International Journal of Molecular Sciences — Open Access Journal

Seed protein and oil content are the two important traits determining the quality and value of soybean. Development of improved cultivars requires detailed understanding of the genetic basis underlying the trait of interest. However, it is prerequisite to have a high-density linkage map for precisely mapping genomic regions, and therefore the present study used high-density genetic map containing 2267 recombination bin markers distributed on 20 chromosomes and spanned 2453.79 cM with an average distance of 1.08 cM between markers using restriction-site-associated DNA sequencing (RAD-seq) approach. A recombinant inbred line (RIL) population of 104 lines derived from a cross between Linhefenqingdou and Meng 8206 cultivars was evaluated in six different environments to identify main- and epistatic-effect quantitative trait loci (QTLs)as well as their interaction with environments. A total of 44 main-effect QTLs for protein and oil content were found to be distributed on 17 chromosomes, and 15 novel QTL were identified for the first time. Out of these QTLs, four were major and stable QTLs, viz., qPro-7-1, qOil-8-3, qOil-10-2 and qOil-10-4, detected in at least two environments plus combined environment with R² values >10%. Within the physical intervals of these four QTLs, 111 candidate genes were screened for their direct or indirect involvement in seed protein and oil biosynthesis/metabolism processes based on gene ontology and annotation information. Based on RNA sequencing (RNA-seq) data analysis, 15 of the 111 genes were highly expressed during seed development stage and root nodules that might be considered as the potential candidate genes. Seven QTLs associated with protein and oil content exhibited significant additive and additive × environment interaction effects, and environment-independent QTLs revealed higher additive effects. Moreover, three digenic epistatic QTLs pairs were identified, and no main-effect QTLs showed epistasis. In conclusion, the use of a high-density map identified closely linked flanking markers, provided better understanding of genetic architecture and candidate gene information, and revealed the scope available for improvement of soybean quality through marker assisted selection (MAS). Full article

The interactions between ncRNAs and proteins are critical for regulating various cellular processes in organisms, such as gene expression regulations. However, due to limitations, including financial and material consumptions in recent experimental methods for predicting ncRNA and protein interactions, it is essential to propose an innovative and practical approach with convincing performance of prediction accuracy. In this study, based on the protein sequences from a biological perspective, we put forward an effective deep learning method, named BGFE, to predict ncRNA and protein interactions. Protein sequences are represented by bi-gram probability feature extraction method from Position Specific Scoring Matrix (PSSM), and for ncRNA sequences, k-mers sparse matrices are employed to represent them. Furthermore, to extract hidden high-level feature information, a stacked auto-encoder network is employed with the stacked ensemble integration strategy. We evaluate the performance of the proposed method by using three datasets and a five-fold cross-validation after classifying the features through the random forest classifier. The experimental results clearly demonstrate the effectiveness and the prediction accuracy of our approach. In general, the proposed method is helpful for ncRNA and protein interacting predictions and it provides some serviceable guidance in future biological research. Full article

Lipoproteins containing apolipoprotein B modify associations of elevated urinary albumin excretion (UAE) with cardiovascular disease (CVD). Additionally, it is known that elevated UAE alters high-density lipoprotein functionality. Accordingly, we examined whether HDL features might also modify UAE-associated CVD. Multivariable Cox proportional-hazards modeling was performed on participants of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study at the baseline screening with standard lipid/lipoprotein analyses and, three-to-four years later (second screen), with nuclear magnetic resonance lipoprotein analyses focusing on HDL parameters including HDL particle (HDL-P) and apolipoprotein A-I concentrations. These were used with UAE and derived measures of HDL apoA-I content (apoA-I/HDL-C and apoA-I/HDL-P) in risk models adjusted for gender, age, apoB, diabetes, past CVD history, CRP and GFR. Interaction analysis was also performed. Baseline screening revealed significant associations inverse for HDL-C and apoA-I and direct for apoA-I/HDL-C. The second screening demonstrated associations inverse for HDL-P, large HDL-P, medium HDL-P, HDL size, and apoA-I/HDL-P. Significant interactions with UAE included apoA-I/HDL-C at the baseline screening, and apoA-I/HDL-P and medium HDL-P but not apoA-I/HDL-C at the second screening. We conclude that features of HDL particles including apoA-I/HDL-P, indicative of HDL apoA-I content, and medium HDL-P modify associations of elevated UAE with CVD risk. Full article

In recent years, photovoltaic cell technology has grown extraordinarily as a sustainable source of energy, as a consequence of the increasing concern over the impact of fossil fuel-based energy on global warming and climate change. The different photovoltaic cells developed up to date can be classified into four main categories called generations (GEN), and the current market is mainly covered by the first two GEN. The 1GEN (mono or polycrystalline silicon cells and gallium arsenide) comprises well-known medium/low cost technologies that lead to moderate yields. The 2GEN (thin-film technologies) includes devices that have lower efficiency albeit are cheaper to manufacture. The 3GEN presents the use of novel materials, as well as a great variability of designs, and comprises expensive but very efficient cells. The 4GEN, also known as “inorganics-in-organics”, combines the low cost/flexibility of polymer thin films with the stability of novel inorganic nanostructures (i.e., metal nanoparticles and metal oxides) with organic-based nanomaterials (i.e., carbon nanotubes, graphene and its derivatives), and are currently under investigation. The main goal of this review is to show the current state of art on photovoltaic cell technology in terms of the materials used for the manufacture, efficiency and production costs. A comprehensive comparative analysis of the four generations is performed, including the device architectures, their advantages and limitations. Special emphasis is placed on the 4GEN, where the diverse roles of the organic and nano-components are discussed. Finally, conclusions and future perspectives are summarized. Full article

Kaempferol (Kae) is a natural flavonoid with potent antioxidant activity, but its therapeutic use is limited by its low aqueous solubility. Here, a series of Kae derivatives were synthesized to improve Kae dissolution property in water and antioxidant activity. These compounds included sulfonated Kae (Kae-SO₃), gallium (Ga) complexes with Kae (Kae-Ga) and Kae-SO₃ (Kae-SO₃-Ga). The compound structures were characterized by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and thermal methods (TG/DSC). The results showed that a sulfonic group (-SO₃) was successfully tethered on the C3’ of Kae to form Kae-SO₃. And in the metal complexation, 4-CO and 3-OH of the ligand participated in the coordination with Ga(III). The metal-to-ligand ratio 1:2 was suggested for both complexes. Interestingly, Kae-SO₃-Ga was obviously superior to other compounds in terms of overcoming the poor water-solubility of free Kae, and the solubility of Kae-SO₃-Ga was about 300-fold higher than that of Kae-Ga. Furthermore, the evaluation of antioxidant activities in vitro was carried out for Kae derivatives by using α,α-diphenyl-β-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) free radical scavenging. The results showed that Kae-SO₃-Ga was also optimal for scavenging free radicals in a dose-dependent manner. These data demonstrate that sulfonate kaempferol-gallium complex has a promising future as a potential antioxidant and as a potential therapeutic agent for further biomedical studies. Full article

Niacin (also known as “vitamin B₃” or “vitamin PP”) includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair and cell death. In the central nervous system, vitamin B₃ has long been recognized as a key mediator of neuronal development and survival. Here, we will overview available literature data on the neuroprotective role of niacin and its derivatives, especially focusing especially on its involvement in neurodegenerative diseases (Alzheimer’s, Parkinson’s, and Huntington’s diseases), as well as in other neuropathological conditions (ischemic and traumatic injuries, headache and psychiatric disorders). Full article

Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental control of gene expression. This was reversed by the maternal supply with folic acid (3 mg/kg/day) during the last third of gestation, resulting in a significant reduction of associated birth defects. Since the postnatal brain is subject to intensive developmental processes, we tested whether further folate supplementation during lactation could bring additional benefits. Vitamin deficiency resulted in weaned pups (21 days) in growth retardation, delayed ossification, brain atrophy and cognitive deficits, along with unchanged brain level of let-7a and decreased expression of miR-34a and miR-23a. Whereas maternal folic acid supplementation helped restore the levels of affected microRNAs, it led to a reduction of structural and functional defects taking place during the perinatal/postnatal periods, such as learning/memory capacities. Our data suggest that a gestational B-vitamin deficiency could affect the temporal control of the microRNA regulation required for normal development. Moreover, they also point out that the continuation of folate supplementation after birth may help to ameliorate neurological symptoms commonly associated with developmental deficiencies in folate and B12. Full article

The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases consisting of 4 RSK isoforms (RSK1-4), of which RSK1 is also designated as p90RSK. p90RSK plays an important role in the Ras-mitogen-activated protein kinase (MAPK) signalling cascade and is the direct downstream effector of Ras-extracellular signal-regulated kinase (ERK1/2) signalling. ERK1/2 activation directly phosphorylates and activates p90RSK, which, in turn, activates various signalling events through selection of different phosphorylation substrates. Upregulation of p90RSK has been reported in numerous human diseases. p90RSK plays an important role in the regulation of diverse cellular processes. Thus, aberrant activation of p90RSK plays a critical role in the pathogenesis of organ dysfunction and damage. In this review, we focus on the current understanding of p90RSK functions and roles in the development and progression of kidney diseases. Roles of p90RSK, as well as other RSKs, in cardiovascular disorders and cancers are also discussed. Full article

The initiative strategy for the development of novel anti-microbial agents usually uses the virulence factors of bacteria as a target, without affecting their growth and survival. The type III secretion system (T3SS), one of the essential virulence factors in most Gram-negative pathogenic bacteria because of its highly conserved construct, has been regarded as an effective target that developed new anti-microbial drugs. Xanthomonas oryzae pv. oryzae (Xoo) causes leaf blight diseases and is one of the most important pathogens on rice. To find potential anti-virulence agents against this pathogen, a number of natural compounds were screened for their effects on the T3SS of Xoo. Three of 34 compounds significantly inhibited the promoter activity of the harpin gene, hpa1, and were further checked for their impact on bacterial growth and on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results indicated that treatment of Xoo with CZ-1, CZ-4 and CZ-9 resulted in an obviously attenuated HR without affecting bacterial growth and survival. Moreover, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that the expression of the Xoo T3SS was suppressed by treatment with the three inhibitors. The mRNA levels of representative genes in the hypersensitive response and pathogenicity (hrp) cluster, as well as the regulatory genes hrpG and hrpX, were reduced. Finally, the in vivo test demonstrated that the compounds could reduce the disease symptoms of Xoo on the rice cultivar (Oryza sativa) IR24. Full article

Prostate cancer (PCa) has remarkably emerged as a prominent disease in the face of the male population. Conventional treatments like prostatectomy or radiation can be curative only if PCa is diagnosed at an early stage. In the field of targeted therapy, a bevy of novel therapeutic approaches have left a landmark in PCa treatment and have proven to extend survival via distinct modes of actions. Nanotherapy has started to take root and has become the hype of the century by virtue of its abundant advantages. Scientists have invested a great deal of interest in the development of nanostructures such as gold nanoparticles (AuNPs), which hold particularly great hope for PCa theranostics. In this article, we present an overview of the studies published after 1998 that involve the use of different functionalized AuNPs to treat and diagnose PCa. Special reference is given to various in vitro and in vivo methods employed to shuttle AuNPs to PCa cells. Major studies show an enhancement of either detection or treatment of PCa when compared to their non-targeted counterparts, especially when AuNPs are tagged with specific ligands, such as antibodies, tea natural extracts, folate, anisamide, receptor inhibitors, and chitosan. Future approaches of treatment are dependent on those worthy multifunctional molecules, and are dictated by their ability to achieve a more versatile cancer therapeutic approach. Full article

The importance of magnesium (Mg) for plant growth is well-documented. Silicon (Si)-mediated alleviation of mineral deficiencies has been also reported in a number of plant species; however, there is no report on the relevance of Si nutrition in plants grown in Mg-deficient condition. Therefore, in the present work, an attempt was undertaken to study the role of Si nutrition in maize plants exposed to Mg deficiency. Plants were grown either under low (0.02 mM) or normal (0.5 mM) levels of Mg, with or without Si supplement. We have shown that Mg-deficient plants treated with Si maintained their growth and increased significantly the levels of chlorophyll and soluble sugars compared to those plants which did not receive Si. In addition, the concentrations of hexose-P, and glycolytic intermediate metabolites—mainly organic acids (isocitric and glutamic acids)—were increased in response to Si nutrition, which was associated with an increase in the levels of stress amino acids such as gamma-aminobutyric-acid (GABA), serine and glycine, as well as polyamines putrescine, which overall contributed to Mg stress tolerance. In addition, Si enhanced the levels of phytohormones cytokinin iso-pentenyladenine (IP), iso-pentenyladenine riboside (IPR), jasmonic acid (JA) and its derivate l-isoleucine (JA-ILE). The increase in cytokinin maintained the growth of Mg-deficient plants, while JA and JA-IEA were induced in response to carbohydrates accumulation. Altogether, our study reveals the vital role of Si under Mg deficiency by regulating plant primary metabolite and hormonal changes. Full article

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification. Full article

Taste receptors were first described as sensory receptors located on the tongue, where they are expressed in small clusters of specialized epithelial cells. However, more studies were published in recent years pointing to an expression of these proteins not only in the oral cavity but throughout the body and thus to a physiological role beyond the tongue. The recent observation that taste receptors and components of the coupled taste transduction cascade are also expressed during the different phases of spermatogenesis as well as in mature spermatozoa from mouse to humans and the overlap between the ligand spectrum of taste receptors with compounds in the male and female reproductive organs makes it reasonable to assume that sperm “taste” these different cues in their natural microenvironments. This assumption is assisted by the recent observations of a reproductive phenotype of different mouse lines carrying a targeted deletion of a taste receptor gene as well as the finding of a significant correlation between human male infertility and some polymorphisms in taste receptors genes. In this review, we depict recent findings on the role of taste receptors in male fertility, especially focusing on their possible involvement in mechanisms underlying spermatogenesis and post testicular sperm maturation. We also highlight the impact of genetic deletions of taste receptors, as well as their polymorphisms on male reproduction. Full article

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process modulated by coactivator and corepressor proteins. Breast Cancer Amplified Sequence 2 (BCAS2), is a poorly studied ERα coactivator. In this work, we characterize some of the mechanisms through which this protein increases ERα activity and how this promotes carcinogenic processes in breast cancer cells. Using protein-protein interaction and luciferase assays we show that BCAS2 interacts with ERα both in vitro and in vivo and upregulates transcriptional activation of ERα directly through its N-terminal region (AF-1) and indirectly through its C-terminal (AF-2) region, acting in concert with AF-2 interacting coactivators. Elevated expression of BCAS2 positively affects proliferation, clonogenicity and migration of breast cancer cells and directly activates ERα regulated genes which have been shown to play a role in tumor growth and progression. Finally, we used signal transduction pathway inhibitors to elucidate how BCAS2 is regulated in these cells and observed that BCAS2 is preferentially regulated by the PI3K/AKT signaling pathway. BCAS2 is an AF-1 coactivator of ERα whose overexpression promotes carcinogenic processes, suggesting an important role in the development of estrogen-receptor positive breast cancer. Full article

Numerous nanoparticles drug delivery systems for therapeutic implications in cancer treatment are in preclinical development as conventional chemotherapy has several drawbacks. A chemotherapeutic approach requires high doses of chemotherapeutic agents with low bioavailability, non-specific targeting, and above all, development of multiple drug resistance. In recent years, inorganic nano-drug delivery platforms (NDDPs; with a metal core) have emerged as potential chemotherapeutic systems in oncology. One of the major goals of developing inorganic NDDPs is to effectively address the targeted anti-cancer drug(s) delivery related problems by carrying the therapeutic agents to desired tumors sites. In this current review, we delve into summarizing the recent developments in targeted release of anti-cancer drugs loaded in inorganic NDDPs such as mesoporous silica nanoparticles, carbon nanotubes, layered double hydroxides, superparamagnetic iron oxide nanoparticles and calcium phosphate nanoparticles together with highlighting their therapeutic performance at tumor sites. Full article

Acyl-CoA:glycerol-sn-3-phosphate acyltransferase (GPAT) is an enzyme responsible for the rate-limiting step in the synthesis of glycerophospholipids and triacylglycerol (TAG). The enzymes of mammalian species are classified into four isoforms; GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, whereas GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane. The activity of each enzyme expressed is associated with physiological and pathological functions. The transcriptional regulation is well known, particularly in GPAT1. GPAT1 mRNA expression is mainly regulated by the binding of the transcriptional factor SREBP-1c to the specific element (the sterol regulatory element) flanking the GPAT1 promoter. The TAG level is controlled by the insulin-induced transcriptional expression of GPAT1, which occupies most of the GPAT activity in the liver. The transcriptional regulation of the other three GPAT isoforms remains undetermined in detail. It is predicted that retinoic acid serves as a transcription factor in the GPAT2 promoter. PPARγ (peroxisome proliferator-activated receptor γ) increases the mRNA expression of GPAT3, which is associated with TAG synthesis in adipose tissues. Although GPAT has been considered to be a key enzyme in the production of TAG, unexpected functions have recently been reported, particularly in GPAT2. It is likely that GPAT2 is associated with tumorigenesis and normal spermatogenesis. In this review, the physiological and pathophysiological roles of the four GPAT isoforms are described, alongside the transcriptional regulation of these enzymes. Full article

Objectives: Obesity is a complex disease that has a strong association with diet and lifestyle. Dietary factors can influence the expression of key genes connected to insulin resistance, lipid metabolism, and adipose tissue composition. In this study, our objective was to determine gene expression and fatty acid (FA) profiles in visceral adipose tissue (VAT) from lean and morbidly obese individuals. We also aimed to study the agonist effect of dietary factors on glucose metabolism. Design and methods: Lean and low and high insulin resistance morbidly obese subjects (LIR-MO and HIR-MO) were included in this study. The gene expression of liver X receptor type alpha (LXR-α) and glucose transporter type 4 (GLUT4) and the FA profiles in VAT were determined. Additionally, the in vivo and in vitro agonist effects of oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) by peroxisome proliferator-activated receptor type gamma 2 (PPAR-γ2) on the activity of GLUT4 were studied. Results: Our results showed a dysregulation of GLUT4 and LXR-α in VAT of morbidly obese subjects. In addition, a specific FA profile for morbidly obese individuals was found. Finally, AA was an PPAR-γ2 agonist that activates the expression of GLUT4. Conclusions: Our study suggests a dysregulation of LXR-α and GLUT4 expression in VAT of morbidly obese individuals. FA profiles in VAT could elucidate their possible role in lipolysis and adipogenesis. Finally, AA binds to PPAR-γ2 to activate the expression of GLUT4 in the HepG2 cell line, showing an alternative insulin-independent activation of GLUT4. Full article

Grain development, as a vital process in the crop’s life cycle, is crucial for determining crop quality and yield. However, the molecular basis and regulatory network of barley grain development is not well understood at present. Here, we investigated the transcriptional dynamics of barley grain development through RNA sequencing at four developmental phases, including early prestorage phase (3 days post anthesis (DPA)), late prestorage or transition phase (8 DPA), early storage phase (13 DPA), and levels off stages (18 DPA). Transcriptome profiling found that pronounced shifts occurred in the abundance of transcripts involved in both primary and secondary metabolism during grain development. The transcripts’ activity was decreased during maturation while the largest divergence was observed between the transitions from prestorage phase to storage phase, which coincided with the physiological changes. Furthermore, the transcription factors, hormone signal transduction-related as well as sugar-metabolism-related genes, were found to play a crucial role in barley grain development. Finally, 4771 RNA editing events were identified in these four development stages, and most of the RNA editing genes were preferentially expressed at the prestore stage rather than in the store stage, which was significantly enriched in “essential” genes and plant hormone signal transduction pathway. These results suggested that RNA editing might act as a ‘regulator’ to control grain development. This study systematically dissected the gene expression atlas of barley grain development through transcriptome analysis, which not only provided the potential targets for further functional studies, but also provided insights into the dynamics of gene regulation underlying grain development in barley and beyond. Full article

Cancer represents a serious global health problem, and its incidence and mortality are rapidly growing worldwide. One of the main causes of the failure of an anticancer treatment is the development of drug resistance by cancer cells. Therefore, it is necessary to develop new drugs characterized by better pharmacological and toxicological profiles. Natural compounds can represent an optimal collection of bioactive molecules. Many natural compounds have been proven to possess anticancer effects in different types of tumors, but often the molecular mechanisms associated with their cytotoxicity are not completely understood. The endoplasmic reticulum (ER) is an organelle involved in multiple cellular processes. Alteration of ER homeostasis and its appropriate functioning originates a cascade of signaling events known as ER stress response or unfolded protein response (UPR). The UPR pathways involve three different sensors (protein kinase RNA(PKR)-like ER kinase (PERK), inositol requiring enzyme1α (IRE1) and activating transcription factor 6 (ATF6)) residing on the ER membranes. Although the main purpose of UPR is to restore this organelle’s homeostasis, a persistent UPR can trigger cell death pathways such as apoptosis. There is a growing body of evidence showing that ER stress may play a role in the cytotoxicity of many natural compounds. In this review we present an overview of different plant-derived natural compounds, such as curcumin, resveratrol, green tea polyphenols, tocotrienols, and garcinia derivates, that exert their anticancer activity via ER stress modulation in different human cancers. Full article