Molecular Components Research Articles

The molecular dialogue between Zymoseptoria tritici and wheat.

Zymoseptoria tritici is a highly damaging pathogen that causes high wheat yield losses in temperate climates. Z. tritici emerged during the domestication of wheat in the Fertile Crescent and has been extensively used as a model system for population genetic and genomic studies. New genetic tools and resources have provided a better understanding of the molecular components involved in the wheat-Z. tritici interaction, highlighted by the cloning of three wheat resistance genes and four Z. tritici avirulence genes. Despite the considerable progress made in the last few years, the mechanisms that mediate Z. tritici colonization remain largely unknown. In this review, we summarize the latest advances in understanding the molecular components mediating wheat-Z. tritici interactions and we discuss future research lines to close current knowledge gaps.

Designing mouthwash formulations with innovative molecular components to control initial dental erosion in vivo.

This study aimed to examine and compare the efficacy of mouthwashes containing different proteins and peptide on the prevention of enamel erosion in vivo, as well as to evaluate the participants' satisfaction with the formulations. Twelve participants were selected and underwent five cross-over mouthwash phases: Water (control); 0.1mg/mL CaneCPI-5; 0.5mg/mL MaquiCPI-3; 0.1mg/mL CsinCPI-2; and 0.037mg/mL Stn15pSpS. After prophylaxis, the participants rinsed (1min), followed by the acquired enamel pellicle (AEP) formation (2h). An erosive challenge was made (biopsy, citric acid 1%, 15s) on the buccal surface of the central maxillary incisors. The Relative Surface Reflection Intensity (%SRI) was assessed and analyzed by ANOVA/Tukey's tests. The calcium release in acid was measured by the Arsenazo method and verified by Kruskal-Wallis/Dunn's tests. The Spearman's correlation was used between analyses. A questionnaire evaluated the satisfaction of participants. For both analyses, the results showed that mouthwashes containing the proteins or peptide were significantly more effective in preventing enamel erosion compared to deionized water, with no significant differences among the active ingredients (p < 0.05). Also, there was a significant negative correlation between %SRI and calcium released (r=-0.5754). The questionnaire revealed that the volunteers were satisfied with the taste of the products. In addition, the experimental procedures were well tolerable, and no side effects were reported. All mouthwashes containing proteins or peptide were acceptable and effective in protecting enamel against initial dental erosion in vivo. This study highlights the potential of these pioneer organic components for the development of mouthwashes designed for people with risk of erosive tooth wear.

Wnt-5a Signaling Mediates Metaplasticity at Hippocampal CA3-CA1 Synapses in Mice.

Wnt signaling plays a role in synaptic plasticity, but the specific cellular events and molecular components involved in Wnt signaling-mediated synaptic plasticity are not well defined. Here, we report a change in the threshold required to induce synaptic plasticity that facilitates the induction of long-term potentiation (LTP) and inhibits the induction of long-term depression (LTD) during brief exposure to the noncanonical ligand Wnt-5a. Both effects are related to the metaplastic switch of hippocampal CA3-CA1 synaptic transmission, a complex mechanism underlying the regulation of the threshold required to induce synaptic plasticity and of synaptic efficacy. We observed an early increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) that persisted over time, including after washout. The first phase involves an increase in the fEPSP amplitude that is required to trigger a spontaneous second phase that depends on Jun N-terminal kinase (JNK) and N-methyl D-aspartate receptor (NMDAR) activity. These changes are prevented by treatment with secreted frizzled-related protein 2 (sFRP-2), an endogenous antagonist of Wnt ligands. Here, we demonstrate the contribution of Wnt-5a signaling to a process associated with metaplasticity at CA3-CA1 synapses that favors LTP over LTD.

A guide for blood-brain barrier models.

Understanding the intricate mechanisms underlying brain-related diseases hinges on unraveling the pivotal role of the blood-brain barrier (BBB), an essential dynamic interface crucial for maintaining brain equilibrium. This review offers a comprehensive analysis of BBB physiology, delving into its cellular and molecular components while exploring a wide range of in vivo and in vitro BBB models. Notably, recent advancements in 3D cell culture techniques are explicitly discussed, as they have significantly improved the fidelity of BBB modeling by enabling the replication of physiologically relevant environments under flow conditions. Special attention is given to the cellular aspects of in vitro BBB models, alongside discussions on advances in stem cell technologies, providing valuable insights into generating robust cellular systems for BBB modeling. The diverse array of cell types used in BBB modeling, depending on their sources, is meticulously examined in this comprehensive review, scrutinizing their respective derivation protocols and implications. By synthesizing diverse approaches, this review sheds light on the improvements of BBB models to capture physiological conditions, aiding in understanding BBB interactions in health and disease conditions to foster clinical developments.

Molecular pathology of skin fragility

The skin's barrier function is primarily maintained by the cohesion of its layers and the specialized stratum corneum. Genetic and autoimmune disorders that result in skin fragility have significantly contributed to understanding the role of various molecular components in the skin. These conditions, characterized by blisters, erosions, wounds, and impaired wound healing, are rare but must be considered in clinical differential diagnoses. Key cutaneous adhesion structures include the epidermal basement membrane, anchoring fibrils, cell-matrix adhesions (e.g., hemidesmosomes and focal adhesions), and cell-cell adhesions (e.g., desmosomes and corneodesmosomes). These multiprotein suprastructures not only provide structural support but also participate in signaling processes and physiological or pathological conditions such as skin aging and wound healing. Additionally, dermal connective tissue plays astructural role and serves as areservoir for proteases, growth factors, and cytokines. Modern techniques like single-cell and spatial transcriptomics, combined with artificial intelligence algorithms, are advancing the molecular mapping of human skin. Moreover, this review highlights the molecular composition of adhesion structures and the specific diseases associated with deficiencies in these components.

TMEM206 Contributes to Cancer Hallmark Functions in Colorectal Cancer Cells and Is Regulated by p53 in a p21-Dependent Manner

Acid-induced ion flux plays a role in pathologies where tissue acidification is prevalent, including cancer. In 2019, TMEM206 was identified as the molecular component of acid-induced chloride flux. Localizing to the plasma membrane, TMEM206 contributes to cellular processes like acid-induced cell death. Since over 50% of human cancers carry loss of function mutations in the p53 gene, we aimed to analyze how TMEM206 is regulated by p53 and its role in cancer hallmark function and acid-induced cell death in HCT116 colorectal cancer (CRC) cells. We generated p53-deficient HCT116 cells and assessed TMEM206-mediated Cl− currents and transcriptional regulation using the patch-clamp and a dual-luciferase reporter assay, respectively. To investigate the contribution of TMEM206 to cancer hallmark functions, we performed migration and metabolic activity assays. The role of TMEM206 in p53-mediated acid-induced cell death was assessed with cell death assays. The TMEM206 mRNA level was significantly elevated in human primary CRC tumors. TMEM206 knockout increased acid-induced cell death and reduced proliferation and migration, indicating a role for TMEM206 in these cancer hallmark functions. Furthermore, we observed increased TMEM206 mRNA levels and currents in HCT116 p53 knockout cells. This phenotype can be rescued by transient overexpression of p53 but not by overexpression of dysfunctional p53. In addition, our data suggest that TMEM206 may mediate cancer hallmark functions within p53-associated pathways. TMEM206 promoter activity is not altered by p53 overexpression. Conversely, knockout of p21, a major target gene of p53, increased TMEM206-mediated currents, suggesting expression control of TMEM206 by p21 downstream signaling. Our results show that in colorectal cancer cells, TMEM206 expression is elevated, contributes to cancer hallmark functions, and its regulation is dependent on p53 through a p21-dependent mechanism.

An Increase in the Rigidity of the Environment Favors MLCT over the MC State in [Ru(bpy)2(Nicotine)2](Cl)2: A Case Study of Photolabile Ligands.

Ru(II)-complexes with photolabile ligands find a wide range of applications, e.g., in drug release and in the design of light-responsive interfaces. While light-driven ligand loss has been studied mechanistically in detail for complexes in solution, comparably few studies are present that investigate the process in a material context, i.e., in a rigid environment and in the absence of solvent. This paper adds to this underrepresented perspective by studying the excited-state dynamics of [Ru(bpy)2(nicotine)2] (Cl)2 (Ru-nico) as a model system in poly(methyl methacrylate) (PMMA) and polyacrylonitrile (PAN) matrices. Femtosecond transient absorption spectroscopy and time-resolved emission spectroscopy are employed to monitor the photodissociation of labile nicotine ligands in polymer environments. Photoexcitation within the metal-to-ligand charge transfer (MLCT) band leads to transient dissociation of the nicotine ligand when the complex is dissolved in water. However, optical excitation of the 1MLCT transition of the complexes embedded in polymer matrices does not result in photodissociation, likely due to the rigidity of the environment, which cannot solvate the undercoordinated complex after ligand dissociation and the dissociated ligand. These insights shed light on the role of the local environment when considering the photophysics of ligand loss from Ru(II)-polypyridyl complexes and, hence, their use in the light-activation of reactive molecular components in materials.

The synergistic enhancement or inhibition of different molecular weight components of mannoproteins after ultrafiltration on the encapsulation.

This study investigated the effects of molecular weight regulation on mannoproteins (MPs) in encapsulating both monomeric and oligomeric proanthocyanidins (MOPC). To achieve this, two different conformations of MPs were fractionated by ultrafiltration into two main molecular weight components. The results indicated that regulating molecular weight through ultrafiltration altered the conformation of MPs chains, which in turn affected the intermolecular forces with MOPC. Specifically, the interactions among the different molecular weight components of MPs formed a cross-linking network. High molecular weight components provided external support to this network, while low molecular weight components contributed to internal stabilization. The dense, flexible, and irregular coil structure of MPs facilitated the entry of MOPC into the internal spaces of the cross-linking network. Additionally, protein unfolding into a more stable β-sheet structure further stabilized MPs' cross-linking network, enhancing its capacity to encapsulate MOPC. The presence of more hydrophobic regions and positive charges within the proteins increased the number of binding sites for MOPC. This study aimed to identify the primary structural forms of MPs with potent initial bitter inhibition capabilities on MOPC, and a proposed ultrafiltration method was introduced to modify the triple helix structure of polysaccharide, offering a foundational theoretical framework for enhancing the functional attributes of current or prospective MPs. Additionally, the mixed regulation of polysaccharides with varying conformations was also beneficial for guiding the production of high-efficiency polysaccharide products.

THE NEUROBEHAVIORAL STATE HYPOTHESIS.

Since the early attempts to understand the brain made by Greek philosophers more than 2000 years ago, one of the main questions in neuroscience has been how the brain perceives all the stimuli in the environment and uses this information to implement a response. Recent hypotheses of the neural code rely on the existence of an ideal observer, whether on specific areas of the cerebral cortex or distributed network composed of cortical and subcortical elements. The Neurobehavioral State hypothesis stipulates that neurons are in a quasi-stable state due to the dynamic interaction of their molecular components. This increases their computational capabilities and electrophysiological behavior further than a binary active/inactive state. Together, neuronal populations across the brain learn to identify and associate internal and external stimuli with actions and emotions. Furthermore, such associations can be stored through the regulation of neuronal components as new quasi-stable states. Using this framework, behavior arises as the result of the dynamic interaction between internal and external stimuli together with previously established quasi-stable states that delineate the behavioral response. Finally, the Neurobehavioral State hypothesis is firmly grounded on present evidence of the complex dynamics within the brain, from the molecular to the network level, and avoids the need for a central observer by proposing the brain configures itself through experience-driven associations.

Structural analysis and theoretical studies of 2-(2-chlorobenzylidene) malononitrile (CS) “a riot controlling agent”

In solvent methanol, malononitrile and 2-chlorobenzaldehyde were stirred in the presence of base piperidine to synthesise the target chemical 2-(2-chlorobenzylidene) malononitrile (CS). The crystal structure of the target compound C10H5ClN2 has been elucidated through X-ray crystallographic analysis. It crystallises in the monoclinic crystal system within the P21 space group, containing four molecules per asymmetric unit. The unit cell dimensions are a = 3.8825(3) Å, b = 21.0202(18) Å, c = 21.3481(18) Å, and β = 95.096(4)°. The phenyl and malononitrile groups, which make up the molecular components, are each planar but slanted towards one another at a dihedral angle of 12.7° (4). Besides this, target molecule is also stabilized by hydrogen bonding, halogen bonding and π stacking interactions. Solid-state structure has been analysed through Hirshfeld surface analysis, including the evaluation of the different energy frameworks, indicating that the molecular sheets are primarily formed by hydrogen bonds and halogen bonds and the stabilization is dominated via the electrostatic energy contribution. Fingerprint plots were carried out to study the relative contribution of noncovalent interactions in the target compound CS. Further, the density functional theory calculations were employed using B3LYP hybrid functional with 6-311++G level basic set to optimize the structural coordinates in gas phase and in different solvents (chloroform, water, and methanol). The chemically active regions of the target compound were identified by the analysis of molecular electrostatic potential surface. Further, from PASS analysis and literature reports, molecular docking of title compounds was carried out with human transient receptor potential ankyrin 1 ion channel (hTRPA1) (PDB-ID 6PQO). ΔGb (docking energy) and inhibition constant was calculated to be −7.53 kcal/mol and 3.33 μM respectively, with the target ion channel.

Venom characterization of Venezuelan scorpion Tityus caripitensis.

Tityus caripitensis is an endemic scorpion species found in the northeastern region from Venezuela, being responsible for sting accidents in this area. This study describes for the first time a biological, biochemical and electrophysiological partial characterization of Tityus caripitensis scorpion venom. The venom is toxic to mice with a LD50 of 20.2 μg/gr mouse. Animals experimentally envenomed with Tityus caripitensis venom gradually manifested clinical signs in response to sublethal doses. SDS-PAGE of the venom resulted in 7 fractions ranging in size from ∼3.5 to ≥ 38 kDa. The 6-8 kDa proteins could correspond to neurotoxins. In addition, the components of Tityus caripitensis venom were similar to those obtained in the electrophoretic profile of Tityus discrepans. The commercial anti- Tityus discrepans IgG showed reactivity against Tityus caripitensis venom. Tityus caripitensis venom could induce hematological changes such as hyperamylasemia and hyperglycemia. The venom modified voltage dependent Na+v1.4 channels and blocked Kv+ channels. Although Tityus caripitensis venom is less toxic than Tityus discrepans, they share molecular and antigenic components. This aspect should be considered in the application of antivenom treatment.

BMSCs-derived exosomes carrying miR-668-3p promote progression of osteoblasts in osteonecrosis of the femoral head: Expression of proteins CD63 and CD9

Recently, exosomes that are derived from bone marrow mesenchymal stem cells (BMSCs) have garnered considerable interest due to their significant roles in the processes of bone regeneration and repair. Among the various molecular components present within these exosomes, miR-668-3p has emerged as a pivotal microRNA that may be instrumental in modulating the function and proliferation of osteoblasts, the cells responsible for bone formation. The primary objective of this research was to examine the enhancing effects of BMSC-derived exosomes that are enriched with miR-668-3p on the advancement of osteoblasts in the context of osteonecrosis of the femoral head. Furthermore, the study aimed to analyze how the expression of specific exosomal proteins, namely CD63 and CD9, influences this biological process. To conduct the investigation, BMSCs were isolated from healthy rat models, followed by the extraction of their secreted exosomes. The subsequent phase of the study involved assessing the proliferation and differentiation of osteoblasts by introducing the exosomes enriched with miR-668-3p into an experimental setup representing osteonecrosis of the femoral head. The findings revealed that exosomes derived from BMSCs, which contained miR-668-3p, significantly enhanced the proliferation of osteoblasts as well as the expression of key osteogenic marker genes. Notably, the levels of CD63 and CD9 proteins were markedly increased in the treated groups, indicating that the mechanisms underlying this promotion might involve cell adhesion and the endocytic uptake of exosomes.

Enhancement of physiology via adaptive transcription.

The enhancement of complex physiological functions such as cognition and exercise performance in healthy individuals represents a challenging goal. Adaptive transcription programs that are naturally activated in animals to mediate cellular plasticity in response to stimulation can be leveraged to enhance physiological function above wild-type levels in young organisms and counteract complex functional decline in aging. In processes such as learning and memory and exercise-dependent muscle remodeling, a relatively small number of molecules such as certain stimulus-responsive transcription factors and immediate early genes coordinate widespread changes in cellular physiology. Adaptive transcription can be targeted by various methods including pharmaceutical compounds and gene transfer technologies. Important problems for leveraging adaptive transcription programs for physiological enhancement include a better understanding of their dynamical organization, more precise methods to influence the underlying molecular components, and the integration of adaptive transcription into multi-scale physiological enhancement concepts.

Molecular Mechanism for Malignant Progression of Gastric Cancer Within the Tumor Microenvironment.

Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of GC, and progress in the development of effective anti-GC drugs has been insufficient. The tumor microenvironment (TME) regulates various functions of tumor cells, and interactions between the cellular and molecular components of the TME-e.g., inflammatory cells, fibroblasts, vasculature cells, and innate and adaptive immune cells-promote the aggressiveness of cancer cells and dissemination to distant organs. This review summarizes the roles of various TME cells and molecules in regulating the malignant progression and metastasis of GC. We also address the important roles of signaling pathways in mediating the interaction between cancer cells and the different components of the GC TME. Finally, we discuss the implications of these molecular mechanisms for developing novel and effective therapies targeting molecular and cellular components of the GC TME to control the malignant progression of GC.

SPP1+ macrophages and FAP+ fibroblasts promote the progression of pMMR gastric cancer

Immunotherapy has become a primary and secondary treatment for gastric cancer (GC) patients with mismatch repair deficiency (dMMR), and is used in both perioperative and advanced stages. The tumor immune microenvironment (TiME) is crucial for immunotherapy efficacy, yet the impact of MMR status on TiME remains understudied. We employed single-cell RNA sequencing (scRNA-seq) to analyze 33 fresh tissue samples from 25 patients, which included 10 normal tissues, 6 dMMR tumor tissues, and 17 pMMR tumor tissues, aiming to characterize the cellular and molecular components of the TiME. The proficient mismatch repair (pMMR) group displayed a significantly higher prevalence of a specific GC cell type, termed GC2, characterized by increased hypoxia, epithelial-mesenchymal transition (EMT), and angiogenic activities compared to the dMMR group. GC2 cells overexpressed BEX3 and GPC3, and they significantly correlated with poorer survival. The pMMR group also showed increased infiltration of SPP1 + macrophages and FAP + fibroblasts, exhibiting strong hypoxic and pro-angiogenic features. Furthermore, a higher proportion of E2 endothelial cells, involved in extracellular matrix (ECM) remodeling and showing heightened VEGF pathway, HIF pathway, and angiogenesis activity, were identified in pMMR patients. Intercellular communication analyses revealed that GC2 cells, SPP1 + macrophages, FAP + fibroblasts, and E2 endothelial cells interact through VEGF, SPP1, and MIF signals, forming a TiME characterized by hypoxia, pro-angiogenesis, and ECM remodeling. This study uncovered TiME heterogeneity among GC patients with different MMR states, highlighting that the pMMR TiME is distinguished by hypoxia, pro-angiogenesis, and ECM remodeling, driven by the presence of GC2 cells, SPP1 + macrophages, FAP + fibroblasts, and E2 endothelial cells. These findings are pivotal for developing targeted immunotherapies for GC patients with pMMR.

An Update on Molecular Mechanisms of Scarring-A Narrative Review.

Fibroblasts, the principal cellular mediators of connective tissue remodeling, play a crucial role in the formation of physiological and pathological scars. Understanding the intricate interplay between fibroblasts and other cellular and molecular components is essential for elucidating the underlying mechanisms driving scar formation. Hypertrophic scars, keloids and atrophic scars arise from dysregulated wound healing processes characterized by persistent inflammation, aberrant collagen deposition, and impaired extracellular matrix remodeling. Fibroblasts play a central role in the pathogenesis of such pathological scars, driving aberrant extracellular matrix remodeling, subsequently contributing to the formation of raised or depressed fibrotic lesions. The investigation of complex interactions between fibroblasts and the microenvironment is crucial for developing targeted therapeutic interventions aimed at modulating fibroblast activity and improving clinical outcomes in patients with pathological scars. Further research into the molecular pathways governing fibroblast behavior and their heterogeneity holds promise for advancing scar management strategies. This narrative review was performed to shed light on the mechanisms behind scar formation, with a special focus on the role of fibroblasts in the formation of different types of scars, providing insights into the pathophysiology of these conditions. Through the analysis of current knowledge, this review seeks to identify the key cellular and molecular mechanisms involved in fibroblast activation, collagen synthesis, and extracellular matrix remodeling in hypertrophic scar, keloid, or atrophic scar formation.

Influence of Hydrogen Additive on Electrophysical Parameters and Emission Spectra of Tetrafluoromethane Plasma

The influence of the addition of hydrogen on the electrophysical parameters and emission spectra of tetrafluoromethane under conditions of a direct current glow discharge has been studied. It has been established that gas temperature changes nonlinearly with increasing proportion of hydrogen in the plasma-forming mixture. The emission spectra of tetrafluoromethane plasma with hydrogen were obtained and analyzed. It is shown that plasma radiation is represented by atomic and molecular components, and the dependences of the line radiation intensities on the external conditions of the discharge are determined by the excitation of emitting states during direct electron impacts.

Management of Plant Diseases with Green Synthesized Nanoparticles Using Plant Extracts

Nanotechnology is a rapidly advancing field that has effectively tackled various issues across multiple industries, including agriculture. Nanoparticles (NPs) can typically be synthesized using two different techniques: top-down approach and bottom-up approach. In top-down approach, NPs are generated by reducing the size of a larger material, resulting in agglomerates with nano sized particles. Bottom-up approach involves building nanoscale structures from atomic and molecular components. In agriculture, nanotechnology plays a role in the production of nanoscale fertilizers, pesticides, and herbicides. Nanoparticles are used in plant disease management as well. The green synthesis of nanoparticles is often referred to as biosynthesis. It uses a range of biological sources like microorganisms or their derivatives as well as plant extracts, instead of synthetic chemicals, with minimal impact on human health and the environment. Green-synthesized nanoparticles (GSNPs) are known for their ease of production and cost-effectiveness. They offer several advantages, including their ability to induce systemic resistance to diseases and exhibit fungicidal and bactericidal properties.

Acute contact with profibrotic macrophages mechanically activates fibroblasts via αvβ3 integrin-mediated engagement of Piezo1.

Fibrosis-excessive scarring after injury-causes >40% of disease-related deaths worldwide. In this misguided repair process, activated fibroblasts drive the destruction of organ architecture by accumulating and contracting extracellular matrix. The resulting stiff scar tissue, in turn, enhances fibroblast contraction-bearing the question of how this positive feedback loop begins. We show that direct contact with profibrotic but not proinflammatory macrophages triggers acute fibroblast contractions. The contractile response depends on αvβ3 integrin expression on macrophages and Piezo1 expression on fibroblasts. The touch of macrophages elevates fibroblast cytosolic calcium within seconds, followed by translocation of the transcription cofactors nuclear factor of activated T cells 1 and Yes-associated protein, which drive fibroblast activation within hours. Intriguingly, macrophages induce mechanical stress in fibroblasts on soft matrix that alone suppresses their spontaneous activation. We propose that acute contact with suitable macrophages mechanically kick-starts fibroblast activation in an otherwise nonpermissive soft environment. The molecular components mediating macrophage-fibroblast mechanotransduction are potential targets for antifibrosis strategies.

Characterization of cellular and molecular immune components of the painted white sea urchin Lytechinus pictus in response to bacterial infection.

Sea urchins are basal deuterostomes that share key molecular components of innate immunity with vertebrates. They are a powerful model for the study of innate immune system evolution and function, especially during early development. Here we characterize the morphology and associated molecular markers of larval immune cell types in a newly developed model sea urchin, Lytechinus pictus. We then challenge larvae through infection with an established pathogenic Vibrio and characterize phenotypic and molecular responses. We contrast these to the previously described immune responses of the purple sea urchin Strongylocentrotus purpuratus. The results revealed shared cellular morphologies and homologs of known pigment cell immunocyte markers (PKS, srcr142) but a striking absence of subsets of perforin-like macpf genes in blastocoelar cell immunocytes. We also identified novel patterning of cells expressing a scavenger receptor cysteine rich (SRCR) gene in the coelomic pouches of the larva (the embryonic stem cell niche). The SRCR signal becomes further enriched in both pouches in response to bacterial infection. Collectively, these results provide a foundation for the study of immune responses in L. pictus. The characterization of the larval immune system of this rapidly developing and genetically enabled sea urchin species will facilitate more sophisticated studies of innate immunity and the crosstalk between the immune system and development.