Current Issues in Molecular Biology最新文献

Background/Objectives: Recent studies have reported the effectiveness of cold plasma technology in treating skin inflammation and wounds. We investigated the effect of an air-based no-ozone cold plasma device (Air NCP) on the inflammatory response in human keratinocytes (HaCaT). Methods: The cytotoxicity of Air NCP was assessed using the sulforhodamine B assay, and its ozone concentration and operating temperature were measured to evaluate safety. To determine its anti-inflammatory effect, inflammation was induced with tumor necrosis factor-alpha (TNF-α), and changes in inflammation-related gene expression were analyzed using reverse transcription-polymerase chain reaction and Western blot analysis. The level of prostaglandin E2 (PGE2), an indicator of inflammation, was measured using an enzyme-linked immunosorbent assay. Results: Air NCP showed no cytotoxicity in HaCaT cells. Moreover, the expression of TNF-α, interleukin-6, and interleukin-1β significantly decreased following treatment (p < 0.001). The levels of phosphorylated nuclear factor kappa B and phosphorylated signal transducer and activator of transcription-3 were also reduced (p < 0.001). Western blot analysis further confirmed that inflammation-activated mitogen-activated protein kinase factors were reduced by Air NCP, while cyclooxygenase-2 and PGE2 levels similarly decreased. Conclusions: These results indicate that Air NCP treatment suppresses the expression of inflammatory mediators in skin inflammation, demonstrating a clear anti-inflammatory effect.

Excitable neurons are intrinsically capable of firing action potentials (AP), yet a state of hyperexcitability is prevented in the central nervous system by powerful GABAergic inhibition. For this inhibition to be effective, it must occur before excitatory signals can initiate runaway activity, implying the existence of a proactive control system. To test for such proactive inhibition, we used Ca²⁺ imaging and patch-clamp recording to measure how hippocampal neurons respond to depolarization and glutamatergic agonists. In mature hippocampal cultures (14 days in vitro (DIV)) and acute brain slices from two-month-old rats, neurons exhibited non-simultaneous responses to various excitatory stimuli, including KCl, NH₄Cl, forskolin, domoic acid, and glutamate. We observed that the Ca²⁺ rise occurred significantly earlier in GABAergic neurons than in glutamatergic neurons. This delay in glutamatergic neurons was abolished by GABA(A) receptor inhibitors, suggesting a mechanism of preliminary γ-aminobutyric acid (GABA) release. We further found that these early-responding GABAergic neurons express calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs). Application of domoic acid induced an immediate Ca²⁺ increase in neurons expressing these receptors, but a delayed response in others. Crucially, when domoic acid was applied in the presence of the AMPA receptor inhibitors NBQX or GYKI-52466, the response delay in glutamatergic neurons was significantly prolonged. This confirms that CP-KARs on GABAergic neurons are responsible for the delayed excitation of glutamatergic neurons. In hippocampal slices from two-month-old rats, depolarization with 50 mM KCl revealed two distinct neuronal populations based on their calcium dynamics: a majority group (presumably glutamatergic) exhibited fluctuating Ca²⁺ signals, while a minority (presumably GABAergic) showed a steady, advancing increase in [Ca²⁺]i. This distinction was reinforced by the application of domoic acid. The "advancing-response" neurons reacted to domoic acid with a similar prompt increase, whereas the "fluctuating-response" neurons displayed an even more delayed and fluctuating reaction (80 s delay). Therefore, we identify a subgroup of hippocampal neurons-in both slices and cultures-that respond to depolarization and domoic acid with an early [Ca²⁺]_i signal. Consistent with our data from cultures, we conclude these early-responding neurons are GABAergic. Their early GABA release directly explains the delayed Ca²⁺ response observed in glutamatergic neurons. We propose that this proactive mechanism, mediated by CP-KARs on GABAergic neurons, is a primary means of protecting the network from hyperexcitation. Furthermore, the activity of these CP-KAR-expressing neurons is itself regulated by GABAergic neurons containing CP-AMPARs.

Over the past three decades, advances in high-throughput technologies have played a major role in the transformation of biomedical science, which has enabled unprecedented exploration of genomes, transcriptomes, and proteomes [...].

Infectious diseases remain a persistent global health threat, intensified by the rapid emergence of antibiotic-resistant pathogens. Despite the transformative impact of antibiotics, the escalating resistance crisis underscores the urgent need for alternative therapeutic approaches. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their broad-spectrum antimicrobial and immunomodulatory activities. The present study investigated 82 honey bee antimicrobial peptides (BAMPs) representing seven families: abaecin, apamin, apisimin, apidaecin, defensin, hymenoptaecin, and melittin among eight honey bee species. Immunoinformatics analyses identified five peptides (P15450, A0A2A3EK62, Q86BU7, C7AHW3, and I3RJI9A) with high antigenicity and non-allergenic profiles. Structural modeling, molecular docking with TLR3 and TLR4-MD2, and molecular dynamics simulations revealed stable receptor-peptide interactions and favorable binding energetics, further supported by silico immune simulations. Overall, these findings suggest that the selected BAMPs exhibit strong immunogenic potential and may serve as effective adjuvants or carrier molecules in subunit vaccine design against drug-resistant pathogens; however, further experimental validation is essential to confirm their safety and immunological efficacy.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous malignancy characterized by the proliferation of skin-homing CD4⁺ T cells and profound immune dysregulation within the tumor microenvironment (TME). This review synthesizes evidence on chemokine-receptor networks that govern malignant T-cell trafficking among blood, skin, and lymph nodes, the formation of immunosuppressive niches, and clinically actionable biomarker candidates. Among the best-supported axes, CCL17/CCL22-CCR4 and CCL27/CCL28-CCR10 mediate skin tropism, CCL19/CCL21-CCR7 contributes to lymph node homing, and CXCL12-CXCR4 supports skin trafficking and is associated with disease progression. In contrast, CCR2/CCR5/CCR6/CCR8-centered circuits and CXCR3/CXCR5 pathways are emerging regulators of myeloid recruitment, regulatory T-cell accumulation, and context-dependent immune activation. Therapeutically, agents targeting chemokine pathways, most notably the CCR4 monoclonal antibody Mogamulizumab, have demonstrated clinical efficacy, while emerging inhibitors of CCR6, CCR5, and CXCR4 offer promising avenues for intervention. We further highlight how recent single-cell and other high-dimensional omics studies refine cell-type-specific chemokine sources and receptor expression, enabling more precise mapping of chemokine-driven intercellular communication programs in CTCL TME remodeling and better prioritization of therapeutic targets and biomarkers.

We present a computational study that precedes the potential interactions between SARS-CoV-2 helicase (NSP13) and selected host proteins implicated in chaperone-assisted folding and polyamine metabolism. Using structure-based modelling and protein-protein docking (BioLuminate v4.6), followed by all-atom molecular dynamics (MD) simulations (GROMACS v2018.6), and comparative MM-GBSA scoring (HawkDock v2), we evaluated the stability and interface properties of NSP13 complexes with cytosolic heat shock proteins; heat shock protein 40 (HSP40), heat shock protein 70 (HSP70), heat shock protein 90 (HSP90) and the polyamine biosynthesis enzyme ornithine decarboxylase (ODC). Docking, MD, and interface analyses indicate distinct complex behaviours: HSP70-NSP13 complexes sampled compact conformations, HSP90-NSP13 ensembles displayed greater conformational heterogeneity but more favourable comparative MM-GBSA estimates, and ODC-NSP13 interfaces were comparatively well packed. Per-residue contact mapping identified a small set of recurrent NSP13 residues, Lys22 and Asn51, as putative interaction hotspots. The reported findings herein generate testable hypotheses about NSP13 recruitment of host chaperones and modulation of polyamine metabolism that may inform downstream experimental studies.

Arboviral diseases are emerging public health challenges in Burkina Faso, largely driven by the proliferation of Aedes aegypti mosquitoes in the environment. Effective surveillance of arbovirus circulation is critical to inform interventions. From August 2022 to June 2023, we implemented a comprehensive entomological surveillance platform in five sectors of Bobo-Dioulasso. Surveillance methods included oviposition traps to collect eggs, larval surveys in some concessions per sector conducted bimonthly, and adult mosquito collections using BG-Sentinel traps and Prokopack aspirators. Mosquito samples colonized by Ae. aegypti were identified morphologically, confirmed by conventional PCR, and screened by RT-PCR for dengue (DENV), chikungunya (CHIKV), yellow fever (YFV), and Zika (ZIKV) viruses. Molecular analysis detected dengue virus and yellow fever virus in mosquito pools from sector 22 and chikungunya virus in sectors 9 and 26; no Zika virus was found. This study demonstrates the successful establishment of an integrated entomological surveillance platform capable of capturing the spatial and temporal dynamics of arboviral vectors and virus circulation in Bobo-Dioulasso. The identification of active dengue and chikungunya transmission underlines the urgent need for sustained vector monitoring and targeted control strategies. Our approach provides a scalable model for arboviral disease surveillance and epidemic preparedness in West African urban settings.

B cells are key drivers of immune dysregulation across systemic autoimmune diseases. Among their progeny, plasmablasts occupy a uniquely revealing niche: short-lived, highly proliferative intermediates that mirror real-time B-cell activation. Their appearance in peripheral blood integrates antigenic stimulation, cytokine-driven differentiation, and aberrant germinal-center dynamics, transforming them into sensitive indicators of ongoing immunological activity. This review synthesizes current knowledge on plasmablast biology and highlights disease-specific phenotypes across systemic lupus erythematosus (SLE), primary Sjögren disease (pSjD), IgG4-related disease (IgG4-RD), ANCA-associated vasculitis (AAV), and rheumatoid arthritis (RA). We incorporate molecular insights from single-cell technologies that have uncovered previously unrecognized plasmablast subsets, metabolic states, and interferon-related signatures with prognostic and mechanistic value. Beyond descriptive immunology, plasmablasts are emerging as dynamic biomarkers capable of informing real-time clinical decisions. One of the most robustly supported applications is the prognostic interpretation of plasmablast kinetics following B-cell-depleting therapies, where early reconstitution patterns consistently predict relapse across multiple autoimmune conditions. As clinical immunology shifts from static serological markers toward kinetic, cell-based monitoring, plasmablast quantification offers a path toward precision immune surveillance. Integrating plasmablast dynamics into routine care may ultimately allow clinicians to anticipate disease flares, time therapeutic reinforcements, and transition from reactive management to preventive intervention.

Background/objectives: Rapid cellular proliferation, a hallmark of malignancy, requires sustained and elevated protein synthesis, which in turn requires efficient ribosome biogenesis. The aim of this study was to evaluate the expression levels of TP53, C-MYC, FBL, and NCL in pre-B ALL and neuroblastoma tissues compared to healthy bone marrow samples-factors that may carry prognostic significance in pediatric malignancies.

Materials and methods: The cohort included 45 pre-B ALL patients, 19 neuroblastoma patients, and 12 healthy bone marrow donors as controls. Total RNA was extracted from bone marrow or tumor samples and cDNA synthesis was performed with the Bio-Rad iScript kit. Quantitative PCR was conducted using SYBR Green chemistry, with GAPDH as the reference gene. Primers targeted TP53, C-MYC, FBL, and NCL, and gene expression was calculated using the 2^-ΔCt method.

Results: The expression of C-MYC and FBL was found to be significantly decreased in patients with pre-B ALL in comparison to the healthy control group. NCL expression was highest in healthy donors, intermediate in pre-B ALL, and lowest in neuroblastoma. In addition to intergroup comparisons, correlations between gene expression levels were assessed within each diagnostic group. In the pre-B ALL group, a positive correlation was observed between TP53 and C-MYC expression, as well as between TP53 and both FBL and NCL. Furthermore, a significant positive correlation was found between FBL and NCL. In the neuroblastoma group, a statistically significant positive correlation was identified between C-MYC and FBL expression. In the control group, TP53 expression was positively correlated with NCL, and FBL expression showed a significant positive correlation with NCL.

Conclusions: This study suggests the altered expression of ribosome biogenesis-related genes in pediatric pre-B acute lymphoblastic leukemia and neuroblastoma. The reported dysregulation suggests a disease-associated disruption in nucleolar function and translational regulation and may contribute to oncogenesis through altered ribosomal assembly, protein synthesis, or proliferative signaling.

Systemic sclerosis (SSc) is a disease in which malfunctioning immune cells lead to the formation of autoantibodies that damage blood vessels and body tissues. Fibrosis then develops in the affected organs. Its complex pathogenesis involves multiple immune and stromal cell types, soluble mediators, and dysregulated tissue repair, resulting in heterogeneous clinical manifestations and poor prognosis. Current disease-modifying therapies provide only modest benefits, often slowing but rarely reversing disease progression, and are associated with considerable adverse effects. These limitations have spurred the development of cell-based therapeutic strategies aimed at restoring immune tolerance and promoting tissue repair. In this review, we summarize recent advances in hematopoietic stem cell transplantation, mesenchymal stem cell therapy, and adoptive regulatory T cell transfer and highlight the emerging role of chimeric antigen receptor (CAR)-T cell therapy as a transformative approach for SSc. Collectively, these evolving strategies hold the potential to improve survival, achieve durable remissions, and significantly enhance quality of life for patients with SSc.