Antimicrobial and cell-penetrating peptides have been the object of extensive studies for more than 60 years. Initially these two families were studied separately, and more recently parallels have been drawn. These studies have given rise to numerous methodological developments both in terms of observation techniques and membrane models. This review presents some of the most recent original and innovative

MicroRNAs (miRNAs) are small non-coding highly conserved RNA molecules that can act as master regulators of gene expression in a sequence-specific manner either by translation repression or mRNA degradation, influencing a wide range of biologic processes that are essential for the maintenance of cellular homeostasis. Chronic pediatric diseases are the leading cause of death worldwide among children

Drug resistance is one of the major challenges for treatment of hepatocellular carcinoma (HCC) with sorafenib. Our present study found that sorafenib resistant (SR) HCC cells showed epithelial-mesenchymal transition (EMT) characteristics with the downregulation of epithelial marker and upregulation of mesenchymal makers. The expression of Snail, a core factor of EMT, was increased in HCC/SR cells,

This review takes a closer look at the structural components of the molecules involved in the processes leading to caspase-1 activation. Interleukins 1β and 18 (IL-1β, IL-18) are well-known proinflammatory cytokines that are produced following cleavage of their respective precursor proteins by the cysteine protease caspase-1. Active caspase-1 is the final step of the NLRP3 inflammasome, a three-protein

Flavin-dependent monooxygenases catalyze a wide variety of redox reactions in important biological processes and are responsible for the synthesis of highly complex natural products. Although much has been learned about FMO chemistry in the last ∼60 years of research, several aspects of the reactions catalyzed by these enzymes remain unknown. In this review, we summarize recent advancements in the

The interaction of a dirhamnolipid biosurfactant secreted by Pseudomonas aeruginosa with calcium ATPase from sarcoplasmic reticulum (SR) was studied by means of different approaches, such as enzyme activity, fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and molecular docking simulations. The ATP hydrolysis activity was fully inhibited

One of the most prevalent cancers in men is prostate cancer and could be managed with immunotoxins or antibody treatment. Because of the substantial rise of the Prostate-Specific Antigen and the Prostate-Specific Membrane Antigen (PSMA), cancer vaccination should be rendered with these antigens. Through pharmacodynamic experiments in a library of natural compounds from ZINC database, the current research

Bovine β-lactoglobulin, an abundant protein in whey, is a promising nanocarrier for peroral administration of drug-like hydrophobic molecules, a process that involves transit through the different acidic conditions of the human digestive tract. Among the several pH-induced conformational rearrangements that this lipocalin undergoes, the Tanford transition is particularly relevant. This transition,

4-hydroxynonenal (HNE, 4-hydroxy-2-nonenal) is a primary α,β-unsaturated aldehyde product of lipid peroxidation. The accumulation of HNE increases with aging and the mechanisms are mainly attributable to increased oxidative stress and decreased capacity of HNE elimination. In this review article, we summarize the studies on age-related change of HNE concentration and alteration of HNE metabolizing

Muscle myosins are molecular motors that hydrolyze ATP and generate force through coordinated interactions with actin filaments, known as cross-bridge cycling. During the cross-bridge cycle, functional sites in myosin ‘sense’ changes in interactions with actin filaments and the nucleotide binding region, resulting in allosteric transmission of information throughout the structure. We investigated whether

Mylia taylorii is an ancient nonseed land plant that accumulates various sesquiterpenes with insecticidal and antibacterial activities. Recently, microbial-type sesquiterpene synthases (STSs) with atypical aspartate-rich metal ion binding motifs have been identified in some liverworts. Here, transcriptome analysis of M. taylorii was performed to identify M. taylorii sesquiterpene synthases (MtSTSs)

In the present study, the inhibitory mechanisms and effects of a synthetic phenazine dye, safranin O (SO) on human plasma butyrylcholinesterase (BChE), human erythrocyte acetylcholinesterase (AChE) and recombinant BChE mutants were investigated. Kinetic studies showed the following information: SO leaded to linear competitive inhibition of human plasma BChE with Ki = 0.44 ± 0.085 μM; α = ∞. It acted

The ubiquitous flavoenzymes commonly catalyze redox chemistry such as the monooxygenation of organic substrates and are both widely utilized in nature (e.g., in primary and secondary metabolism) and of significant industrial interest. In this work, we highlight the structural and mechanistic characteristics of the distinct types of flavoprotein monooxygenases (FPMOs). We thereby illustrate the chemical

Although the use of computational methods within the pharmaceutical industry is well established, there is an urgent need for new approaches that can improve and optimize the pipeline of drug discovery and development. In spite of the fact that there is no unique solution for this need for innovation, there has recently been a strong interest in the use of Artificial Intelligence for this purpose.

The study investigates the effect of LPDBD (Low Pressure Dielectric Barrier Discharge) (Ar + Air) plasma on seed germination, seedling growth and antioxidant enzyme activity of rice. Rice seeds were treated with LPDBD (Ar + Air) plasma for 2min, 4min, 6min, 8min and 10min. Seed germination rate, seedling growth, total chlorophyll content, enzymatic activity, total soluble sugar and protein concentration

Abdominal aortic aneurysm (AAA) is a fatal vascular disease with insidious symptoms. However, the mechanism behind its development remains unclear. The transient receptor potential vanilloid (TRPV) family has crucial protective effects against cardiovascular diseases, but the role of TRPV5 in AAA has yet to be reported. In this study, ApoE−/− mice were intraperitoneally injected with AAV-GFP or AAV-TRPV5

The effects of phosphorylation of histone H3 at serine 10 have been studied in the context of other posttranslational modifications such as lysine methylation. We set out to investigate the impact of phosphoserine-10 on arginine-8 methylation. We performed methylation reactions using peptides based on histone H3 that contain a phosphorylated serine and compared the extent of arginine methylation with

β-Catenin, a key transcriptional factor involved in the canonical Wnt signaling pathway, is regulated by a cascade of phosphorylations and plays a major role in the progression of triple-negative breast cancer (TNBC). However, the phosphorylation induced conformational changes in a β-Catenin is still poorly understood. Hence, we adopted a conventional molecular dynamics approach to study phosphorylations

Nanomechanical properties of living cells, as measured with atomic force microscopy (AFM), are increasingly recognized as criteria that differentiate normal and pathologically altered cells. Locally measured cell elastic properties, described by the parameter known as Young's modulus, are currently proposed as a new diagnostic parameter that can be used at the early stage of cancer detection. In this

Background Myocardial ischemia/reperfusion (I/R) injury is closely related to cardiomyocyte apoptosis. Stimulating β2 adrenergic receptor (β2AR) can effectively combat cardiomyocyte apoptosis. Previous studies demonstrate that the gut microbial metabolite phenylacetylglycine (PAGly) can stimulate β2AR. However, the effect of PAGly on myocardial I/R injury remains unknown. Methods: The hypoxia/reoxygenation

5-Aminolevulinic acid (ALA) is the rate-limiting intermediate in heme biosynthesis in vertebrate species; a reaction catalyzed by the mitochondrial ALA synthase 1 (ALAS1) enzyme. Previously we reported that knockdown of the ubiquitously expressed ALAS1 gene in mice disrupts normal glucose metabolism, attenuates mitochondrial function and results in a prediabetic like phenotype when animals pass 20-weeks

Background Hyperoxia-induced lung injury (HILI) is an acute lung injury (LI) induced by extended periods of exposure to hyperoxia. Alleviating LI by bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) and microRNAs (miRs) has been previously reported. This study is devised to probe the interaction between BMSCs-Exos and miR-425 in HILI. Methods Firstly, BMSCs-Exos were isolated and identified

PCSK9 plays a critical role in cholesterol metabolism via the PCSK9–LDLR axis. Liver-derived, circulating PCSK9 has become a novel drug target in lipid-lowering therapy. Accumulative evidence supports the possible association between PCSK9 and cardiac diseases and their risk factors. PCSK9 exerts various effects in the heart independently of LDL-cholesterol regulation. Acute myocardial infarction (AMI)

Substantial variation in relaxation rate exists among cardiomyocytes within small volumes of myocardium; however, it is unknown how this variability affects the overall relaxation mechanics of heart muscle. In this study, we sought to modulate levels of cellular heterogeneity in a computational model, then validate those predictions using an engineered heart tissue platform. We formulated an in silico

During cellular respiration, radicals, such as superoxide, are produced, and in a large concentration, they may cause cell damage. To combat this threat, the cell employs the enzyme Cu/Zn Superoxide Dismutase (SOD1), which converts the radical superoxide into molecular oxygen and hydrogen peroxide, through redox reactions. Although this is its main function, recent studies have shown that the SOD1

Chemoprevention failure is considered to be the most emerging problem that makes non-small cell lung cancer (NSCLC) as one of the deadliest malignancies in the world. In NSCLC cells, Nuclear factor erythroid 2-related factor 2 (Nrf2), a redox sensitive transcription factor, promotes cancer cell survival and fosters mechanism for drug resistance. Here we report identification of Kaempferol, a dietary

Circadian clock genes are found in almost every cell that has a nucleus; they regulate the rhythmic nature of all processes that are cyclical. Among the genes controlled by the circadian clock, there are numerous factors that regulate key processes in the functioning of the cell. Disturbances in the functioning of the circadian clock are associated with numerous disorders. A recent study has shown

Micro–ribonucleic acids (miRNAs) are a class of conserved small non-coding RNAs (sncRNAs) that post-transcriptionally regulate their downstream target genes. Existing evidence indicates that abnormal expression of mRNAs results in the occurrence and development of pancreatic cancer (PC). In this study, we explored the potential role of miRNA-139 (miR-139) as a biomarker in the monitoring and treatment

Kynurenine-3-monooxygenase (KMO) is an important therapeutic target for several brain disorders that has been extensively studied in recent years. Potent inhibitors towards KMO have been developed and tested within different disease models, showing great therapeutic potential, especially in models of neurodegenerative disease. The inhibition of KMO reduces the production of downstream toxic kynurenine

Metabolic reprogramming confers cancer cells plasticity and viability under harsh conditions. Such active alterations lead to cell metabolic dependency, which can be exploited as an attractive target in development of effective antitumor therapies. Similar to cancer cells, activated T cells also execute global metabolic reprogramming for their proliferation and effector functions when recruited to

The pathogenesis and molecular pathways involved in non-alcoholic fatty liver disease (NAFLD) are reviewed, as well as what is known about mitochondrial dysfunction that leads to heart disease and the progression to steatohepatitis and hepatic fibrosis. We focused our discussion on the role of the antioxidant gene heme oxygenase-1 (HO-1) and its nuclear coactivator, peroxisome proliferator-activated

Mitochondrial diseases are the most common inheritable metabolic diseases, due to defects in oxidative phosphorylation. They are caused by mutations of nuclear or mitochondrial DNA in genes involved in mitochondrial function. The peculiarity of “mitochondrial DNA genetics rules” in part explains the marked phenotypic variability, the complexity of genotype-phenotype correlations and the challenge of

Halogenated organic compounds are extensively used in the cosmetic, pharmaceutical, and chemical industries. Several naturally occurring halogen-containing natural products are also produced, mainly by marine organisms. These compounds accumulate in the environment due to their chemical stability and lack of biological pathways for their degradation. However, a few enzymes have been identified that

In addition to ATP synthesis, mitochondria are highly dynamic organelles that modulate apoptosis, ferroptosis, and inflammasome activation. Through executing these varied functions, the mitochondria play critical roles in the development and progression of neurodegenerative diseases including Alzheimer disease, Parkinson disease, Huntington disease, and Friedreich ataxia, among others. Impaired mitochondrial

The study of calmodulin (CaM) functions in living cells has been tackled up to date using cell-permeant CaM inhibitors or interference-RNA methods. CaM inhibitors may lack specificity and the siRNA interference approach is challenging, as all three CaM genes expressing an identical protein in mammals have to be blocked. Therefore, we recently introduced a novel genetic system using CRISPR/Cas9-mediated

Excessive ethanol consumption causes cellular damage, leading to fetal alcohol syndrome and alcohol liver diseases, which are frequently seen with vitamin D (VD) deficiency. A great deal of progress has been achieved in the mechanisms of ethanol-induced hepatocyte damage. However, there are limited intervention means to reduce or rescue hepatocytes damage caused by ethanol. On the basis of our preliminary

Multiple sclerosis is a neurodegenerative disease causing disability in young adults. Alterations in metabolism and lipid profile have been associated with this disease. Several studies have reported changes in the metabolism of arachidonic acid and the profile of fatty acids, ceramides, phospholipids and lipid peroxidation products. Nevertheless, the understanding of the modulation of circulating

Bone fractures are one of the most frequent injuries in the musculoskeletal system. Despite the best treatment efforts, a large proportion of bone fracture cases still display undesirable outcomes. Here, we verified that calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptides, might be a critical regulator that link the nervous, immune and skeletal systems during bone healing. We used

Mitochondria are one of the most important organelles for eukaryotes, including humans, to produce energy. In the energy-producing process, mitochondria constantly generate reactive oxygen species as a by-product of electrons leaking out from the electron transport chain react with oxygen. The active oxygen, in turn, plays pivotal roles in mediating several signalings, including those that are implicated

Magnesium (Mg2+) plays a critical role in many physiological processes. The AtMRS2/MGT family, which contains nine Arabidopsis genes (and two pseudogenes), belongs to a eukaryotic subset of the CorA superfamily of divalent cation transporters. AtMRS2-11/MGT10 possesses the signature GlyMetAsn sequence (the GMN motif) conserved in the CorA superfamily; however, little is known about the role of the

Multidrug resistance (MDR) caused by overexpressed permeability–glycoprotein (P-gp) in cancer cells is the main barrier for the cure of cancers. P-gp can pump many chemotherapeutic drugs, which is a viable target to overcome P-gp-mediated MDR by efficient inhibitors of P-gp. However, limited understanding of the efflux mechanism by human P-gp hinders the development of efficient inhibitors. Herein

Histoplasma capsulatum is an ascomyceteous fungus and a human lung pathogen, which is present in river valleys of the Americas and other continents. H. capsulatum and two related human pathogens, Blasmomyces dermatitidis and Paracoccidioides brasiliensis, belongs to the Ajellomycetaceae family. The genomes of all three species code for three homologous and tentative enzymes of the linoleate diol synthase

Ischemia reperfusion (I/R) injury is a key contributing factor to the pathogenic mechanism involved in cerebral infarction. Transmembrane protein 126b (TMEM126B), a mitochondrial complex I assembly factor, has been reported to have an intimate association with disease progression, but is little known in ischemia stroke. The present study was designed to explore the effects of TEME126B on oxygen-glucose

Vitiligo is an autoimmune disease of the skin which causes loss of melanocytes from the epidermis. Recently, it is demonstrated that oxidative stress (OS) plays a significant role in the immuno-pathogenesis of vitiligo. A major mechanism in the cellular defense against OS is activation of the nuclear factor erythroid2-related factor (Nrf2)-Kelch-like ECH-associated protein 1(Keap1)-antioxidant responsive

Background Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyl transferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified clear. Methods To determine the

The neurodevelopmental disorder Rett syndrome (RTT) affects mostly females. Upon an apparently normal initial development, cognitive impairment, irregular breathing, motor dysfunction, and epilepsy occur. The complex pathogenesis includes, among others, mitochondrial impairment, redox imbalance, and oxidative damage. As these arise already in neonatal Rett mice, they were proposed contributors of disease