It has a diverse genetic background and in adults, a similarly grim clinical outcome as conventional malignant melanoma. We established a spitzoid melanoma cell line (PF130) from...

Malignant melanoma is the cause of 80% of deaths in skin cancer patients. Treatment of melanoma in the 4th stage of clinical advancement, in which inoperable metastasis occur, does not provide sufficient effects. Ketoprofen has phototoxic properties and it can...

The most important biological function of vitamin B12 is to accomplish DNA synthesis, which is necessary for cell division. Cobalamin deficiency may be especially acute for rapidly dividing cells, such as glioblastoma cells. Therefore, cobalamin antagonists offer a medicinal potential...

A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of...

Multidrug resistance (MDR) of cancer cells reduces chemotherapeutic efficacy by preventing drug accumulation in the cells through a drug efflux pump and lysosomal sequestration/exocytosis. Herein, to overcome such anticancer resistance, lysosome-targeted self-assembly of perylene diimide (PDI) derivatives is presented as...

Hepatocellular carcinoma (HCC) is a global health problem. Currently, there is no effective therapeutic strategy for HCC. Methyl gallate (MG), from plant-derived phenolic gallic acid, has exhibited antitumor efficacy. However, the effect of MG on HCC is unclear. In vitro...

Foot and mouth disease is a livestock acute disease, causing economic losses in affected areas. Currently, control of this disease is performed by mandatory vaccination campaigns using inactivated viral vaccines. In this work, we describe the development of a chimeric...

Minocycline is a semisynthetic tetracycline antibiotic. In addition to its antibacterial activity, minocycline shows many non-antibiotic, beneficial effects, including antioxidative action. The property is responsible, e.g., for anti-inflammatory, neuroprotective, and cardioprotective effects of the drug. However, long-term pharmacotherapy with minocycline...

In this study, we investigated whether humidifier disinfectants (HDs) induce asthmatic airway inflammation in an animal model and compared the features of HD-induced inflammatory symptoms with ovalbumin (OVA)-induced allergic asthma. Mice were intratracheally instilled three times with either the control...

Recent technical developments brought negative side effects such as air pollution and large-scale fires, increasingly exposing people to diesel engine exhaust particles (DEP). Testing how DEP inhalation triggers pathophysiology in animal models could be useful in determining how it affects...

Diesel exhaust particulates (DEP) adversely affect the respiratory system and exacerbate lung diseases, resulting in high mortality rates. However, its pathogenesis is complicated, and the mechanisms involved are incompletely understood. We investigated the effects of DEP pre-exposure on lipopolysaccharide (LPS)-induced...

Levan is an exopolysaccharide produced by Bacillus licheniformis (strain FRI MY-55) that shows promising pharmacological activity. Phosphorylation is a chemical modification that can increase the biological and antioxidant properties of levan. In this study, levan was phosphorylated by microwave-assisted synthesis...

The addition of nutrients and accumulation of metabolites in a fed-batch culture of Chinese hamster ovary (CHO) cells leads to an increase in extracellular osmolality in late stage culture. Herein, we explore the effect of osmolality on CHO cell growth,...

Culture-expanded mesenchymal stromal cells (MSCs) are promising candidates for clinical cell-based therapies. MSC products are heterogeneous and we therefore investigated whether acoustophoresis, an ultrasound-based separation technology, could be used for the label-free enrichment of functionally different MSC populations. Acoustophoresis uses...

Finding targetable gene fusions can expand the limited treatment options in radioactive iodine-refractory (RAI-r) thyroid cancer. To that end, we established a novel cell line ‘JVE404′ derived from an advanced RAI-r papillary thyroid cancer (PTC) patient, harboring an EML4-ALK gene...

The toxic substances of cigarette smoke (CS) induce inflammatory responses in the lung by recruiting inflammatory cells. In this study, we investigated the effects of CS on the progression of lung disease in bleomycin (BLM) and lipopolysaccharide (LPS)-induced lung injury...

Cancer patients, in particular patients with hematological malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T cell responses in unexposed and SARS-CoV-2-infected cancer patients to characterize SARS-CoV 2...

Recently, some researchers have demonstrated that inhaled zinc oxide nanoparticles (ZnONPs) induce an acute systemic inflammatory response in workers. Considering nonhuman primates are preferably considered an animal model for translational research due to their proven similarity with humans in terms...

Therapies to treat patients infected with human immunodeficiency virus (HIV) aim at preventing viral replication but fail to eliminate the virus. Although transplantation of allogeneic CCR5Δ32 homozygous stem cell grafts provided a cure for a few patients, this approach is...

Genome editing has shown great promise for clinical translation but also revealed the risk of genotoxicity caused by off-target effects of programmable nucleases. Here we describe chromosomal aberrations analysis by single targeted linker-mediated PCR sequencing (CAST-Seq), a preclinical assay to...

Saccharomyces paradoxus is commonly isolated from environmental samples in Northern Europe and North America, but is rarely found associated with fermentation. However, as novelty has become a selling point in beer markets, interest toward non-conventional and local yeasts is increasing....

The overexpression of GATA-3, T-bet and TGF-ß may theoretically induce IL-4/A, IFN-γ and IL-17A expression, respectively. Whether this also applies to fish is not yet known. The plasmid vectors encoding reporter gene (RFP)-tagged T-bet, GATA-3 and TGF-β were used as...

Interferon-induced proteins with tetratricopeptide repeats (IFITs) are involved in antiviral defense. Members of this protein family contain distinctive multiple structural motifs comprising tetratricopeptides that are tandemly arrayed or dispersed along the polypeptide. IFIT-encoding genes are upregulated by type I interferons...

For every 1 tonne of bananas produced, 3 tonnes of pseudostem waste is also created. The aim of this research is to improve the pre-treatment methods used in converting this renewable resource to bioethanol. The microwave-assisted liquid hot water and...

The use of wild yeasts in fermentation is becoming a viable option for the differentiation of beers. To achieve good fermentation rates and alcohol yields, however, such yeasts must have the ability to utilize the wort sugars maltose and maltotriose,...

Background: Fructose and single cell protein are important products for the food market. Abundant amounts of low-grade dates worldwide are annually wasted. In this study, highly concentrated fructose syrups and single cell protein were obtained through selective fermentation of date...

The potential of yeasts isolated from traditional chichas as starter cultures, either for controlled production of the native beverage or for industrial beer production, has been investigated. Three S. cerevisiae strains and one T. delbrueckii strain isolated from four different...

The transwell assay is currently the most popular approach to studying cellular invasion due to its ease of use and readout, and the possibility for quantitative measurements. However, it only allows end-point measurements without the possibility for real-time tracking of...

Barrier organ models need a scaffold structure to create a two compartment culture. Technical filter membranes used most often as scaffolds may impact cell behaviour and present a barrier themselves, ultimately limiting transferability of test results. In this work we...

Insulin is a peptide hormone produced by the pancreas. The physiological role of insulin is the regulation of glucose metabolism. Under certain pathological conditions the insulin levels can be reduced leading to the metabolic disorder diabetes mellitus (DM). For type...

Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes....

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; however, apoptosis of lung alveolar epithelial cells plays a role in disease progression. This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the...

Human induced pluripotent stem cells (hiPSCs) have generated a great deal of attention owing to their capacity for self-renewal and differentiation into the three germ layers of the body. Their discovery has facilitated a new era in biomedicine for understanding...

Background: Liver cirrhosis results from chronic hepatitis, and is characterized by advanced fibrosis due to long-term hepatic inflammation. Cirrhosis ultimately leads to manifestations of jaundice, ascites, and encephalopathy, and increases the risk of hepatocellular carcinoma. Once cirrhosis is established, resulting...

Background: Degeneration of smooth muscles in sphincters can cause debilitating diseases such as fecal incontinence. Skeletal muscle-derived cells have been effectively used in clinics for the regeneration of the skeletal muscle sphincters, such as the external anal or urinary sphincter....

Microcarriers, including crosslinked porous gelatin beads (Cultispher G) are widely used as cell carriers for cell therapy applications. Microcarriers can support a range of adherent cell types in stirred tank bioreactor culture, which is scalable up to several thousands of...

Human mesenchymal stem/stromal cells (hMSCs) have been investigated and proven to be a well-tolerated, safe therapy for a variety of indications, as shown by over 900 registered hMSC-based clinical trials. To meet the commercial demand for clinical manufacturing of hMSCs,...

Aims/hypothesis: Compared with the general population, individuals with diabetes have a higher risk of developing severe acute pancreatitis, a highly debilitating and potentially lethal inflammation of the exocrine pancreas. In this study, we investigated whether 1-deoxysphingolipids, atypical lipids that increase...

Nanomaterial (NM) characteristics may affect the pulmonary toxicity and inflammatory response, including specific surface area, size, shape, crystal phase or other surface characteristics. Grouping of TiO2 in hazard assessment might be challenging because of variation in physicochemical properties. We exposed...

Despite broad application of magnetic nanoparticles in biomedicine and electronics, only a few in vivo studies on biocompatibility are available. In this study, toxicity of magnetic metal oxide nanoparticles on the respiratory system was examined in vivo by single intratracheal...

Exposure to metal oxide nanomaterials potentially occurs at the workplace. We investigated the toxicity of two Fe-oxides: Fe2O3 nanoparticles and nanorods; and three MFe2O4 spinels: NiZnFe4O8, ZnFe2O4, and NiFe2O4 nanoparticles. Mice were dosed 14, 43 or 128 μg by intratracheal...

Methods for the quantification of antisense oligonucleotides (AONs) provide insightful information on biodistribution and intracellular trafficking. However, the established methods have not provided information on the absolute number of molecules in subcellular compartments or about how many AONs are needed...

To improve the understanding of the complex biological processes underlying the development of non-alcoholic steatohepatitis (NASH), a multi-omics approach combining bulk RNA-sequencing based transcriptomics, quantitative proteomics and single-cell RNA-sequencing was used to characterize tissue biopsies from histologically validated diet-induced obese...

Our understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human embryo and identify expression for the insulin and insulin growth factor 1...

Molecular signalling mediated by the phosphatidylinositol-3-kinase (PI3K)-Akt axis is a key regulator of cellular functions. Importantly, alteration of the PI3K-Akt signalling underlies the development of different human diseases, thus prompting the investigation of the pathway as a molecular target for...

Aim: Neurons in the arcuate nucleus of the hypothalamus are involved in regulation of food intake and energy expenditure, and dysregulation of signalling in these neurons promotes development of obesity. The role of the rate-limiting enzyme in the NAD+ salvage...

Traumatic brain injury (TBI) causes a profound inflammatory response within the central nervous system and peripheral immune system, which contributes to secondary brain injury and further morbidity and mortality. Preclinical investigations have demonstrated that treatments that downregulate microglia activation and...

Embryonic stem cells (ESCs) have almost unlimited proliferation capacity in vitro and can retain the ability to contribute to all cell lineages, making them an ideal platform material for cell-based therapies. ESCs are traditionally cultured in static flasks on a...

Cell replacement therapies hold great therapeutic potential. Nevertheless, our knowledge of the mechanisms governing the developmental processes is limited, impeding the quality of differentiation protocols. Generating insulin-expressing cells in vitro is no exception, with the guided series of differentiation events...

Cell therapy products represent an exciting new class of medicinal products, which must be parenterally administered. Thus, compliance with parenteral preparation guidelines is required. One requirement for parenteral products is the characterization of particle contaminations. As cell-based products are turbid...

Metabolic engineering of mammalian cells has to-date focused primarily on biopharmaceutical protein production or the manipulation of native metabolic processes towards therapeutic aims. However, significant potential exists for expanding these techniques to diverse applications by looking across the taxonomic tree...

Background: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing. Objective: In the present work we...

IgE-mediated peanut allergic is common, often serious, and usually lifelong. Not all individuals who produce peanut-specific IgE will react upon consumption of peanut and can eat the food without adverse reactions, known as sensitized tolerance. Here, we employ high-dimensional mass...

Gastrointestinal microbiota and immune cells interact closely and display regional specificity; however, little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterization...

Allogeneic cell-based therapies using adipose tissue-derived stromal cells (ASCs) offer an off-the-shelf alternative to autologous therapy. An underlying assumption is that ASC can modulate the immune response of the recipient. However, in vitro models are required to explore and identify...

The ability of bacteria to aggregate and form biofilms impairs phagocytosis by polymorphonuclear leukocytes (PMNs). The aim of this study was to examine if the size of aggregates is critical for successful phagocytosis and how bacterial biofilms evade phagocytosis. We...

The intestinal gut microbiota is essential for maintaining host health. Concerns have been raised about the possible connection between antibiotic use, causing microbiota disturbances, and the increase in allergic and autoimmune diseases observed during the last decades. To elucidate the...

This report covers the methodology for generation of stable heterohybridoma clones producing Foot-and-mouth disease virus (FMDV) reactive porcine monoclonal antibodies (mAbs). Swine received five inoculations of an inactivated O1 Manisa FMDV vaccine prior to the harvest of splenocytes. Due to...

Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic...

Introduction: Stroke often causes residual hemiparesis, and upper extremity motor impairment is usually more disabling than lower extremity in those who are suffering from post-stroke hemiparesis. Cell therapy is one of the promising therapies to reduce post-stroke disability. Patient concerns:...

Brain metastases are common in patients with non-small-cell lung cancer (NSCLC). The efficacy of bevacizumab, an anti-vascular endothelial growth factor (VEGF) humanized antibody, has been demonstrated in patients with nonsquamous NSCLC. We established a transplantable NSCLC cell line (Nluc-H1915) that...

The activating-mutation of JAK2V617F drives the development of myeloproliferative neoplasms (MPNs). Several JAK2 inhibitors such as ruxolitinib and gandotinib (LY2784544) currently in clinical trials and, provide improvements in MPNs including myelofibrosis. However, JAK2 inhibitors are non-curative and murine experiments show...

Rhabdomyosarcoma (RMS) and rhabdoid tumors (RT) are rare soft-tissue malignancies with the highest incidence in infants, children, and adolescents. Advanced, recurrent, and/or metastatic RMS and RT exhibit poor response to treatment. One of the main mechanisms behind resistance to treatment...

Long non-coding RNAs (lncRNAs) are emerging as regulators in cancer development and progression, and aberrant lncRNA profiles have been reported in several cancers. Here, we evaluated the potential of using the maternally expressed gene 3 (MEG3) tissue level as a...

Chinese hamster ovary (CHO) cells are the preferred workhorse for the biopharmaceutical industry, and CRISPR/Cas9 has proven powerful for generating targeted gene perturbations in CHO cells. Here, we expand the CRISPR engineering toolbox with CRISPR activation (CRISPRa) to increase transcription...

In mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we...

Sialic acid, a terminal monosaccharide present in N-glycans, plays an important role in determining both the in vivo half-life and the therapeutic efficacy of recombinant glycoproteins. Low sialylation levels of recombinant human erythropoietin (rhEPO) in recombinant Chinese hamster ovary (rCHO)...

Reliable scale-up of biopharmaceutical production processes is key in Quality by Design. In this study, a model-based workflow is described to evaluate the bioprocess dynamics during process transfer and scale-up computationally. First, a mathematical model describes the bioprocess dynamics of...

Host cell proteins (HCPs) are process-related impurities generated during biotherapeutic protein production. HCPs can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. Here, we present an effort to create a “clean”...

In most cases, Mycobacterium tuberculosis (Mtb) causes life-long chronic infections, which poses unique challenges for the immune system. Most of the current tuberculosis (TB) subunit vaccines incorporate immunodominant antigens and at this point, it is poorly understood how the CD4...

Human Adipose Tissue Stem Cells (hASCs) are a valuable source of cells for clinical applications (e.g., treatment of acute myocardial infarction and inflammatory diseases), especially in the field of regenerative medicine. However, for autologous (patient-specific) and allogeneic (off-the-shelf) hASC-based therapies,...

Adipose-derived stromal/stem cells (ASCs) are currently being considered for clinical use for a number of indications. In order to develop standardized clinical protocols, it is paramount to have a full characterization of the stem cell preparations. The surface marker expression...

One of the neuropathological hallmarks of Alzheimer’s disease (AD) is cerebral deposition of amyloid plaques composed of amyloid β (Aβ) peptides and the cerebrospinal fluid concentrations of those peptides are used as a biomarker for AD. Mature induced pluripotent stem...

Generating insulin-producing β-cells from human induced pluripotent stem cells is a promising cell replacement therapy for improving or curing insulin-dependent diabetes. The transplantation of end-stages differentiating cells into living hosts was demonstrated to improve β-cell maturation. Nevertheless, the cellular and...

In the future, stem cell-based technologies may be harnessed to replace conventional dialysis and transplantation in patients with diabetic nephropathy. Recently, there has been considerable effort to improve methods for the differentiation of human pluripotent stem cells (hPSCs) into kidney...

Self-healing injectable hydrogel biomaterials uniquely enable precise therapeutic deposition and deployment at specific bodily locations through versatile and minimally invasive processes that can preserve cargo integrity and cell viability. Despite the distinct advantages that injectable hydrogels offer in tissue engineering...

Context: The calcium-sensing receptor (CaSR) is essential to maintain a stable calcium concentration in serum. Spermatozoa are exposed to immense changes in concentrations of CaSR ligands such as calcium, magnesium, and spermine during epididymal maturation, in the ejaculate, and in...

Cellular senescence is defined by irreversible cell-cycle arrest and is an evolutionarily conserved hallmark of aging. In this study, we generate senescent microglial cells via exposure to the chemotherapy drug doxorubicin. Compared to control cells, doxorubicin-treated microglia exhibited an altered...

Mutations of many PDSS and COQ genes are associated with primary coenzyme Q10 (CoQ10) deficiency, whereas mitochondrial DNA (mtDNA) mutations might cause secondary CoQ10 deficiency. Previously, we found that COQ5 and COQ9 proteins are present in different protein complexes in...

Ambient particulate matter (PM) is a leading global environmental health risk. Current air quality regulations are based on airborne mass concentration. However, PM from different sources have distinct chemical compositions and varied toxicity. Connections between emission control measures, air quality,...

Extrachromosomal circular DNA (eccDNA) elements of chromosomal origin are known to be common in a number of eukaryotic species. However, it remains to be addressed whether genomic features such as genome size, the load of repetitive elements within a genome,...

In vitro 3D tissue-engineered (TE) structures have been shown to better represent in vivo tissue morphology and biochemical pathways than monolayer culture, and are less ethically questionable than animal models. However, to create systems with even greater relevance, multiple integrated...

Purpose: Human corneal endothelial cells (hCECs) have limited regenerative capacity in vivo. Reduced hCEC density results in bullous keratopathy requiring corneal transplantation. This study reveals the role of transcription factor 4 (TCF4) in hCEC diseases and suggests that TCF4 may...

Background: The replicative senescence of human dermal fibroblasts (HDFs) is accompanied by growth arrest. In our previous study, the treatment of senescent HDFs with Rg3(S) lowered the intrinsic reactive oxygen species (ROS) levels and reversed cellular senescence by inducing peroxiredoxin-3,...

Background: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is the most frequent fatty acid oxidation (FAO) defect in humans. MCAD-deficient fibroblasts are more resistant to oxidative stress-induced cell death than other FAO defects and healthy controls. Methods: Herein we investigate the...

Single-cell RNA sequencing (scRNA-seq) of human primary tissues is a rapidly emerging tool for investigating human health and disease at the molecular level. However, optimal processing of solid tissues presents a number of technical and logistical challenges, especially for tissues...

Background: Emissions from road traffic are under constant discussion since they pose a major threat to human health despite the increasingly strict emission targets and regulations. Although the new passenger car regulations have been very effective in reducing the particulate...

Life is completely dependent on water. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O) and investigated the biological effects by a wide range of techniques, using Schizosaccharomyces pombe as model...

Pulmonary surfactant or its components can function as barriers toward nanomaterials (NMs) entering pulmonary systems. However, since pulmonary surfactant mainly consists of lipids, it may be necessary to investigate the effects of co-exposure to NMs and pulmonary surfactant or its...

High-contrast brightfield (HCBF) microscopy has emerged as a strong tool for noninvasive counting of cells in culture. HCBF imaging delivers precise cell growth data and is completely label free rendering it an attractive alternative to common cell counting procedures that...

The influence of food components on nanoparticle (NP) internalization indicates a need to investigate the behaviors of NPs in a complex system. This study measured the changes of TiO2 NP colloidal stability and quenching of anthocyanin fluorescence to indicate NP-anthocyanin...

Blood vessels are constantly exposed to shear stress, a biomechanical force generated by blood flow. Normal shear stress sensing and barrier function are crucial for vascular homeostasis and are controlled by adherens junctions (AJs). Here we show that AJs are...

Insect cells have shown a high versatility to produce multiple recombinant products. The ease of culture, low contamination risk with human pathogens and high expression capacity makes an attractive platform to generate virus-like particles (VLPs). The baculovirus expression vector system...

Virus-like particles (VLPs) offer great promise in the field of nanomedicine. Enveloped VLPs are a class of these nanoparticles and their production process occurs by a budding process, which is known to be the most critical step at intracellular level....

Porous lightweight polycaprolactone (LPCL)-based microcarriers (MC) can be used for large-scale production of human mesenchymal stromal cells (MSC) in stirred bioreactors. These biodegradable MC can serve in delivering MSC, which exhibit improved bone healing in a rat calvarial defect model....

Aim: Evidence suggests that bisphenol A diglycidyl ether (BADGE), bisphenol A (BPA), and BPA analogs can interfere with human male fertility. However, the effect directly on human sperm function is not known. The CatSper Ca2+ channel in human sperm controls...

Establishing how to effectively manufacture cell therapies is an industry-level problem. Decentralised manufacturing is of increasing importance, and its challenges are recognised by healthcare regulators with deviations and comparability issues receiving specific attention from them. This paper is the first...

The production of virus-like particles (VLPs) has gained importance over the last few years owing to the benefits they provide compared to conventional vaccines. The biopharmaceutical industry is currently searching for safer candidates based on VLPs for new and existing...

Virus-like particles (VLPs) offer great promise in the field of nanomedicine. Enveloped VLPs are a class of these nanoparticles and their production process occurs by a budding process, which is known to be the most critical step at intracellular level....

Advances in the DNA nanotechnology have enabled the fabrication of DNA-based hydrogels with precisely controlled structures and tunable mechanical and biological properties. Compared to DNA hydrogel, preparation of RNA-based hydrogel remains challenging due to the inherent instability of naked RNA....

Background: Mesenchymal stem cells (MSCs) serve as an attractive vehicle for cell-directed enzyme prodrug therapy (CDEPT) due to their unique tumour-nesting ability. Such approach holds high therapeutic potential for treating solid tumours including glioblastoma multiforme (GBM), a devastating disease with...

The nature of enveloped virus-like particles (VLPs) has triggered high interest in their application to different research fields, including vaccine development. The baculovirus expression vector system (BEVS) has been used as an efficient platform for obtaining large amounts of these...

Children from low- and middle-income countries, where there is a high incidence of infectious disease, have the greatest need for the protection afforded by vaccination, but vaccines often show reduced efficacy in these populations. An improved understanding of how age,...

Previous studies focused on biocompatibility of graphene oxide (GO) to macrophages, but the impact of GO on lipid profiles in macrophages was less investigated. Herein, we investigated the interactions between THP-1 macrophages and GO of different sizes (GO of size...

We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if...

Exposure to multi-walled carbon nanotubes (MWCNTs) might induce lipid droplet (LD) biogenesis, but the roles of physicochemical properties of MWCNTs, as well as the mechanisms, remain poorly understood. In this study, we investigated lipid laden foam formation in THP-1 macrophages...

Spinocerebellar ataxia type 2 (SCA2), a rare polyglutamine neurodegenerative disorder caused by a CAG repeat expansion in the ataxin-2 gene, exhibits common cellular phenotypes with other neurodegenerative disorders, including oxidative stress and mitochondrial dysfunction. Here, we show that SCA2 patient...

Background: Gilles de la Tourette syndrome (GTS) is a neurodevelopmental condition characterized by motor and vocal tics. The underlying etiology remains largely unknown, and GTS is considered as a complex multifactorial disorder associated with effects of several genes in combination...

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible...

Aurora kinases are Ser/Thr kinases that function as mitotic regulators. 5-Methoxy-2-(2-methoxynaphthalen-1-yl)-4H-chromen-4-one (DK1913) is a synthetic pan-Aurora kinase inhibitor. However, the mode of action of DK1913 concerning the induction of apoptosis is unclear. Here, we report that DK1913 triggered apoptosis, as...

Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the...

Metastatic melanoma is the most aggressive type of skin cancer. Previously, we identified the plasma membrane Ca2+ pump isoform 4b (PMCA4b or ATP2B4) as a putative metastasis suppressor in BRAF mutant melanoma cells. Metastasis suppressors are often downregulated in cancer,...

The Marrubium genus (horehound) has proved to be an abundant source of biologically active compounds, but there is little knowledge about its potential anticancer activity. Moreover, some Marrubium species have not been the subject of study in this regard. In...

Background: Radiation is an important therapeutic tool. However, radiotherapy has the potential to promote co-evolution of genetic and epigenetic changes that can drive tumour heterogeneity, formation of radioresistant cells and tumour relapse. There is a clinical need for a better...

Mcl-1 is a potent antiapoptotic protein and amplifies frequently in many human cancer. Currently, it is considered that the extensively expressed of Mcl-1 protein in melanoma cells is associated with rapid tumor progression, poor prognosis and low chemosensitivity. Therefore, the...

Mcl-1 is a potent antiapoptotic protein which is amplified in many human cancer, while microphthalmia associated transcription factor (MITF) promotes cell proliferation and has pro-survival role. The study was designed to examine whether the interaction between ciprofloxacin, one of the...

Bisphosphonates, despite proven antitumor effect in vitro in many tumor types, are currently used only for treatment of osteoporosis and bone metastasis. Colorectal cancer is the third most commonly diagnosed type of cancer and lacks targeted therapy for RAS or...

Kidney cancer is one of the most lethal urological malignancies associated with a high risk of mortality. Recent studies have shown that several antidiabetic drugs may limit the risk of the growth of different types of cancer. Pioglitazone (PIO) belongs...

Malignant melanoma is a high aggressive malignancy in humans and causes 60-80% of deaths from skin cancer. Defect in an intrinsic pathway of apoptosis via overexpression of Mcl-1 is responsible for malignant melanoma development and progression, and also for resistance...

Application of substances from medicinal mushrooms is one of the interesting approaches to improve cancer therapy. In this study, we commenced a new attempt in the field of Heterobasidion annosum (Fr.) Bref. sensu lato to further extend our knowledge on...

hiosemicarbazide is a useful structural moiety that has the biological potential. Optimization of this structure can result in groundbreaking discovery of a new class of therapeutic agents. In the light of this, 1-(2,4-dichlorophenoxy)acetyl-4-(1-naphthyl)thiosemicarbazide (1) and 1,4-bis[(2,4-dichlorophenoxy)acetylthiosemicarbazide]phenyl (2) were synthesized and...

Acoustofluidics has been increasingly applied in biology, medicine and chemistry due to its versatility in manipulating fluids, cells and nano-/micro-particles. In this paper, we develop a novel and simple technology to fabricate a surface acoustic wave (SAW)-based acoustofluidic device by...

We performed a small interfering RNA screen to identify targets for cutaneous squamous cell carcinoma (cSCC) therapy in the ubiquitin/ubiquitin-like system. We provide evidence for selective anti-cSCC activity of knockdown of the E3 ubiquitin ligase MARCH4, the ATPase p97/VCP, the...

Thyroid cancer is the most commonly diagnosed endocrine cancer. Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer and has a poor prognosis. Loss of p53 function has been reported to lead to poorly differentiated thyroid tumors;...

Propolis and Bacopa monnieri (L.) Wettst. (Brahmi) are natural products that contain many active substances and possess anticancer properties. The aim of this study was to investigate the chemical composition of Polish propolis extract (PPE) by gas chromatography-mass spectrometry (GC-MS),...

Novel quinazolinone compounds have been studied in the field of drug discovery for a long time. Among their broad range of pharmacological effects, certain compounds effectively inhibit cancer cell proliferation. MJ‑33 is a quinazolinone derivative with proposed anticancer activities that...

Oxidoreductase protein disulphide isomerases (PDI) are involved in the regulation of a variety of biological processes including the modulation of endoplasmic reticulum (ER) stress, unfolded protein response (UPR), ER‑mitochondria communication and the balance between pro‑survival and pro‑death pathways. In the...

Background: Reactive oxygen species (ROS) generation specifically in cancer cells may be a promising strategy for their selective killing. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP23) exerts antitumor activity through ROS-mediated apoptosis in cancer cells but not in healthy cells. However,...

Background/aims: Proline availability for proline dehydrogenase/proline oxidase (PRODH/POX) may represent switching mechanism between PRODH/POX-dependent apoptosis and autophagy. The aim of the study was to evaluate the impact of overexpression of prolidase (proline releasing enzyme) on apoptosis/autophagy in breast cancer MCF-7...

While papillary thyroid cancer (PTC) has largely favorable prognosis, anaplastic thyroid cancer (ATC) is a rare but extremely aggressive malignancy with grim clinical outcome. Even though new therapeutic options are emerging for ATC, additional preclinical models and novel combinations are...

Melanoma, the most dangerous type of cutaneous neoplasia, contributes to about 75% of all skin cancer-related deaths. Thus, searching for new melanoma treatment options is an important field of study. The current study was designed to assess whether the condition...

Multiple myeloma (MM) is a plasma cell neoplasm that remains incurable due to innate or acquired resistance. Although MM cells produce high intracellular levels of reactive oxygen species (ROS), we hypothesised that they could remain sensitive to ROS unbalance. We...

The XPO1 gene encodes exportin 1 (XPO1) that controls the nuclear export of cargo proteins and RNAs. Almost 25% of primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) cases harboured a recurrent XPO1 point mutation (NM_003400, chr2:g61718472C>T) resulting...

Nanoparticles generated by recombinant technologies are receiving increased interest in several applications, particularly the use of virus like particles (VLPs) for the generation of safer vaccines. The characterization and quantification of these nanoparticles with complex structures is very relevant for...

Doxycycline is a semisynthetic, second generation tetracycline. Currently, it is used, among others, in the treatment of acne and skin infections. Moreover, doxycycline has many valuable nonantibiotic properties, including anti-inflammatory, immunosuppressive and anticancer effects. Recent studies showed that the drug...

Titanate nanotubes (TiNTs) have been considered as biocompatible nanomaterials (NMs) for biomedical uses. Hereby, we compared the toxicity of TiNTs and TiO2 nanoparticles (NPs) to human umbilical vein endothelial cells (HUVECs). Our results showed that TiNTs were less effectively internalized...

Adipose tissue plays an active role in the regulation of the body´s energy balance. Mesenchymal stem/stromal cells from adipose tissue (adMSC) are the precursor cells for repair and adipogenesis. Since the balance of the differentiation state of adipose tissue-resident cells...

Background: The production of large quantities of cardiomyocyte is essential for the needs of cellular therapies. This study describes the selection of a human-induced pluripotent cell (hiPSC) line suitable for production of cardiomyocytes in a fully integrated bioprocess of stem...

The circadian clock is an intrinsic oscillator that imparts 24 h rhythms on immunity. This clock drives rhythmic repression of inflammatory arthritis during the night in mice, but mechanisms underlying this effect are not clear. Here we show that the...

A hydrocyclone is a macroscale separation device employed in various industries, with many advantages, including high-throughput and low operational costs. Translating these advantages to microscale has been a challenge due to the microscale fabrication limitations that can be surmounted using...

Bortezomib (BOZ) is a proteasome inhibitor chemotherapeutic agent utilized to treat multiple myeloma and recently offered to cure melanoma. Bortezomib-induced neuropathy is one of the dose-limiting side-effects, which can be treated with antioxidants (e.g. alpha-lipoic acid-ALA and Vitamin B1-vit B1)....

Inherited defects in MyD88 and IRAK4, two regulators in Toll-like receptor (TLR) signaling, are clinically highly relevant, but still incompletely understood. MyD88- and IRAK4-deficient patients are exceedingly susceptible to a narrow spectrum of pathogens, with ∼50% lethality in the first...

Drug resistance limits the therapeutic efficacy in cancers and leads to tumor recurrence through ill-defined mechanisms. Glioblastoma (GBM) are the deadliest brain tumors in adults. GBM, at diagnosis or after treatment, are resistant to temozolomide (TMZ), the standard chemotherapy. To...

The formation and function of highly specialized cells and tissues in a multicellular organism from a single genome are enabled through differential spatiotemporal access to the information contained in the genomic DNA. The epigenome plays an essential role in how...

The conventional outflow pathway is a complex tissue responsible for maintaining intraocular pressure (IOP) homeostasis. The coordinated effort of multiple cells with differing responsibilities ensures healthy outflow function and IOP maintenance. Dysfunction of one or more resident cell types results...

The ever-growing biopharmaceutical industry relies on the production of recombinant therapeutic proteins in Chinese hamster ovary (CHO) cells. The traditional timelines of CHO cell line development can be significantly shortened by the use of targeted gene integration (TI). However, broad...

Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is...

The potential of adoptive cell therapy can be extended when combined with genome editing. However, variation in the quality of the starting material and the different manufacturing steps are associated with production failure and product contamination. Here, we present an...

The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to...

Currently available toxicity data on humidifier disinfectants are primarily limited to polyhexamethylene guanidine phosphate-induced lung fibrosis. We, therefore, investigated whether the sterilizer component Kathon, which is a mixture of chloromethylisothiazolinone and methylisothiazolinone, induces fibrotic lung injury following direct lung exposure...

Device-encapsulated human stem cell-derived pancreatic endoderm (PE) can generate functional β-cell implants in the subcutis of mice, which has led to the start of clinical studies in type 1 diabetes. Assessment of the formed functional β-cell mass (FBM) and its...

This work proposes a non-invasive method to estimate the number of red blood cells in the blood. To achieve the development of this research, first, a photosensitive device was designed, which is formed by a phototransistor with a transparent casing...

Several types of engineered nanoparticles (ENP) have been shown to adversely affect male reproduction in rodent studies, but the airway route of exposure has been little investigated. This precludes adequate risk assessment of ENP exposure in occupational settings. Titanium dioxide...

Although clinicians and researchers have long appreciated the detrimental effects of excessive acute inflammation after myocardial infarction (MI), less is known about the role of the adaptive immune system in MI complications including heart failure. Yet, abundant cardiac self-antigens released...

Self-assembled vesicles composed of amino acid-based cationic/anionic surfactant mixtures show promise as novel effective drug nanocarriers. Here, we report the in vitro performance of vesicles based on cationic (16Ser) and anionic (8-8Ser) serine-based surfactants using a cancer cell model for...

This work proposes a non-invasive method to estimate the number of red blood cells in the blood. To achieve the development of this research, first, a photosensitive device was designed, which is formed by a phototransistor with a transparent casing...

Computational fluid dynamics (CFD) modeling can be applied to understand hydrodynamics in stirred suspension bioreactors, which can in turn affect cell viability, proliferation, pluripotency and differentiation. In this study, we developed a CFD model to determine the effects of average...

Liver-on-a-Chip technology holds considerable potential for applications in drug screening and chemical-safety testing. To establish such platforms, functional hepatocytes are required; however, primary hepatocytes are commonly used, despite problems involving donor limitations, lot-to-lot variation, and unsatisfactory two-dimensional culture methods. Although...

Supplementation with NAD precursors such as nicotinamide riboside (NR) has been shown to enhance mitochondrial function in the liver and to prevent hepatic lipid accumulation in high-fat diet (HFD)-fed rodents. Hepatocyte-specific knockout of the NAD+-synthesizing enzyme nicotinamide phosphoribosyltransferase (NAMPT) reduces...

Background and objectives: Low-clearance drugs are widely used by industry mostly because of their often longer half-life, allowing for lower or less frequent dosing. Nevertheless, prediction of human clearance for these molecules from in vitro models presents a great challenge...

Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral...

Evaluating studies over the past almost 40 years, this review outlines the current knowledge and research gaps in the use of isolated leucocytes in salmonid immunology understanding. This contribution focuses on the techniques used to isolate salmonid immune cells and...

Background: Results of studies using current pre-clinical multiple myeloma (MM) models are limited in their ability to incorporate the effects bone marrow microenvironment has on cell proliferation, cell death, and drug resistance. 3D constructs, or organoids, have recently been tested...

Combining single-cell RNA sequencing (scRNA-seq) with upstream cell preservation procedures such as cryopreservation or methanol fixation has recently become more common. By separating cell handling and preparation, from downstream library generation, scRNA-seq workflows are more flexible and manageable. However, the...

A new generation of in vitro human brain models is vital to surpass the limitations of current cell culture platforms and animal cell lines in studying brain function and diseases. Brain-on-chip technology can generate well-defined and reproducible platforms to control...

Freshly isolated, uncultured, autologous adipose derived regenerative cells (ADRCs) have emerged as a promising tool for regenerative cell therapy. The Transpose RT system (InGeneron, Inc., Houston, TX, USA) is a system for isolating ADRCs from adipose tissue, commercially available in...

Gene therapy and viral vaccine are becoming attractive therapeutic options for the treatment of different malignant diseases. Viral vector productions are often using static culture vessels and small volume stainless steel bioreactors (SSB). However, the yield of each vessel can...

Industrialization of stem-cell based therapies requires innovative solutions to close the gap between research and commercialization. Scalable cell production platforms are needed to reliably deliver the cell quantities needed during the various stages of development and commercial supply. Human pluripotent...

Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor-intensive, require a large footprint, and are not suited to meet clinical and commercial...

Human mesenchymal stromal cell (hMSC) secretomes have shown to influence the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair. The angiogenic potential is of particular interest for the treatment of ischemic diseases. Interestingly, hMSC secretomes isolated from different tissue...

Mesenchymal stromal cell (MSC) therapies have been pursued for a broad spectrum of indications but mixed reports on clinical efficacy have given rise to some degree of skepticism regarding the effectiveness of this approach. However, recent reports of successful clinical...

Loss of anorectal resting pressure due to internal anal sphincter (IAS) dysfunctionality causes uncontrolled fecal soiling and leads to passive fecal incontinence (FI). The study is focused on immediate and long-term safety and potential efficacy of bioengineered IAS BioSphincters to...

The prerequisite for a successful clinical use of autologous adipose-tissue-derived cells is the highest possible regenerative potential of the applied cell population, the stromal vascular fraction (SVF). Current isolation methods depend on high enzyme concentration, lysis buffer, long incubation steps...

CARD9 is an immune adaptor protein in myeloid cells that is involved in C-type lectin signaling and antifungal immunity. CARD9 is implicated in autoimmune and inflammatory-related diseases, such as rheumatoid arthritis, IgA nephropathy, ankylosing spondylitis, and inflammatory bowel disease (IBD)....

The interleukin (IL)-23/IL-17 axis plays a central role in the pathogenesis of psoriasis and is elevated in lesional psoriatic skin. Different murine models have been developed to mimic this pathophysiology each carrying specific merits and limitations. In an attempt to...