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OBJECTIVES: Cervical alignment and range of motion (ROM) changes after cervical spine surgery are related to cervical biomechanical and functions. Few studies compared these parameters between posterior laminoplasty and anterior 3-level hybrid surgery incorporating anterior cervical discectomy and fusion (ACDF) with cervical disc replacement (CDR). This study is aimed to detect the differences of cervical alignment and ROM changes of the two surgeries in a matched-cohort study. METHODS: From January 2018 and May 2020, 51 patients who underwent 3-level hybrid surgery incorporating ACDF with ACDR were included. A 1:1 match of the patients who underwent cervical laminoplasty based on age, gender, duration of symptoms, body mass index, and cervical alignment type was utilized as control group. General data (operative time, blood loss, etc.), Japanese Orthopaedic Association (JOA) score, VAS (Visual Analog Score), NDI (The Neck Disability Index), cervical sagittal alignment, and cervical range of motion (ROM) were recorded and compared. RESULTS: Both groups gained significant improvement in JOA, VAS, NDI scores postoperatively (p < 0.05). Cervical alignment significantly increased in hybrid group and decreased in control group after surgeries (p < 0.001). ROM decrease was similar in two groups. For cervical lordosis, though cervical alignment angle in control group decreased, the final follow-up cervical alignment and cervical alignment changes were not significantly different between hybrid and control groups. For cervical non-lordosis, cervical alignment decreased in control group while increased in hybrid group. At final follow-up, cervical alignment and the changes between the two groups were significantly different. Both control group and hybrid group had similar ROM decrease after the surgery no matter whether there was cervical lordosis or non-lordosis. Hybrid surgery showed cervical alignments significantly improved and similar ROM preservation compared with control group at final follow-up both for 1-level and 2-level disc replacement subgroups. CONCLUSIONS: The hybrid surgery demonstrated advantages of preserving cervical alignment and gaining similar cervical ROM preservation compared with cervical laminoplasty, especially for cervical non-lordosis. Given the importance of restoring lordotic cervical alignment, hybrid surgery may be preferred over laminoplasty to treat multilevel cervical disc herniation.
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Vertèbres cervicales , Discectomie , Laminoplastie , Amplitude articulaire , Arthrodèse vertébrale , Humains , Vertèbres cervicales/chirurgie , Femelle , Laminoplastie/méthodes , Mâle , Adulte d'âge moyen , Arthrodèse vertébrale/méthodes , Études de cohortes , Discectomie/méthodes , Adulte , Études rétrospectives , Remplacement total de disque/méthodes , Sujet âgéRÉSUMÉ
Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate deficiency due to low dietary intake, poor absorption of folate, and alterations in folate metabolism due to genetic defects or drug interactions significantly increases the risk of diseases such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have shown that folate deficiency can cause hyperhomocysteinemia, which increases the risk of hypertension and cardiovascular disease, and that high homocysteine levels are an independent risk factor for liver fibrosis and cirrhosis. In addition, folate deficiency results in increased secretion of pro-inflammatory factors and impaired lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. There is substantial evidence that folate deficiency contributes to the development and progression of a variety of liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Here we review key studies on the role of folate in the pathophysiology of liver diseases, summarize the current status of studies on folate in the treatment of liver diseases, and speculate that folate may be a potential therapeutic target for liver diseases.
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Carence en acide folique , Acide folique , Maladies du foie , Stéatose hépatique non alcoolique , Humains , Acide folique/métabolisme , Maladies du foie/métabolisme , Maladies du foie/étiologie , Stéatose hépatique non alcoolique/métabolisme , Cirrhose du foie/métabolisme , Foie/métabolisme , Animaux , Tumeurs du foie/métabolisme , Hyperhomocystéinémie , Homocystéine/métabolisme , Métabolisme lipidiqueRÉSUMÉ
BACKGROUND: Environmental temperature is critical in regulating biological functions in fish. S. prenanti is a kind of cold-water fish, but of which we have little knowledge about the metabolic adaptation and physiological responses to long-term cold acclimation. RESULTS: In this study, we determined the physiological responses of S. prenanti serum after 30 days of exposure to 6â. Compared with the control group, the levels of TC, TG, and LDL-C in the serum were significantly (P < 0.05) increased, and the level of glucose was significantly (P < 0.05) decreased under cold acclimation. Cold acclimation had no effect on the gene expression of pro-inflammatory factors and anti-inflammatory factors of S. prenanti. Metabolomics analysis by LC-MS showed that a total of 60 differential expressed metabolites were identified after cold acclimation, which involved in biosynthesis of amino acids, biosynthesis of unsaturated fatty acids, steroid degradation, purine metabolism, and citrate cycle pathways. CONCLUSION: The results indicate that cold acclimation can alter serum metabolites and metabolic pathways to alter energy metabolism and provide insights for the physiological regulation of cold-water fish in response to cold acclimation.
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Acclimatation , Basse température , Cyprinidae , Métabolome , Métabolomique , Animaux , Cyprinidae/métabolisme , Cyprinidae/physiologie , Cyprinidae/sang , Cyprinidae/génétiqueRÉSUMÉ
INTRODUCTION: Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. OBJECTIVES: To explore the role of Midline-1 (Mid1) in synovial activation. METHODS: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1-/-, Dpp4-/-, and Mid1-/-Dpp4-/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. RESULTS: An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. CONCLUSION: Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.
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Arthrite expérimentale , Polyarthrite rhumatoïde , Dipeptidyl peptidase 4 , Souris de lignée C57BL , Maturation post-traductionnelle des protéines , Synovite , Ubiquitin-protein ligases , Animaux , Humains , Mâle , Souris , Arthrite expérimentale/métabolisme , Arthrite expérimentale/anatomopathologie , Polyarthrite rhumatoïde/métabolisme , Prolifération cellulaire , Dipeptidyl peptidase 4/métabolisme , Dipeptidyl peptidase 4/génétique , Souris de lignée NOD , Souris knockout , Membrane synoviale/métabolisme , Membrane synoviale/anatomopathologie , Cellules synoviales/métabolisme , Cellules synoviales/anatomopathologie , Synovite/métabolisme , Synovite/anatomopathologie , Facteurs de transcription/métabolisme , Facteurs de transcription/génétique , Ubiquitine/métabolisme , Ubiquitin-protein ligases/métabolisme , Ubiquitin-protein ligases/génétique , UbiquitinationRÉSUMÉ
Objectives: To investigate whether 3-methyladenine (3-MA) can protect the kidney of streptozotocin (STZ) - induced diabetes mice, and explore its possible mechanism. Materials and Methods: STZ was used to induce diabetes in C57BL/6J mice. The mice were divided into normal control group (NC), diabetes group (DM), and diabetes+3-MA intervention group (DM+3-MA). Blood glucose, water consumption, and body weight were recorded weekly. At the end of the 6th week of drug treatment, 24-hour urine was collected. Blood and kidneys were collected for PAS staining to evaluate the degree of renal injury. Sirius red staining was used to assess collagen deposition. Blood urea nitrogen (BUN), serum creatinine, and 24-hour urine albumin were used to evaluate renal function. Western blot was used to detect fibrosis-related protein, inflammatory mediators, high mobility group box 1 (HMGB1)/NF-κB signal pathway molecule, vascular endothelial growth factor (VEGF), and podocin, and immunohistochemistry (IHC) was used to detect the expression and localization of autophagy-related protein and fibronectin. Results: Compared with the kidney of normal control mice, the kidney of diabetes control mice was more pale and hypertrophic. Hyperglycemia induces renal autophagy and activates the HMGB1/NF-κB signal pathway, leading to the increase of inflammatory mediators, extracellular matrix (ECM) deposition, and proteinuria in the kidney. In diabetic mice treated with 3-MA, blood glucose decreased, autophagy and HMGB1/NF-κB signaling pathways in the kidneys were inhibited, and proteinuria, renal hypertrophy, inflammation, and fibrosis were improved. Conclusion: 3-MA can attenuate renal injury in STZ-induced diabetic mice through inhibition of autophagy and HMGB1/NF-κB signaling pathway.
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Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.
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Schistosomiase artérioveineuse , Schistosomiase , Humains , Souris , Animaux , Interleukine-4 , Cirrhose du foie , Schistosomiase/complications , Foie , Cytokines/métabolisme , Facteur de nécrose tumorale alpha/métabolisme , ImmunitéRÉSUMÉ
High mobility group protein 1 (HMGB1) plays a complex role in tumor biology. When released into the extracellular space, it binds to the receptor for advanced glycation end products (RAGE) located on the cell membrane, playing an important role in tumor development by regulating a number of biological processes and signal pathways. In this review, we outline the multifaceted functions of the HMGB1/RAGE axis, which encompasses tumor cell proliferation, apoptosis, autophagy, metastasis, and angiogenesis. This axis is instrumental in tumor progression, promoting tumor cell proliferation, autophagy, metastasis, and angiogenesis while inhibiting apoptosis, through pivotal signaling pathways, including MAPK, NF-κB, PI3K/AKT, ERK, and STAT3. Notably, small molecules, such as miRNA-218, ethyl pyruvate (EP), and glycyrrhizin exhibit the ability to inhibit the HMGB1/RAGE axis, restraining tumor development. Therefore, a deeper understanding of the mechanisms of the HMGB1/RAGE axis in tumors is of great importance, and the development of inhibitors targeting this axis warrants further exploration.
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Background: Effector T cell activation, migration, and proinflammatory cytokine production are crucial steps in autoimmune disorders such as multiple sclerosis (MS). While several therapeutic approaches targeting T cell activation and proinflammatory cytokines have been developed for the treatment of autoimmune diseases, there are no therapeutic agents targeting the migration of effector T cells, largely due to our limited understanding of regulatory mechanisms of T cell migration in autoimmune disease. Here we reported that midline-1 (Mid1) is a key regulator of effector T cell migration in experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS. Methods: Mid1-/- mice were generated by Crispr-Cas9 technology. T cell-specific Mid1 knockout chimeric mice were generated by adoptive transfer of Mid1-/- T cells into lymphocyte deficient Rag2-/- mice. Mice were either immunized with MOG35-55 (active EAE) or received adoptive transfer of pathogenic T cells (passive EAE) to induce EAE. In vitro Transwell® assay or in vivo footpad injection were used to assess the migration of T cells. Results: Mid1 was significantly increased in the spinal cord of wild-type (Wt) EAE mice and disruption of Mid1 in T cells markedly suppressed the development of both active and passive EAE. Transcriptomic and flow cytometric analyses revealed a marked reduction in effector T cell number in the central nervous system of Mid1-/- mice after EAE induction. Conversely, an increase in the number of T cells was observed in the draining lymph nodes of Mid1-/- mice. Mice that were adoptively transferred with pathogenic Mid1-/- T cells also exhibited milder symptoms of EAE, along with a lower T cell count in the spinal cord. Additionally, disruption of Mid1 significantly inhibited T-cell migration both in vivo and in vitro. RNA sequencing suggests a suppression in multiple inflammatory pathways in Mid1-/- mice, including mTOR signaling that plays a critical role in cell migration. Subsequent experiments confirmed the interaction between Mid1 and mTOR. Suppression of mTOR with rapamycin or microtubule spindle formation with colcemid blunted the regulatory effect of Mid1 on T cell migration. In addition, mTOR agonists MHY1485 and 3BDO restored the migratory deficit caused by Mid1 depletion. Conclusion: Our data suggests that Mid1 regulates effector T cell migration to the central nervous system via mTOR/microtubule pathway in EAE, and thus may serve as a potential therapeutic target for the treatment of MS.
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Encéphalomyélite auto-immune expérimentale , Lymphocytes T , Ubiquitin-protein ligases , Animaux , Souris , Mouvement cellulaire , Système nerveux central/anatomopathologie , Cytokines/métabolisme , Souris de lignée C57BL , Sclérose en plaques/métabolisme , Moelle spinale/métabolisme , Sérine-thréonine kinases TOR/métabolisme , Ubiquitin-protein ligases/métabolisme , MicrotubulesRÉSUMÉ
Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation. Furthermore, accumulated intracellular iron activates various signaling pathways or risk factors for AS, such as abnormal lipid metabolism, oxidative stress, and inflammation, which can eventually lead to the disordered function of macrophages, vascular smooth muscle cells, and vascular endothelial cells. However, the molecular pathways through which ferroptosis affects AS development and progression are not entirely understood. This review systematically summarizes the interactions between AS and ferroptosis and provides a feasible approach for inhibiting AS progression from the perspective of ferroptosis.
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Athérosclérose , Ferroptose , Accident vasculaire cérébral ischémique , Humains , Cellules endothéliales , Fer , Espèces réactives de l'oxygène , Peroxydation lipidiqueRÉSUMÉ
AIM: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism. METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injection of streptozotocin (STZ) 60 mg/kg·d for 5 consecutive days. DM mice were randomly subdivided into untreated group (DM group), 3-MA (10 mg/kg·d by gavage) treated group (DM+3-MA group) and chloroquine (CQ; 50 mg/kg by intraperitoneal injection) treated group (DM+CQ group). The fasting blood glucose (FBG) levels were recorded every week. At the end of experiment, retinal samples were collected. The expression levels of pro-apoptotic proteins cleaved caspase-3, cleaved poly ADP-ribose polymerase 1 (PARP1) and Bax, anti-apoptotic protein Bcl-2, fibrosis-associated proteins Fibronectin and type 1 collagen α1 chain (COL1A1), vascular endothelial growth factor (VEGF), inflammatory factors interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, as well as autophagy related proteins LC3, Beclin-1 and P62 were determined by Western blotting. The oxidative stress indicators 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were detected by commercial kits. RESULTS: Both 3-MA and CQ had short-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1ß and TNF-α in DM mice. 3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA, decreased the expression of fibrosis-related proteins Fibronectin and COL1A1, pro-apoptotic proteins cleaved caspase-3, cleaved PARP1, as well as the ratio of Bax/Bcl-2. CQ had no significant impact on the oxidative stress indicators, fibrosis, and apoptosis related proteins. The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment, and the expression of P62 was further increased by CQ treatment. CONCLUSION: 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.
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During the dam discharging period, the strong aeration of high-speed water leads to the supersaturation of total dissolved gas (TDG) in the downstream water, which causes gas bubble disease (GBD) in fish and threatens their survival. TDG supersaturation has now become an ecological and environmental issue of global concern; however, the molecular mechanism underlying the physiological effect of TDG supersaturation on fish is poorly known. Here, we comprehensively investigated the effect of TDG supersaturation on Pelteobagrus fulvidraco at the histopathological, biochemical, transcriptomic, and metabolomic levels. After exposure to 116% TDG, P. fulvidraco exhibited classic GBD symptoms and pathological changes in gills. The level of superoxide dismutase was highly significantly decreased. Transcriptomic results revealed that heat shock proteins (HSPs) and a large number of genes involved in immunity were increased by TDG stress. A key environmental sensor PI3K/Akt/mTOR pathway was significantly stimulated for defence against stress. Integrated transcriptomic and metabolomic analyses revealed that key metabolites and genes were upregulated in the triacylglycerol synthesis pathway and that amino acid levels decreased, which might be associated with TDG supersaturation stress. The present study demonstrated that TDG supersaturation could cause severe physiological damage in fish. HSP genes, immune functions, and energy metabolic pathways were enhanced to counteract the adverse effects.
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Poissons-chats , Animaux , Phosphatidylinositol 3-kinases , Analyse de profil d'expression de gènes , Transcriptome , Acides aminésRÉSUMÉ
OBJECTIVE: Although direct isthmic repair, such as PSVPH, did not affect the mobility of the fixed segment and adjacent segment, it has a relatively low rate of isthmic fusion compared with conventional fusion. The Isobar TTL dynamic internal fixation system has been widely used in clinical practice and has achieved satisfactory clinical results. However, the use of the Isobar TTL system in combination with direct isthmic repair for lumbar spondylolysis has rarely been reported. The aim of this study was to compare the clinical and radiologic outcomes between patients who underwent Isobar TTL system and PSVPH with direct repair of defect for lumbar spondylolysis. METHODS: Stepwise propensity score matching (PSM) for age and sex were performed to keep comparable clinical data between groups in this retrospective and matched-pair case control study. A total of 50 patients diagnosed with lumbar spondylolysis underwent surgical implantation of the Isobar TTL group (n = 25) or PSVPH group (n = 25) from June 2009 to June 2016. Clinical outcomes were assessed using the Oswestry disability index (ODI), and visual analog score (VAS). Radiographic evaluations included range of motion (ROM) and the disc heights of stabilized segment and adjacent segment, adjacent segment degeneration (ASD) and bony fusion. Three-dimensional reconstruction of lumbar CT scan was obtained to evaluate bone fusion of the isthmic at final follow-up. The independent Student's t test and chi-square test were applied to compare the differences between groups. RESULTS: A total of 25 patients from TTL group were matched to 25 patients in PSVPH group for age, sex, body mass index (BMI), defect side, spondylolisthesis meyerding, and follow-up duration. The intervertebral space height (IH) of stabilized segment at postoperative 1 week and final follow-up in the TTL group was higher than those in the PSVPH group, respectively (P = 0.030; P = 0.013). The ROM of stabilized segment at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P < 0.001). The bony fusion rate at the final follow-up was 88.0% (22/25 cages) in the TTL group and 80.0% (20/25 cages) in the PSVPH group. The ODI score at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P = 0.007). CONCLUSION: Overall, our data suggest that the Isobar TTL system outcomes are comparable to those in the PSVPH, with a similar high bony fusion rate as PSVPH, especially its wider indications as a new surgery.
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Vis pédiculaires , Arthrodèse vertébrale , Spondylolyse , Humains , Études cas-témoins , Études rétrospectives , Transplantation osseuse , Vertèbres lombales/imagerie diagnostique , Vertèbres lombales/chirurgie , Arthrodèse vertébrale/méthodes , Résultat thérapeutique , Spondylolyse/imagerie diagnostique , Spondylolyse/chirurgieRÉSUMÉ
To analyze the differences between different-sized Acipenser dabryanus, we randomly selected 600 3-month-old A. dabryanus juveniles. Four months later, the blood and white muscle of these fish were analyzed. The results showed no significant difference in the length-weight relationship (LWR) b value between the large and small A. dabryanus. The levels of serum growth hormone (gh) and insulin-like growth factor 1 (igf1) in the large A. dabryanus were significantly lower than those in the small, whereas the activity levels of Total superoxide dismutase (T-sod) and catalase (cat) were opposite to the results of gh and igf1. A total of 212 and 245 metabolites showed significant changes in the positive and negative polarity mode, respectively. Among 3,308 proteins identified, 69 proteins showed upregulated expression, and 185 proteins showed downregulated expression. These results indicated that the growth advantage of A. dabryanus was closely related to glycolysis, protein synthesis, and antioxidant function.
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In atherosclerosis, macrophage-derived foam cell formation is considered to be a hallmark of the pathological process; this occurs via the uptake of modified lipoproteins. In the present study, we aim to determine the role of transaldolase in foam cell formation and atherogenesis and reveal the mechanisms underlying its role. Bone marrow-derived macrophages (BMDMs) isolated from mice successfully form foam cells after treatment with oxidized low-density lipoprotein (80 µg/mL). Elevated transaldolase levels in the foam cell model are assessed by quantitative polymerase chain reaction and western blot analysis. Transaldolase overexpression and knockdown in BMDMs are achieved via plasmid transfection and small interfering RNA technology, respectively. We find that transaldolase overexpression effectively attenuates, whereas transaldolase knockdown accelerates, macrophage-derived foam cell formation through the inhibition or activation of cholesterol uptake mediated by the scavenger receptor cluster of differentiation 36 (CD36) in a p38 mitogen-activated protein kinase (MAPK) signaling-dependent manner. Transaldolase-mediated glutathione (GSH) homeostasis is identified as the upstream regulator of p38 MAPK-mediated CD36-dependent cholesterol uptake in BMDMs. Transaldolase upregulates GSH production, thereby suppressing p38 activity and reducing the CD36 level, ultimately preventing foam cell formation and atherosclerosis. Thus, our findings indicate that the transaldolase-GSH-p38-CD36 axis may represent a promising therapeutic target for atherosclerosis.
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Athérosclérose , Cellules spumeuses , Souris , Animaux , Transaldolase/métabolisme , Transaldolase/pharmacologie , Antigènes CD36/génétique , Antigènes CD36/métabolisme , Macrophages/métabolisme , Lipoprotéines LDL/métabolisme , Athérosclérose/métabolisme , Glutathion/métabolisme , p38 Mitogen-Activated Protein Kinases/métabolisme , Cholestérol/métabolismeRÉSUMÉ
OBJECTIVE: At present, the influence of Modic changes (MCs) on postoperative fusion rate of lumbar interbody fusion (LIF) is mainly focused on the medium- and long-term fusion rate, while the short-term fusion rate has not been reported. The aim of this study was to compare the short-term fusion rate of lumbar degenerative disease patients with and without MCs after single level transforaminal lumbar interbody fusion (TLIF). METHODS: In this retrospective and matched-pair case control study, we included 100 patients who underwent TLIF from January 2017 to January 2020 and had at least two follow-up visits over a two-year period. Fifty patients with MCs (MCs group) were matched with 50 patients without MCs (non MCs group) for age, sex, surgical level, diagnosis, operative time, and intraoperative blood loss. We collected the X-ray and computed tomography (CT) data of patients from 3 months to 2 years after the operation to assess bony fusion and the cage union ratio. According to the type of cage, the MCs group was further divided into the nano-hydroxyapatite/polyamide 66 (n-HA/PA66) group and polyetheretherketone (PEEK) group, and the fusion performance between the two groups was compared. Finally, age, sex, body mass index (BMI), smoking and cage type were included in the logistic regression model for risk factor analysis. RESULTS: The bony fusion rates in the MCs group at 3 months, 6 months, 1 year and 2 years after surgery were significantly lower than those in the non MCs group (P < 0.05) (23.8% vs 62.5%, 52.6% vs 78.9%, 61.1% vs 83.3%, 74.0% vs 90.0%). The average coronal cage union ratios of the upper and lower endplates in the MCs group were significantly lower than those in the non MCs group (54.3% ± 17.5% vs 75.0% ± 17.2%, P < 0.05; 73.3% ± 12.0% vs 84.9% ± 8.0%, P < 0.05). Similarly, analogous results were obtained by comparing the MCs and non MCs groups' three-dimensional CT sagittal plane images (62.5% ± 16.5% vs 76.1% ± 12.4%, P < 0.05; 67.0% ± 13.9% vs 79.8% ± 11.5%, P < 0.05). CONCLUSION: Short-term fusion rates were lower in the MCs group than in the non MCs group. The coronal and sagittal cage union ratio in the MCs group was lower than that in the non MCs group. The fusion performance of n-HA/PA66 and PEEK cages in the MCs group was comparable.
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Vertèbres lombales , Arthrodèse vertébrale , Humains , Études cas-témoins , Études rétrospectives , Résultat thérapeutique , Vertèbres lombales/imagerie diagnostique , Vertèbres lombales/chirurgie , Arthrodèse vertébrale/méthodes , Polyéthylène glycols , Cétones , DurapatiteRÉSUMÉ
BACKGROUND: Accumulating data indicate that N6-methyladenosine (m6A) RNA methylation and lncRNA deregulation act crucial roles in cancer progression. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) as an m6A "reader" has been reported to be an oncogene in multiple malignancies. We herein aimed to elucidate the role and underlying mechanism by which HNRNPA2B1-mediated m6A modification of lncRNAs contributes to non-small cell lung cancer (NSCLC). METHODS: The expression levels of HNRNPA2B1 and their association with the clinicopathological characteristics and prognosis in NSCLC were determined by RT-qPCR, Western blot, immunohistochemistry and TCGA dataset. Then, the role of HNRNPA2B1 in NSCLC cells was assessed by in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. HNRNPA2B1-mediated m6A modification of lncRNAs was screened by m6A-lncRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (Me-RIP). The lncRNA MEG3-specific binding with miR-21-5p was evaluated by luciferase gene report and RIP assays. The effects of HNRNPA2B1 and (or) lncRNA MEG3 on miR-21-5p/PTEN/PI3K/AKT signaling were examined by RT-qPCR and Western blot analyses. RESULTS: We found that upregulation of HNRNPA2B1 was associated with distant metastasis and poor survival, representing an independent prognostic factor in patients with NSCLC. Knockdown of HNRNPA2B1 impaired cell proliferation and metastasis in vitro and in vivo, whereas ectopic expression of HNRNPA2B1 possessed the opposite effects. Mechanical investigations revealed that lncRNA MEG3 was an m6A target of HNRNPA2B1 and inhibition of HNRNPA2B1 decreased MEG3 m6A levels but increased its mRNA levels. Furthermore, lncRNA MEG3 could act as a sponge of miR-21-5p to upregulate PTEN and inactivate PI3K/AKT signaling, leading to the suppression of cell proliferation and invasion. Low expression of lncRNA MEG3 or elevated expression of miR-21-5p indicated poor survival in patients with NSCLC. CONCLUSIONS: Our findings uncover that HNRNPA2B1-mediated m6A modification of lncRNA MEG3 promotes tumorigenesis and metastasis of NSCLC cells by regulating miR-21-5p/PTEN axis and may provide a therapeutic target for NSCLC.
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Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , microARN , ARN long non codant , Humains , Phosphatidylinositol 3-kinases , Protéines proto-oncogènes c-akt , Transformation cellulaire néoplasique , Carcinogenèse , Phosphohydrolase PTENRÉSUMÉ
Hepatitis B has become one of the major global health threats, especially in developing countries and regions. Hepatitis B virus infection greatly increases the risk for liver diseases such as cirrhosis and cancer. However, treatment for hepatitis B is limited when considering the huge base of infected people. The immune response against hepatitis B is mediated mainly by CD8+ T cells, which are key to fighting invading viruses, while regulatory T cells prevent overreaction of the immune response process. Additionally, follicular T helper cells play a key role in B-cell activation, proliferation, differentiation, and formation of germinal centers. The pathogenic process of hepatitis B virus is generally the result of a disorder or dysfunction of the immune system. Therefore, we present in this review the critical functions and related biological processes of regulatory T cells and follicular T helper cells during HBV infection.
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Virus de l'hépatite B , Hépatite B , Humains , Lymphocytes T régulateurs , Lymphocytes T auxiliaires/anatomopathologieRÉSUMÉ
Ultrasound elastography (USE) provides complementary information of tissue stiffness and elasticity to conventional ultrasound imaging. It is noninvasive and free of radiation, and has become a valuable tool to improve diagnostic performance with conventional ultrasound imaging. However, the diagnostic accuracy will be reduced due to high operator-dependence and intra- and inter-observer variability in visual observations of radiologists. Artificial intelligence (AI) has great potential to perform automatic medical image analysis tasks to provide a more objective, accurate and intelligent diagnosis. More recently, the enhanced diagnostic performance of AI applied to USE have been demonstrated for various disease evaluations. This review provides an overview of the basic concepts of USE and AI techniques for clinical radiologists and then introduces the applications of AI in USE imaging that focus on the following anatomical sites: liver, breast, thyroid and other organs for lesion detection and segmentation, machine learning (ML) - assisted classification and prognosis prediction. In addition, the existing challenges and future trends of AI in USE are also discussed.
RÉSUMÉ
Macrophages, as central components of innate immunity, feature significant heterogeneity. Numerus studies have revealed the pivotal roles of macrophages in the pathogenesis of liver fibrosis induced by various factors. Hepatic macrophages function to trigger inflammation in response to injury. They induce liver fibrosis by activating hepatic stellate cells (HSCs), and then inflammation and fibrosis are alleviated by the degradation of the extracellular matrix and release of anti-inflammatory cytokines. MicroRNAs (miRNAs), a class of small non-coding endogenous RNA molecules that regulate gene expression through translation repression or mRNA degradation, have distinct roles in modulating macrophage activation, polarization, tissue infiltration, and inflammation regression. Considering the complex etiology and pathogenesis of liver diseases, the role and mechanism of miRNAs and macrophages in liver fibrosis need to be further clarified. We first summarized the origin, phenotypes and functions of hepatic macrophages, then clarified the role of miRNAs in the polarization of macrophages. Finally, we comprehensively discussed the role of miRNAs and macrophages in the pathogenesis of liver fibrotic disease. Understanding the mechanism of hepatic macrophage heterogeneity in various types of liver fibrosis and the role of miRNAs on macrophage polarization provides a useful reference for further research on miRNA-mediated macrophage polarization in liver fibrosis, and also contributes to the development of new therapies targeting miRNA and macrophage subsets for liver fibrosis.
Sujet(s)
Maladies du foie , microARN , Humains , microARN/génétique , microARN/métabolisme , Activation des macrophages/génétique , Cirrhose du foie/génétique , Cirrhose du foie/anatomopathologie , Maladies du foie/métabolisme , Macrophages , InflammationRÉSUMÉ
In the dam discharge season, the supersaturation of total dissolved gas (TDG) in the downstream channel can seriously affect the survival of aquatic organisms. However, few studies have revealed the mechanism by which TDG supersaturation affects the physiology of fish thus far. The present study was conducted to study the mechanism of the effect of TDG supersaturation on Schizothorax davidi, a species that is very sensitive to gas bubble disease. S. davidi was exposed to 116 % TDG supersaturation stress for 24 h. Serum biochemical tests showed that the aspartate aminotransferase and alanine aminotransferase levels after TDG supersaturation exposure were significantly decreased compared to those in the control group, while superoxide dismutase activity was significantly increased. RNA-Seq of gill tissues identified 1890 differentially expressed genes (DEGs), which consisted of 862 upregulated genes and 1028 downregulated genes, in the TDG supersaturation group vs. the control group. Pathway enrichment analysis revealed that the cell cycle, apoptosis and immune signaling pathways were affected by TDG stress. The results of this study may contribute to our understanding of the underlying molecular mechanism of environmental stress in fish.