Rate Of Metabolic Activity Research Articles

Oxidative Stress in an African Ground Squirrel, a Case of Healthy Aging and Reproduction.

Oxidative stress plays a crucial role in mediating life-history processes, where it can compromise survival and reproduction through harmful alterations to DNA, lipids, and proteins. In this study, we investigated oxidative stress in Cape ground squirrels (Xerus inauris), a longer-lived African ground squirrel species with a high reproductive skew and unique life history strategies. We measured oxidative stress as total antioxidant capacity (TAC), total oxidant status (TOS), and an oxidative stress index (OSI) in blood plasma from individuals of approximately known ages. Our results reveal a distinct pattern of decreasing oxidative stress with age, consistent across both sexes. Females exhibited lower OSI and TOS levels than males. Males employing different life-history strategies, namely natal (staying at home), had significantly lower oxidative stress compared to the band (roaming male groups), likely due to variations in metabolic rate, activity, and feeding rates. However, both strategies exhibited reduced oxidative stress with age, though the underlying mechanisms require further investigation. We propose that selection pressures favoring survival contributed to the observed reduction in oxidative stress with age, potentially maximizing lifetime reproductive success in this species.

Effect of viscosity of gelatin methacryloyl-based bioinks on bone cells

The viscosity of gelatin methacryloyl (GelMA)-based bioinks generates shear stresses throughout the printing process that can affect cell integrity, reduce cell viability, cause morphological changes, and alter cell functionality. This study systematically investigated the impact of the viscosity of GelMA-gelatin bioinks on osteoblast-like cells in 2D and 3D culture conditions. Three bioinks with low, medium, and high viscosity prepared by supplementing a 5% GelMA solution with different concentrations of gelatin were evaluated. Cell responses were studied in a 2D environment after printing and incubation in non-cross-linked bioinks that caused the gelatin and GelMA to dissolve and release cells for attachment to tissue culture plates. The increased viscosity of the bioinks significantly affected cell area and aspect ratio. Cells printed using the bioink with medium viscosity exhibited greater metabolic activity and proliferation rate than those printed using the high viscosity bioink and even the unprinted control cells. Additionally, cells printed using the bioink with high viscosity demonstrated notably elevated expression levels of alkaline phosphatase and bone morphogenetic protein-2 genes. In the 3D condition, the printed cell-laden hydrogels were photo-cross-linked prior to incubation. The medium viscosity bioink supported greater cell proliferation compared to the high viscosity bioink. However, there were no significant differences in the expression of osteogenic markers between the medium and high viscosity bioinks. Therefore, the choice between medium and high viscosity bioinks should be based on the desired outcomes and objectives of the bone tissue engineering application. Furthermore, the bioprinting procedure with the medium viscosity bioink was used as an automated technique for efficiently seeding cells onto 3D printed porous titanium scaffolds for bone tissue engineering purposes.

Differential regulation of mitochondrial uncoupling protein 2 in cancer cells

The persistent growth of cancer cells is underscored by complex metabolic reprogramming, with mitochondria playing a key role in the transition to aerobic glycolysis and representing new therapeutic targets. Mitochondrial uncoupling protein 2 (UCP2) has attracted interest because of its abundance in rapidly proliferating cells, including cancer cells, and its involvement in cellular metabolism. However, the specific contributions of UCP2 to cancer biology remain poorly defined. Our investigation of UCP2 expression in various human and mouse cancer cell lines aimed to elucidate its links to metabolic states, proliferation, and adaptation to environmental stresses such as hypoxia and nutrient deprivation. We observed significant variability in UCP2 expression across cancer types, with no direct correlation to their metabolic activity or proliferation rates. UCP2 abundance was also differentially affected by nutrient availability in different cancer cells, but UCP2 was generally downregulated under hypoxia. These findings challenge the notion that UCP2 is a marker of malignant potential and suggest its more complex involvement in the metabolic landscape of cancer.

Ultrasonic-assisted extraction, anti-biofilm activity, and mechanism of action of Ku Shen (Sophorae Flavescentis Radix) extracts against Vibrio parahaemolyticus.

The objective of this study is to optimize the ultrasonic-assisted extraction process of Ku Shen (Sophorae Flavescentis Radix) extracts (KSE) against Vibrio parahaemolyticus and explore their anti-biofilm activity and mechanism of action. The ultrasonic-assisted extraction process of KSE optimized by single factor experiment, Box-Behnken design and response surface methodology was as follows: 93% ethanol as solvent, liquid/material ratio of 30 mL/g, ultrasonic power of 500 W, extraction temperature of 80°C and time of 30 min. Under these conditions, the diameter of inhibition circle of KSE was 15.60 ± 0.17 mm, which had no significant difference with the predicted value. The yield of dried KSE is 32.32 ± 0.57% and the content of total flavonoids in KSE was 57.02 ± 5.54%. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of KSE against V. parahaemolyticus were 0.25 and 0.5 mg/mL, respectively. Crystal violet staining, Congo red plate, spectrophotometry, CCK-8 and scanning electron microscopy were used to investigate the activity and mechanism of action of KSE against V. parahaemolyticus biofilm. The results showed that the sub-MIC of KSE could significantly inhibit biofilm formation, reduce the synthesis of polysaccharide intercellular adhesin (PIA) and the secretion of extracellular DNA. In addition, the inhibition rate of biofilm formation and clearance rate of mature biofilm of 1.0 mg/mL KSE were 85.32 and 74.04%, and the reduction rate of metabolic activity of developing and mature biofilm were 77.98 and 74.46%, respectively. These results were confirmed by visual images obtained by scanning electron microscopy. Therefore, KSE has the potential to further isolate the anti-biofilm agent and evaluate it for the preservation process of aquatic products.

Preparation and in vitro evaluation of cell adhesion and long-term proliferation of stem cells cultured on silibinin co-embedded PLGA/Collagen electrospun composite nanofibers

The present research aims to evaluate the efficacy of Silibinin-loaded mesoporous silica nanoparticles (Sil@MSNs) immobilized into polylactic-co-glycolic acid/Collagen (PLGA/Col) nanofibers on the in vitro proliferation of adipose-derived stem cells (ASCs) and cellular senescence. Here, the fabricated electrospun PLGA/Col composite scaffolds were coated with Sil@MSNs and their physicochemical properties were examined by FTIR, FE-SEM, and TGA. The growth, viability and proliferation of ASCs were investigated using various biological assays including PicoGreen, MTT, and RT-PCR after 21 days. The proliferation and adhesion of ASCs were supported by the biological and mechanical characteristics of the Sil@MSNs PLGA/Col composite scaffolds, according to FE- SEM. PicoGreen and cytotoxicity analysis showed an increase in the rate of proliferation and metabolic activity of hADSCs after 14 and 21 days, confirming the initial and controlled release of Sil from nanofibers. Gene expression analysis further confirmed the increased expression of stemness markers as well as hTERT and telomerase in ASCs seeded on Sil@MSNs PLGA/Col nanofibers compared to the control group. Ultimately, the findings of the present study introduced Sil@MSNs PLGA/Col composite scaffolds as an efficient platform for long-term proliferation of ASCs in tissue engineering.

Substrate softness increases magnetic microdiscs-induced cytotoxicity.

Cytotoxicity of nanoparticles is primarily assessed on cells grown in plastic culture plates, a mechanical environment that is a million times stiffer than most of the human tissues. Here we question whether nanoparticles cytotoxicity is sensitive to the stiffness of the extracellular environment. To this end, we compare the metabolic activity, the proliferation and death rates, and the motility of a glioblastoma cancer cell line and a fibroblast cell line exposed to gold-coated Ni80Fe20 microdiscs when grown on a glass substrate or on a soft substrate whose mechanical properties are close to physiology. Our main result is that cells grown on soft substrates take up more microdiscs which results in greater toxic effects, but also that toxicity at similar particle load is more pronounced on soft substrates especially at large concentration of nanoparticles. These results suggest that both microdiscs uptake and their intracellular processing differ between soft and rigid substrates.

Adverse effect of Tamarindus indica and tamoxifen combination on redox balance and genotoxicity of breast cancer cell

BackgroundBreast cancer is the most significant threat to women worldwide. Most chemotherapeutic drugs cause cancer cell death and apoptosis by inducing oxidative stress and producing reactive oxygen species (ROS). Cancer cells have a higher rate of metabolic activity than normal cells and thus produce more ROS. Glutathione and its related enzymes are the most significant antioxidant defense mechanisms that protect cells from oxidative and chemotherapeutic impacts. The anticancer actions of phenolic compounds were greatly confirmed. Using phenolic compounds as drugs in combination with chemotherapy may improve health, improve treatment outcomes, and reduce dose and damage. The goal of the study was to treat breast cancer cell lines (MCF-7) with Tamarindus indica extract individually and in combination with the anticancer drug tamoxifen (TAM) to improve therapeutic efficacy. ResultsAfter 48 h of incubation at IC25 concentrations of T. indica extract (47.3 g/mL), tamoxifen (0.8 g/mL), and their co-treatments, the biochemical and genotoxic effects on MCF-7 cell lines were investigated. In MCF7 cell lines, T. indica extract increased reduced glutathione levels as well as glutathione transferase, glutathione peroxidase, and glutathione reductase activities. The same was true for oxidative state indicators, where higher levels of catalase and lactate dehydrogenase activity were associated with higher levels of malondialdehyde. T. indica has almost no effect on the DNA damage parameters. All of these variations can produce alterations in cancer cell genotoxicity and apoptotic pathways, explaining the restoration of DNA moment to normal levels and enhanced survival. ConclusionCytotoxic and genotoxic effect of treatment with T. indica extract could be attributed to the dynamic interaction of glutathione cycle and antioxidant enzymes to combat oxidative stress, which can be considered as a positive therapeutic effect. On the other hand, the negative response of tamoxifen efficacy when co-treated with T. indica reversed tamoxifen’s genotoxicity and enhanced survival.

Hipoxia modulates the secretion of growth factors of human umbilical cord-derived mesenchymal stem cells.

Mesenchymal stem cell (MSC) has great potential as therapies due its ability to regenerate tissue damage and promote tissue homeostasis. Preconditioning of MSC in low oxygen concentration has been shown to affect the therapeutic potential of these cells. This study aimed to compare the characteristic and secretion of trophic factors of MSCs cultured under hypoxia and normoxia. MSCs were isolated from Wharton's jelly of human umbilical cord (UC) tissue by explant method and characterized by flow cytometry. Following 24 h of CoCl2-induced hypoxic culture, the viability and metabolic activity of MSC were analyzed by trypan blue exclusion test and methyl thiazolyl tetrazolium (MTT) assay, respectively. The secretion of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) was assessed in conditioned medium using enzyme-linked immunosorbent assay (ELISA) method. Flow cytometry analysis showed >99% of the population of MSCs cells were positive for CD73 and CD90 and > 62% were positive for CD105. While the cell viability of MSC was not affected by hypoxic cultured condition, the metabolic activity rate of these cells was decreased under hypoxic conditioning. In line with reduced metabolic activity, hypoxic human UC-derived MSC produced less HGF than normoxic counterpart. Compared to normoxic MSC, hypoxic preconditioned MSC secreted higher level of VEGF in the conditioned medium (p < 0.05). Hypoxia decreased the metabolic activity of MSCs associated with the modulation of HGF and VEGF secretions. It is suggested that hypoxia may also affect the therapeutic capacity of MSC cells.

Computational reactive–diffusive modeling for stratification and prognosis determination of patients with breast cancer receiving Olaparib

Mathematical models based on partial differential equations (PDEs) can be exploited to handle clinical data with space/time dimensions, e.g. tumor growth challenged by neoadjuvant therapy. A model based on simplified assessment of tumor malignancy and pharmacodynamics efficiency was exercised to discover new metrics of patient prognosis in the OLTRE trial. We tested in a 17-patients cohort affected by early-stage triple negative breast cancer (TNBC) treated with 3 weeks of olaparib, the capability of a PDEs-based reactive–diffusive model of tumor growth to efficiently predict the response to olaparib in terms of SUVmax detected at 18FDG-PET/CT scan, by using specific terms to characterize tumor diffusion and proliferation. Computations were performed with COMSOL Multiphysics. Driving parameters governing the mathematical model were selected with Pearson's correlations. Discrepancies between actual and computed SUVmax values were assessed with Student’s t test and Wilcoxon rank sum test. The correlation between post-olaparib true and computed SUVmax was assessed with Pearson’s r and Spearman’s rho. After defining the proper mathematical assumptions, the nominal drug efficiency (εPD) and tumor malignancy (rc) were computationally evaluated. The former parameter reflected the activity of olaparib on the tumor, while the latter represented the growth rate of metabolic activity as detected by SUVmax. εPD was found to be directly dependent on basal tumor-infiltrating lymphocytes (TILs) and Ki67% and was detectable through proper linear regression functions according to TILs values, while rc was represented by the baseline Ki67-to-TILs ratio. Predicted post-olaparib SUV*max did not significantly differ from original post-olaparib SUVmax in the overall, gBRCA-mutant and gBRCA-wild-type subpopulations (p > 0.05 in all cases), showing strong positive correlation (r = 0.9 and rho = 0.9, p < 0.0001 both). A model of simplified tumor dynamics was exercised to effectively produce an upfront prediction of efficacy of 3-week neoadjuvant olaparib in terms of SUVmax. Prospective evaluation in independent cohorts and correlation of these outcomes with more recognized efficacy endpoints is now warranted for model confirmation and tailoring of escalated/de-escalated therapeutic strategies for early-TNBC patients.

Tcf20 deficiency is associated with increased liver fibrogenesis and alterations in mitochondrial metabolism in mice and humans.

Transcription co-activator factor 20 (TCF20) is a regulator of transcription factors involved in extracellular matrix remodelling. In addition, TCF20 genomic variants in humans have been associated with impaired intellectual disability. Therefore, we hypothesized that TCF20 has several functions beyond those described in neurogenesis, including the regulation of fibrogenesis. Tcf20 knock-out (Tcf20-/- ) and Tcf20 heterozygous mice were generated by homologous recombination. TCF20 gene genotyping and expression was assessed in patients with pathogenic variants in the TCF20 gene. Neural development was investigated by immufluorescense. Mitochondrial metabolic activity was evaluated with the Seahorse analyser. The proteome analysis was carried out by gas chromatography mass-spectrometry. Characterization of Tcf20-/- newborn mice showed impaired neural development and death after birth. In contrast, heterozygous mice were viable but showed higher CCl4 -induced liver fibrosis and a differential expression of genes involved in extracellular matrix homeostasis compared to wild-type mice, along with abnormal behavioural patterns compatible with autism-like phenotypes. Tcf20-/- embryonic livers and mouse embryonic fibroblast (MEF) cells revealed differential expression of structural proteins involved in the mitochondrial oxidative phosphorylation chain, increased rates of mitochondrial metabolic activity and alterations in metabolites of the citric acid cycle. These results parallel to those found in patients with TCF20 pathogenic variants, including alterations of the fibrosis scores (ELF and APRI) and the elevation of succinate concentration in plasma. We demonstrated a new role of Tcf20 in fibrogenesis and mitochondria metabolism in mice and showed the association of TCF20 deficiency with fibrosis and metabolic biomarkers in humans.

Enhancement of nitrogen removal in coupling Anammox and DAMO via Fe-modified granular activated carbon

Anaerobic ammonium oxidation (Anammox) coupled with Denitrifying anaerobic methane oxidation (DAMO) is an attractive technology to simultaneously remove nitrogen and mitigate methane emissions from wastewater. However, its nitrogen removal rate is usually limited due to the low methane mass transfer efficiency, low metabolic activity and slow growth rate of functional microorganisms. In this study, GAC and Fe-modified GAC (Fe-GAC) were added into Anammox-DAMO process to investigate their effects on nitrogen removal rates and then reveal the mechanism. The results showed that after 80-day experiments, the total nitrogen removal rate was slightly improved in the presence of GAC (3.94 mg L−1·d−1), while it reached high as 16.66 mg L−1·d−1 in the presence of Fe-GAC, which was ca.17 times that of non-amended control group (0.96 mg L−1·d−1). The addition of Fe-GAC stimulated the secretion of extracellular polymeric substance (EPS), improved the electron transfer capability and promoted the production of Cytochrome C. Besides, the key functional enzyme activities (HZS, HDH and NAR) were highest in the Fe-GAC group, which were approximately 1.06–1.56 times higher than those of GAC-amended and blank control groups. Microbial community analysis showed that the abundance of the DAMO archaea (Candidatus Methanoperedens) and Anammox bacteria (Candidatus Brocadia) were remarkably increased with the addition of Fe-GAC. Functional genes associated with nitrogen removal and methane oxidation in Fe-GAC system were up-regulated. This study provides a promising strategy for achieving high rate of nitrogen removal upon Anammox-DAMO process.

Microbioreactors for nutrient-controlled microbial cultures: Bridging the gap between bioprocess development and industrial use.

It is common practice in the development of bioprocesses to genetically modify a microorganism and study a large number of resulting mutants in order to select the ones that perform best for use at the industrial scale. At industrial scale, strict nutrient-controlled growth conditions are imposed to control the metabolic activity and growth rate of the microorganism, thereby enhancing the expression of the product of interest. Although it is known that microorganisms that perform best under these strictly controlled conditions are not the same as the ones that perform best under uncontrolled batch conditions, screening, and selection is predominantly performed under batch conditions. Tools that afford high throughput on the one hand and dynamic control over cultivation conditions on the other hand are not yet available. Microbioreactors offer the potential to address this problem, resolving the gap between bioprocess development and industrial scale use. In this review, we highlight the current state-of-the-art of microbioreactors that offer the potential to screen microorganisms under dynamically controlled conditions. We classify them into: (i) microtiter plate-based platforms, (ii) microfluidic chamber-based platforms, and (iii) microfluidic droplet-based platforms. We conclude this review by discussing the opportunities of nutrient-fed microbioreactors in the field of biotechnology. This article is protected by copyright. All rights reserved.

Chemical Characteristics and Source Apportionment of Biogenic Primary and Secondary Organic Aerosols in an Alpine Ecosystem of Tibetan Plateau

AbstractThe knowledge about the chemical characteristics of organic aerosols in alpines were still limited. Fifty samples were collected in an alpine site in Tibetan Plateau during May 2015 and April 2016 to measure the concentrations of sugar and biogenic secondary organic aerosol (BSOA) compounds. The annual mean concentrations of anhydrosugar, primary sugars, and sugar alcohols in Mt. Gongga were 86.6 ± 43.1, 168 ± 40.0 and 204 ± 62.9 ng/m3, respectively. All of the anhydrosugars displayed the highest concentrations in winter, followed by spring, autumn, and the lowest ones in summer, which was contributed by dense biomass burning (BB) in winter. In contrast, nearly all of the primary sugar and sugar alcohol levels peaked in summer, which might be associated with the higher rates of vegetation growth and microbial metabolic activities during the warming season. The levels of BSOA tracers also suffered from markedly seasonal variations. The sesquiterpene SOA displayed the highest level in winter (27.3 ± 16.8 ng/m3), which might be associated with the biomass burning in the surrounding regions. However, most of the species of isoprene and monoterpene SOA tracers suffered from the higher levels in summer, which was contributed by the higher biogenic volatile organic compounds (BVOC) emission and reaction rates. Based on source apportionment result, BB (26%) was the dominant contributor to sugar and BSOA species in Mt. Gongga, followed by airborne pollen (24%), plant release (19%), soil emission (13%), fungal spore (9%), and isoprene oxidation (8%). The result of this study reveals mixed contributions of BB and vegetation emission promote the formation of biogenic organic aerosols in Tibetan Plateau.

Industrial Biotechnology Conservation Processes: Similarities with Natural Long-Term Preservation of Biological Organisms

Cryopreservation and lyophilization processes are widely used for conservation purposes in the pharmaceutical, biotechnological, and food industries or in medical transplantation. Such processes deal with extremely low temperatures (e.g., -196 °C) and multiple physical states of water, a universal and essential molecule for many biological lifeforms. This study firstly considers the controlled laboratory/industrial artificial conditions used to favor specific water phase transitions during cellular material cryopreservation and lyophilization under the Swiss progenitor cell transplantation program. Both biotechnological tools are successfully used for the long-term storage of biological samples and products, with reversible quasi-arrest of metabolic activities (e.g., cryogenic storage in liquid nitrogen). Secondly, similarities are outlined between such artificial localized environment modifications and some natural ecological niches known to favor metabolic rate modifications (e.g., cryptobiosis) in biological organisms. Specifically, examples of survival to extreme physical parameters by small multi-cellular animals (e.g., tardigrades) are discussed, opening further considerations about the possibility to reversibly slow or temporarily arrest the metabolic activity rates of defined complex organisms in controlled conditions. Key examples of biological organism adaptation capabilities to extreme environmental parameters finally enabled a discussion about the emergence of early primordial biological lifeforms, from natural biotechnology and evolutionary points of view. Overall, the provided examples/similarities confirm the interest in further transposing natural processes and phenomena to controlled laboratory settings with the ultimate goal of gaining better control and modulation capacities over the metabolic activities of complex biological organisms.

Microbial electrosynthesis with Clostridium ljungdahlii benefits from hydrogen electron mediation and permits a greater variety of products.

Microbial electrosynthesis (MES) is a very promising technology addressing the challenge of carbon dioxide recycling into organic compounds, which might serve as building blocks for the (bio)chemical industry. However, poor process control and understanding of fundamental aspects such as the microbial extracellular electron transfer (EET) currently limit further developments. In the model acetogen Clostridium ljungdahlii, both direct and indirect electron consumption via hydrogen have been proposed. However, without clarification neither targeted development of the microbial catalyst nor process engineering of MES are possible. In this study, cathodic hydrogen is demonstrated to be the dominating electron source for C. ljungdahlii at electroautotrophic MES allowing for superior growth and biosynthesis, compared to previously reported MES using pure cultures. Hydrogen availability distinctly controlled an either planktonic- or biofilm-dominated lifestyle of C. ljungdahlii. The most robust operation yielded higher planktonic cell densities in a hydrogen mediated process, which demonstrated the uncoupling of growth and biofilm formation. This coincided with an increase of metabolic activity, acetate titers, and production rates (up to 6.06 g L-1 at 0.11 g L-1 d-1). For the first time, MES using C. ljungdahlii was also revealed to deliver other products than acetate in significant amounts: here up to 0.39 g L-1 glycine or 0.14 g L-1 ethanolamine. Hence, a deeper comprehension of the electrophysiology of C. ljungdahlii was shown to be key for designing and improving bioprocess strategies in MES research.

Long-term proliferation and delayed senescence of bone marrow-derived human mesenchymal stem cells on metformin co-embedded HA/Gel electrospun composite nanofibers

The current work was going to assess the efficacy of hyaluronic acid/Gelatin (HA/GEL) encapsulated with metformin-loaded mesoporous silica nanoparticles (MET@MSNs) on the prolonged in vitro proliferation of bone marrow-derived human mesenchymal stem cells (BM-hMSCs) without prompting aging. For this purpose, composite scaffolds consisting of MET and MET@MSNs in combination with HA were manufactured by convenient and green electrospinning technique. The surface morphology and biochemical characteristics of manufactured scaffolds were evaluated using FE-SEM, TGA, and FTIR. The enhanced proliferation rate and metabolic activity of the BM-hMSCs seeded on MET@MSNs incorporated into HA/Gel scaffolds (MET@MSNs HA/Gel NFs) were confirmed via PicoGreen and MTT test assay, respectively, over 21 days of culture. Moreover, the mRNA expression levels of senescence and stemness marker after a long-term in vitro culturing by qPCR. According to the high proliferation rate and proper metabolic activity of the BM-hMSCs after 21 days of culture on the MET@MSNs HA/Gel NFs, the prepared NFs represented great capacity for both initial and controlled release of MET. The obtained data from MTT and PicoGreen examination also revealed improved metabolic activity and expansion rate for BM-hMSCs grown on the MET@MSNs-NFs compared to the other treated groups after 1, 14 and 21 days of incubation. On the other hand, the hTERT and telomerase expression was significantly increased in BM-hMSCs cultured on MET@MSNs HA/Gel NFs compared to the control group. These results confirmed the capability of MET@MSNs HA/Gel NFs for persistent and controlled discharge of MET in the designing of a novel platform for neutralizing cellular aging and attaining adequate quantities of fresh BM-hMSCs for tissue engineering applications.

β-Hydroxybutyrate preferentially enhances neuron over astrocyte respiration while signaling cellular quiescence

While ketone bodies support overall brain energy metabolism, it is increasingly clear specific brain cell types respond differently to ketone body availability. Here, we characterized how SH-SY5Y neuroblastoma cell, primary neuron, and primary astrocyte bioenergetics and nutrient sensing pathways respond to β-hydroxybutyrate (βOHB). SH-SY5Y cells and primary neurons, but not astrocytes, exposed to βOHB increased respiration and decreased PI3K-Akt-mTOR signaling. Despite increased carbon availability and respiration, SH-SY5Y cells treated with βOHB reduced their overall metabolic activity and cell cycling rate. Levels of the quiescence-regulating Yamanaka factors increased to a broader extent in SH-SY5Y cells and primary neurons. We propose a βOHB-induced increase in neuron respiration, accompanied by activation of quiescence associated pathways, could alleviate bioenergetic stress and limit cell senescence. This in turn could potentially benefit conditions, including brain aging and neurodegenerative diseases, that feature bioenergetic decline and cell senescence.

Dark biosphere: Just at the very tip of the iceberg.

Dark biosphere: Just at the very tip of the iceberg.

IKCa channels control breast cancer metabolism including AMPK-driven autophagy

Ca2+-activated K+ channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic activity and energy consumption rates, which are fundamental for rapidly growing cells. Using BC cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis and mitochondrial ATP-production are reduced in cells derived from IK-deficient breast tumors. Loss of IK altered the sub-/cellular K+- and Ca2+- homeostasis and mitochondrial membrane potential, ultimately resulting in reduced ATP-production and metabolic activity. Consequently, we find that BC cells lacking IK upregulate AMP-activated protein kinase activity to induce autophagy compensating the glycolytic and mitochondrial energy shortage. Our results emphasize that IK by modulating cellular Ca2+- and K+-dynamics contributes to the remodeling of metabolic pathways in cancer. Thus, targeting IK channel might disturb the metabolic activity of BC cells and reduce malignancy.

Production of biofilm by Staphylococcus aureus: Association with infective endocarditis?

ObjectivesStaphylococcus aureus is a well-known biofilm-producing pathogen that is capable of causing chronic infections owing to its ability to resist antibiotic treatment and obstruct the immune response. However, the possible association between high biofilm production and infective endocarditis (IE) has not been assessed. Our objective was to compare production of biofilm by S. aureus strains isolated from patients with bacteremia and IE, catheter-related bloodstream infection (C-RBSI), or non-device associated bacteremia. MethodsWe isolated 260 S. aureus strains from the blood of patients with bacteremia who were diagnosed during hospital admission between 2012 and 2015. Patients were divided into 3 groups according to whether they had IE, C-RBSI, or non-device associated bacteremia. Biofilm production was measured in terms of biomass and metabolic activity using the crystal violet and XTT assays, respectively. High biomass and metabolic activity rates (based on tertile ranks classification) were compared between the 3 groups. ResultsThe high biomass and metabolic activity rates of each group were 41.9% and 37.2% for IE, 32.5% and 35.0%, for C-RBSI, and 29.0% and 33.3% for non-device associated bacteremia (p=0.325 and p=0.885, respectively). ConclusionsHigh biomass and metabolic activity levels for S. aureus isolates from IE were similar to those of S. aureus isolates from C-RBSI or non-device associated bacteremia.