Publications

High-resolution respirometry (HRR) can assess PBMC bioenergetics, but no standardized medium for PBMC preparation and HRR analysis exist. Here, we study the effect of four different media (MiR05, PBS, RPMI, Plasmax) on quantification, size, and HRR analysis (Oxygraph-O2k) of intact...

This study explored the radioprotective effects and possible underlying mechanisms of KR-31831 against radiation-induced injury in a mouse model. KR-31831 (30 and 50 mg/kg) was administered to mice 24 h and 30 min before exposure to a single lethal or...

Carnosine (β-alanyl-L-histidine) is found in beef and fish. The present study aimed to investigate the effects of carnosine on the cell proliferation of human colorectal cancer cells. After human colorectal cancer HCT-116 cells were treated carnosine for 72 or 96...

The aim of the present study was to investigate the cytotoxicity induced by an omega-3 derivative, didocosahexaenoin (Dido) on human prostate carcinoma cells and to compare the cytotoxicity to that of docosahexaenoic acid (DHA). Different carcinoma- and non-carcinoma cells were...

Novel (Z)-3-((4,6-diphenylpyrimidin-2-ylamino)methylene)-2,3-dihydrochromen-4-one derivatives were designed and synthesized to find chemotherapeutic agents. Derivative 9 was selected based on its clonogenicity against cancer cells and synthetic yield for further biological experiments. It showed decreases in aurora kinase A, B, and C phosphorylation...

Small intestine adenocarcinoma is a rare intestinal malignancy with distinct clinical, pathological, and molecular characteristics. Recently, a fusion of the intestinal stem-cell marker olfactomedin 4 (OLFM4) and the proto-oncogene RET has been identified in a small intestine adenocarcinoma patient. Here...

Cultured meat is an emergent technology with the potential for significant environmental and animal welfare benefits. Accurate mimicry of traditional meat requires fat tissue; a key contributor to both the flavour and texture of meat. Here, we show that fibro-adipogenic...

Background and aims: Autologous keratinocyte sheets constitute an important component of the burn wound treatment toolbox available to a surgeon and can be considered a life-saving procedure for patients with severe burns over 50% of their total body surface area....

Nickel oxide nanoparticles (NiO NPs) are highly redox active nanoparticles. They can cause acute and chronic inflammation in rat lungs. Unlike the gut microbiome, the association between the lung microbiome’s role and pulmonary inflammatory response to inhaled nanoparticles remains largely...

Three-dimensional (3D)-bioprinted lipoaspirate-derived adipose tissue (LAT) is a potential alternative to lipo-injection for correcting soft-tissue defects. This study investigated the long-term in vivo survival of 3D-bioprinted LAT and its proteomic signature and cellular composition. We performed proteomic and multicolour flow...

Chimeric antigen receptor T (CAR-T) cell therapy has led to a paradigm change in cancer treatment. To allow widespread use of this therapy, it is important to reduce the costs associated with cells manufacturing whilst ensuring a high-quality production. Online...

Cell therapy using multipotential stromal cells (MSCs) is being used in a variety of clinical settings to induce tissue regeneration. Promising results have also been achieved in the therapy of osteoarthritis. MSCs have been demonstrated to be safe (Borakati et...

Erectile dysfunction is a common complication associated with type 2 diabetes mellitus (T2DM) and after prostatectomy in relation to cancer. The regenerative effect of cultured adipose-derived stem cells (ASCs) for ED therapy has been documented in multiple preclinical trials as...

Despite the relatively long history of captive breeding, the Arctic charr still exhibits a generally low, but highly variable reproductive performance in aquaculture. A recent publication exposed potential paternal factors influencing the reproductive outcome of Arctic charr broodstock from the...

This study emphasis improved semen cryopreservation protocol for commercial scale fertilization in European perch. The optimized procedure involves a new extender (GM 25 K) containing 0.30 M glucose, 7.5% methanol and 25 mM KCl at 3.0 × 109/mL spermatozoa. The...

The growing and widespread use of glyphosate-based herbicides (GBHs) has raised an intense public debate about the impact of environmental contamination on animal and human health, including male fertility. The aim of this study was to deepen the impact of...

Although several protocols for cryopreserving buck semen are described in the literature, they differ widely in factors such as season and method of semen collection, extender and sperm concentration. Therefore, choosing a protocol that is suitable for a particular on-farm...

The junction between the double-stranded and single-stranded telomeric DNA (ds-ss junction) is fundamental in the maintenance of the telomeric chromatin, as it directs the assembly of the telomere binding proteins. In budding yeast, multiple Rap1 proteins bind the telomeric dsDNA,...

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...

Background aims: Next-generation immune cell therapy products will require complex modifications using engineering technologies that can maintain high levels of cell functionality. Non-viral engineering methods have the potential to address limitations associated with viral vectors. However, while electroporation is the...

Early-onset epileptic encephalopathies are severe disorders often associated with specific genetic mutations. In this context, the CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by early-onset seizures, intellectual delay, and motor dysfunction. Although crucial for proper brain development, the...

STUDY QUESTION Do selective serotonin reuptake inhibitor (SSRI) antidepressants affect the function of human sperm? SUMMARY ANSWER The SSRI antidepressant Sertraline (e.g. Zoloft) inhibits the sperm-specific Ca2+ channel CatSper and affects human sperm function in vitro. WHAT IS KNOWN ALREADY...

Hepatocellular carcinoma (HCC) is a worldwide health problem. Currently, there is no effective therapeutic strategy for HCC patients. Chewing areca nut is closely associated with oral cancer and liver cirrhosis. The therapeutic effect of areca nut extract (ANE) on HCC...

Lemon (Citrus limon) has antioxidant, immunoregulatory, and blood lipid-lowering properties. This study aimed to determine the effect of the lemon fermented product (LFP) which is lemon fermented with Lactobacillus OPC1 to prevent obesity. The inhibition of lipid accumulation in 3T3-L1...

Background/aim: Magnetic resonance imaging (MRI) is a technique for evaluating patients with primary and metastatic tumors. The contrast agents improve the diagnostic accuracy of MRI. Large quantities of a contrast agent must be administrated into the patient to obtain useful...

Aim: Mesenchymal stromal cells (MSCs) emerged as a promising therapeutic option for osteoarthritis (OA) management, in particular those isolated from adipose tissue (hASCs) and amniotic membrane (hAMSCs). The cartilage protective and immunomodulatory features of hASCs and hAMSCs are ascribed to...

Super-enhancers are clusters of enhancers associated with cell lineage. They can be powerful gene-regulators and may be useful in cell-type specific viral-vector development. Here, we have screened for endothelial super-enhancers and identified an enhancer from within a cluster that conferred...

Background: Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity....

Scaffolds of recombinant spider silk protein (spidroin) and hyaluronic acid (HA) hydrogel hold promise in combination with cell therapy for spinal cord injury. However, little is known concerning the human immune response to these biomaterials and grafted human neural stem/progenitor...

Human induced pluripotent stem cells (iPSCs) and macrophages derived from them are increasingly popular tools for research into both infectious and degenerative diseases. However, as the field strives for greater modeling accuracy, it is becoming ever more challenging to justify...

Background/aim: The pathway of initiation of psoriasis comprises the differentiation and infiltration of T-helper 17 (Th17) cells into the skin, characterized by the production of interleukin 17A and 17F (IL-17A/IL-17F) among other cytokines, resulting in a downstream cascade of events....

Tubular nanomaterials (NMs), such as multi-walled carbon nanotubes (MWCNTs) and halloysite nanotubes (HNTs), may be used in biomedicine, but previous studies showed that MWCNTs induced toxicity to endothelial cells (ECs). However, the influence of tubular NMs on EC lipid profiles...

DNA-RNA hybrid structures have been detected at the vicinity of DNA double-strand breaks (DSBs) occurring within transcriptional active regions of the genome. The induction of DNA-RNA hybrids strongly affects the repair of these DSBs, but the nature of these structures...

The success of graphene oxide (GO) has attracted extensive research interests in developing novel 2D nanomaterials (NMs). Graphdiyne (GDY) is a new member of carbon-based 2D NMs possessing sp- and sp2 -hybridized carbon atoms. However, the toxicity of GDY is...

Arginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with arginine synthesis deficiency. Arginine-deprived cancer cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we...

T cell based treatments in the setting of allogenic haematopoietic stem cell transplantation (HSCT) have been used for decades. In addition, the use of chimeric antigen receptor (CAR) T cells has been introduced as a promising cancer immunotherapy. A prerequisite...

Nrf2 is one of the important therapeutic targets studied extensively in several cancers including the carcinomas of the colon and rectum. However, to date, not many Nrf2 inhibitors showed promising results for retarding the growth of colorectal cancers (CRCs). Therefore,...

Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome, and the current standard of care is the use of tyrosine kinase inhibitors (TKI). However, some patients will not achieve a molecular response and may progress to...

Titanium dioxide (TiO2) nanomaterials have been shown to promote atherosclerosis through endothelial dysfunction. This study investigated the toxicity of TiO2 nanosheets (NSs) to vascular smooth muscle cells (VSMCs), one of the pivotal cells involved in all stages of atherosclerosis. Only...

Messenger RNA (mRNA) delivery provides gene therapy with the potential to achieve transient therapeutic efficacy without risk of insertional mutagenesis. Amongst other applications, mRNA can be employed as a platform to deliver gene editing molecules, to achieve protein expression as...

The wide uses of graphene oxide (GO) lead to the contact of GO with vascular systems, so it is necessary to investigate the toxicological effects of GO to endothelial cells. Recently, we reported that GO of small lateral size (

Next-generation sequencing (NGS) has revolutionized genomics, decreasing sequencing costs and allowing researchers to draw correlations between diseases and DNA or RNA changes. Technical advances have enabled the analysis of RNA expression changes between single cells within a heterogeneous population, known...

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...

The Coalition for Epidemic Preparedness Innovations’ ‘100-day moonshot’ aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work to optimize adenovirus vector manufacturing for rapid response, by minimizing time to clinical trial and first...

The aim of this work is the design, preparation and characterization of membranes based on cyclosporine A (CsA) and chitosan carboxylate (CC) to be used as an implantable subcutaneous medical device for a prolonged therapeutic effect in the treatment of...

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...

Human adipose stem cells (hASCs) are promising candidates for cell-based therapies, but they need to be efficiently expanded in vitro as they cannot be harvested in sufficient quantities. Recently, dynamic bioreactor systems operated with microcarriers achieved considerable high cell densities....

Mitochondria are cellular organelles critical for numerous cellular processes and harboring their own circular mitochondrial DNA (mtDNA). Most mtDNA associated disorders (either deletions, mutations, or depletion) lead to multisystemic disease, often severe at a young age, with no disease-modifying therapies....

Chronic kidney disease (CKD) is a common condition and leading cause of mortality in cats. Mesenchymal stromal cells (MSCs) may have a therapeutic effect on CKD. The aim of this pilot study was to determine efficacy of systemically-administered allogeneic uterine...

In this study, we investigated the combination of extracellular (nano) vesicles (EVs) from pig adipose tissue-derived stromal cells (ADSCs) and a thermoresponsive gel, Pluronic® F-127 (PF-127), to prevent stricture formation after endoscopic resection in a porcine model. ADSC EVs were...

Full term pregnancy at an early age is the only factor known to consistently protect against breast cancer. Because hormone receptor positive progenitors in the human breast relay endocrine signaling, we here sought to determine whether an experimental mimicry of...

Background: Mesenchymal stem cells have been proven to promote cellular recruitment and remodeling during healing. Considering challenges encountered in the healing process of esophageal injury, we sought to evaluate the effect of human adipose derived stem cells (hASC) on esophageal...

Follicular lymphoma (FL), a non-Hodgkin lymphoma, is an indolent cancer of the B cell lineage that runs a chronic deterioration course that can result in multiple treatment episodes leading to resistance and possible transformation to diffuse large B cell lymphoma....

Polo-like kinase 1 (PLK1) is an important cell cycle kinase and an attractive target for anticancer treatments. An ATP-competitive small molecular PLK1 inhibitor, volasertib, has reached phase III in clinical trials in patients with refractory acute myeloid leukemia as a...

Little is known about the involvement of type 2 immune response-promoting intestinal tuft cells in metabolic regulation. We here examined the temporal changes in small intestinal tuft cell number and activity in response to high-fat diet-induced obesity in mice and...

Carbon nanotubes (CNTs) are speculated to cause mesothelioma by persistent inflammation, oxidative stress, tissue injury, and genotoxicity. To investigate the pleural response to CNTs, we exposed C57BL/6 mice by intrapleural injection of 0.2 or 5 µg multiwalled CNTs (MWCNT-7, NM-401,...

Traumatic brain injury (TBI) causes both physical disruption of the blood brain barrier (BBB) and altered immune responses that can lead to significant secondary brain injury and chronic inflammation within the central nervous system (CNS). Cell therapies, including mesenchymal stromal...

Following European regulation 1394/2007, mesenchymal stromal cell (MSCs) have become an advanced therapy medicinal product (ATMP) that must be produced following the good manufacturing practice (GMP) standards. We describe the upgrade of our existing clinical-grade MSC manufacturing process to obtain...

Integration-free induced pluripotent stem cells from related human donors’ exhibit great potential to the ongoing development of organ models. Blood cells from two different human donors were isolated, purified and reprogrammed into induced pluripotent stem cells. These induced pluripotent stem...

The SpinVessel system provides a methodology using pulsed radial flow to gently mix and uniformly suspend particulates (cells, magnetic beads, silica beads, and microcarrier beads) for automated assays. SpinVessels are well suited for aliquoting on robotic liquid handlers and with...

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic...

The human embryonal kidney 293 cell (HEK-293) is a widely used expression host for transient gene expression. The genes or plasmids used for the transient transfections are usually propagated and extracted from the gram-negative bacterium Escherichia coli, the workhorse for...

Background Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) revealed their key role in immune regulation, offering promising therapeutic perspectives for immune and inflammatory diseases. We aimed to develop a production process of an UC-MSC-based product and then to characterize UC-MSC properties...

Background: Use of donor granulocyte concentrate (GC) has been limited due to its short storage time of 6-24 h, which is partially due to residual red blood cells (RBCs) and platelets and the resulting lactate production leading to an acidotic...

Objectives: The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present a structured workflow to extract process relevant information...

Preparation and growth factor characterization of cord blood-derived plasma, serum, growth factor-rich plasma and induced serum

Background: Human Mesenchymal stromal cells (hMSCs) from various tissue sources are widely investigated in clinical trials. These MSCs are often administered to patients immediately after thawing the cryopreserved product (out-of-thaw), yet little is known about the single-cell transcriptomic landscape and...

Background: Pulmonary exposure to high doses of engineered carbonaceous nanomaterials (NMs) is known to trigger inflammation in the lungs paralleled by an acute phase response. Toll-like receptors (TLRs), particularly TLR2 and TLR4, have recently been discussed as potential NM-sensors, initiating...

Mesenchymal stem cells (MSCs) have emerged as a new therapy for various immune-mediated inflammatory diseases. In this study we perform the first double-blinded, placebo-controlled evaluation of the efficacy of adipose-derived allogenic canine MSCs for the treatment of canine atopic dermatitis...

Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many...

The promise of human induced pluripotent stem cells (iPSCs) lies in their ability to serve as a starting material for autologous, or patient-specific, stem cell-based therapies. Since the first publications describing the generation of iPSCs from human tissue in 2007,...

The objective of this study was to investigate bulk tank somatic cell count and associated risk factors influencing the hygienic quality and chemical composition of raw milk; additionally, to assess the impact of somatic cell count (SCC/ml) on the microbial...

The use of safe feed additives in diets of lactating animals has gained increasing interest. The effects of feeding lactating goats on diet supplemented with crude coriander oil at different levels were evaluated. Thirty multiparous lactating Damascus × Baladi goats...

Refreezing freeze-thawed sperm has been found to improve the effectiveness of cryopreserved semen in mammals. However, such options have been never tested in fish. The objectives of this study were (i) to assess the effects of two freeze–thaw cycles on...

Within the study, attempts towards standardized cryopreservation procedure for cultured pikeperch semen were undertaken. The specific aims of this study were to examine the effects of final glucose and sperm concentrations on the cryopreservation success of cultured pikeperch semen measured...

Antifreeze protein (AFP) has been shown to have beneficial effects on frozen mammalian spermatozoa. However, rare reports have been published regarding the use of AFPs in storage of goat spermatozoa. The aim of this study was to investigate the effects...

Under in vitro conditions, stallion sperm might preferentially use energy substrates that primarily undergo mitochondrial metabolism. The present study sought to determine the effects of glucose, pyruvate, lactate, or their combinations on the quality of stallion sperm subjected to cooled...

In modern livestock breeding, cryopreserved semen is routinely used for artificial insemination. Sperm cryopreservation allows for long-term storage of insemination doses and secures reproduction at a desired time point. In order to cryopreserve semen, it needs to be carefully processed...

We compared the results of using egg yolk plasma (EYP) instead of egg yolk (EY) in a TRIS-based Equex STM Paste freezing extender system for dog semen [25]. We also tested whether the addition of lecithin and catalase to the...

Besides classical semen parameters, semen stress tests (SSTs) are helpful tools to assess the fertilizing capacity of sperm. However, valid studies on SSTs in relation to fertility are rare because several corrections of common fertility parameters for female and male...

Sperm mitochondrial function is essential for normal physiology and fertility, but the importance of mitochondrial activity to support specific sperm functions, such as motility, varies between species. It was previously believed that mitochondrial function was not necessary for bull sperm...

Artificial insemination using semen from genetically superior sires remains one of the most effective biotechnologies ever commercialized for animal breeding purposes. Genetic progress, however, cannot begin until conception occurs. Processing laboratories that provide cryopreserved bull semen for commercial use depend...

The conventional storage temperature of 16-18 °C provides optimal conditions for the preservation of boar sperm quality, which are extremely cold sensitive cells. On the other hand, however, it requires the addition of antibiotics to inhibit bacterial growth. Rising numbers...

Semen evaluation is a fundamental part of breeding soundness examination of males, including stallions. New technologies have been implemented in both the research arena and clinical practice for analysis of stallion sperm; therefore, theriogenologists and general equine practitioners should become...

Sperm DNA fragmentation compromises fertilization and early embryo development. Since spermatozoa lack the machinery to repair DNA damage, to improve the likelihood of establishing a healthy pregnancy, it is preferable to process ejaculates of stallions with a high sperm DNA...

Control of the reproduction of domesticated stocks is considered a prerequisite for aquaculture development of pikeperch. However, knowledge about the physiology of the captive pikeperch male reproductive system and the biology of semen is very limited, especially regarding protein characteristics....

Mitochondrial function is essential for sperm viability, not only from a sperm metabolism perspective, but also for improvement of sperm storage in liquid and frozen states. Bull sperm have notable metabolic variability with energy production for motility and subsequently for...

Purpose: To define the effect of sperm agglutination, associated with incubation under capacitating conditions, on accuracy of membrane assessment via flow cytometry and to develop methods to mitigate that effect. Methods: Sperm motility was measured by CASA. Sperm were stained...

It is known that sperm cells will settle out of extender over time which could impact the concentration per dose within a batch. The objective of this study to investigate the effects of mixing prior to packaging on concentration of...

Microorganisms, including pathogenic or opportunistic bacteria and fungi, may gain access to the uterus during breeding, and infectious endometritis plays a major role in equine subfertility. This study aimed to assess the post-breeding inflammatory response, endometrial culture, and embryo recovery...

The objective of this study was to evaluate the repeatability and accuracy of canine sperm motility (total and progressive) assessment with a tablet-based Canine iSperm instrument compared to computer-assisted sperm analysis (CASA). The experiment used fresh and frozen/thawed canine semen...

Coenzyme Q-10 (CoQ-10) is a cofactor for mitochondrial electron transport chain and may be an alternative to improve sperm quality of cryopreserved equine semen. This work aimed to improve stallion semen quality after freezing by adding CoQ-10 to the cryopreservation...

Background: Centrifugation is routinely employed in handling the ejaculates of some species, but it is not part of the commonly used protocols in ram. However, the development and implementation of new assisted reproductive technologies, alternative preservation models based on washing...

This experiment was conducted to assess the effect of different antibiotics in tris-fructose egg yolk-based diluent on bacterial load and sperm quality of dromedary camels during processing and cold storage. Ten semen ejaculates were collected from five male dromedary camels....

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...

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...

Electroconductive hydrogels and scaffolds have great potential for strain sensing and in tissue engineering. Herein, we designed electroconductive self-healing hydrogels and shape-recoverable scaffolds with injectability, strain/motion-sensing ability, and neural regeneration capacity. The crosslinked network of hydrogels and scaffolds was synthesized...

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...

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...

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...

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...

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...

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”...

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...

Hepatocyte-like cells derived from human pluripotent stem cells (hPSC-HLCs) offer an alternative to primary hepatocytes commonly used for drug screenings and toxicological tests. Although tremendous efforts have been made to facilitate hepatic functions of hPSC-HLCs using growth factors and chemicals,...

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...

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...

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...

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...

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...

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...

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...

Objective: (1) Determine if sequential administration of standard chemotherapy (paclitaxel and cisplatin, P/C) with epigenetic drugs effectively targets ovarian cancer and limits toxicity to normal cells. (2) Define whether epigenetic treatment can shorten the exposure to P/C. Methods: Normal cells—adipocyte-derived...

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...

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,...

Mastitis is the most common infection of dairy goats impairing milk production and quality, which is usually recognized by mammary gland visual inspection and palpation. Subclinical forms of the disease are also widely represented, which lack the typical signs of...

In Egypt, inadequate information on prevalence and epidemiology of caprine mastitis is available. This study was designed to investigate prevalence and etiological agents of caprine mastitis and assess the efficacy of somatic cell count (SCC) as marker of subclinical mastitis...

The objectives of the present study were to analyze systematic effects on semen quality traits from fresh and frozen-thawed semen collected in and outside season. A total of 4,681 reports on semen traits of 121 stallions representing Arabian, Thoroughbred, Quarter...

Urospermia is a major ejaculatory dysfunction affecting stallions. It has been thought that urine-contaminated semen should not be cryopreserved; however, on select cases, urine contamination of semen cannot be avoided. A recent study suggested that urospermic semen can be cryopreserved...

Centrifugation of boar semen through one layer of 40% colloid (Porcicoll) was previously shown to separate spermatozoa from bacteria without having a detrimental effect on sperm quality. However, some spermatozoa were lost. The purpose of the present study was to...

Oxidative stress is regarded as an important cause of sperm damage during cryopreservation. However, seasonal changes in oxidative status in unfrozen and frozen-thawed stallion sperm have not been well established. We tested the hypothesis that sperm ROS concentrations and lipid...

The purpose of the present study was to evaluate the effects of season on the in vitro fertilizing ability of bovine spermatozoa and subsequent embryo development. Bovine oocytes were matured and fertilized in vitro with Holstein dairy bull sperm cells...