UNASSIGNED: Toxoplasma gondii, a neurotropic protozoan, infects up one to third of the world population. The parasite can invade a wide variety of nucleated cells but preferably glial cells. Glia maturation factor β (GMFβ), a 17KD protein expressed at high levels in the central nervous system is predominantly related to neurodegenerative diseases such as Alzheimer\'s disease, Parkinson\'s disease, and Multiple sclerosis. We aimed to determine the expression level of GMFβ and its relation to other pro-inflammatory factors (IL33, SDF1, and CCL2) on T. gondii infected human neuroblastoma cell line.
UNASSIGNED: The human neuroblastoma (SK_NMC C535) cell line was infected by 5×106 (1:1 ratio). The supernatant was collected after cell lysis and centrifugation. Total RNA was extracted using the Yekta Tajhiz RNA extraction kit. cDNA was synthesized based on RevertAid First Strand cDNA Synthesis Kit manufacturer\'s protocol (Parstous, cDNA synthesis kit, Iran). The specificity of each primer pair (GMFβ, IL33, SDF1, and CCL2) was provided by NCBI BLAST. Gene expression level was measured using Real-Time PCR. All experiments were conducted at the Hamadan University of Medical Sciences, western Iran in 2022.
UNASSIGNED: The GMFβ increased significantly up to 1.35-fold (P=0.007). The increase in GMFβ expression in neuroblastoma cells was consistent with the increase in pro-inflammatory factors (CCL2 (0.47), IL33 (0.152) and, SDF1 (1.33)).
UNASSIGNED: GMFβ upregulation can be a novel indicator of the destruction of nerve cells.

BACKGROUND: Glia maturation factor beta (GMFB) is a growth and differentiation factor that acts as an intracellular regulator of signal transduction pathways. The small ubiquitin-related modifier (SUMO) modification, SUMOylation, is a posttranslational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. However, the relationship between GMFB and SUMOylation is unclear.
RESULTS: Here, we report for the first time that GMFB and SUMO1 are markedly increased in retinal pigment epithelial (RPE) cells at the early stage of diabetes mellitus (DM) under hyperglycemia. The GMFΒ protein could be mono-SUMOylated by SUMO1 at the K20, K35, K58 or K97 sites. SUMOylation of GMFB led to its increased protein stability and subcellular translocation. Furthermore, deSUMOylation of GMFΒ downregulates multiple signaling pathways, including the Jak-STAT signaling pathway, p38 pathway and NF-kappa B signaling pathway.
CONCLUSIONS: This work provides novel insight into the role of SUMOylated GMFB in RPE cells and provides a novel therapeutic target for diabetic retinopathy (DR).

Recent evidence suggests that glia maturation factor β (GMFβ) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFβ can be involved in pulmonary vascular remodeling and to explore the role of the IL-6-STAT3 pathway in this process, the expression of GMFβ in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin-6 (IL-6) is measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The location and expression of POSTN is also tested in PAH rats using immunofluorescence. It is proved that GMFβ is upregulated in the lungs of PAH rats. Knockout GMFβ alleviated the MCT-PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFβ absent. In addition, the IL-6-STAT3 signaling pathway is activated in PAH; knockout GMFβ reduced POSTN and IL-6 production by inhibiting the IL-6-STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFβ ameliorates PAH in rats by inhibiting the IL-6-STAT3 signaling pathway.

Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.

The public perspective on genetically modified foods (GMFs) has been intensely debated and scrutinized. Often, discussions surrounding GMF tend to revolve solely around the potential health risks associated with their consumption. However, it is essential to acknowledge that public perceptions of genetically modified foods are multifaceted, encompassing environmental concerns, ethical considerations, and economic implications. This paper studies the factors predicting GMF acceptance employing the representative sample of the Czech population (N = 884, aged 18-90 years, M ± SD: 48.17 ± 17.72; 53.40% women, 18.04% with higher education). The research relies on the Behavioral Change Model and the Health Belief Model. We employ hierarchical ordinal regressions to study the effects of information, environmental concerns, perceived health risks, food habits, purchasing habits, and socio-demographics on GMF acceptance. The results suggest that the (un)willingness to purchase GMF is primarily driven by the health risks - the environmental concerns were largely unimportant. The impact of information provision on GMF acceptance proved positive, suggesting information and education to be the main channels of creating public acceptance. The intrinsic interest regarding information related to GMF had an adverse impact on the perception of GMF morality. The benefits of the GMF proved unrelated to the GMF acceptance, indicating the gap in the information campaign. The research provides valuable insights for policymakers, public health professionals, and market researchers to communicate the GMF agenda effectively to the general public.

In this work, a microfluidic paper-based analytical device (μPAD) was developed to detect the biopesticide azadirachtin (Aza) through a colorimetric assay. High precision estimation of Aza is classically carried out using high performance liquid chromatography (HPLC), which requires highly skilled personnel. Acidified vanillin is a commonly used colorimetric indicator in thin layer chromatography for detection of various phytochemicals. However, the assay involves concentrated acid, which limits the choice of paper substrates for paper-based sensors and raises safety concerns. In this work, we show how the assay can be extended from the liquid phase to a paper substrate. Glass microfiber (GMF) filter paper was found to be suitable paper as it was acid resistant; besides, its hydrophilicity enabled smooth flow of reagents. A microfluidic paper-based sensor (μPAD) was developed by sandwiching 5 mm sized GMF dots between two parafilm sheets. We demonstrate the use of colorimetric assay on the μPAD for on-site detection of Aza in neem kernels. The magenta color developed upon the reaction of acidified vanillin with Aza was captured using a smart-phone and analysed using RGB levels in the image. Calibration was established using neem kernel extract of known concentration. Linearity was seen in the concentration range of 5 to 25 mg L-1 Aza. A limit of detection of 2.3 mg L-1 was obtained using this method. The colorimetric assay showed a relative recovery of >85% when compared with the values obtained from HPLC. The stability of the reagents on the GMF sensor was investigated to understand the storage conditions and shelf life of the reagents and sensor. The present work demonstrates the development of a portable sensor for on-site detection of phytochemicals that can be an integral part of the agricultural supply chain.

Parkinson\'s disease (PD) is the second most common progressive neurodegenerative disease characterized by the presence of dopaminergic neuronal loss and motor disorders. PD dementia (PDD) is a cognitive disorder that affects many PD patients. We have previously demonstrated the proinflammatory role of the glia maturation factor (GMF) in neuroinflammation and neurodegeneration in AD, PD, traumatic brain injury (TBI), and experimental autoimmune encephalomyelitis (EAE) in human brains and animal models. The purpose of this study was to investigate the expression of the GMF in the human PDD brain. We analyzed the expression pattern of the GMF protein in conjunction with amyloid plaques (APs) and neurofibrillary tangles (NFTs) in the substantia nigra (SN) and striatum of PDD brains using immunostaining. We detected a large number of GMF-positive glial fibrillary acidic protein (GFAP) reactive astrocytes, especially abundant in areas with degenerating dopaminergic neurons within the SN and striatum in PDD. Additionally, we observed excess levels of GMF in glial cells in the vicinity of APs, and NFTs in the SN and striatum of PDD and non-PDD patients. We found that the majority of GMF-positive immunoreactive glial cells were co-localized with GFAP-reactive astrocytes. Our findings suggest that the GMF may be involved in the pathogenesis of PDD.

BACKGROUND: Children with spastic diplegia experience tonicity, lack of selective motor control, subnormal postural stability and delayed motor development. Selective dorsal rhizotomy followed by physical therapy is a permanent procedure aimed to alleviate hypertonicity.
OBJECTIVE: To explore the efficacy of selective dorsal rhizotomy (SDR) followed by a physical training on gross motor function (GMF), functional balance, walking capacity, selective motor control (SMC) and energy cost of walking (ECW) of ambulant children with spastic diplegia.
METHODS: Forty-two children with spastic diplegia aged 5 to 8 years were randomly assigned into the control or SDR-group. Both groups received a designed physical training of progressive functional strength training and standard orthotic management (SOM) 3 times a week for 6 months. GMF, functional balance, ECW, functional capacity and SMC were assessed by gross motor function measure (GMfM-88), pediatric balance scale (PBS), energy expenditure index (EEI), six-minute walking test (6MWT) and selective control assessment of lower extremity (SCALE), respectively. Assessment was carried out before the treatment (baseline), after 6 months (post I) and 1-year follow-up (post II).
RESULTS: From baseline to post I and post II assessments, changes of GMF, functional balance, ECW, functional capacity and SMC within the control and SDR groups showed significant improvements (P < 0.001). Moreover, group comparison showed significant differences in favor of the SDR group.
CONCLUSIONS: Integrated physical training followed SDR demonstrated qualitative changes and enhancement in motor function, achieved by spasticity reduction.

How cells tightly control the formation and turnover of branched actin filament arrays to drive cell motility, endocytosis, and other cellular processes is still not well understood. Here, we investigated the mechanistic relationship between two binding partners of the Arp2/3 complex, glia maturation factor (GMF) and cortactin. Individually, GMF and cortactin have opposite effects on the stability of actin filament branches, but it is unknown how they work in concert with each other to govern branch turnover. Using TIRF microscopy, we observe that GMF\'s branch destabilizing activities are potently blocked by cortactin (IC50 = 1.3 nM) and that this inhibition requires direct interactions of cortactin with Arp2/3 complex. The simplest model that would explain these results is competition for binding Arp2/3 complex. However, we find that cortactin and GMF do not compete for free Arp2/3 complex in solution. Further, we use single molecule analysis to show that cortactin\'s on-rate (3 ×107 s-1 M-1) and off-rate (0.03 s-1) at branch junctions are minimally affected by excess GMF. Together, these results show that cortactin binds with high affinity to branch junctions, where it blocks the destabilizing effects of GMF, possibly by a mechanism that is allosteric in nature. In addition, the affinities we measure for cortactin at actin filament branch junctions (Kd = 0.9 nM) and filament sides (Kd = 206 nM) are approximately 20-fold stronger than previously reported. These observations contribute to an emerging view of molecular complexity in how Arp2/3 complex is regulated through the integration of multiple inputs.

UNASSIGNED: Granulomatous cutaneous T-cell lymphoma includes mycosis fungoides with significant granulomatous inflammation (GMF) and granulomatous slack skin (GSS), listed in the WHO classification as a subtype of mycosis fungoides (MFs). 1 These overlapping entities have shared clinical and histopathologic features which can present a diagnostic challenge. The dominance of the granulomatous infiltrate and the often sparse lymphocytic infiltrate frequently with minimal cytological atypia are features that distract from the correct diagnosis, even when raised by the clinician. We describe the clinical and histopathologic characteristics of 3 cases of granulomatous cutaneous T-cell lymphoma, illustrate the close clinical and pathologic relationship between GMF and GSS and emphasize the diagnostic difficulties that the granulomatous infiltrate can present. Furthermore, we demonstrate, for the first time, considerable elastolysis in a significant proportion of classical (Alibert-Bazin) MF lesions and therefore postulate that the differences observed between GMF and GSS are one of degree and secondary to their anatomic location rather than reflecting meaningful separate entities.