Research progress on icariin, a traditional Chinese medicine extract, in the treatment of asthma.

Bronchial asthma is a common chronic airway disease, and long-term management of asthma is the focus and challenge of clinical treatment. Glucocorticoids are often used as the first choice for the treatment of asthma. However, the occurrence of hormone dependence, hormone resistance, and local and systemic adverse reactions caused by hormone application also creates problems for the treatment of asthma. Finding new, safe, and effective therapeutic drugs is an important research direction at present. Icariin is an effective ingredient of the traditional Chinese medicine, Epimedium. It has various biological attributes such as anti-inflammatory and antioxidative activities, and immune regulation. It has high safety and a wide range of clinical applications. Icariin has the characteristics of multitargeted intervention in the treatment of asthma. Here, we review the specific mechanisms of icariin in treating asthma, and icariin is considered a novel therapy in controlling asthma; however, the mechanism is still worth further investigation.

VNN1 promotes atherosclerosis progression in apoE-/- mice fed a high-fat/high-cholesterol diet.

Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE(-/-) mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPARα signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL-cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL-induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE(-/-) mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF-α (148.74%), interleukin (IL)-1ß (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE(-/-) mice with LV-VNN1. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis.

RP5-833A20.1/miR-382-5p/NFIA-dependent signal transduction pathway contributes to the regulation of cholesterol homeostasis and inflammatory reaction.

OBJECTIVE: Cardiovascular disease caused by atherosclerosis is the number one cause of death in Western countries and threatens to become the major cause of morbidity and mortality worldwide. Long noncoding RNAs are emerging as new players in gene regulation, but how long noncoding RNAs operate in the development of atherosclerosis remains unclear. APPROACH AND RESULTS: Using microarray analysis, we found that long noncoding RNA RP5-833A20.1 expression was upregulated, whereas nuclear factor IA (NFIA) expression was downregulated in human acute monocytic leukemia macrophage-derived foam cells. Moreover, we showed that long noncoding RNA RP5-833A20.1 may decreases NFIA expression by inducing hsa-miR-382-5p expression in vitro. We found that the RP5-833A20.1/hsa-miR-382-5p/NFIA pathway is essential to the regulation of cholesterol homeostasis and inflammatory responses in human acute monocytic leukemia macrophages. Lentivirus-mediated NFIA overexpression increased high-density lipoprotein cholesterol circulation, reduced low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol circulation, decreased circulation of inflammatory cytokines, including interleukin-1ß, interleukin-6, tumor necrosis factor-α, and C-reactive protein, enhanced reverse cholesterol transport, and promoted regression of atherosclerosis in apolipoprotein E-deficient mice. CONCLUSIONS: Our findings indicated that the RP5-833A20.1/miR-382-5p/NFIA pathway was essential to the regulation of cholesterol homeostasis and inflammatory reactions and suggested that NFIA may represent a therapeutic target to ameliorate cardiovascular disease.

The miR-573/apoM/Bcl2A1-dependent signal transduction pathway is essential for hepatocyte apoptosis and hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with an increasing incidence worldwide. Apolipoprotein M (apoM) is a novel apolipoprotein that is mainly expressed in liver and kidney tissues. However, the anti-tumor properties of apoM remain largely unknown. We evaluated the anti-tumor activities and mechanisms of apoM in HCC both in vivo and in vitro. Bioinformatic analysis and luciferase reporter assay results showed that apoM was a potential target of hsa-miR-573 and was downregulated after transfection with hsa-miR-573 mimics. Overexpression of apoM suppressed migration, invasion, and proliferation of hepatoma cells in vitro. Overexpression of hsa-miR-573 in hepatoma cells reduced apoM expression, leading to promotion of the invasion, migration, and proliferation of hepatoma cells in vitro. In addition, hsa-miR-573 markedly promoted growth of xenograft tumors in nude mice with an accompanying reduction in cell apoptosis. ApoM markedly inhibited growth of xenograft tumors in nude mice and promoted cell apoptosis. Moreover, Bcl2A1 mRNA and protein levels were inhibited by apoM overexpression and an increase in apoptosis rate by apoM was markedly compensated by Bcl2A1 overexpression in HepG2 cells. These results provide evidence that hsa-miR-573 promoted tumor growth by inhibition of hepatocyte apoptosis and this pro-tumor effect might be mediated through Bcl2A1 in an apoM-dependent manner. Therefore, our findings may be useful to improve understanding of the critical effects of hsa-miR-573 and apoM in HCC pathogenesis.

Ginsenoside Rg1 relieves tert-Butyl hydroperoxide-induced cell impairment in mouse microglial BV2 cells.

Microglial activation plays an important role in neurodegenerative diseases associated with oxidative stress. tert-Butyl hydroperoxide (t-BHP), an analog of hydroperoxide, mimics the oxidative damage to microglial cells. It has been reported that ginsenoside Rg1 (G-Rg1), an active ingredient of Panax ginseng, has anti-stress and anti-inflammatory properties. The present study aims to investigate the ability of G-Rg1 to decrease the t-BHP-mediated cell damage of BV2 microglial cells. We performed flow cytometry assays to facilitate the detection of reactive oxygen species as well as Western blotting analyses and immunofluorescence assays using specific antibodies, such as antibodies against phospho-mitogen-activated protein kinases (p-MAPKs), phospho-nuclear factor-κB (p-NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), Caspase-3, autophagy marker light chain 3 (LC3), and Becline-1. We found that treatment with 50 µM G-Rg1 protected microglial cells against oxidative damage induced by 10 µM t-BHP.

A lincRNA-DYNLRB2-2/GPR119/GLP-1R/ABCA1-dependent signal transduction pathway is essential for the regulation of cholesterol homeostasis.

Accumulated evidence shows that G protein-coupled receptor 119 (GPR119) plays a key role in glucose and lipid metabolism. Here, we explored the effect of GPR119 on cholesterol metabolism and inflammation in THP-1 macrophages and atherosclerotic plaque progression in apoE(-/-) mice. We found that oxidized LDL (Ox-LDL) significantly induced long intervening noncoding RNA (lincRNA)-DYNLRB2-2 expression, resulting in the upregulation of GPR119 and ABCA1 expression through the glucagon-like peptide 1 receptor signaling pathway. GPR119 significantly decreased cellular cholesterol content and increased apoA-I-mediated cholesterol efflux in THP-1 macrophage-derived foam cells. In vivo, apoE(-/-) mice were randomly divided into two groups and infected with lentivirus (LV)-Mock or LV-GPR119 for 8 weeks. GPR119-treated mice showed decreased liver lipid content and plasma TG, interleukin (IL)-1ß, IL-6, and TNF-α levels, whereas plasma levels of apoA-I were significantly increased. Consistent with this, atherosclerotic lesion development was significantly inhibited by infection of apoE(-/-) mice with LV-GPR119. Our findings clearly indicate that, Ox-LDL significantly induced lincRNA-DYNLRB2-2 expression, which promoted ABCA1-mediated cholesterol efflux and inhibited inflammation through GPR119 in THP-1 macrophage-derived foam cells. Moreover, GPR119 decreased lipid and serum inflammatory cytokine levels, decreasing atherosclerosis in apoE(-/-) mice. These suggest that GPR119 may be a promising candidate as a therapeutic agent.

Dihydrocapsaicin down-regulates apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.

BACKGROUND: Apolipoprotein M (apoM), as a novel apolipoprotein which is mainly expressed in liver and kidney tissues, is associated with development and progression of atherosclerosis and diabetes. Our group have recently shown that Dihydrocapsaicin(DHC)can significantly decrease atherosclerotic plaque formation in apoE-/- mice. However, the effect and possible mechanism of DHC on apoM expression remain unclear. METHODS: HepG2 cells were treated with 0 µM, 25 µM, 50 µM and 100 µM DHC for 24 h or were treated with 100 µM DHC for 0, 6, 12, and 24 h, respectively. The mRNA levels and protein levels were measured by real-time quantitative PCR and western blot analysis, respectively. RESULTS: We found that DHC markedly decreased expression of apoM at both mRNA and protein level in HepG2 cells in a dose-dependent and time-dependent manner. Expression of Foxa2 was decreased while expression of LXRα was increased by DHC treatment in HepG2 cells. In addittion, overexpression of Foxa2 markedly compensated the inhibition effect induced by DHC on apoM expression. LXRα small interfering RNA significantly abolished the inhibition effect which induced by DHC on apoM expression. The liver of C57BL/6 mice treated with DHC had significantly lower expression of apoM. Furthermore, the liver had lower expression of Foxa2 while had higher expression of LXRα. CONCLUSIONS: DHC could down-regulate apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.

[Treatment of massive rotator cuff tears with modified Chinese-way technique].

OBJECTIVE: To explore clinical effect of modified Chinese-way technique under shoulder arthroscopy in treating massive rotator cuff tears. METHODS: From January 2019 to June 2022, 22 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair with improved Chinese-way technique, including 10 males and 12 females, aged from 46 to 76 years old with an average of(64.14±7.45) years old;the courses of disease ranged from 5 to 14 months with an average of(8.32±2.42) months;19 patients were complete repaired, and 3 patients were partial repaired. Visual analogue scale (VAS) and University of California at Los Angeles (UCLA) scale were used to evaluate pain and function of shoulder joint preoperatively and 1 year postoperatively. Postoperative complications, the integrity of reconstructed tissue structure and the size of subacromial space were observed. RESULTS: All patients were followed up from 12 to 34 months with an average of (17.14±5.93) months. Re-tear were occurred in 4 patients during MRI follow-up, but clinical symptoms of patients were improved significantly and they were satisfied with the treatment, the others were no complications such as incision infection, peripheral nerve injury, loosening and falling off of internal fixation anchors. Preoperative and 1 year after operation VAS were (8.05±1.12) and (1.82±1.50), UCLA scores were (7.45±1.65) and (31.41±2.87) respectively, and the difference was statistically significant (P<0.05). CONCLUSION: The modified Chinese-way technique under shoulder arthroscopy for the massive rotator cuff tear could relieve pain obviously and recovery postoperative function well, with satisfactory curative effect.

Anti-inflammatory effects of propofol are mediated by apolipoprotein M in a hepatocyte nuclear factor-1α-dependent manner.

Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous hypnotic agent in daily practice. However, its anti-inflammatory properties have seldom been addressed. In this study, we evaluated the anti-inflammatory activity and mechanisms of propofol on lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro and found that propofol markedly inhibited LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, and expression of inducible nitric oxide synthase (iNOS). At the same time, the expression of hepatocyte nuclear factor-1α (HNF-1α) and apolipoprotein M (APOM) was inhibited by treatment with LPS and LPS-induced down-regulation of HNF-1α expression and APOM expression could be compensated by propofol treatment. However, propofol could not compensate LPS-induced down-regulation of APOM expression by treatment with HNF-1α siRNA and the suppressive effect on LPS-induced pro-inflammatory cytokines production by propofol was significantly compensated by treatment with APOM siRNA. These results provide evidence that propofol may first up-regulate APOM expression by enhancing HNF-1α expression and then inhibit pro-inflammatory cytokine production in LPS-stimulated cells. Therefore, our study may be useful in understanding the critical effect of propofol in patients with systemic inflammatory response syndrome.

Exploring Dysregulated Ferroptosis-Related Genes in Septic Myocardial Injury Based on Human Heart Transcriptomes: Evidence and New Insights.

Introduction: Sepsis is currently a common condition in emergency and intensive care units, and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Cardiac dysfunction caused by septic myocardial injury (SMI) is associated with adverse prognosis and has significant economic and human costs. The pathophysiological mechanisms underlying SMI have long been a subject of interest. Recent studies have identified ferroptosis, a form of programmed cell death associated with iron accumulation and lipid peroxidation, as a pathological factor in the development of SMI. However, the current understanding of how ferroptosis functions and regulates in SMI remains limited, particularly in the absence of direct evidence from human heart. Methods: We performed a sequential comprehensive bioinformatics analysis of human sepsis cardiac transcriptome data obtained through the GEO database. The lipopolysaccharide-induced mouse SMI model was used to validate the ferroptosis features and transcriptional expression of key genes. Results: We identified widespread dysregulation of ferroptosis-related genes (FRGs) in SMI based on the human septic heart transcriptomes, deeply explored the underlying biological mechanisms and crosstalks, followed by the identification of key functional modules and hub genes through the construction of protein-protein interaction network. Eight key FRGs that regulate ferroptosis in SMI, including HIF1A, MAPK3, NOX4, PPARA, PTEN, RELA, STAT3 and TP53, were identified, as well as the ferroptosis features. All the key FRGs showed excellent diagnostic capability for SMI, part of them was associated with the prognosis of sepsis patients and the immune infiltration in the septic hearts, and potential ferroptosis-modulating drugs for SMI were predicted based on key FRGs. Conclusion: This study provides human septic heart transcriptome-based evidence and brings new insights into the role of ferroptosis in SMI, which is significant for expanding the understanding of the pathobiological mechanisms of SMI and exploring promising diagnostic and therapeutic targets for SMI.

Advanced lung cancer patient with isolated heparin-induced thrombocytopenia: A case report.

RATIONALE: Heparin-induced thrombocytopenia (HIT), a potentially devastating form of drug-induced thrombocytopenia, occurs in patients receiving heparin for thrombosis prevention or treatment. An isolated HIT is characterized by decreased platelet counts without thrombosis, which are atypical and difficult to clinically find. SYMPTOMS AND CLINICAL FINDINGS: A 33-year-old female patient's admission examination revealed elevated D-dimer levels. After prophylactic anticoagulation using low-molecular weight heparin, her blood platelet counts were rapidly decreased, whereas her D-dimer levels increased, followed by presentations of chest tightness, abdominal pain, and skin itching without thrombosis. After excluding all the other causes of thrombocytopenia, HIT was suspected. Her 4Ts score was 5 points, and enzyme-linked immunoassay for platelet factor 4 (PF4)/heparin antibodies was positive, indicating isolated HIT. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient was diagnosed with advanced lung cancer presenting with isolated HIT. We immediately stopped low-molecular weight heparin and initiated rivaroxaban for anticoagulation. We administered thrombopoietin (TPO) and avatripopal maleate tablets to increase blood platelet counts, whereas intravenous immunoglobulin (IVIG) was administered to stimulate her immune system. The patient's thrombocytopenia was successfully treated without thrombosis and bleeding complications. LESSONS: Rivaroxaban is a potential option for tumor preventive anticoagulation and HIT treatment. Early HIT identification is necessary. After identification, the 4Ts score as well as PF4/heparin antibodies should be assessed and appropriate anticoagulants selected based on patients' conditions.

Promising Therapeutic Functions of Bone Marrow Mesenchymal Stem Cells Derived-Exosome in Asthma.

Asthma is a chronic inflammatory disturbance of the airways in which many cells and cellular elements are involved. Wheezing, breathlessness, chest tightness, and coughing, especially at night or in the early morning, are typical symptoms of asthma. At present, inhaled corticosteroid (ICS) and long-acting ß-agonists (LABAs) are standard treatments for regular management. Oral corticosteroids (OCSs) were recommended for controlling asthma exacerbation but only for a short-term treatment because of the side effects on organs. Biologic therapies have achieved exciting and notable effects in clinical treatment but are not applicable for all phenotypes of asthma. At present, some new approaches are under exploration to lessen side effects and improve curative effects. Studies have revealed that bone marrow mesenchymal stem cells (BMMSCs) hold various curative effects in asthma and may benefit in the long term with high safety. Extracellular vesicles (EVs) enriched in body fluid were characterized as subcomponents of extracellular vesicles and delivered carriers combined with genetic messages in vivo. The therapeutic potential of exosomes has become a research hotspot in many diseases. BMMSC-derived exosomes were considered as the dominant part of BMMSCs in cell-to-cell communications and playing curative effects. Points also hold that BMMSC-Exo could interfere with airway inflammation and airway remolding in asthma via modulating the immune response, regulating gene expression, adjusting the phenotype of macrophage, etc. However, BMMSC-Exo still lacked more clinical trials for evaluating the effects on asthma, and the technology of extraction and purification still needs to be improved for wide use. This review aims to draw the relationship among asthma, BMMSC, and exosome, which may provide innovate ideas for treatment of asthma, and arouse attention about the curative potential of BMMSC-Exo.

Tanshinone IIA prevents acute lung injury by regulating macrophage polarization.

OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION: This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.

[Spatial Distribution and Eco-stoichiometric Characteristics of Soil Nutrient Elements Under Different Vegetation Types in the Yellow River Delta Wetland].

To clarify the distribution characteristics and the ecological stoichiometric characteristics of nutrient elements in soils under different vegetation types, four typical natural wetlands, i.e., Phragmites australis wetland, Tamarix chinensis wetland, Suaeda salsa wetland, and Tidal flat wetland, as well as Gossypium spp. fields that were reclaimed from natural wetlands, were selected as study sites in the Yellow River Delta, and comparisons between the agricultural reclamation land and natural wetlands were conducted. The results showed that the soil total organic carbon (TOC) and total nitrogen (TN) contents in the natural wetlands were as follows:P. australis wetland and T. chinensis wetland>S. salsa wetland>Tidal flat, and the contents of TOC and TN were significantly negatively related to electrical conductivity (EC) and pH values (P<0.05). The contents of TOC, TN, and total phosphorus (TP) in Gossypium spp. fields were significantly higher than those in natural wetlands (P<0.05), especially the contents of nitrate nitrogen (NO3--N) in Gossypium spp. fields, which were 9.4-11.4 times that of natural wetlands. However, no significant correlations between TOC, TN, and TP and EC and pH values (P>0.05) were observed in Gossypium spp. fields. The results of correlation analysis showed that the C/N of natural wetlands were mainly controlled by the contents of TN (P<0.05), and the C/N of the Gossypium spp. fields were significantly lower than those of natural wetlands (P<0.05). The soil C/P and N/P of natural wetlands and Gossypium spp. fields in the Yellow River Delta were low, and the variation trends were consistent with those of soil TOC and TN. Comparative analysis revealed, on the whole, that there were significantly different soil nutrient element contents, C/N, C/P, and N/P in Gossypium spp. fields compared to those of natural wetlands (P<0.05). The process of reclamation could significantly change the spatial distribution of nutrient elements in wetlands. Our results should be of importance in revealing the biogeochemical process of soil nutrient elements in coastal wetland and the influence of agricultural reclamation activities on the differentiation of soil nutrient elements.

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy.

PURPOSE: The aim of the present study was to further elucidate the role of JAK2/STAT3-CAV-1-NR2B on painful diabetic neuropathy. METHODS: In vivo, the mechanical withdrawal threshold and thermal withdrawal latency were measured to evaluate neuropathic pain behaviors (n= 8), while western blot (n= 5) and an immunofluorescence double staining experiment (n= 6) were performed to understand the molecular mechanism. In vitro, the individual culture of BV2 mouse microglia cell lines, the co-culture of BV2 mouse microglia cell lines and PC12 rat neuron cell lines, and western blot analysis were performed to understand the molecular mechanism between microglia and neurons. RESULTS: The expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B was upregulated in the dorsal horn of DNP rats throughout the experiment. Through the immunofluorescence double staining experiment, it was found that p-STAT3 was mainly expressed in activated microglia, and this condition can be stably maintained for approximately 2 weeks after the establishment of the DNP model. The intrathecal injection of JAK2 inhibitor AG490 can relieve the abnormal expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B, and relieve pain. The remission of AG490 began on the third day, and it could be stably sustained for 14 days. In vitro high-glucose induced the activation of p-STAT3 in microglia, thereby upregulating the expression of p-CAV-1 and p-NR2B in neurons in the co-culture system. JAK2 inhibitor AG490 can alleviate the abnormal expression of these proteins in the JAK2/STAT3-CAV-1-NR2B signaling pathway in vitro. CONCLUSIONS: Microglial JAK2/STAT3 signaling probably contributes to neuropathic pain by activating the CAV-1-NR2B pathway.

Primary repair for injury of medial collateral ligament during total-knee arthroplasty.

The aim of this study was to determine whether primary repair for intraoperative injury of the medial collateral ligament (MCL) can achieve satisfactory clinical results when compared to the clinical results of patients with no MCL injury. Simultaneously, we sought to determine the differences between 2 methods of primary repair (anchor suture and staple) in terms of their clinical outcomes.In our institute, 3897 total-knee arthroplasties (TKAs) were performed between 2003 and 2014. Sixty-five patients who suffered an MCL injury during the TKA procedure and in whom the injury was repaired with a suture anchor or staple (suture anchor: 36 vs staple: 29) were studied. A matched group of 65 patients without an MCL injury was selected to serve as the control group. Subjective feelings of instability and functional outcomes were assessed using the knee society (KS) score and the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC). Objective stability was evaluated by the measurement of opening angles in extension and at 30° of knee flexion on valgus stress radiographs. The clinical outcomes and stability results were compared between the suture anchor and staple methods.The KS and WOMAC scores in patients who received primary repair of MCL injury during TKA improved from 50.6 ±â€Š13.1 to 87.3 ±â€Š7.3 (P < .001) and 65.9 ±â€Š14.4 to 17.7 ±â€Š6.6 (P < .001), respectively. However, there were no statistically significant differences in the KS (P = .84) and WOMAC (P = .71) scores when comparing the group that received primary repair to the control group. Radiographic stability also showed no differences between the repair and control groups in extension and at 30° of flexion (P = .48 and P = .11, respectively). In the subgroups, there were no significant differences between the suture anchor and staple repair methods in terms of stability and clinical outcomes.Primary repair of an MCL injury during TKA may have clinical outcomes comparable to that in the no MCL injury group. Both staple and suture anchor repair methods could provide excellent clinical and stability outcomes in these types of cases, although a further cohort study is required to validate our results.

Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells.

Early reports suggest that nuclear factor IA (NFIA) is important in the pathogenesis of glioma. Our previous study demonstrated that the long non­coding RNA (lncRNA), RP5­833A20.1, suppressed the expression of NFIA in THP­1 macrophage-derived foam cells. However, the effect and possible mechanism of RP5­833A20.1 on glioma remains to be fully elucidated, and whether the NFIA-dependent pathway is involved in its progression has not been investigated. In the present study, the mechanisms by which RP5­833A20.1 regulates the expression of NFIA in glioma were investigated. The expression levels of RP5­833A20.1 and NFIA were determined in U251 cells and clinical samples using reverse transcription­quantitative polymerase chain reaction (PCR) analysis. The effects of RP5­833A20.1 on cell proliferation, invasion, cell cycle and apoptosis were evaluated using in vitro assays. The potential changes in protein expression were investigated using western blot analysis. The methylation status of the CpG island in the NFIA promoter was determined using bisulfite PCR (BSP) sequencing. It was found that the expression of RP5­833A20.1 was downregulated, whereas the expression of NFIA was upregulated in glioma tissues, compared with corresponding adjacent nontumor tissues from 20 patients with glioma. The overexpression of RP5­833A20.1 inhibited proliferation and cell cycle progression, and induced apoptosis in the U251 cells. The mRNA and protein levels of NFIA were markedly inhibited by overexpression of RP5­833A20.1 in the U251 cells. The overexpression of RP5­833A20.1 increased the expression of microRNA­382­5p in the U251 cells. The BSP assay revealed that the overexpression of RP5­833A20.1 enhanced the methylation level of the NFIA promoter. These results demonstrated that RP5­833A20.1 inhibited tumor cell proliferation, induced apoptosis and inhibited cell­cycle progression by suppressing the expression of NFIA in U251 cells. Collectively, these results indicated RP5­833A20.1 as a novel therapeutic target for glioma.

Propofol Attenuates Lipopolysaccharide-Induced Monocyte Chemoattractant Protein-1 Production Through Enhancing apoM and foxa2 Expression in HepG2 Cells.

Monocyte chemoattractant protein-1 (MCP-1) is a cytokine that mediates the influx of cells to sites of inflammation. Our group recently reported that propofol exerted an anti-inflammatory effect and could inhibit lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines. However, the effect and possible mechanisms of propofol on MCP-1 expression remain unclear. LPS-stimulated HepG2 cells were treated with 50 µM propofol for 0, 6, 12, and 24 h, respectively. The transcript and protein levels were measured by real-time quantitative PCR and Western blot analyses, respectively. We found that propofol markedly decreased both MCP-1 messenger RNA (mRNA) and protein levels in LPS-stimulated HepG2 cells in a time-dependent manner. Expression of apolipoprotein M (apoM) and forkhead box protein A2 (foxa2) was increased by propofol treatment in HepG2 cells. In addition, the inhibitory effect of propofol on MCP-1 expression was significantly abolished by small interfering RNA against apoM and foxa2 in LPS-stimulated HepG2 cells. Propofol attenuates LPS-induced MCP-1 production through enhancing apoM and foxa2 expression in HepG2 cells.

Ox-LDL upregulates CRP expression through the IGF2 pathway in THP-1 macrophages.

C-reactive protein (CRP) is an acute-phase reactant protein that not only plays a predictive role in determining atherogenesis risk but also represents an active participant in atherogenesis onset and progression. Moreover, an increasing number of studies have reported that oxidized low-density lipoprotein (Ox-LDL) plays a significant role in the initiation and progression of atherosclerosis. However, the effect and underlying mechanism of Ox-LDL on CRP expression remains unclear. THP-1 macrophages were treated with 0, 25, 50, or 100 µg/mL of Ox-LDL for 48 h, or 50 µg/mL of Ox-LDL for 0, 12, 24, and 48 h, respectively. Messenger RNA (mRNA) and protein levels were measured by real-time quantitative PCR and Western blot analysis, respectively. We found that Ox-LDL markedly increased insulin-like growth factor 2 (IGF2) and CRP mRNA and protein levels in a dose- and time-dependent manner in THP-1 macrophages. Treatment with Ox-LDL increased CRP protein expression, and this effect was completely abolished by siRNA-mediated silencing of IGF2 in THP-1 macrophages. Moreover, treatment with pcDNA3.1-IGF2 significantly enhanced CRP protein expression in Ox-LDL-stimulated THP-1 macrophages. CRP expression is upregulated by Ox-LDL through the IGF2 pathway in THP-1 macrophages.

ApoM Suppresses TNF-α-Induced Expression of ICAM-1 and VCAM-1 Through Inhibiting the Activity of NF-κB.

To explore the anti-inflammatory effect of apolipoprotein M (apoM) on regulation of tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and further investigate the molecular mechanism of apoM in this process. We found that TNF-α could decrease expression of apoM and inhibitor of NF-κB-α (IκBα) in HepG2 cells. Overexpression of apoM caused a significant decrease of ICAM-1 and VCAM-1 expression, while it caused a significant increase of IκBα expression in HepG2 cells. Furthermore, the treatment with TNF-α could increase ICAM-1 and VCAM-1 expression, decrease IκBα protein expression, and increase nuclear factor-κB (NF-κB) activity, and these effects were markedly enhanced by small interfering RNA (siRNA)-mediated silencing of apoM in HepG2 cells. Our findings demonstrated that apoM suppressed TNF-α-induced expression of ICAM-1 and VCAM-1 through inhibiting the activity of NF-κB.