This study investigated the association between aerobic exercise preconditioning and macrophage migration inhibitory factor (MIF) expression, as well as myelination in sciatic nerve in experimental autoimmune neuritis (EAN) rats. Female Lewis rats underwent 4-week swimming protocols including High-intensity daily (HI-Daily), Moderate-intensity daily (MOD-Daily), and Moderate-intensity alternate-day (MOD-AltDay) regimens prior to EAN induction, with control groups of EAN without exercise and Sham operation. Assessment of disease severity, nerve conduction velocity, and sciatic nerve pathology revealed that the moderate-intensity alternate-day exercise regimen significantly delayed disease onset, lowered peak clinical scores, and improved neurological function. Molecular analyses demonstrated that this protective effect was mediated through divergent regulation of MIF: systemic MIF was substantially suppressed (27205.94 ± 4291.76 pg/mL vs EAN 71075.61 ± 10166.41 pg/mL; p<0.001) with concomitant reduction in macrophage infiltration, while local MIF expression within the sciatic nerve was significantly elevated (p<0.01), correlating with enhanced remyelination as evidenced by increased myelin sheath area (LFB: 67.42 ± 3.26% vs EAN 40.64 ± 9.63%, p<0.01) and elevated myelin basic protein expression (0.92 ± 0.14 AU vs EAN 0.59 ± 0.02 AU, p<0.05). Crucially, both high-intensity daily and moderate-intensity daily exercise protocols failed to confer comparable benefits. These findings indicate that the protective effect of MOD-AltDay exercise preconditioning on EAN is associated with tissue-specific regulation of MIF, and this change correlates with reduced systemic inflammation and enhanced local remyelination. Pharmacological/genetic studies are needed to confirm mechanisms and evaluate this exercise regimen as a non-pharmacological intervention for autoimmune neuropathy.

GNAO1-related neurodevelopmental disorders are caused by mutations in the GNAO1 gene encoding the major neuronal G protein, Gαo. GNAO1 encephalopathies manifest in a range of symptoms, including epilepsy, movement disorder, hypotonia, and developmental delay, affecting >400 patients worldwide to date. A growth in the number of diagnosed cases is expected due to the wider availability of whole genome sequencing. One of the most recurrent pathogenic variants causing GNAO1 encephalopathy is an intronic mutation c.724-8G>A, which results in an in-frame insertion of two amino acid residues Pro-Gln after Thr241: Gαo[T241_N242insPQ]. We previously performed in-depth profiling of Gαo[insPQ] using structural, biochemical, and cellular studies. Compared to the wild-type protein, Gαo[insPQ] exhibits faster GTP binding and decreased hydrolysis. Importantly, Gαo[insPQ] is deficient in interacting with regulators of G protein signaling (RGS), GTPase-activating proteins that deactivate Gαo. These defects render Gαo[insPQ] as a constitutively active mutant loaded with GTP in the G protein signaling. Patients harboring Gαo[insPQ] variant are in urgent need of novel therapy as they are refractory to available medications. In this study, we performed a high-throughput screening to find molecules that might suppress the constitutive GTP loading by Gαo[insPQ]. We used a high-diversity chemical library of 54,080 compounds, identifying a novel compound, N-[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]-1H-1,2,3-benzotriazole-5-carboxamide, that decreases the GTP binding rate of Gαo, likely acting as a competitive inhibitor with higher selectivity to the pathogenic protein. This small-molecule inhibitor of Gαo opens new opportunities to drug discovery towards Gαo-dependent pathologies.

Toxoplasma gondii is a globally prevalent protozoan parasite capable of establishing lifelong infections in its host. While acute infection is often asymptomatic, reactivation of latent bradyzoites can cause severe disease, particularly in immunocompromised individuals. Current therapies are ineffective against chronic infection, underscoring critical gaps in our understanding of bradyzoite biology and the molecular mechanisms governing stage conversion. Recent studies have identified translational control as a central regulator of T. gondii differentiation. This review highlights the roles of canonical translation initiation factors (eIF2α, eIF1.2, and eIF4E1), RNA-binding proteins (RBPs; BFD2/ROCY1, Alba1, and Alba2), and RNA modifications (with pseudouridylation representing the best-characterized modification currently linked to differentiation), as well as alternative splicing and non-coding RNAs in shaping stage-specific translational programs. This review further discusses underexplored mechanisms, including non-canonical initiation pathways, upstream open reading frames, transcript-level RNA modifications, ribosome heterogeneity and rRNA modifications, elongation and termination control, uncharacterized RBPs, and post-translational modifications of translation factors, that may coordinate proteome remodeling during differentiation. Together, established translational regulators and these emerging pathways highlight translational control as a central driver of parasite persistence and a promising therapeutic target for chronic toxoplasmosis.

This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board.This follows the receipt of a notification from a reader, alerting the Editorial Board to unexpected similarities between the Figure 2G bottom si-NC colony assay, after a 90-degree rotation, and the Figure 5C OSCC3/si-NC colony assay from Zhang et al. 2017 (doi: 10.1038/s41598-017-13431-y). The authors were contacted with regards to the concerns and retraction but have not responded to the Journal's queries or the concerns raised.Given the extent of the issues raised, the Editorial Board stand by the decision to retract the article.

This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board. This follows the receipt of a notification from a reader, alerting the Editorial Board to irregularities in the Western Blots of Figures 1B and C.Specifically, there are background details in Figure 1B that unexpectedly repeat, and a region of the CC column of Figure 1C has a smudged appearance. The Editorial Board also has concerns surrounding the authorship of the manuscript.The authors have been contacted with regards to the retraction, but they have not responded to the Journal's queries or the concerns raised. Given the extent of the issues raised, the Editorial Board stands by the decision to retract the article.

Taenia solium cysticerci are the etiological agents of neurocysticercosis, a leading cause of acquired epilepsy worldwide and a significant public health problem in endemic regions. The chronicity of the infection reflects a complex host-parasite interaction in which the parasite establishes long-term persistence through immunomodulatory mechanisms. In recent years, extracellular vesicles (EVs) have emerged as important mediators for some of these interactions. EVs are membrane-bound structures released by virtually every organism studied, which carry a diverse set of molecules that mediate intercellular communication. We isolated Taenia solium extracellular vesicles (TsEVs) from racemose cysticerci recovered from a patient, subsequently cultured in vitro, in order to characterize them by transmission electron microscopy, nanoparticle tracking analysis, and mass spectrometry-based proteomics. Effect of TsEVs on the production of reactive oxygen species (ROS) and myeloperoxidase (MPO) activity was evaluated in human neutrophils using fluorometric and colorimetric assays under basal and chemically stimulated conditions. Obtained TsEVs were under 200nm in diameter. Proteomic analysis of four independent TsEV samples allowed identification of a core set of 336 proteins. Gene Ontology analysis of these vesicles was consistent with exosomes, as a number of exosome-associated marker proteins such as tetraspanins were identified. Proteins linked to immunomodulation and redox metabolism were also identified, suggesting a potential role in interactions with host cells. Finally, the effect of TsEVs on the respiratory burst of human neutrophils was evaluated, revealing a reduction in ROS production, primarily through inhibition of MPO activity, adding up evidence for the role of these vesicles in parasite's survival against the host immune response.

This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board. This follows the receipt of a notification from a reader, alerting the Editorial Board to similarities between this article and one published in the Journal of Cancer (2020) by overlapping authors (DOI: 10.7150/jca.46697). During the investigation, the Editorial Office and the authors identified additional similarities.Specifically: The Figure 1A control panels appear in both articlesA degree of similarity has been noted between the Figure 3A AKT and mTOR bands of this article (after a mirror-image rotation of the mTOR bands).The Figure 5C Control and CQ scatter plot panels also appear in Figure 4C of DOI: 10.7150/jca.46697.The Figure 5C IVM + CQ/U251and IVM + CQ/C6 scatterplot panels also appear as the Figure 4C MOX/U251 and MOX + CQ/U251 panels respectively in DOI: 10.7150/jca.46697.Regions of the Figure 7D Ki67/Control panel overlap with regions of the Figure 6D Ki67/Control and CQ panels of DOI: 10.7150/jca.46697The authors cooperated with the investigation. They provided raw data for many of the figures and disagree with the similarities noted between the Figure 3A western blot bands (for which raw blots were provided for all except the mTOR bands). They explained that the image similarities were due to oversights during export and figure preparation of the two manuscripts. They also noted an erratum that has been published in the Journal of Cancer that replaces various figure panels of Figure 4C. However, whilst investigating the new data, new concerns have arisen, and it was not felt that the erratum alleviated the original concerns.Given the lack of raw data for the mTOR bands and concerns over original and new data, the Editorial Board has lost confidence in the validity of the data and stands by the decision to retract. All authors were contacted regarding the retraction, with one agreeing to the action being taken. All other authors either disagree or did not comment.

This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board. This follows the receipt of a notification from a reader, alerting the Editorial Board to concerns over the potential use of inappropriate primers.Upon investigation, the Editorial Office identified what appears to be two regions of duplication. Specifically, one of the cells in the Figure 14A miR-384 mimic panel has high similarity to a cell in the miR-384 inhibitor + siRNA-COL10A1 panel. In addition, the Figure 13A NC panel from this article appears to be the same as the Figure 4A Blank panel in the article Tang et al. (2019) https://doi.org/10.1002/jcb.28600.The authors have been contacted with regard to the retraction. They stated that the U6 snRNA was not amplified using inappropriate primers and disagreed with the similarities in Figure 14A. They did not respond to further contact regarding the Figure 13A panel similarity.Given the extent of the issues raised, the Editorial Board stands by the decision to retract the article. The authors disagree to the retraction.

The cytoskeleton is a key component of eukaryotic cells, including protists. It is composed of microtubules, microfilaments, and intermediate filaments. Here, we review the available information on the cytoskeleton of several relevant pathogenic protists, including Trypanosomatidae, Apicomplexa, Trichomonadidae, Giardia intestinalis, and Entamoeba histolytica. In protists, the first two components, made of tubulins and actin, predominate. Usually, they associate with each other and with other components to form complex structures. Emphasis is given to the following structures: flagellum, flagellar-cell body adhesion zone, paraflagellar rod, sub-pellicular microtubules, cytostome, conoid, adhesive disc, funis, median body, costa, axostyle, parabasal filaments, and clockwise filaments. On the other hand, filamentous structures made of not yet completely characterized proteins form structures such as the costa. Each structure is analyzed using morphological information obtained through modern microscopy techniques and biochemical data.