Macrophage infiltration and polarization have been increasingly observed in intervertebral disc (IVD) degeneration (IDD). However, their biological roles in IDD are still unrevealed. We harvested ...conditioned media (CM) derived from a spectrum of macrophages induced from THP-1 cells, and examined how they affect nucleus pulposus cells (NPCs)
in vitro
, by studying cell proliferation, extracellular matrix (ECM) synthesis, and pro-inflammation expression; and
in vivo
by injection CM in a rat IDD model. Then, high-throughput sequencing was used to detect differentially expressed genes (DEGs). Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to further analysis. Higher CCR7+ (M1 marker) and CD206+ (M2 marker) cell counts were found in the degenerated human IVD tissues as compared with the control. Furthermore, the cell co-culture model showed M1CM attenuated NPC proliferation, downregulated the expression of ECM anabolic genes encoding aggrecan and collagen IIα1, upregulated the expression of ECM catabolic genes encoding MMP-13, and inflammation-related genes encoding IL-1β, IL-6, and IL-12, while M2CM showed contrasting trends. In IDD model, higher histological scores and lower disc height index were found following M1CM treatment, while M2CM exhibited opposite results. M1CM injection decreased ECM anabolic and increased ECM catabolic, as well as the upregulation of inflammation-related genes after 8 weeks treatment, while M2CM slowed down these trends. Finally, a total of 637 upregulated and 655 downregulated genes were detected in M1CM treated NPCs, and 975 upregulated genes and 930 downregulated genes in the M2CM groups. The top 30 GO terms were shown and the most significant KEGG pathway was cell cycle in both groups. Based on the PPI analysis, the five most significant hub genes were PLK1, KIF20A, RRM2, CDC20, and UBE2C in the M1CM groups and RRM2, CCNB1, CDC20, PLK1, and UBE2C in the M2CM groups. In conclusion, macrophage polarization exhibited diverse roles in IDD progression, with M1CM exacerbating cell proliferation suppression and IVD degeneration, while M2CM attenuated IDD development. These findings may facilitate the further elucidation of the role of macrophage polarization in IDD, and provide novel insights into the therapeutic potential of macrophages.
The Ficus carica polysaccharide (FCPS) components of the common fig fruit have been demonstrated to exhibit antioxidant and immunity-enhancing activities. However, it is unclear whether it could ...prevent the ulcerative colitis development. Here, we reported that 5 week orally administered FCPS (150–300 mg per kg bw) significantly prevented DSS-induced colitis in C57BL/6J mice by improving the colon length and suppressing the infiltration of inflammatory cells in the gut. FCPS treatment protected the goblet cells, elevated the expression of tight junction protein claudin-1, and suppressed the formation of cytokines including TNF-α and IL-1β. FCPS supplementation significantly reformed the gut microbiome by enhancing the abundance of S24-7, Bacteroides , and Coprococus , and suppressing the abundance of Escherichia and Clostridium at the genus level. Consistently, the formation of beneficial microbial metabolites, short chain fatty acids, especially acetate and butyrate, were improved in FCPS-treated colitis mice. The correlation analysis indicated that the protective effects of FCPS on ulcerative colitis might be highly correlated with the microbiota composition changes and the formation of SCFAs. In conclusion, these results indicated that FCPS supplementation could be a promising nutritional strategy for reducing inflammatory bowel disease and the gut microbes play essential roles in providing these beneficial effects.
Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in ...herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro‐inflammatory cytokine TNF‐α; and anti‐inflammatory factor IL‐4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro‐ and anti‐inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF‐α + proportions were identified in the high‐intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non‐HIZ and protrude NP tissue. Higher CD206+ and IL‐4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+, CCR7+, and CD206+ cell proportions, and TNF‐α and IL‐4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage‐like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Low back pain or sciatic pain because of lumbar intervertebral disc herniation (LDH) is caused by mechanical compression and/or an inflammatory component on the nerve root. However, it is ...difficult to define to what extent each component contributes to the pain. This study attempted to explore the effects of macrophage polarization on clinical symptoms in patients experiencing LDH after surgery, and investigated the association between macrophage cell percentages and clinical efficacy.
Methods
This study retrospectively harvested nucleus pulposus (NP) tissue samples from 117 patients. Clinical symptoms and efficacy using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated at different time points preoperatively and postoperatively. CD68, CCR7, CD163, and CD206 were selected as macrophage phenotypic markers.
Results
Seventy‐six samples showed positive expression of macrophage markers in NP samples of patients with LDH, whereas 41 patients displayed negative results. No significant differences were detected between the two groups, involvement of several demographic data, and preoperative clinical findings. With respect to the macrophage‐positive group, no significant correlation was detected between the positive rate of the four markers and the VAS score or ODI after surgery. However, patients with NP samples positive for CD68 and CCR7 expression showed significantly lower VAS scores 1 week after surgery compared with those in the negative group. Moreover, the improvement in VAS score showed a strong positive correlation with CD68‐ and CCR7‐positive cell percentages.
Conclusions
Our results indicated that pro‐inflammatory M1 macrophages may be associated with the reduction of chronic pain after surgery. Therefore, these findings contribute to better personalized pharmacological interventions for patients with LDH, considering the heterogeneity of pain.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neonatal hypoxic‐ischemic encephalopathy (NHIE) induces severe cerebral damage and neurological dysfunction, with seldom effective therapy. Aquaporin‐4 (AQP4) is involved in aggravating brain damage ...induced by NHIE. This study aimed to investigate the role of AQP4 underlying the pathogenesis of NHIE. Neonatal Sprague–Dawley rats were used to establish neonatal hypoxic‐ischemic (HI) models, and the expression of AQP4 in the cortex, hippocampus, and lung tissues was detected by real‐time quantitative polymerase chain reaction as well as Western blot. Primary cortical neurons were cultured for the oxygen‐glucose deprivation (OGD) model, and siRNA was used to silence the expression of AQP4. Immunostaining of Tuj1 was performed to observe the axonal growth. CRISPER/Cas9 technology was used to knock out AQP4. The results demonstrated that AQP4 was upregulated in the cortex, hippocampus, and lung tissues in neonatal rats with HI and OGD neurons. Besides, silencing AQP4 promoted axonal growth of OGD neurons, and AQP4 knockout notably improved long‐term neurobehavioral impairment. Furthermore, GAP43 was found closely correlated with AQP4 via GeneMANIA prediction. Significant downregulation of GAP43 was induced in OGD neurons, while AQP4 knockout markedly upregulated its expression in rats. This indicated that the depletion of AQP4 may enhance axonal regeneration and promote the long‐term neurobehavioral recovery associated with the upregulation of GAP43 expression.
Neonatal Sprague–Dawley rats (7 days old) were applied to establish hypoxic‐ischemic (HI) models; moreover, siRNA and CRISPER‐/Cas9‐mediated gene‐editing technologies were then employed to explore the role of AQP4 in the neurological damages at 24 h after HI in vitro and in vivo. The results revealed that silencing AQP4 could promote the outgrowth of the length in oxygen‐glucose deprivation (OGD) neurons. Moreover, AQP4‐knockout could notably improve long‐term neurobehavioral impairment compared with AQP4‐wild type 1 month after HI reflected by the tests of neurological severity score, water maze, and Y‐maze. Furthermore, growth‐associated protein‐43 (GAP43) was closely correlated with AQP4 in both pathway and co‐expression channels via GeneMANIA prediction. As expected, OGD induced significant downregulation of GAP43, while AQP4 knockout could markedly upregulate its expression. These indicated that AQP4 silencing could enhance axon regeneration and promote long‐term neurobehavioral recovery after HI; the underlying mechanism was associated with GAP43 upregulation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The exact mechanism of myocardial hypertrophy has not been completely elucidated. NOD-like receptor protein 3 (NLRP3) and the pyroptotic cascade play a critical role in cardiac hypertrophy and ...inflammation. The myokine irisin can inhibit NLRP3 activation, although its exact mechanism of action is unknown. In this study, we induced cardiac hypertrophy in a mouse model via aortic constriction (TAC) to further explore the pathological role of NLRP3 inflammasome-mediated pyroptosis and the potential therapeutic effects of irisin. Cardiac hypertrophy significantly increased the percentage of apoptotic cells and upregulated IL-1β, cleaved caspase-1, and GSDMD-N that lie downstream of the NLRP3 inflammasome. Subsequently, irisin was co-administered to the TAC mice or angiotensin II (Ang-II)-treated cardiomyocytes to observe whether it could attenuate pyroptosis and cardiac hypertrophy. We established a direct association between pyroptosis and cardiac hypertrophy and found that pharmacological or genetic inhibition of NLRP3 attenuated cardiac hypertrophy. Furthermore, ectopic overexpression of NLRP3 abrogated the cardioprotective effects of irisin. To summarize, pyroptosis is a pathological factor in cardiac hypertrophy, and irisin is a promising therapeutic agent that inhibits NLRP3-mediated pyroptosis of cardiomyocytes.
Objectives
To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein ...(ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions.
Methods
We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients’ nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions.
Results
Patients with Eos+Neu+ and Eos+Neu−CRS scored highest in most clinical symptom scores, while Eos−Neu+ and Eos−Neu−CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (
R
= 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (
R
= 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu−CRS from Eos−Neu−CRS in Neu−CRS, the highest AUC (0.8801) was determined for ECP in secretions.
Conclusions
Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Two sterically shielded anthracene derivatives are developed with modification of peripheral phenyl groups (PPGs).•The influence of PPGs decoration on the photoluminescence and electroluminescence ...properties is studied to unveil the structure-property relationship.•PPGs can significantly suppress electronic coupling in solid state due to its steric-demanding geometry•High efficiency with EQE of up to 5.05% and deep-blue electroluminescence with color index of (0.15, 0.09) are demonstrated.
Two new anthracene derivatives are designed with a sterically shielded strategy for deep-blue electroluminescence applications. The naphthyl groups of the widely used blue emitter 9,10-di-(2-naphthyl)anthracene (ADN) were modified with four peripheral phenyl groups (PPGs) to enhance intermolecular spacing in solid-state thin film for suppressing electronic coupling. Influence of the PPGs decoration on photoluminescence and electroluminescence are investigated to reveal the structure-property relationship. A nondoped organic light-emitting diode with the new emitter 9-(naphthalen-2-yl)-10-(5,6,7,8-tetraphenylnaphthalen-2-yl)anthracene (M1) exhibits excellent performance with a maximum external quantum efficiency of 5.05% and deep-blue color index of (0.15, 0.09). Although the use of bulky peripheral substituents does improve device performance, it should be paid attention to the non-conductive effect induced by the larger molecular spacing in the design of deep-blue electroluminescence materials. This work provides a promising molecular design for deep-blue electroluminescence materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Many long-term maintenance hemodialysis patients have symptoms of protein-energy wasting caused by malnutrition. Each session of hemodialysis removes about 10 to 12 g of amino acids and 200 to 480 ...kcal of energy. Patients receiving hemodialysis for chronic kidney disease may be undernourished for energy, protein consumption, or both. Non-diabetic hemodialysis patients were randomized to three treatment groups: oral supplementation, oral supplementation plus high-concentration glucose solution (250 mL containing 50% glucose) and these two interventions plus 8.5% amino acids solution. The post-treatment energy status of the glucose group was significantly higher than its baseline level, whereas the control group's status was significantly lower. The glucose group had significantly higher concentrations of asparagine, glutamine, glycine, alanine, and lysine after treatment. All treatment groups had significantly increased hemoglobin levels but significantly decreased transferrin levels after treatment compared to baseline. After treatment, the amino acid group had significantly higher albumin level compared to the glucose group (p = 0.001) and significantly higher prealbumin level compared to the control group (p = 0.017). In conclusion, long-term intervention with high-concentration glucose solution at each hemodialysis session is a simple and cheap method that replenished energy stores lost during hemodialysis of non-diabetic patients.
Chronic kidney disease (CKD) is a serious condition associated with early mortality, decreased quality of life, and increased health-care expenditures.
Data from the National Health and Nutrition ...Examination Survey (NHANES) collected from 1999 to 2012 were used. Subjects were divided into 4 estimated glomerular filtration rate (eGFR) categories: stage 1: eGFR≥90mL/min/1.73m2, stage 2: eGFR 60–89, stage 3: eGFR 30–59, and stage 4/5: eGFR<30, and 3 age strata (<45y, 45–64, 65+). Associations between protein intake and albuminuria were determined.
A total of 45,259 subjects were included. Despite decreasing protein intake, there was a significant increase in the prevalence of albuminuria with decreasing levels of eGFR. Multivariable analysis showed that albuminuria was associated with daily protein intake in patients ≥65years old with stage 1 disease, and that diabetes was associated with albuminuria in patients ≥65years old with stage 2 and 3 diseases. Overall, albuminuria in patients with stage 1 disease was associated with hours of sitting per day and blood glucose level.
Albuminuria was associated with daily protein intake in patients of 45–64years old with stage 1 CKD disease, and was associated with hours of sitting per day and blood glucose level. These data further support the importance of lifestyle changes in the management of CKD, especially in patients with early-stage disease.
•Albuminuria in stage 1 chronic kidney disease (CKD) is associated with activity level.•Albuminuria in stage 1 CKD is associated with blood glucose level.•Albuminuria is associated with protein intake in those 45–65years with stage 1 CKD.•Diabetes is associated with albuminuria in those ≥65years with stage 2 and 3 CKD.•These data support the importance of lifestyle changes in the management of CKD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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