Changes In Metabolic Activity Research Articles

Effects of Microcystin-LR on Metabolic Functions and Structure Succession of Sediment Bacterial Community under Anaerobic Conditions.

Microcystins (MCs), which are produced by harmful cyanobacteria blooms, pose a serious threat to environmental health. However, the effect of MCs on the bacterial community under anaerobic conditions is still unclear. This study examined the dynamic changes of MC-degrading capacity, metabolic activity, and structure of the bacterial community in lake sediment repeatedly treated with 1 mg/L microcystin-LR (MC-LR) under anaerobic conditions. The results showed that the MC-degrading capacity of the bacterial community was increased nearly three-fold with increased treatment frequency. However, the metabolic profile behaved in exactly opposite trend, in which the overall carbon metabolic activity was inhibited by repeated toxin addition. Microbial diversity was suppressed by the first addition of MC-LR and then gradually recovered. The 16S amplicon sequencing showed that the dominant genera were changed from Exiguobacterium and Acinetobacter to Prosthecobacter, Dechloromonas, and Agrobacterium. Furthermore, the increase in the relative abundance of Dechloromonas, Pseudomonas, Hydrogenophaga, and Agrobacterium was positively correlated with the MC-LR treatment times. This indicates that they might be responsible for MC degradation under anaerobic conditions. Our findings reveal the relationship between MC-LR and the sediment bacterial community under anaerobic conditions and indicate that anaerobic biodegradation is an effective and promising method to remediate MCs pollution.

Overview of mathematical modeling of myocardial blood flow regulation

The oxygen consumption by the heart and its extraction from the coronary arterial blood are the highest among all organs. Any increase in oxygen demand due to a change in heart metabolic activity requires an increase in coronary blood flow. This functional requirement of adjustment of coronary blood flow is mediated by coronary flow regulation to meet the oxygen demand without any discomfort, even under strenuous exercise conditions. The goal of this article is to provide an overview of the theoretical and computational models of coronary flow regulation and to reveal insights into the functioning of a complex physiological system that affects the perfusion requirements of the myocardium. Models for three major control mechanisms of myogenic, flow, and metabolic control are presented. These explain how the flow regulation mechanisms operating over multiple spatial scales from the precapillaries to the large coronary arteries yield the myocardial perfusion characteristics of flow reserve, autoregulation, flow dispersion, and self-similarity. The review not only introduces concepts of coronary blood flow regulation but also presents state-of-the-art advances and their potential to impact the assessment of coronary microvascular dysfunction (CMD), cardiac-coronary coupling in metabolic diseases, and therapies for angina and heart failure. Experimentalists and modelers not trained in these models will have exposure through this review such that the nonintuitive and highly nonlinear behavior of coronary physiology can be understood from a different perspective. This survey highlights knowledge gaps, key challenges, future research directions, and novel paradigms in the modeling of coronary flow regulation.

Abrogation of esophageal carcinoma development in miR-31 knockout rats

MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following N-nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to 45% (P = 0.038) and miR-31 gene knockout abrogated development of ESCC (P = 1 × 10-6). Transcriptomics, genome sequencing, and metabolomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout. Our identification of EGLN3, a known negative regulator of nuclear factor κB (NF-κB), as a direct target of miR-31 establishes a functional link between oncomiR-31, tumor suppressor target EGLN3, and up-regulated NF-κB-controlled inflammation signaling. Interaction among oncogenic miR-31, EGLN3 down-regulation, and inflammation was also documented in human ESCCs. miR-31 deletion resulted in suppression of miR-31-associated EGLN3/NF-κB-controlled inflammatory pathways. ESCC-free, Zn-deficient miR-31-/- rat esophagus displayed no genome instability and limited metabolic activity changes vs. the pronounced mutational burden and ESCC-associated metabolic changes of Zn-deficient wild-type rats. These results provide conclusive evidence that miR-31 expression is necessary for ESCC development.

Crosstalk Between ER Stress, Unfolded Protein Response (UPR) and Wnt Signaling Pathway in Cancer

Abstract: 1. Context Endoplasmic reticulum stress (ER stess) is associated with endoplasmic reticulum perturbation homeostasis. Prolonged ER stress conditions may induce cell death. Unfolded protein response (UPR) attempts to restore normal cell conditions. 2. Evidence Acquisition There now exists an emergent body of evidence identifying the WNT signaling network as a regulator of cancer cell metabolism. Given that existing findings show that the WNT pathway and ER stress regulates changes in metabolic activities of cancer cells suggesting these signaling pathways represent critical nodes in the regulation of central metabolism in tumors. 3. Results Findings suggest that the molecular cross-talks between hypoxic ER stress, Wnt/βcatenin signaling, may represent an important mechanism that enables some tumor subtypes to survival and grow in hypoxic conditions. 4. Conclusions The present article disuses differential effects of the activation of the three arms of UPR, namely endoplasmic reticulum kinase (PERK), activation transcription factor -6 (ATF-6), and inositol –requiring enzyme (IRE-1) on cancer. This review also highlights regulators and downstream effectors of Wnt cascade and addresses the increasingly apparent crosstalk of Wnt with other tumorigenic signaling pathways.

Metabolic Imaging of Pain Matrix Using 18F Fluoro-deoxyglucose Positron Emission Tomography/Computed Tomography for Patients Undergoing L2 Dorsal Root Ganglion Stimulation for Low Back Pain

Nociceptive signals from lumbar intervertebral discs ascend in the sympathetic chain via the L2 dorsal root ganglion (L2 DRG), a potential target for discogenic low back pain in neuromodulation. Positron Emission Tomography/Computed Tomography (PET-CT) measures functional changes in the brain metabolic activity, identified by the changes in the regional cerebral blood flow (rCBF) as determined by the changes of F-18 Fluoro-deoxyglucose (18 F FDG) tracer within brain tissues. Nine patients were recruited to explore the changes in PET-CT imaging at baseline and four-weeks post implantation of bilateral L2 DRG neurostimulation leads and implantable pulse generator (IPG). PET-CT scans were performed 30 min following an IV injection of 250±10% MBq of 18 F FDG tracer. Fifteen frames were acquired in 15 min. PET list-mode raw data were reconstructed and normalized appropriately to a brain anatomical atlas. Nine patients were recruited to the study, where PET-CT imaging data for five patients were analyzed. The right and left insular cortex, primary and secondary somato-sensory cortices, prefrontal cortex, anterior cingulate cortex, thalamus, amygdala, hippocampus and the midline periaqueductal areas, were assessed for any changes in the metabolic activity. A total of 85 pain matrix regions were delineated SUV (standardized uptake value)MAX , SUV MEAN ± SD, and SUVPEAK were calculated for each of these regions of the brain and were compared pre- and post-L2 DRG stimulation. Sixty-one of the 85 matrices showed an increase in metabolic activity whereas 24 matrices showed a reduction in metabolic activity. This is the first ever study reporting the changes in cerebral metabolic activity and multi-frame static brain 18 F FDG PET imaging after L2 DRG stimulation for discogenic low back pain. Predominantly an increased metabolic activity in nociceptive brain matrices are seen with an increased in F18 F FDG uptake following L2 DRG stimulation.

Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response.

Mesenchymal stem cells (MSCs) have fueled ample translation for the treatment of immune-mediated diseases. They exert immunoregulatory and tissue-restoring effects. MSC-mediated transfer of mitochondria (MitoT) has been demonstrated to rescue target organs from tissue damage, yet the mechanism remains to be fully resolved. Therefore, we explored the effect of MitoT on lymphoid cells. Here, we describe dose-dependent MitoT from mitochondria-labeled MSCs mainly to CD4+ T cells, rather than CD8+ T cells or CD19+ B cells. Artificial transfer of isolated MSC-derived mitochondria increases the expression of mRNA transcripts involved in T-cell activation and T regulatory cell differentiation including FOXP3, IL2RA, CTLA4, and TGFβ1, leading to an increase in a highly suppressive CD25+ FoxP3+ population. In a GVHD mouse model, transplantation of MitoT-induced human T cells leads to significant improvement in survival and reduction in tissue damage and organ T CD4+ , CD8+ , and IFN-γ+ expressing cell infiltration. These findings point to a unique CD4+ T-cell reprogramming mechanism with pre-clinical proof-of-concept data that pave the way for the exploration of organelle-based therapies in immune diseases.

Effects of Low Frequency-Low Voltage Alternating Electric Current on Apoptosis Progression in Bioelectrical Reactor Biofilm.

Bioelectrochemical systems have undergone several modifications to promote the enzymes or pathways used to reduce the energy required for microbial metabolism. Changes in dominant bacteria, population, and growth rates occur when an electric current is applied intermittently. Applying electricity to bioelectrical reactor (BER) biofilms can either stimulate cells or lead to cell death; therefore, determining the applied voltage range that leads to viable and stimulated bacteria is crucial. We investigated the progression of apoptosis induced by a low frequency-low voltage alternating electric current (AC) in a BER biofilm and found that biofilms on carbon cloth (CC) and stainless steel (SS) 304 electrodes had pHzpc values of 8.67. The pHzpc of the biofilms increased by two compared to that of the inoculant bacteria mass. Furthermore, the Henderson–Hasselbalch equation reveals that the compositions of cell walls of the biofilms that formed on the CC and SS304 electrodes are very similar. In contrast, the CC and SS304 biofilms differ from the inoculant biomass without the influence of an AC field; this indicates that there are differences in the compositions of the cell walls in the present bacteria. Fourier transform infrared spectroscopy was used to compare spectra of the biofilms with that of the inoculation mass, and there were differences in shape and absorbance intensity, indicating variability in the composition, and quantity of each individual biofilm component. In addition, the dehydrogenase activity (DHA) content varied under different applied voltages; the highest DHA was obtained at 8 Vpp. A flow cytometry analysis showed a relatively low number of apoptotic cells (10.93 ± 5.19%) for the AC amplitudes studied. Thus, a low voltage-low frequency AC likely induces significant changes in bacterial metabolic activity but causes no significant change in their viability.

Physical, Mechanical, and Bioactive Properties of Pig Lung-Derived ECM Hydrogels are Dependent on the Duration of Pepsin Digestion

Extracellular matrix (ECM) hydrogels derived from decellularized lungs are promising materials for tissue engineering, in the development of clinical therapies, and for modeling the lung ECM in vitro. Characterizing and controlling the resulting physical, biochemical, mechanical, and biologic properties of decellularized ECM after enzymatic solubilization and gelation is thus of key interest. As the role of enzymatic pepsin digestion in effecting these properties has been understudied, we investigated the digestion time-dependency on key parameters of the resulting ECM hydrogel. Using resolubilized homogenized decellularized pig lung ECM (dECM) as a model system, significant time-dependent alterations in the protein concentration, turbidity, and gelation potential occurred between 4 and 24 hours of digestion, plateauing at longer digestion times. These results correlated with qualitative SEM images and quantitative analysis of hydrogel interconnectivity and average fiber diameter. Interestingly, the time-dependent changes in the storage modulus tracked with the hydrogel interconnectivity results, while the Young's modulus values were more closely related to average fiber size at each time point. The structural and biochemical alterations translated to significant changes in metabolic activity of several representative lung cells seeded onto the hydrogels with progressive decreases in cell viability and alterations in morphology observed in cells cultured on hydrogels produced with dECM digested for greater than 12 and up to 72 hours of digestion. These studies demonstrate that 12hr structured pepsin digest of pig lung dECM provides an optimal balance between desirable physical dECM hydrogel properties and effects on lung cell behaviors.

Dynamics of soil microbial metabolic activity during grassland succession after farmland abandonment

Secondary succession has a major influence on vegetation and soil biogeochemical processes, however, the dynamics of microbial metabolic activity and the driving factors during grassland succession after farmland abandonment remain unclear. Therefore, we examined variations in microbial biomass carbon (Cmic), soil basal respiration (BR), microbial quotient (Cmic:Corg), and metabolic quotient (qCO2) in sloping farmlands that had been abandoned for 0, 3, 8, 13, 18, 23 and 30 years on the Loess Plateau in China. Moreover, the plant, soil and microbial properties were determined to reveal the forces driving soil microbial metabolic activity. The results showed that compared to those of farmland, the Cmic significantly increased by 104.7% and 168.0%, while the qCO2 significantly decreased by 54.3% and 70.5%, respectively, in the late succession stages (23 and 30 years). Long-term succession (30 years) significantly enhanced the Cmic:Corg by 51.4%. In contrast, except for a decrease at 8 years, the BR changed little during grassland succession following farmland abandonment. These changes in microbial metabolic activity indicators were associated with shifts in litter biomass, soil organic carbon, available nitrogen, and soil fungi. Litter biomass and fungi were strongly affected the changes in microbial metabolic activity. This study provided new information regarding the dynamics of microbial metabolic activity during long-term secondary succession and enhanced our understanding of the linkages among plant, soil and microorganisms in semiarid ecosystems.

Functional Ultrasound (fUS) During Awake Brain Surgery: The Clinical Potential of Intra-Operative Functional and Vascular Brain Mapping.

Background and PurposeOncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of real-time image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling. We have applied fUS during conventional awake brain surgery to determine its clinical potential for both intra-operative functional and vascular brain mapping, with the ultimate aim of achieving maximum safe tumor resection.MethodsDuring awake brain surgery, fUS was used to image tumor vasculature and task-evoked brain activation with electrocortical stimulation mapping (ESM) as a gold standard. For functional imaging, patients were presented with motor, language or visual tasks, while the probe was placed over (ESM-defined) functional brain areas. For tumor vascular imaging, tumor tissue (pre-resection) and tumor resection cavity (post-resection) were imaged by moving the hand-held probe along a continuous trajectory over the regions of interest.ResultsA total of 10 patients were included, with predominantly intra-parenchymal frontal and temporal lobe tumors of both low and higher histopathological grades. fUS was able to detect (ESM-defined) functional areas deep inside the brain for a range of functional tasks including language processing. Brain tissue could be imaged at a spatial and temporal resolution of 300 μm and 1.5–2.0 ms respectively, revealing real-time tumor-specific, and healthy vascular characteristics.ConclusionThe current study presents the potential of applying fUS during awake brain surgery. We illustrate the relevance of fUS for awake brain surgery based on its ability to capture both task-evoked functional cortical responses as well as differences in vascular characteristics between tumor and healthy tissue. As current neurosurgical practice is still pre-dominantly leaning on inherently limited pre-operative imaging techniques for tumor resection-guidance, fUS enters the scene as a promising alternative that is both anatomically and physiologically informative.

Comparative Analysis of the Effects of Upconversion Nanoparticles on Normal and Tumor Brain Cells.

Glioma is the most aggressive type of brain tumors encountered in medical practice. The high frequency of diagnosed cases and risk of metastasis, the low efficiency of traditional therapy, and the usually unfavorable prognosis for patients dictate the need to develop alternative or combined approaches for an early diagnosis and treatment of this pathology. High expectations are placed on the use of upconversion nanoparticles (UCNPs). In this study, we have produced and characterized UCNPs doped with the rare-earth elements ytterbium and thulium. Our UCNPs had photoluminescence emission maxima in the visible and infrared spectral regions, which allow for deep optical imaging of tumor cells in the brain. Moreover, we evaluated the toxicity effects of our UCNPs on a normal brain and glioma cells. It was revealed that our UCNPs are non-toxic to glioma cells but have a moderate cytotoxic effect on primary neuronal cultures at high concentrations, a condition that is characterized by a decreased cellular viability and changes in the functional metabolic activity of neuron-glial networks. Despite the great potential associated with the use of these UCNPs as fluorescent markers, there is a need for further studies on the rate of the UCNPs accumulation and excretion in normal and tumor brain cells, and the use of their surface modifications in order to reduce their cytotoxic effects.

CHANGES OF AQUEOUS HUMOR MÜLLER CELLS' BIOMARKERS IN HUMAN PATIENTS AFFECTED BY DIABETIC MACULAR EDEMA AFTER SUBTHRESHOLD MICROPULSE LASER TREATMENT.

To evaluate the changes in activity of biomarkers of Mu[Combining Diaeresis]ller cells (MC) in aqueous humor of patients with diabetic macular edema after subthreshold micropulse laser, over 1 year. Patients with untreated diabetic macular edema and central retinal thickness ≤ 400 μm were enrolled. Best-corrected visual acuity, full ophthalmic examination, and optical coherence tomography were performed. Subthreshold micropulse laser was applied every 3 months. Glial fibrillary acidic protein and inwardly rectifying potassium channel (Kir 4.1), MC activity markers, and vascular endothelial growth factor were quantified in the aqueous humor collected at baseline and at 1, 3, and 12 months after laser. Changes in the macular thickness and inner nuclear layer thickness, where MC bodies are located, were measured. Ten eyes of 10 patients were included. Best-corrected visual acuity improved at 3 months (P = 0.047) and remained stable. Inner nuclear layer thickness significantly reduced at 12 months (P = 0.012). Glial fibrillary acidic protein, Kir 4.1, and vascular endothelial growth factor decreased at 1 and/or 3 and/or 12 months compared with baseline (P < 0.05). Subthreshold micropulse laser improves visual function in diabetic macular edema. Kir 4.1 and glial fibrillary acidic protein decrease and inner nuclear layer thickness reduction demonstrate that subthreshold micropulse laser may restore MC function. Subthreshold micropulse laser also reduces vascular endothelial growth factor concentration. The effect of subthreshold micropulse laser in diabetic macular edema may in part be due to changes of MC metabolic activity.

Piceatannol Increases Antioxidant Defense and Reduces Cell Death in Human Periodontal Ligament Fibroblast under Oxidative Stress.

Piceatannol is a resveratrol metabolite that is considered a potent antioxidant and cytoprotector because of its high capacity to chelate/sequester reactive oxygen species. In pathogenesis of periodontal diseases, the imbalance of reactive oxygen species is closely related to the disorder in the cells and may cause changes in cellular metabolism and mitochondrial activity, which is implicated in oxidative stress status or even in cell death. In this way, this study aimed to evaluate piceatannol as cytoprotector in culture of human periodontal ligament fibroblasts through in vitro analyses of cell viability and oxidative stress parameters after oxidative stress induced as an injury simulator. Fibroblasts were seeded and divided into the following study groups: control, vehicle, control piceatannol, H2O2 exposure, and H2O2 exposure combined with the maintenance in piceatannol ranging from 0.1 to 20 μM. The parameters analyzed following exposure were cell viability by trypan blue exclusion test, general metabolism status by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method, mitochondrial activity through the ATP production, total antioxidant capacity, and reduced gluthatione. Piceatannol was shown to be cytoprotective due the maintenance of cell viability between 1 and 10 μM even in the presence of H2O2. In a concentration of 0.1 μM piceatannol decreased significantly cell viability but increased cellular metabolism and antioxidant capacity of the fibroblasts. On the other hand, the fibroblasts treated with piceatannol at 1 μM presented low metabolism and antioxidant capacity. However, piceatannol did not protect cells from mitochondrial damage as measured by ATP production. In summary, piceatannol is a potent antioxidant in low concentrations with cytoprotective capacity, but it does not prevent all damage caused by hydrogen peroxide.

Is rapid cold-hardening an aerobic process? Characterization of changes in metabolic activity during its induction and effects of anoxia in flesh fly

Rapid cold-hardening (RCH) is a type of phenotypic plasticity that promotes a swift improvement of cold tolerance in insects. A brief exposure to mild cold dramatically increases insect survival to a subsequent cold exposure that would be lethal otherwise. In adult male flesh fly, Sarcophaga bullata, as little as 15 min at 5 °C significantly improved organismal survival at −7°C from 0 to 66.7 ± 11.1%. In this study, we investigated whether this RCH response is an aerobic process in S. bullata by characterizing changes in metabolic activity during its induction. At the level of whole organism, CO2 production continued at a level above our detection limit, and a relatively greater rate was observed during the early phase before it stabilized after ~1 h of the RCH induction. Similarly, in isolated flight muscle tissues, those maintained at 5 °C for 10 min exhibited significantly greater rates of oxygen consumption, compared to those maintained at 5 °C for 1 h (2.82 ± 0.29 vs. 1.36 ± 0.22 μl O2 mg−1 DM h−1). When these tissues were exposed to LaCl3, a treatment that should inhibit RCH ex vivo, oxygen consumption rates of the muscles were reduced significantly to a level similar to those that had been maintained at 5 °C for 1 h. Interestingly, however, the RCH response was still evident among individuals exposed to chilling under anoxia. Compared to those exposed to anoxia for 30 min only at 25 °C, flies exposed to 5 °C for 2 h under anoxia following the initial exposure exhibited a significantly greater level of cold tolerance at −7.5 °C (41.7 ± 7.1 vs. 91.8 ± 3.9%). Our results suggest that while relatively greater rates of metabolic activity are associated with the early phase of the RCH induction, it can proceed under the anoxic condition, thereby suggesting its independence to aerobic respiration.

Polyamines Deficient Diet is a Complementary Strategy in Fighting Cancer: Analysis on Selected Medicinal Fruits

Polyamines are one of the oldest substances known in biochemistry consist of putrescine, spermidine and spermine. They are essential components of all living cells primarily involve in cell growth and proliferation. Upregulation of polyamines in human body is highly associated with various diseases, including cancer. Therefore, polyamines deficient diet (PDD) has become one of the strategies to inhibit carcinogenesis. This study was aimed to determine the polyamines content in selected anticancer fruits and their effect on polyamine polyamine metabolic enzymes was explored in human lung adenocarcinoma cells (A549). In this study, the selected medicinal fruits are Phoenix dactylifera (ajwa dates),Ficus auriculata (fig),Beta vulgaris (beetroot), Ziziphus jujube (jujube) and Vitis vinifera (raisin). The selected medicinal fruits were initially grouped into classes based on total polyamines content using High performance Liquid Chromatography (HPLC). The ability of selected fruits to reduce A549 intracellular polyamines was determined using the same technique. Accordingly, changes in polyamine metabolic enzymes activities; ornithine decarboxylase (ODC) and spermidine/spermine N-acetyltransferase (SSAT) were measured correspondingly using quantitative polymerase chain reactions (qPCR). Results suggested Beetroot, ajwa dates, fig and raisin are classified as low polyamines fruits while jujube demonstrates high content of polyamines. Significant decreased of total intracellular polyamine content after 24 h of treatments with these fruits were identified when compared with untreated A549 cells.Ornithine decarboxylase (ODC) activity showed downregulation upon treatment with ajwa dates, jujube and raisin while SSAT activity displayed alterations in beetroot and jujube treated A549 cells. Thus, we concluded that beetroot, ajwa dates, fig and raisins are the promising candidates for PDD strategy for their low polyamines, ability to reduce A549 intracellular polyamines and modification on ODC and SSAT activities.

Increase in bone metabolic markers and circulating osteoblast-lineage cells after orthognathic surgery

Increased mineralisation rate and bone formation after surgery or fracture is the regional acceleratory phenomenon (RAP), and its systemic impact is the systemic acceleratory phenomenon (SAP). The proportion of circulating osteoblast lineage cells, including osteocalcin-positive (OCN+) cells, in the peripheral blood is markedly higher during pubertal growth and in patients with bone fractures. This study aimed to elucidate the dynamic changes in bone metabolic activity after orthognathic surgery by longitudinal prospective observation. Peripheral venous blood samples were collected from patients who had undergone orthognathic surgery, and serum bone metabolic markers and the proportion of OCN+ cells were measured. Orthognathic surgery induces systemic dynamic changes in bone metabolic activity by targeting steps in the bone healing process and related proteins, such as surgical stress/inflammation (C-reactive protein), bone resorption (type I collagen C-telopeptide), and bone formation (alkaline phosphatase and bone-specific alkaline phosphatase). During the early post-operative period, the population of OCN+ cells significantly increased. Confocal microscopy revealed that OCN proteins were localised in the cytoplasm in Triton X-100-treated OCN+ cells. Furthermore, OCN, ALP, and COL1A1 gene expression was detected in OCN+ cells, suggesting the contribution of the local maturation of bone marrow-derived OCN+ cells at the site of bone healing.

Regional brain susceptibility to neurodegeneration: what is the role of glial cells?

The main pathological feature of the neurodegenerative diseases is represented by neuronal death that represents the final step of a cascade of adverse/hostile events. Early in the neurodegenerative process, glial cells (including astrocytes, microglial cells, and oligodendrocytes) activate and trigger an insidious neuroinflammatory reaction, metabolic decay, blood brain barrier dysfunction and energy impairment, boosting neuronal death. How these mechanisms might induce selective neuronal death in specific brain areas are far from being elucidated. The last two decades of neurobiological studies have provided evidence of the main role of glial cells in most of the processes of the central nervous system, from development to synaptogenesis, neuronal homeostasis and integration into, highly specific neuro-glial networks. In this mini-review, we moved from in vitro and in vivo models of neurodegeneration to analyze the putative role of glial cells in the early mechanisms of neurodegeneration. We report changes of transcriptional, genetic, morphological, and metabolic activity in astrocytes and microglial cells in specific brain areas before neuronal degeneration, providing evidence in experimental models of neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases. Understanding these mechanisms might increase the insight of these processes and pave the way for new specific glia-targeted therapeutic strategies for neurodegenerative disorders.

Organs-On-Chip Models of the Female Reproductive System

Microfluidic-based technology attracts great interest in cell biology and medicine, in virtue of the ability to better mimic the in vivo cell microenvironment compared to conventional macroscale cell culture platforms. Recent Organs-on-chip (OoC) models allow to reproduce in vitro tissue and organ-level functions of living organs and systems. These models have been applied for the study of specific functions of the female reproductive tract, which is composed of several organs interconnected through intricate endocrine pathways and communication mechanisms. To date, a disease and toxicology study of this system has been difficult to perform. Thus, there is a compelling need to develop innovative platforms for the generation of disease model and for performing drug toxicity/screening in vitro studies. This review is focused on the analysis of recently published OoC models that recreate pathological and physiological characteristics of the female reproductive organs and tissues. These models aim to be used to assess changes in metabolic activity of the specific cell types and the effect of exposure to hormonal treatment or chemical substances on some aspects of reproduction and fertility. We examined these models in terms of device specifications, operating procedures, accuracy for studying the biochemical and functional activity of living tissues and the paracrine signalling that occurs within the different tissues. These models represent a powerful tool for understanding important diseases and syndromes affecting women all around the world. Immediate adoption of these models will allow to clarify diseases, causes and adverse events occurring during pregnancy such as pre-eclampsia, infertility or preterm birth, endometriosis and infertility.

Time-resolved characterization of the mechanisms of toxicity induced by silica and amino-modified polystyrene on alveolar-like macrophages

Macrophages play a major role in the removal of foreign materials, including nano-sized materials, such as nanomedicines and other nanoparticles, which they accumulate very efficiently. Because of this, it is recognized that for a safe development of nanotechnologies and nanomedicine, it is essential to investigate potential effects induced by nano-sized materials on macrophages. To this aim, in this work, a recently established model of primary murine alveolar-like macrophages was used to investigate macrophage responses to two well-known nanoparticle models: 50 nm amino-modified polystyrene, known to induce cell death via lysosomal damage and apoptosis in different cell types, and 50 nm silica nanoparticles, which are generally considered non-toxic. Then, a time-resolved study was performed to characterize in detail the response of the macrophages following exposure to the two nanoparticles. As expected, exposure to the amino-modified polystyrene led to cell death, but surprisingly no lysosomal swelling or apoptosis were detected. On the contrary, a peculiar mitochondrial membrane hyperpolarization was observed, accompanied by endoplasmic reticulum stress (ER stress), increased cellular reactive oxygen species (ROS) and changes of metabolic activity, ultimately leading to cell death. Strong toxic responses were observed also after exposure to silica, which included mitochondrial ROS production, mitochondrial depolarization and cell death by apoptosis. Overall, these results showed that exposure to the two nanoparticles led to a very different series of intracellular events, suggesting that the macrophages responded differently to the two nanoparticle models. Similar time-resolved studies are required to characterize the response of macrophages to nanoparticles, as a key parameter in nanosafety assessment.

Serum prolidase level in patients with brucellosis and its possible relationship with pathogenesis of the disease: a prospective observational study

Background/aimChanges in collagen metabolism and fibroblastic activity may play a role in the pathogenesis of brucellosis. The prolidase enzyme plays an important role in collagen synthesis. We aimed to investigate the association of prolidase levels with brucellosis.Materials and methodsSerum prolidase levels in 20 patients newly diagnosed with brucellosis were compared with levels in 30 healthy control subjects. Patients with brucellosis were reassessed 3 months later for prolidase, other laboratory measurements, and response to treatment.ResultsThe levels of serum prolidase were significantly higher in brucellosis patients compared with those of healthy controls. Prolidase, sedimentation, and C-reactive protein levels were significantly lower after antibrucellosis treatment than before treatment.ConclusionThe current study is the first to demonstrate significantly increased serum prolidase levels in patients with brucellosis compared with healthy controls. Prolidase levels also significantly decreased with antibrucellosis treatment. This finding provides a new experimental basis to understand the pathogenesis of brucellosis in relation to collagen metabolism. The increase in serum prolidase levels might be related to several factors such as tissue destruction, increased fibroblastic activity, and granuloma formation, all of which are involved in the natural history of brucellosis.