Biology, Volume 9, Issue 7 (July 2020) – 39 articles

Light around twilight provides the primary entrainment signal for circadian rhythms. Here we review the mechanisms and responses of the mouse and human circadian systems to light. Both utilize a network of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). In both species action spectra and functional expression of OPN4 in vitro show that melanopsin has a λ_max close to 480 nm. Anatomical findings demonstrate that there are multiple pRGC sub-types, with some evidence in mice, but little in humans, regarding their roles in regulating physiology and behavior. Studies in mice, non-human primates and humans, show that rods and cones project to and can modulate the light responses of pRGCs. Such an integration of signals enables the rods to detect dim light, the cones to detect higher light intensities and the integration of intermittent light exposure, whilst melanopsin measures bright light over extended periods of time. Although photoreceptor mechanisms are similar, sensitivity thresholds differ markedly between mice and humans. Mice can entrain to light at approximately 1 lux for a few minutes, whilst humans require light at high irradiance (>100’s lux) and of a long duration (>30 min). The basis for this difference remains unclear. As our retinal light exposure is highly dynamic, and because photoreceptor interactions are complex and difficult to model, attempts to develop evidence-based lighting to enhance human circadian entrainment are very challenging. A way forward will be to define human circadian responses to artificial and natural light in the “real world” where light intensity, duration, spectral quality, time of day, light history and age can each be assessed. Full article

The Cucumber aphid (Myzus persicae), a destructive cucumber aphid usually managed by chemical pesticides, is responsible for enormous annual agricultural losses. A protein elicitor, PeBL1, was investigated in the present work for its ability to induce a defense response against M. persicae in cucumber. The rates of population growth (Intrinsic rate of increase) of M. persicae (second and third generations) decreased with PeBL1-treated cucumber seedlings as compared to positive (water) and negative 70.58 μg mL⁻¹ controls (50 mM Tris-HCl, pH 8.0). In an assay on host selection, M. persicae had a preference for colonizing control plants as compared to the PeBL1-treated cucumber seedlings. The nymphal development time of the aphid was extended with the PeBL1-treated cucumber seedlings. Likewise, fecundity was reduced, with less offspring produced in the PeBL1-treated cucumber seedlings as compared to the positive (water) and negative 70.58 μg mL⁻¹ controls (50 mM Tris-HCl, pH 8.0). The cucumber leaves treated with PeBL1 had a hazardous surface environment for M. persicae, caused by trichomes and wax formation. Jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) levels were significantly higher, exhibiting significant accumulation in the PeBL1-treated cucumber seedlings. The following results showed that PeBL1 considerably altered the height of the cucumber plant and the surface structure of the leaves to minimize M. persicae reproduction, and it prevented colonization. Defensive processes also included the activation of pathways (JA, SA, and ET). This study provides evidence of biocontrol for the use of PeBL1 in cucumber defense against M. persicae. Full article

Achieving high embryo quality following IVF and ICSI procedures is a key factor in increasing fertility outcomes in human infertile couples. While the male factor is known to underlie infertility in about 50% of cases, studies performed in human infertile couples have not been able to define the precise effect of sperm affectations upon embryo development. This lack of consistency is, in most cases, due to the heterogeneity of the results caused by the multiple male and female factors that mask the concrete effect of a given sperm parameter. These biases can be reduced with the use of animal gametes, being a good approach for basic researchers to design more homogeneous studies analyzing the specific consequences of a certain affectation. Herein, we conducted a systematic review (March 2020) that assessed the relationship between sperm oxidative stress alterations and IVF/ICSI outcomes in nonhumans mammals. The review was conducted according to PRISMA guidelines and using the MEDLINE-PubMed and EMBASE databases. Thirty articles were included: 11 performed IVF, 17 conducted ICSI, and two carried out both fertilization methods. Most articles were conducted in mouse (43%), cattle (30%) and pig models (10%). After IVF treatments, 80% of studies observed a negative effect of sperm oxidative stress on fertilization rates, and 100% of studies observed a negative effect on blastocyst rates. After ICSI treatments, a positive relationship of sperm oxidative stress with fertilization rates (75% of studies) and with blastocyst rates (83% of studies) was found. In conclusion, the present systematic review shows that sperm oxidative stress is associated with a significant reduction in fertilization rates and in vitro embryo development. Full article

Cadmium (Cd) is one of the most toxic metals in the environment, and has noxious effects on plant growth and production. Cd-accumulating plants showed reduced growth and productivity. Therefore, remediation of this non-essential and toxic pollutant is a prerequisite. Plant-based phytoremediation methodology is considered as one a secure, environmentally friendly, and cost-effective approach for toxic metal remediation. Phytoremediating plants transport and accumulate Cd inside their roots, shoots, leaves, and vacuoles. Phytoremediation of Cd-contaminated sites through hyperaccumulator plants proves a ground-breaking and profitable choice to combat the contaminants. Moreover, the efficiency of Cd phytoremediation and Cd bioavailability can be improved by using plant growth-promoting bacteria (PGPB). Emerging modern molecular technologies have augmented our insight into the metabolic processes involved in Cd tolerance in regular cultivated crops and hyperaccumulator plants. Plants’ development via genetic engineering tools, like enhanced metal uptake, metal transport, Cd accumulation, and the overall Cd tolerance, unlocks new directions for phytoremediation. In this review, we outline the physiological, biochemical, and molecular mechanisms involved in Cd phytoremediation. Further, a focus on the potential of omics and genetic engineering strategies has been documented for the efficient remediation of a Cd-contaminated environment. Full article

Placental mitochondrial dysfunction plays a central role in the pathogenesis of preeclampsia. Since preeclampsia is a hyperandrogenic state, we hypothesized that elevated maternal testosterone levels induce damage to placental mitochondria and decrease bioenergetic profiles. To test this hypothesis, pregnant Sprague–Dawley rats were injected with vehicle or testosterone propionate (0.5 mg/kg/day) from gestation day (GD) 15 to 19. On GD20, the placentas were isolated to assess mitochondrial structure, copy number, ATP/ADP ratio, and biogenesis (Pgc-1α and Nrf1). In addition, in vitro cultures of human trophoblasts (HTR-8/SVneo) were treated with dihydrotestosterone (0.3, 1.0, and 3.0 nM), and bioenergetic profiles using seahorse analyzer were assessed. Testosterone exposure in pregnant rats led to a 2-fold increase in plasma testosterone levels with an associated decrease in placental and fetal weights compared with controls. Elevated maternal testosterone levels induced structural damage to the placental mitochondria and decreased mitochondrial copy number. The ATP/ADP ratio was reduced with a parallel decrease in the mRNA and protein expression of Pgc-1α and Nrf1 in the placenta of testosterone-treated rats compared with controls. In cultured trophoblasts, dihydrotestosterone decreased the mitochondrial copy number and reduced PGC-1α, NRF1 mRNA, and protein levels without altering the expression of mitochondrial fission/fusion genes. Dihydrotestosterone exposure induced significant mitochondrial energy deficits with a dose-dependent decrease in basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. In summary, our study suggests that the placental mitochondrial dysfunction induced by elevated maternal testosterone might be a potential mechanism linking preeclampsia to feto-placental growth restriction. Full article

In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-β (Aβ) peptides have been shown to play a causal role. Among different Aβ species, Aβ_25–35 has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble Aβ forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of Aβ_25–35 we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to Schaffer collaterals. Aβ_25–35 was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in Aβ_25–35 amyloidosis model. Full article

The quality of honey bee drone semen is relevant in different contexts, ranging from colony productivity to pathology, toxicology and biodiversity preservation. Despite its importance, considerably less knowledge is available on this subject for the honey bee when compared to other domestic animal species. A proper assessment of sperm quality requires a multiple testing approach which discriminates between the different aspects of sperm integrity and functionality. Most studies on drone semen quality have only assessed a few parameters, such as sperm volume, sperm concentration and/or sperm plasma membrane integrity. Although more recent studies have focused on a broader variety of aspects of semen quality, some techniques currently used in vertebrates, such as computer-assisted sperm analysis (CASA) or multiparametric sperm quality testing, still remain to be developed in the honey bee. This may be attributed to the particular sperm morphology and physiology in this species, requiring the development of technologies specifically adapted to it. This article reviews the present knowledge of sperm quality in honey bee drones, highlighting its peculiarities and proposing future lines of research. Full article

Edge-to-edge repair for mitral valve regurgitation is being increasingly performed in high-surgical risk patients using minimally invasive mitral clipping devices. Known procedural complications include chordal rupture and mitral leaflet perforation. Hence, it is important to quantitatively evaluate the effect of edge-to-edge repair on chordal integrity. in this study, we employ a computational mitral valve model to simulate functional mitral regurgitation (FMR) by creating papillary muscle displacement. Edge-to-edge repair is then modeled by simulated coaptation of the mid portion of the mitral leaflets. in the setting of simulated FMR, edge-to-edge repair was shown to sustain low regurgitant orifice area, until a two fold increase in the inter-papillary muscle distance as compared to the normal mitral valve. Strain in the chordae was evaluated near the papillary muscles and the leaflets. Following edge-to-edge repair, strain near the papillary muscles did not significantly change relative to the unrepaired valve, while strain near the leaflets increased significantly relative to the unrepaired valve. These data demonstrate the potential for computational simulations to aid in the pre-procedural evaluation of possible complications such as chordal rupture and leaflet perforation following percutaneous edge-to-edge repair. Full article

Magnetic fields are an unavoidable physical factor affecting living organisms. Lettuce seeds (Lactuca sativa var. cabitat L.) were subjected to various intensities of the static magnetic field (SMF) viz., MF0 (control), SMF1 (0.44 Tesla (T), SMF2 (0.77 T), and SMF3 (1 T) for three exposure times (1, 2, and 3 h). SMF-treated seedlings showed induction in growth parameters and metabolism comparing to control. All photosynthetic pigments were induced markedly under SMF, especially chlorophyll a. SMF at different intensities boosted osmolytes, non-enzymatic antioxidants, and the phenylalanine ammonia-lyase activity over non-magnetized seedlings. Oxidative damage criteria viz., hydrogen peroxide, superoxide radical, and lipid peroxidation, as well as polyphenol oxidase activity, were kept at low values under SMF-treated seeds relative to control, especially SMF2. Electron donors to antioxidant enzymes including nitrate reductase, nitric oxide, and hydrogen sulfide induced via SMF exposure and consequently the activities of superoxide dismutase, glutathione-S-transferases, catalase, and peroxidases family enzymes were also stimulated under SMF, whatever the intensity or the exposure period applied. All these regulations reflected on the enhancement of lettuce yield production which reached 50% over the control at SMF3. Our findings offered that SMF-seed priming is an innovative and low-cost strategy that can improve the growth, bioactive constituents, and yield of lettuce. Full article

At present, De Man, Rogosa and Sharpe (MRS) broth is the medium of choice for promoting bacteriocin production. However, this medium is expensive and not applicable for large-scale production. Therefore, a low-cost and high-efficiency culture medium for bacteriocin Lac-B23 production by Lactobacillus plantarum J23 was developed. First, the effects of the composition of MRS broth on bacteriocin Lac-B23 production and bacterial growth were researched by a one variable at a time approach. Then, a Plackett-Burman design was used to screen significant components for production. Finally, the steepest ascent and central composite designs were used to obtain an optimum medium. The final composition of the modified MRS was much simpler than MRS broth, and the modified MRS contained only glucose, yeast extract, dipotassium phosphate, manganese sulfate monohydrate, Tween 80 and sodium acetate anhydrous. The highest bacteriocin Lac-B23 production reached 2560 activity units (AU)/mL in the modified MRS, which is nine times higher than that in MRS broth (280 AU/mL). Meanwhile, the cost per liter of the modified MRS (8.56 Ren Min Bi (RMB)/L) is 34.70% the cost of MRS broth (13.11 RMB/L), and the cost per arbitrary units of bacteriocin Lac-B23 in the modified MRS is approximately fourteen times more convenient (3.34 RMB/10⁶ AU) than in the MRS broth (46.82 RMB/10⁶ AU). Full article

Proteolysis degree, biological activities, and water-soluble peptide patterns were evaluated in 12 month-ripened Parmigiano Reggiano (PR) cheeses collected in different dairy farms and showing different salt and fat content. Samples classified in high-salt and high-fat group (HH) generally showed lower proteolysis degree than samples having low-salt and low-fat content (LL). This positive correlation between salt/fat reduction and proteolysis was also confirmed by the analysis of biological activities, as the LL group showed higher average values of angiotensin-converting enzyme (ACE)-inhibitory and antioxidant activities. UHPLC/HR-MS allowed the identification of 805 unique peptides: LL and HH groups shared 59.3% of these peptides, while 20.9% and 19.9% were LL and HH specific, respectively. Frequency analysis of peptides identified a core of 183 peptides typical of 12-month ripened PR cheeses (corresponding to the 22.7% of total peptides), but no significant differences were detected in peptide patterns between LL and HH groups. Forty bioactive peptides, including 18 ACE-inhibitors and 12 anti-microbial peptides, were identified, of which 25 firstly found in PR cheese. Globally, this work contributed to unraveling the potentially healthy benefits of peptides fraction in PR cheese and provided prior evidence that PR with reduced fat/salt content showed the highest antihypertensive and antioxidant activities. Full article

Microalgae have a wide industrial potential because of their high metabolic diversity and plasticity. Selection of optimal cultivation methods is important to optimize multi-purpose microalgal biotechnologies. In this research, Chlorella sorokiniana AM-02 that was isolated from a freshwater lake was cultured under various high photosynthetic photon flux density (PPFD) conditions and CO₂ gas levels in standard Bold’s basal medium (BBM). Furthermore, a wide range of nitrate levels (180–1440 mg L⁻¹) was tested on the growth of C. sorokiniana. Microalgae growth, pigment concentration, medium pH, exit gas composition, as well as nitrate, phosphate, and sulfate levels were measured during an experimental period. The preferred high PPFD and optimal CO₂ levels were found to be 1000–1400 μmol photons m⁻² s⁻¹ and 0.5–2.0% (v/v), respectively. The addition of nitrate ions (up to 1440 mg L⁻¹) to the standard growth medium increased final optical density (OD₇₅₀), cell count, pigment concentration, and total biomass yield but decreased the initial growth rate at high nitrate levels. Our findings can serve as the basis for a robust photoautotrophic cultivation system to maximize the productivity of large-scale microalgal cultures. Full article

Although it was already described more than fifty years ago, there is yet no in-depth knowledge regarding the process of osseointegration as far as its mechanism of action is concerned. It could be one of the body’s ways of reacting to a foreign body, where the individual’s immune response capacity is involved. It is known that the nervous system has an impact on bone health and that the role of the autonomic nervous system in bone remodeling is an attractive field for current research. In the future, immuno/neuromodulatory techniques will open new and exciting lines of research. Full article

The early cellular response to infection has been investigated extensively, generating valuable information regarding the mediators of acute infection response. Various cytokines have been highlighted for their critical roles, and the actions of these cytokines are related to intracellular phosphorylation changes to promote infection resolution. However, the development of chronic infections has not been thoroughly investigated. While it is known that wound healing processes are disrupted, the interactions of cytokines and phosphoproteins that contribute to this dysregulation are not well understood. To investigate these relationships, this study used a network centrality approach to assess the impact of individual cytokines and phosphoproteins during chronic inflammation and infection. Tissues were taken from patients undergoing total knee arthroplasty (TKA) and total knee revision (TKR) procedures across two tissue depths to understand which proteins are contributing most to the dysregulation observed at the joint. Notably, p-c-Jun, p-CREB, p-BAD, IL-10, IL-12p70, IL-13, and IFN-γ contributed highly to the network of proteins involved in aseptic inflammation caused by implants. Similarly, p-PTEN, IL-4, IL-10, IL-13, IFN-γ, and TNF-α appear to be central to signaling disruptions observed in septic joints. Ultimately, the network centrality approach provided insight into the altered tissue responses observed in chronic inflammation and infection. Full article

Skeletal muscle dysfunction and reduced physical capacity are characteristic features of chronic obstructive pulmonary disease (COPD). However, the search for a reliable biomarker to assess muscle health in CODP remains elusive. We analyzed the course of hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in COPD in relation to spirometry decline and plasma extracellular heat shock protein-72 (eHSP72) and c-terminal fragment of agrin-22 (CAF22) levels. We evaluated male, 62–73 years old patients of COPD (N = 265) and healthy controls (N = 252) at baseline and after 12 and 24 months for plasma biomarkers, spirometry and HGS measurements. HGS declined significantly over time and plasma CAF22, but not eHSP72 levels, had a significant negative association with HGS and ASMI in COPD. Plasma CAF22 also had an association with walking speed and daily steps count in advanced COPD. Lower ASMI was associated with reduced HGS at all time-point. Narrow age-span of the study cohort and exclusion of lower-limb muscles from the analysis are limitations of this study. Taken together, we report that the plasma CAF22 may be a useful tool to assess muscle weakness and atrophy in COPD patients. Full article

Long noncoding RNAs (lncRNAs) are being increasingly recognised as key modulators of various biological mechanisms, including the immune response. Although investigations in teleosts are still lagging behind those conducted in mammals, current research indicates that lncRNAs play a pivotal role in the response of fish to a variety of pathogens. During the last several years, interest in lncRNAs has increased considerably, and a small but notable number of publications have reported the modulation of the lncRNA profile in some fish species after pathogen challenge. This study was the first to identify lncRNAs in the commercial species European sea bass. A total of 12,158 potential lncRNAs were detected in the head kidney and brain. We found that some lncRNAs were not common for both tissues, and these lncRNAs were located near coding genes that are primarily involved in tissue-specific processes, reflecting a degree of cellular specialisation in the synthesis of lncRNAs. Moreover, lncRNA modulation was analysed in both tissues at 24 and 72 h after infection with nodavirus. Enrichment analysis of the neighbouring coding genes of the modulated lncRNAs revealed many terms related to the immune response and viral infectivity but also related to the stress response. An integrated analysis of the lncRNAs and coding genes showed a strong correlation between the expression of the lncRNAs and their flanking coding genes. Our study represents the first systematic identification of lncRNAs in European sea bass and provides evidence regarding the involvement of these lncRNAs in the response to nodavirus. Full article

The study focused on the changes in vegetation and soils on an undeveloped area of coal mine spoil heaps. The process of vegetation changes was evaluated on the basis of historical cartographic materials and fieldwork. Changes of vegetation in nearly 200 years are presented herein. The main purpose of this study is to present an analysis of spatio-temporal changes in vegetation and their influence on soil features. The diversity of ecological species in terms of habitat requirements, tendency of hornbeam communities formation, and the relationship between forest communities and soil features was found. The basic soil properties were examined under selected plant communities (pH, C_org, N_t), available forms of elements (P, K, Mg), and as plant nutrients and heavy metal occurrence (Fe, Zn, Mn, Co, Cd, Pb, Sr, Cr, Cu). The soil organic carbon (C_org) content varied from 3.17 ± 0.007% to 17.7 ± 0.21% and significant differences were observed between sites. The highest total nitrogen (N_t) content was recorded in the soils of the sites that were represented by Populus-Betula stands (0.60 ± 0.01%). Soil acidity (pH) varied greatly, ranging from acidic (pH = 4.1) to weakly acidic (pH = 5.9). The highest value for Mg_avail (205.43 ± 0.5 mg·kg⁻¹) was noted in the soils under Calamagrostis epegijos (L.) Roth community and for P_avail (184.07 ± 3.77) and K_avail (346.19 ± 2.92 mg·kg⁻¹) under the Quercus-Pinus stand. On all sites, Zn was a dominant element and its concentration ranged from 526.1 to 1060.4 mg·kg⁻¹. Obtained results show how important it is to study the issue of vegetation changes and the formation of the landscape within an industrial city. The described results are important for the management of urban greening issues. Human influence on the disintegration and development of the natural environment is clearly visible. Due to the diversity of former mining areas and their time of creation, the studied area is one of the most important experimental areas for the determination link between vegetation and soil. Full article

Matthiola incana (L.) R. Br. (Brassicaceae) is widely cultivated for ornamental purposes and utilized as a medicinal plant. In the present work, the hydroalcoholic extract from the aerial parts of this species has been evaluated in different bioassays in order to detect potential pharmacological applications. The cytotoxic capacity against the human colorectal adenocarcinoma (CaCo-2) and breast cancer (MCF-7) cell lines was tested using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The extract was investigated as a neuroprotective inhibitor of central nervous system (CNS) enzymes such as monoamine oxidase A, tyrosinase, acetylcholinesterase, and as a natural enzyme inhibitor of α-glucosidase and lipase involved in some metabolic disorders such as obesity or type 2 diabetes. The antioxidant ability was also evaluated in an enzymatic system (xanthine/xanthine oxidase assay). Results showed that the M. incana extract displayed moderate to low cytotoxicity vs. CaCo-2 cells. The extract acted as a superoxide radical scavenger and enzymatic inhibitor of monoamine oxidase A, tyrosinase, α-glucosidase, and lipase. The best results were found in the α-glucosidase assay, as M. incana hydroalcoholic extract was able to inhibit the enzyme α-glucosidase up to 100% without significant differences, compared to the antidiabetic drug acarbose. Matthiola incana has been demonstrated to exert different biological properties. These are important in order to consider this species as a source of bioactive compounds. Full article

After the discovery in 1967 of plant glyoxysomes, aconitase, one the five enzymes involved in the glyoxylate cycle, was thought to be present in the organelles, and although this was found not to be the case around 25 years ago, it is still suggested in some textbooks and recent scientific articles. Genetic research (including the study of mutants and transcriptomic analysis) is becoming increasingly important in plant biology, so metabolic pathways must be presented correctly to avoid misinterpretation and the dissemination of bad science. The focus of our study is therefore aconitase, from its first localization inside the glyoxysomes to its relocation. We also examine data concerning the role of the enzyme malate dehydrogenase in the glyoxylate cycle and data of the expression of aconitase genes in Arabidopsis and other selected higher plants. We then propose a new model concerning the interaction between glyoxysomes, mitochondria and cytosol in cotyledons or endosperm during the germination of oil-rich seeds. Full article

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide. Full article

Mesenchymal stem cells (MSCs) have the capacity for self-renewal and multilineage differentiation potential, and are considered a promising cell population for cell-based therapy and tissue regeneration. MSCs are isolated from various organs including dental pulp, which originates from cranial neural crest-derived ectomesenchyme. Recently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) have been isolated from dental pulp tissue of adult permanent teeth and deciduous teeth, respectively. Because of their MSC-like characteristics such as high growth capacity, multipotency, expression of MSC-related markers, and immunomodulatory effects, they are suggested to be an important cell source for tissue regeneration. Here, we review the features of these cells, their potential to regenerate damaged tissues, and the recently acquired understanding of their potential for clinical application in regenerative medicine. Full article

Chitosan is a polysaccharide commonly used, together with its derivatives, in the preparation of hydrogel formulations, scaffolds and films for tissue engineering applications. Chitosan can be used as such, but it is commonly stabilized by means of chemical crosslinkers. Genipin is one of the crosslinkers that has been considered that is a crystalline powder extracted from the fruit of Gardenia jasminoides and processed to obtain an aglycon compound. Genipin is gaining interest in biological applications because of its natural origin and anti-inflammatory actions. In this paper, the ability of chitosan-based materials crosslinked with genipin to exert anti-inflammation properties in applications such as bone regeneration was studied. Powders obtained from chitosan–genipin scaffolds have been tested in order to mimic the natural degradation processes occurring during biomaterials implantation in vivo. The results from osteoblast-like cells showed that specific combinations of chitosan and genipin stimulate high permissiveness towards cells, with higher performance than the pure chitosan. In parallel, evidences from monocyte-like cells showed that the crosslinker, genipin, seems to promote slowing of the monocyte-macrophage transition at morphological level. This suggests a sort of modularity of pro-inflammatory versus anti-inflammatory behavior of our chitosan-based biomaterials. Being both the cell types exposed to microscale powders, as an added value our results bring information on the cell–material interactions in the degradative dynamics of chitosan scaffold structures during the physiological resorption processes. Full article

Sweet basil (Ocimum basilicum L.) is a leafy green with a short-production cycle that is emerging as a model species among aromatic plants. Modulating the mineral composition of the nutrient solution has proved to be a valuable tool to uncover the mechanisms and responses that higher plants adopt in relation to the availability of mineral nutrients. The aim of this work was to examine the effects on basil of four isosmotic nutrient solutions with different nitrate to chloride ratios. These two anions share uptake and transport mechanisms in plants and are often considered antagonist. To this goal, we analyzed morpho-anatomical and physiological parameters as well as quality-related traits, such as the antioxidant capacity, the leaf color, the mineral composition, and the aromatic profile in relation to the nutrient ratios. Moreover, using a full factorial design, we analyzed leaves in two consecutive harvests. The data indicated a broad, multifaceted plant response to the different nutritional ratios, with almost all the recorded parameters involved. Overall, the effects on basil can be explained by considering an interdependent combination of the nitrate and chloride roles in plant nutrition and physiology. Our work revealed the extent of the modification that can be achieved in basil through the modification of the nutrient solution. It also provided indications for more nutrient efficient growing conditions, because a moderate increase in chloride limits the expected negative impact of a sub-optimal nitrate fertilization. Full article

MicroRNA-122 (miR-122) has been identified as a marker of various liver injuries, including hepatitis- virus-infection-, alcoholic-, and non-alcoholic steatohepatitis (NASH)-induced liver fibrosis. Here, we report that the extracellular miR-122 from hepatic cells can be delivered to hepatic stellate cells (HSCs) to modulate their proliferation and gene expression. Our published Argonaute crosslinking immunoprecipitation (Ago-CLIP) data identified several pro-fibrotic genes, including Ctgf, as miR-122 targets in mice livers. However, treating Ctgf as a therapeutic target failed to rescue the fibrosis developed in the miR-122 knockout livers. Alternatively, we compared the published datasets of human cirrhotic livers and miR-122 KO livers, which revealed upregulation of BCL2, suggesting its potential role in regulating fibrosis. Notably, ectopic miR-122 expression inhibited BCL2 expression in human HSC (LX-2) cells). Publicly available ChIP-seq data in human hepatocellular cancer (HepG2) cells and mice livers suggested miR-122 could regulate BCL2 expression indirectly through c-MYC, which was confirmed by siRNA-mediated depletion of c-MYC in Hepatocellular Carcinoma (HCC) cell lines. Importantly, Venetoclax, a potent BCL2 inhibitor approved for the treatment of leukemia, showed promising anti-fibrotic effects in miR-122 knockout mice. Collectively, our data demonstrate that miR-122 suppresses liver fibrosis and implicates anti-fibrotic potential of Venetoclax. Full article

Policy decision-making for system resilience to a hazard requires the estimation and prediction of the trends of growth and decline of the impacts of the hazard. With focus on the recent worldwide spread of CoVid-19, we take the infection rate as the relevant metric whose trend of evolution to follow for verifying the effectiveness of the countermeasures applied. By comparison with the theories of growth and recovery in coupled socio-medical systems, we find that the data for many countries show infection rate trends that are exponential in form. In particular, the recovery trajectory is universal in trend and consistent with the learning theory, which allows for predictions useful in the assistance of decision-making of emergency recovery actions. The findings are validated by extensive data and comparison to medical pandemic models. Full article

Diatoms are major contributors to global primary production and their populations in the modern oceans are affected by availability of iron, nitrogen, phosphate, silica, and other trace metals, vitamins, and infochemicals. However, little is known about the role of phosphorylation in diatoms and its role in regulation and signaling. We report a total of 2759 phosphorylation sites on 1502 proteins detected in Phaeodactylum tricornutum. Conditionally phosphorylated peptides were detected at low iron (n = 108), during the diel cycle (n = 149), and due to nitrogen availability (n = 137). Through a multi-omic comparison of transcript, protein, phosphorylation, and protein homology, we identify numerous proteins and key cellular processes that are likely under control of phospho-regulation. We show that phosphorylation regulates: (1) carbon retrenchment and reallocation during growth under low iron, (2) carbon flux towards lipid biosynthesis after the lights turn on, (3) coordination of transcription and translation over the diel cycle and (4) in response to nitrogen depletion. We also uncover phosphorylation sites for proteins that play major roles in diatom Fe sensing and utilization, including flavodoxin and phytotransferrin (ISIP2A), as well as identify phospho-regulated stress proteins and kinases. These findings provide much needed insight into the roles of protein phosphorylation in diel cycling and nutrient sensing in diatoms. Full article

Sepsis-associated acute kidney injury (AKI) is a leading cause of death in hospitalized patients worldwide. Despite decades of effort, there is no effective treatment for preventing the serious medical condition. Bee venom has long been used to treat a variety of inflammatory diseases. However, whether bee venom has protective effects against lipopolysaccharide (LPS)-induced AKI has not been explored. The aim of this study was to evaluate the effects of bee venom on LPS-induced AKI. The administration of bee venom alleviated renal dysfunction and structural injury in LPS-treated mice. Increased renal levels of tubular injury markers after LPS treatment were also suppressed by bee venom. Mechanistically, bee venom significantly reduced plasma and tissue levels of inflammatory cytokines and immune cell infiltration into damaged kidneys. In addition, mice treated with bee venom exhibited reduced renal expression of lipid peroxidation markers after LPS injection. Moreover, bee venom attenuated tubular cell apoptosis in the kidneys of LPS-treated mice. In conclusion, these results suggest that bee venom attenuates LPS-induced renal dysfunction and structural injury via the suppression of inflammation, oxidative stress, and tubular cell apoptosis, and might be a useful therapeutic option for preventing endotoxemia-related AKI. Full article

Armillaria sinapina, a fungal pathogen of primary timber species of North American forests, causes white root rot disease that ultimately kills the trees. A more detailed understanding of the molecular mechanisms underlying this illness will support future developments on disease resistance and management, as well as in the decomposition of cellulosic material for further use. In this study, RNA-Seq technology was used to compare the transcriptome profiles of A. sinapina fungal culture grown in yeast malt broth medium supplemented or not with betulin, a natural compound of the terpenoid group found in abundance in white birch bark. This was done to identify enzyme transcripts involved in the metabolism (redox reaction) of betulin into betulinic acid, a potent anticancer drug. De novo assembly and characterization of A. sinapina transcriptome was performed using Illumina technology. A total of 170,592,464 reads were generated, then 273,561 transcripts were characterized. Approximately, 53% of transcripts could be identified using public databases with several metabolic pathways represented. A total of 11 transcripts involved in terpenoid biosynthesis were identified. In addition, 25 gene transcripts that could play a significant role in lignin degradation were uncovered, as well as several redox enzymes of the cytochromes P450 family. To our knowledge, this research is the first transcriptomic study carried out on A. sinapina. Full article

Myogenesis is the biological process by which skeletal muscle tissue forms. Regulation of myogenesis involves a variety of conventional, epigenetic, and epigenomic mechanisms that control chromatin remodeling, DNA methylation, histone modification, and activation of transcription factors. Chromatin remodeling enzymes utilize ATP hydrolysis to alter nucleosome structure and/or positioning. The mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) family of chromatin remodeling enzymes is essential for myogenesis. Here we review diverse and novel mechanisms of regulation of mSWI/SNF enzymes by kinases and phosphatases. The integration of classic signaling pathways with chromatin remodeling enzyme function impacts myoblast viability and proliferation as well as differentiation. Regulated processes include the assembly of the mSWI/SNF enzyme complex, choice of subunits to be incorporated into the complex, and sub-nuclear localization of enzyme subunits. Together these processes influence the chromatin remodeling and gene expression events that control myoblast function and the induction of tissue-specific genes during differentiation. Full article

Hepatic fibrosis is the accumulation of excess collagen as a result of chronic liver injury. If left unabated, hepatic fibrosis can lead to the disruption of the liver architecture, portal hypertension, and increased risk of progression to cirrhosis and hepatocellular carcinoma. The thiazolidinedione class of antidiabetic drugs, through their target peroxisome proliferator-activated receptor γ (PPARγ), have protective effects against liver fibrosis, and can inhibit the profibrotic activity of hepatic stellate cells, the major collagen-producing liver cells. However, these drugs have been ineffective in the treatment of established fibrosis, possibly due to side effects such as increased weight and adiposity. Recently, selective PPARγ modulators that lack these side effects have been identified, but their role in treating fibrosis has not been studied. In this study, we tested the effectiveness of one of these selective modulators, SR1664, in the mouse carbon tetrachloride model of established hepatic fibrosis. Treatment with SR1664 reduced the total and type 1 collagen content without increasing body weight. The abundance of activated hepatic stellate cells was also significantly decreased. Finally, SR1664 inhibited the profibrotic phenotype of hepatic stellate cells. In summary, a selective PPARγ modulator was effective in the reduction of established hepatic fibrosis and the activated phenotype of hepatic stellate cells. This may represent a new treatment approach for hepatic fibrosis. Full article