ISSN / EISSN : 2218273X / 2218273X
Current Publisher: MDPI (10.3390)
Total articles ≅ 945
Latest articles in this journal
Biomolecules, Volume 9; doi:10.3390/biom9080338
Abstract:The aim of the present experiment is to study the effects of oral ingestion of a mixture of two probiotic bacteria on sperm quality and progenies. Three homogeneous groups of juvenile zebrafish were created. Once having reached adulthood (3 months postfertilization; mpf), each group received different feeding regimens: a standard diet (control), a maltodextrin-supplemented diet (vehicle control), or a probiotic-supplemented diet (a mixture (1:1) of Lactobacillus rhamnosus CECT8361 and Bifidobacterium longum CECT7347). The feeding regime lasted 4.5 months. Growth parameters (weight and length) were determined at 3, 5, and 7.5 mpf. Sperm motility was evaluated using computer-assisted sperm analysis at 5 and 7.5 mpf. Progeny survival, hatching rate, and malformation rate were also evaluated. Results showed that probiotic-supplemented diet improved growth parameters compared with the standard diet. The highest percentage of motile spermatozoa was reported in the probiotic-fed group. Concomitantly, the percentage of fast sperm subpopulation was significantly lower in samples derived from control males. Furthermore, there was a significant difference in progeny survival between the probiotic-fed group and the control group at three developmental times (24 hours postfertilization (hpf), 5 days postfertilization (dpf) and 7 dpf). In conclusion, in zebrafish, prolonged ingestion of a mixture of Lactobacillus rhamnosus CECT8361 and Bifidobacterium longum CECT7347 has positive effects on growth, sperm quality, and progeny survival.
Biomolecules, Volume 9; doi:10.3390/biom9080339
Abstract:Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called intermittent hypoxia or IH). Cyclic hypoxia is mimicked in vitro and in vivo by periodic exposure to cycles of hypoxia and reoxygenation (H–R cycles). Compared to chronic hypoxia, cyclic hypoxia has been shown to augment various hallmarks of cancer to a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling hypoxia has also been shown to be the major contributing factor in increasing the risk of cancer in obstructive sleep apnea (OSA) patients. Here, we first compare and contrast the effects of acute, chronic and intermittent hypoxia in terms of molecular pathways activated and the cellular processes affected. We highlight the underlying complexity of these differential effects and emphasize the need to investigate various combinations of factors impacting cellular adaptation to hypoxia: total duration of hypoxia, concentration of oxygen (O2), and the presence of and frequency of H–R cycles. Finally, we summarize the effects of cycling hypoxia on various hallmarks of cancer highlighting their dependence on the abovementioned factors. We conclude with a call for an integrative and rigorous analysis of the effects of varying extents and durations of hypoxia on cells, including tools such as mechanism-based mathematical modelling and microfluidic setups.
Biomolecules, Volume 9; doi:10.3390/biom9080340
Abstract:Vaccine adjuvants help to enhance the immunogenicity of weak antigens. The adjuvant effect of certain substances was noted long ago (the 40s of the last century), and since then a large number of adjuvants belonging to different groups of chemicals have been studied. This review presents research data on the nonspecific action of substances originated from marine organisms, their derivatives and complexes, united by the name ‘adjuvants’. There are covered the mechanisms of their action, safety, as well as the practical use of adjuvants derived from marine hydrobionts in medical immunology and veterinary medicine to create modern vaccines that should be non-toxic and efficient. The present review is intended to briefly describe some important achievements in the use of marine resources to solve this important problem.
Biomolecules, Volume 9; doi:10.3390/biom9080341
Abstract:Stress-induced premature cellular senescence is a significant factor in the onset of age-dependent disease in the cardiovascular system. Plasminogen activator inhibitor-1 (PAI-1), a major TGF-β1/p53 target gene and negative regulator of the plasmin-based pericellular proteolytic cascade, is elevated in arterial plaques, vessel fibrosis, arteriosclerosis, and thrombosis, correlating with increased tissue TGF-β1 levels. Additionally, PAI-1 is necessary and sufficient for the induction of p53-dependent replicative senescence. The mechanism of PAI-1 transcription in senescent cells appears to be dependent on caveolin-1 signaling. Src kinases are upstream effectors of both FAK and caveolin-1 activation as FAKY577,Y861 and caveolin-1Y14 phosphorylation are not detected in TGF-β1-stimulated src family kinase (pp60c-src, Yes, Fyn) triple-deficient (SYF−/−/−) cells. However, restoration of pp60c-src expression in SYF-null cells rescued both caveolin-1Y14 phosphorylation and PAI-1 induction in response to TGF-β1. Furthermore, TGF-β1-initiated Src phosphorylation of caveolin-1Y14 is critical in Rho-ROCK-mediated suppression of the SMAD phosphatase PPM1A maintaining and, accordingly, SMAD2/3-dependent transcription of the PAI-1 gene. Importantly, TGF-β1 failed to induce PAI-1 expression in caveolin-1-null cells, correlating with reductions in both Rho-GTP loading and SMAD2/3 phosphorylation. These findings implicate caveolin-1 in expression controls on specific TGF-β1/p53 responsive growth arrest genes. Indeed, up-regulation of caveolin-1 appears to stall cells in G0/G1 via activation of the p53/p21 cell cycle arrest pathway and restoration of caveolin-1 in caveolin-1-deficient cells rescues TGF-β1 inducibility of the PAI-1 gene. Although the mechanism is unclear, caveolin-1 inhibits p53/MDM2 complex formation resulting in p53 stabilization, induction of p53-target cell cycle arrest genes (including PAI-1), and entrance into premature senescence while stimulating the ATM→p53→p21 pathway. Identification of molecular events underlying senescence-associated PAI-1 expression in response to TGF-β1/src kinase/p53 signaling may provide novel targets for the therapy of cardiovascular disease.
Biomolecules, Volume 9; doi:10.3390/biom9080334
Abstract:Solanesol, an aliphatic terpene alcohol composed of nine isoprene units, is mainly found in solanaceous plants. Particularly, tobacco (Nicotiana tabacum), belonging to the Solanaceae family, is the richest plant source of solanesol, and its leaves have been regarded as the ideal material for solanesol extraction. Since the discovery of solanesol in tobacco, significant progress has been achieved in research on solanesol’s bioactivities, medicinal value, accumulation, extraction technology, and determination methods. Solanesol possesses strong free radical absorption ability and antioxidant activity owing to the presence of several non-conjugated double bonds. Notably, solanesol’s anti-inflammatory, neuroprotective, and antimicrobial activities have been previously demonstrated. Solanesol is a key intermediate in the synthesis of coenzyme Q10, vitamin K2, and the anticancer agent synergiser N-solanesyl-N,N′-bis(3,4-dimethoxybenzyl) ethylenediamine. Other applications of solanesol include solanesol derivative micelles for hydrophobic drug delivery, solanesol-derived scaffolds for bioactive peptide multimerization, and solanesol-anchored DNA for mediating vesicle fusion. Solanesol accumulation in plants is influenced by genetic and environmental factors, including biotic stresses caused by pathogen infections, temperature, illumination, and agronomic measures. Seven extraction technologies and seven determination methods of solanesol are also systematically summarized in the present review. This review can serve as a reference for solanesol’s comprehensive application.
Biomolecules, Volume 9; doi:10.3390/biom9080336
Abstract:Acid-sensing ion channels (ASICs) are proton-gated sodium-selective channels that are expressed in the peripheral and central nervous systems. ASIC1a is one of the most intensively studied isoforms due to its importance and wide representation in organisms, but it is still largely unexplored as a target for therapy. In this study, we demonstrated response of the ASIC1a to acidification in the presence of the daurisoline (DAU) ligand. DAU alone did not activate the channel, but in combination with protons, it produced the second peak component of the ASIC1a current. This second peak differs from the sustained component (which is induced by RF-amide peptides), as the second (DAU-induced) peak is completely desensitized, with the same kinetics as the main peak. The co-application of DAU and mambalgin-2 indicated that their binding sites do not overlap. Additionally, we found an asymmetry in the pH activation curve of the channel, which was well-described by a mathematical model based on the multiplied probabilities of protons binding with a pool of high-cooperative sites and a single proton binding with a non-cooperative site. In this model, DAU targeted the pool of high-cooperative sites and, when applied with protons, acted as an inhibitor of ASIC1a activation. Moreover, DAU’s occupation of the same binding site most probably reverses the channel from steady-state desensitization in the pH 6.9–7.3 range. DAU features disclose new opportunities in studies of ASIC structure and function.
Biomolecules, Volume 9; doi:10.3390/biom9080337
Abstract:Euphorbia genus (Euphorbiaceae family), which is the third largest genus of angiosperm plants comprising ca. 2000 recognized species, is used all over the world in traditional medicine, especially in the traditional Chinese medicine. Members of this taxa are promptly recognizable by their specialized inflorescences and latex. In this review, an overview of Euphorbia-derived natural products such as essential oils, extracts, and pure compounds, active in a broad range of biological activities, and with potential usages in health maintenance, is described. The chemical composition of essential oils from Euphorbia species revealed the presence of more than 80 phytochemicals, mainly oxygenated sesquiterpenes and sesquiterpenes hydrocarbons, while Euphorbia extracts contain secondary metabolites such as sesquiterpenes, diterpenes, sterols, flavonoids, and other polyphenols. The extracts and secondary metabolites from Euphorbia plants may act as active principles of medicines for the treatment of many human ailments, mainly inflammation, cancer, and microbial infections. Besides, Euphorbia-derived products have great potential as a source of bioactive extracts and pure compounds, which can be used to promote longevity with more health.
Biomolecules, Volume 9; doi:10.3390/biom9080335
Abstract:Insulin plays a key role in glucose homeostasis and is hence used to treat hyperglycemia, the main characteristic of diabetes mellitus. Annulohypoxylon annulatum is an inedible ball-shaped wood-rotting fungus, and hypoxylon F is one of the major compounds of A. annulatum. The aim of this study is to evaluate the effects of hypoxylonol F isolated from A. annulatum on insulin secretion in INS-1 pancreatic β-cells and demonstrate the molecular mechanisms involved. Glucose-stimulated insulin secretion (GSIS) values were evaluated using a rat insulin ELISA kit. Moreover, the expression of proteins related to pancreatic β-cell metabolism and insulin secretion was evaluated using Western blotting. Hypoxylonol F isolated from A. annulatum was found to significantly enhance glucose-stimulated insulin secretion without inducing cytotoxicity. Additionally, hypoxylonol F enhanced insulin receptor substrate-2 (IRS-2) levels and activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Interestingly, it also modulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and pancreatic and duodenal homeobox 1 (PDX-1). Our findings showed that A. annulatum and its bioactive compounds are capable of improving insulin secretion by pancreatic β-cells. This suggests that A. annulatum can be used as a therapeutic agent to treat diabetes.
Biomolecules, Volume 9; doi:10.3390/biom9080329
Abstract:Oils and fats are important raw materials in food products, animal feed, cosmetics, and pharmaceuticals among others. The market today is dominated by oils derive, d from African palm, soybean, oilseed and animal fats. Colombia’s Amazon region has endemic palms such as Euterpe precatoria (açai), Oenocarpus bataua (patawa), and Mauritia flexuosa (buriti) which grow in abundance and produce a large amount of ethereal extract. However, as these oils have never been used for any economic purpose, little is known about their chemical composition or their potential as natural ingredients for the cosmetics or food industries. In order to fill this gap, we decided to characterize the lipids present in the fruits of these palms. We began by extracting the oils using mechanical and solvent-based approaches. The oils were evaluated by quantifying the quality indices and their lipidomic profiles. The main components of these profiles were triglycerides, followed by diglycerides, fatty acids, acylcarnitine, ceramides, ergosterol, lysophosphatidylcholine, phosphatidyl ethanolamine, and sphingolipids. The results suggest that solvent extraction helped increase the diglyceride concentration in the three analyzed fruits. Unsaturated lipids were predominant in all three fruits and triolein was the most abundant compound. Characterization of the oils provides important insights into the way they might behave as potential ingredients of a range of products. The sustainable use of these oils may have considerable economic potential.
Biomolecules, Volume 9; doi:10.3390/biom9080332
Abstract:Endothelial cells form the inner lining of blood vessels, in a process known as angiogenesis. Excessive angiogenesis is a hallmark of several diseases, including cancer. The number of studies in endothelial cell metabolism has increased in recent years, and new metabolic targets for pharmacological treatment of pathological angiogenesis are being proposed. In this work, we wanted to address experimental evidence of substrate (namely glucose, glutamine and palmitate) dependence in immortalized dermal microvascular endothelial cells in comparison to primary endothelial cells. In addition, due to the lack of information about lactate metabolism in this specific type of endothelial cells, we also checked their capability of utilizing extracellular lactate. For fulfilling these aims, proliferation, migration, Seahorse, substrate uptake/utilization, and mRNA/protein expression experiments were performed. Our results show a high glycolytic capacity of immortalized dermal microvascular endothelial cells, but an early independence of glucose for cell growth, whereas a total dependence of glutamine to proliferate was found. Additionally, in contrast with reported data in other endothelial cell lines, these cells lack monocarboxylate transporter 1 for extracellular lactate incorporation. Therefore, our results point to the change of certain metabolic features depending on the endothelial cell line.