Search

IntroductionThe cartilage endplate (CEP) plays a crucial role as both a mechanical barrier and nutrient channel for the intervertebral disc, but it is vulnerable to excessive axial loading. We modified the Ilizarov external fixator and applied it to the CEP of the rat tail to impose diurnal, controllable excess axial loading. The objective was to measure morphological changes in the CEP when subjected to loading during the aging process.MethodsTwo Kirschner wires were, respectively, inserted into the center of the eighth and ninth coccygeal vertebrae (Co8/9) of rat (n = 54) to apply axial loading to the CEP. A remote control device was used to establish the diurnal loading schedule. At the end of 4, 8, and 12-week periods, the Co8/9 CEPs in each group were analyzed using MRI, histological staining, and immunohistochemical staining techniques.ResultsThe novel Ilizarov model that we modified successfully induced degeneration of the rat coccygeal CEP. MRI analysis revealed significant degenerative changes in the loaded Co8/9 CEP, including decreased signal intensity and the formation of Schmorl’s nodes at 8 and 12 weeks. Histological examination showed progressive CEP degeneration (CEPD), characterized by decreased microporosity, thinning, and structural irregularities. Immunohistochemical analysis demonstrated a significant reduction in Aggrecan and Collagen II expression in the CEP and nucleus pulposus over time. Control and sham groups maintained normal CEP structure and composition throughout the study period.ConclusionExcessive axial loading induced CEPD in the rat tail, primarily characterized by the formation of Schmorl’s nodes and a reduction in CEP microporosity in this study. Our modified Ilizarov rat tail compression model, featuring stable and controllable axial loading capabilities, provided an alternative experimental paradigm for further investigation into CEPD.

Abstract The JAK/STAT pathway plays a crucial role in the pathogenesis of rheumatoid arthritis (RA) and JAK inhibitors have emerged as a new group of effective drugs for RA treatment. Recently, high STAT3 levels have been associated with the upregulation of the scaffold protein NEDD9, which is a regulator of T‐cell trafficking and promotes collagen‐induced arthritis (CIA). In this study, we aimed to reveal how treatment with JAK inhibitors affects NEDD9 in CD4+ T cells from RA patients. We analyzed NEDD9 expression in CD4+ T cells from 50 patients treated with either baricitinib, tofacitinib, or upadacitinib and performed cell migration assays to assess the potential influence of JAK inhibitor treatment on CD4+ T‐cell migration. We observed that treatment with baricitinib and upadacitinib is associated with reduced NEDD9 expression in CD4+ T cells. In contrast, NEDD9 levels were not altered during treatment with tofacitinib. Moreover, treatment with baricitinib was associated with a significantly reduced migratory capacity of effector CD4+ T cells but not with impaired migration of Treg cells. This study reveals previously unknown associations between JAK inhibitor treatment and NEDD9 expression and indicates that JAK inhibitors could reduce effector T‐cell migration.

Regulatory T (Treg) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of Treg cells contribute to the pathogenesis of RA, a common autoimmune disease which leads to systemic inflammation and erosive joint destruction. Treg cells from patients with RA are characterized by impaired functions and by an altered phenotype. They show increased plasticity towards Th17 cells and a reduced suppressive capacity. Besides the suppressive function of Treg cells, their effectiveness is determined by their ability to migrate into inflamed tissues. In the past years, new mechanisms involved in Treg cell migration have been identified. One example of such a mechanism is the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Efficient migration of Treg cells requires the presence of VASP. IL-6, a cytokine which is abundantly present in the peripheral blood and in the synovial tissue of RA patients, induces posttranslational modifications of VASP. Recently, it has been shown in mice with collagen-induced arthritis (CIA) that this IL-6 mediated posttranslational modification leads to reduced Treg cell trafficking. Another protein which facilitates Treg cell migration is G-protein-signaling modulator 2 (GPSM2). It modulates G-protein coupled receptor functioning, thereby altering the cellular activity initiated by cell surface receptors in response to extracellular signals. The almost complete lack of GPSM2 in Treg cells from RA patients contributes to their reduced ability to migrate towards inflammatory sites. In this review article, we highlight the newly identified mechanisms of Treg cell migration and review the current knowledge about impaired Treg cell homeostasis in RA.

Objective SLE is an autoimmune disease with a complex pathogenesis. T-cell infiltration into organs contributes to inflammation and organ damage in SLE. Recently, G-protein signalling modulator 2 (GPSM2) has been shown to be implicated in T-cell migration.Methods We analysed the expression levels of GPSM2 and of a truncated isoform of GPSM2 containing the GoLoco motif region in CD4+ T cells from patients with SLE and from healthy individuals by western blot. In a next step, we studied the role of the truncated GPSM2 isoform using a CD4+ T-cell migration assay.Results Our experiments revealed comparable levels of GPSM2 in CD4+ T cells from patients with SLE and healthy controls. In contrast, the truncated 35 kDa isoform of GPSM2 was significantly more highly expressed in CD4+ T cells from patients with SLE as compared with healthy subjects. Antibody-mediated blockade of the 35 kDa GPSM2 isoform reduced the in vitro capacity of CD4+ T cells to migrate towards the chemokine CCL20.Conclusions A truncated GPSM2 isoform containing the GoLoco motif region is upregulated in CD4+ T cells from patients with SLE and promotes CD4+ T-cell migration. Targeting this isoform with specific antibodies might be a promising approach to reduce CD4+ T-cell infiltration into inflamed tissues and to prevent organ damage in SLE.

Abstract Background This study was performed to investigate the morphological changes of contralateral intervertebral foramen (IVF) based on computed tomography images of patients with lumbar spinal stenosis after unilateral transforaminal lumbar interbody fusion (TLIF) and to compare the influence of different orientation of cage insertion on these changes. Methods This is a retrospective cohort study. Sixty-nine patients with lumbar spinal stenosis who had undergone single-level unilateral TLIF were retrospectively analyzed. The patients were divided into two groups according to the cage insertion orientation: the oblique group (o-group, 39 cases) and the transverse group (t-group, 30 cases). The morphological parameters of contralateral IVF were measured before and 6 months after the operation. Changes in these parameters were compared and analyzed between the two groups. The 6-month clinical outcomes of the two groups were also collected and analyzed. Results There was a significant difference in the rate of increase in the segmental angle (p

Regulatory T (Treg) cells play an important role in immune tolerance and contribute to the prevention of autoimmune diseases, including rheumatoid arthritis (RA). The differentiation, function and stability of Treg cells is controlled by members of the Ikaros zinc finger transcription factor family. In this study, we aimed to reveal how the expression of Ikaros transcription factors is affected by disease activity in RA. Therefore, we analyzed the ex vivo expression of Ikaros, Helios, Aiolos and Eos in Treg cells, Th17 cells and Th1 cells from RA patients by flow cytometry. We found significantly reduced expression of Helios, Aiolos and Eos in Treg cells from RA patients as compared to healthy controls. Moreover, Helios and Aiolos levels correlated with disease activity, as assessed by DAS28-CRP. In addition, Ikaros, Helios and Aiolos were significantly downregulated in Th1 cells from RA patients, while no difference between healthy individuals and RA was observed in Th17 cells. In summary, Helios and Aiolos expression in Treg cells correlates with disease activity and the expression levels of Ikaros transcription factors are diminished in Treg cells from RA patients. This observation could explain the reduced stability of Treg cells in RA.

Regulatory T (Treg) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of Treg cells contribute to the pathogenesis of RA, a common autoimmune disease which leads to systemic inflammation and erosive joint destruction. Treg cells from patients with RA are characterized by impaired functions and by an altered phenotype. They show increased plasticity towards Th17 cells and a reduced suppressive capacity. Besides the suppressive function of Treg cells, their effectiveness is determined by their ability to migrate into inflamed tissues. In the past years, new mechanisms involved in Treg cell migration have been identified. One example of such a mechanism is the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Efficient migration of Treg cells requires the presence of VASP. IL-6, a cytokine which is abundantly present in the peripheral blood and in the synovial tissue of RA patients, induces posttranslational modifications of VASP. Recently, it has been shown in mice with collagen-induced arthritis (CIA) that this IL-6 mediated posttranslational modification leads to reduced Treg cell trafficking. Another protein which facilitates Treg cell migration is G-protein-signaling modulator 2 (GPSM2). It modulates G-protein coupled receptor functioning, thereby altering the cellular activity initiated by cell surface receptors in response to extracellular signals. The almost complete lack of GPSM2 in Treg cells from RA patients contributes to their reduced ability to migrate towards inflammatory sites. In this review article, we highlight the newly identified mechanisms of Treg cell migration and review the current knowledge about impaired Treg cell homeostasis in RA. [ABSTRACT FROM AUTHOR]

This is a paper in the field of mineral processing engineering.With the continuous development of mineral processing technology and the improvement of the degree of attention to mineral resources, more and more researches on the comprehensive utilization of tailings have been carried out. Chemical multivariate analysis, SEM and other techniques were used to characterize the copper ore in a vanadium titanomagnetite iron tailings, the study shows that the main valence element is copper, and mainly exists in the form of copper sulfide. A vanadium-titanium magnetite tailings in Hebei was used as a research object. Using butyl xanthate, A8 and MK305 for flotation recovery of copper in iron tailings, it is determined that the optimum flotation technical index is obtained when the A8∶MK305 dosage ratio is 1∶1 and the crude collector dosage is 45 g/t, 2# oil is 7.5 g/t, through single collector test, combined collector test, collector dosage test and 2#oil dosage test. The results of closed circuit test show that the coarse concentrate obtained after one coarse separation and one sweep of iron tailings is ground again to -0.074 mm content ≥85%, and the copper concentrate of 18.94% grade can be obtained by adding quicklime 12 kg/t, coarse concentrate after one coarse separation, three cleaning and two sweep operation, and the recovery rate is 60.88%. In this experiment, the recovery and utilization of metal copper in iron tailings are realized.

Moyamoya disease (MMD), also known as abnormal cerebral vascular network disease, is characterized by progressive occlusion or stenosis of the internal carotid and cerebral arteries, as well as the formation of an abnormal cerebral vascular network. It can occur anywhere in the world but is most common in China, Japan, and the Republic of Korea. In recent years, there have been increasing reports on the coexistence of thyroid diseases and MMD, but the mechanism of their coexistence is still unclear. For this article, we used keywords such as “moyamoya disease”, “thyroid”, “Grave disease”, “thyrotoxicosis”, and “thyroid autoimmune antibodies” to search for 52 articles that met the requirements in medical databases such as PubMed and Web of Science. This article also reviews the research on the role of thyroid hormone, the mechanism of immune antibodies, the possible correlation between thyroid diseases and MMD disease genes, and the treatment methods, and discusses the possible relationship between MMD and thyroid diseases to provide a reference for the pathogenesis and treatment of MMD with thyroid diseases.

Background: Low-dose lipopolysaccharide (LPS) protects against early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanism underlying the neuroprotective roles of low-dose LPS remain largely undefined. Methods: A SAH mice model was established and the pathological changes of brain were evaluated by wet-dry weight method, HE and Nissl staining, and blood-brain barrier (BBB) permeability assay. Cell apoptosis and inflammation were monitored by TUNEL, flow cytometry and ELISA assays. qRT-PCR, immunofluorescence and Western blot were used to detect the expression of microglial polarization-related or oxidative stress-associated markers. Bioinformatics analysis, luciferase and ChIP assays were employed to detect the direct association between FOXO1 and IL-10 promoter. The ubiquitination of FOXO1 in the in vitro SAH model was detected by co-IP. Results: Low-dose LPS alleviated SAH-induced neurological dysfunction, brain edema, BBB disruption, damage in the hippocampus, neuronal apoptosis and inflammation via modulating microglial M1/M2 polarization by IL-10/IL-10R1 signaling. Mechanistic studies showed that FOXO1 acted as a transcriptional activator of IL-10. USP19 mediated the deubiquitination of FOXO1 to activate IL-10/IL-10R1 signaling, thereby regulating microglial M1/M2 polarization. Functional experiments revealed that low-dose LPS upregulated USP19 to modulate microglial M1/M2 polarization via FOXO1/IL-10/IL-10R1 signaling in SAH mice. Conclusion: Low-dose LPS protected against EBI after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.

Background: Glioblastoma multiforme (GBM) is the most malignant type of glioma. GBM tumors grow rapidly, have a high degree of malignancy, and are characterized by a fast disease progression. Unfortunately, there is a lack of effective treatments. An effective strategy for the treatment of GBM would be to identify key biomarkers correlating with the occurrence and progression of GBM and developing these biomarkers into therapeutic targets. Method and Results: In this study, using integrated bioinformatics analysis, we identified differentially expressed genes (DEGs), including 130 genes that were upregulated in GBM compared to normal brain tissue, and 128 genes that were downregulated in GBM. Based on Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, these genes were associated with regulation of tumor cell adhesion, differentiation, morphology in GBM and were mainly enriched in Complement and coagulation cascades pathway. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to construct a Protein-Protein Interaction network. Ten hub genes were identified, including FN1, CD44, MYC, CDK1, SERPINE1, COL3A1, COL1A2, LOX, POSTN and EZH2, all of which were significantly upregulated in GBM, these results were confirmed by oncomine database exploration. Alteration analysis of hub genes found that patients with alteration in at least one of the hub genes showed shorter median survival times (p = 0.013) and shorter median disease-free survival times (p = 2.488E-3) than patients without alterations in any of the hub genes. Multiple tests for survival analysis showed that among individual hub genes only expression of LOX was correlated with patient survival (P < 0.05).GDS4467 data set was used to analyze the expression of LOX in gliomas with different degrees of malignancy, and it was found that the expression level of LOX was positively correlated with the malignant degree of gliomas.By analyzing GDS 4535 data set showed that the expression level of LOX was positively correlated with the differentiation degree of GBM cells Conclusion: This research suggests that FN1, CD44, MYC, CDK1, SERPINE1, COL3A1, COL1A2, LOX, POSTN and EZH2 are key genes in GBM. However, only LOX is correlated with patient survival and promotes glioblastoma cell differentiation and tumor recurrence. LOX may be a candidate prognostic biomarker and potential therapeutic target for GBM.

BackgroundMoyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. The underlying pathophysiological mechanism of moyamoya disease remains to be elucidated, but recent studies have increasingly highlighted that abnormal immune response may be a potential trigger for MMD. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are inflammatory markers that can reflect the immune-inflammation state of the disease.ObjectiveThe purpose of this study was to investigate SII, NLR, and PLR in patients with moyamoya disease.MethodsA total of 154 patients with moyamoya disease (MMD group) and 321 age- and sex-matched healthy subjects (control group) were included in this retrospective case–control study. Complete blood count parameters were assayed to calculate the SII, NLR, and PLR values.ResultsThe SII, NLR, and PLR values in the moyamoya disease group were significantly higher than those in the control group [754 ± 499 vs. 411 ± 205 (P < 0.001), 2.83 ± 1.98 vs. 1.81 ± 0.72 (P < 0.001), and 152 ± 64 vs. 120 ± 42 (P < 0.001), respectively]. The SII in the medium-moyamoya vessels of moyamoya disease was higher than that in the high-moyamoya vessels and low-moyamoya vessels (P = 0.005). Using the receiver operating characteristic (ROC) curve analysis to predict MMD, the highest area under the curve (AUC) was determined for SII (0.76 for SII, 0.69 for NLR, and 0.66 for PLR).ConclusionBased on the results of this study, patients with moyamoya disease admitted for inpatient care due to acute or chronic stroke have significantly higher SII, NLR, and PLR when compared to blood samples drawn from completely healthy controls in a non-emergent outpatient setting. While the findings may suggest that inflammation plays a role in moyamoya disease, further studies are warranted to corroborate such an association. In the middle stage of moyamoya disease, there may be a more intense imbalance of immune inflammation. Further studies are needed to determine whether the SII index contributes to the diagnosis or serves as a potential marker of an inflammatory response in patients with moyamoya disease.

Moyamoya disease (MMD) is an idiopathic cerebrovascular disease which was first described by Suzuki and Takaku in 1969. Moyamoya disease is a non-atherosclerotic cerebrovascular structural disorder. MMD has been found all over the world, especially in Japan, Korea, and China. In recent years, many reports pointed out that the changes of vascular stenosis in patients with moyamoya disease occurred not only in intracranial vessels, but also in extracranial vessels, especially the changes of renal artery. Renovascular hypertension (RVH) is considered to be one of the important causes of hypertension in patients with moyamoya disease. The pathogenesis of moyamoya disease combined with renovascular hypertension is still unclear, and the selection of treatment has not yet reached a consensus. This article reviews the latest research progress in epidemiology, RNF213 gene, pathomorphology, clinical characteristics and treatment of moyamoya disease combined with renovascular hypertension, in order to provide reference for clinical workers.

Mitochondrial autophagy is an early defense and protection process that selectively clears dysfunctional or excessive mitochondria through a distinctive mechanism to maintain intracellular homeostasis. Mitochondrial dysfunction during cerebral stroke involves metabolic disbalance, oxidative stress, apoptosis, endoplasmic reticulum stress, and abnormal mitochondrial autophagy. This article reviews the research progress on the mechanism of mitochondrial autophagy in ischemic stroke to provide a theoretical basis for further research on mitochondrial autophagy and the treatment of ischemic stroke.