Highly aligned electroactive ultrafine fibers promote the differentiation of mesenchymal stem cells into Schwann-like cells for nerve regeneration.

This study investigates the efficacy of a novel tissue-engineered scaffold for nerve repair and functional reconstruction following injury. Utilizing stable jet electrospinning, we fabricated aligned ultrafine fibers from dopamine and poly(L-lactic acid) (PLLA), further developing a biomimetic, oriented, and electroactive scaffold comprising poly(pyrrole) (PPy), polydopamine (PDA), and PLLA through dual in situ polymerizations. The scaffold demonstrated enhanced cell adhesion and reactive oxygen species (ROS) scavenging capabilities and promoted the differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells, essential for nerve regeneration. In vivo assessments revealed significant peripheral nerve regeneration in 10 mm sciatic nerve defects in rats, with observations made 12 weeks post-transplantation. This included facilitated myelination and increased muscle density on the injured side, leading to improved motor function recovery. Our results suggest that the aligned PPy/PDA/PLLA fibrous scaffold offers a promising approach for promoting the differentiation of MSCs into Schwann-like cells conducive to nerve regeneration and represents a significant advancement in nerve repair technologies. This study provides a foundational basis for future research into tissue-engineered solutions for nerve damage, potentially impacting clinical strategies for nerve reconstruction.

[Corrigendum] Macrophage­secreted IL­8 induces epithelial­mesen-chymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that a possible error had been identified in the selection of images in Figs. 1 and/or 7. After having consulted their original data, the authors realized that an erroneous image appeared on p. 593, in Fig. 7F [the 'Hep­G2 / IL­8 (5 ng/ml)' data panel], where part of this figure panel was overlapping with an image on p. 589 in Fig. 1C (the 'Hep­G2 Co­cultured' data panel). After a thorough review and verification of the data by all the authors, they have confirmed that the original data presented in the paper were accurate, and the error was solely due to the selection of an incorrect image during figure arrangement. The authors confirm that this mistake in image selection did not affect the overall conclusions reported in the article. A corrected version of Fig. 7, including the correct data for the 'Hep­G2 / IL­8 (5 ng/ml)' panel in Fig. 7F, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for granting them the opportunity to publish this Corrigendum. All the authors agree to the publication of this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 587­596, 2015; DOI: 10.3892/ijo.2014.2761].

Analysis of Protein Degradation in Ferroptosis.

The ubiquitin-proteasome system (UPS) is a highly conserved cellular mechanism that degrades and recycles proteins in eukaryotic cells. It involves the tagging of specific target proteins with ubiquitin, a small regulatory protein, which marks them for degradation by the proteasome, a large protein complex that acts as a molecular shredder. Dysfunction of the UPS has been implicated in a wide range of diseases, including cancer, neurodegenerative disorders, and viral infections. Therefore, targeting the UPS has become an attractive therapeutic strategy for many diseases. Ferroptosis is an iron-dependent cell death process that is regulated by multiple levels, including protein degradation. In this chapter, we introduce the detection of UPS-mediated protein degradation in ferroptosis using several techniques such as western blotting, co-immunoprecipitation, in vitro ubiquitination assay, and proteasome assay.

Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO.

BACKGROUND: Bladder cancer (BLCA) is a malignancy that frequently metastasizes and leads to poor patient prognosis. It is essential to understand the molecular mechanisms underlying the progression and metastasis of BLCA and identify potential biomarkers. METHODS: The expression of peptidase inhibitor 16 (PI16) was analysed using quantitative PCR, immunoblotting and immunohistochemistry assays. The functional roles of PI16 were evaluated using wound healing, transwell, and human umbilical vein endothelial cell tube formation assays, as well as in vivo tumour models. The effects of PI16 on nuclear factor κB (NF-κB) signalling activation were examined using luciferase reporter gene systems, immunoblotting and immunofluorescence assays. Co-immunoprecipitation was used to investigate the interaction of PI16 with annexin-A1 (ANXA1) and NEMO. RESULTS: PI16 expression was downregulated in bladder cancer tissues, and lower PI16 levels correlated with disease progression and poor survival in patients with BLCA. Overexpressing PI16 inhibited BLCA cell growth, motility, invasion and angiogenesis in vitro and in vivo, while silencing PI16 had the opposite effects. Mechanistically, PI16 inhibited the activation of the NF-κB pathway by interacting with ANXA1, which inhibited K63 and M1 ubiquitination of NEMO. CONCLUSIONS: These results indicate that PI16 functions as a tumour suppressor in BLCA by inhibiting tumour growth and metastasis. Additionally, PI16 may serve as a potential biomarker for metastatic BLCA.

Dynamic Double Cross-Linked Self-Healing Polysaccharide Hydrogel Wound Dressing Based on Schiff Base and Thiol-Alkynone Reactions.

In this study, a hydrogel composite wound dressing with antibacterial and self-healing ability was prepared using cysteine-modified carboxymethyl chitosan, sodium oxidized alginate, and but-3-yn-2-one base on Schiff base and thiol-alkynone double cross-links. The structure and properties of the hydrogel were characterized by scanning electron microscope, Fourier-transform infrared, and rheological test, followed by antibacterial and in vivo biocompatibility tests. The results showed that the hydrogel exhibited good self-healing, mechanical properties, good antibacterial effect, and in vivo biocompatibility, and can inhibit inflammation and promote skin tissue regeneration in mice. This novel self-healing hydrogel dressing has a broad application prospect in skin tissue engineering.

Extracellular vesicles-transferred SBSN drives glioma aggressiveness by activating NF-κB via ANXA1-dependent ubiquitination of NEMO.

Glioma is the most common malignant primary brain tumor with aggressiveness and poor prognosis. Although extracellular vesicles (EVs)-based cell-to-cell communication mediates glioma progression, the key molecular mediators of this process are still not fully understood. Herein, we elucidated an EVs-mediated transfer of suprabasin (SBSN), leading to the aggressiveness and progression of glioma. High levels of SBSN were positively correlated with clinical grade, predicting poor clinical prognosis of patients. Upregulation of SBSN promoted, while silencing of SBSN suppressed tumorigenesis and aggressiveness of glioma cells in vivo. EVs-mediated transfer of SBSN resulted in an increase in SBSN levels, which promoted the aggressiveness of glioma cells by enhancing migration, invasion, and angiogenesis of recipient glioma cells. Mechanistically, SBSN activated NF-κB signaling by interacting with annexin A1, which further induced Lys63-linked and Met1-linear polyubiquitination of NF-κB essential modulator (NEMO). In conclusion, the communication of SBSN-containing EVs within glioma cells drives the formation and development of tumors by activating NF-κB pathway, which may provide potential therapeutic target for clinical intervention in glioma.

SBSN drives bladder cancer metastasis via EGFR/SRC/STAT3 signalling.

BACKGROUND: Patients with metastatic bladder cancer have very poor prognosis and predictive biomarkers are urgently needed for early clinical detection and intervention. In this study, we evaluate the effect and mechanism of Suprabasin (SBSN) on bladder cancer metastasis. METHODS: A tissue array was used to detect SBSN expression by immunohistochemistry. A tumour-bearing mouse model was used for metastasis evaluation in vivo. Transwell and wound-healing assays were used for in vitro evaluation of migration and invasion. Comprehensive molecular screening was achieved by western blotting, immunofluorescence, luciferase reporter assay, and ELISA. RESULTS: SBSN was found markedly overexpressed in bladder cancer, and indicated poor prognosis of patients. SBSN promoted invasion and metastasis of bladder cancer cells both in vivo and in vitro. The secreted SBSN exhibited identical biological function and regulation in bladder cancer metastasis, and the interaction of secreted SBSN and EGFR could play an essential role in activating the signalling in which SBSN enhanced the phosphorylation of EGFR and SRC kinase, followed with phosphorylation and nuclear location of STAT3. CONCLUSIONS: Our findings highlight that SBSN, and secreted SBSN, promote bladder cancer metastasis through activation of EGFR/SRC/STAT3 pathway and identify SBSN as a potential diagnostic and therapeutic target for bladder cancer.

Effectiveness of benzbromarone versus febuxostat in gouty patients: a retrospective study.

OBJECTIVES: Benzbromarone and febuxostat use different mechanisms to reduce serum urate. However, the effectiveness of benzbromarone versus febuxostat in reducing serum urate in gouty patients classified with different types of hyperuricaemia remains unclear. METHOD: In this retrospective study from January 1, 2018, to September 30, 2020, subjects were identified if they were newly treated with benzbromarone 25 mg daily or febuxostat 20 mg daily. The subjects were classified into four types according to their 24-h urinary uric acid and fractional excretion of uric acid. The baseline data and follow-up information after 28 ± 3 days of treatment were collected. RESULTS: Seventy-three subjects with gout were finally enrolled. Among them, 50 were treated with benzbromarone. The percent changes in serum urate from the baseline were - 33.71 ± 13.59% and - 29.45 ± 10.62% in the benzbromarone and febuxostat group, respectively, without a significant difference between the groups (P = 0.188). No differences were found between the groups in subjects classified as the renal underexcretion type, combined type, or "normal" type. In patients with eGFR ≥ 70 mL/min/1.73 m2, the rate of serum urate lowering was higher in those treated with benzbromarone than in those treated with febuxostat. Febuxostat treatment significantly lowered serum creatinine from the baseline (P = 0.001). CONCLUSIONS: Benzbromarone 25 mg daily and febuxostat 20 mg daily may have comparable effectiveness in lowering the serum urate among different types of hyperuricaemia. Benzbromarone was more effective than febuxostat in lowering serum urate in subjects with eGFR ≥ 70 mL/min/1.73 m2, while febuxostat had a renal protective effect. Key Points • Benzbromarone 25 mg daily and febuxostat 20 mg daily may have comparable effectiveness in lowering the serum urate in patients with different types of hyperuricaemia. • Benzbromarone 25 mg daily was more effective than febuxostat 20 mg daily in lowering serum urate in subjects with eGFR ≥ 70 mL/min/1.73 m2. • Febuxostat had a renal protective effect after about 1 month treatment.

N-Acetyl-Cysteine-Loaded Biomimetic Nanofibrous Scaffold for Osteogenesis of Induced-Pluripotent-Stem-Cell-Derived Mesenchymal Stem Cells and Bone Regeneration.

To regenerate bone tissues, we investigated the osteogenic differentiation of induced-pluripotent-stem-cell-derived mesenchymal stem cells (iPSC-MSCs) and bone regeneration capacities using N-acetyl cysteine (NAC)-loaded biomimetic nanofibers of hydroxyapatite/silk fibroin (HAp/SF). The addition of HAp and NAC decreased the diameters of the electrospun fibers and enhanced the mechanical properties of the silk scaffold. The release kinetic curve indicated that NAC was released from NAC/HAp/SF nanofibers in a biphasic pattern, with an initial burst release stage and a later sustained release stage. This pattern of release of NAC encapsulated on the NAC/HAp/SF scaffolds prolonged the release of high concentrations of NAC, thereby largely affecting the osteogenic differentiation of iPSC-MSCs and bone regeneration. Thus, a new silk electrospun scaffold was developed. HAp was used as a separate nanocarrier for recharging the NAC concentration, which demonstrated the promising potential for the use of NAC/HAp/SF for bone tissue engineering.

Collagen and chondroitin sulfate functionalized bioinspired fibers for tendon tissue engineering application.

Functional tendon tissue engineering depends on harnessing the biochemical and biophysical cues of the native tendon extracellular matrix. In this study, we fabricated highly-aligned poly(L-lactic acid) (PLLA) fibers with surfaces decorated by two of the crucial tendon ECM components, type 1 collagen (COL1) and chondroitin sulfate (CS), through a coaxial stable jet electrospinning approach. Effects of the biomimetic COL1-CS (shell)/PLLA (core) fibers on the tenogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro were investigated. Higher rates of cell spreading and proliferation are observed on the aligned COL1-CS/PLLA fibers compared to that on the plain PLLA fibers. Expression of the tendon-associated genes scleraxis (SCX) and COL1 as well as protein tenomodulin (TNMD) are significantly increased. Introduction of mechanical stimulation gives rise to synergistic effect on tenogenic differentiation of hMSCs. Higher expression of TGF-ß2, TGFßR-II, and Smad3 by the cells on the COL1-CS/PLLA fiber substrates are observed, which indicates that COL1-CS/PLLA ultrafine fibers dictate the hMSC tenogenic differentiation through activating the TGF-ß signaling pathway. Animal study in rat Achilles tendon repair model corroborated the promoting role of COL1-CS/PLLA in regenerating a tendon-like tissue. Thus, our highly aligned biomimicking fibers may serve as an efficient scaffolding system for functional tendon regeneration.

NCAPG confers trastuzumab resistance via activating SRC/STAT3 signaling pathway in HER2-positive breast cancer.

HER2+ breast cancer (BC) is characterized by rapid growth, early recurrence, early metastasis, and chemoresistance. Trastuzumab is the most effective treatment for HER2+ BC and effectively reduces the risk of recurrence and death of patients. Resistance to trastuzumab results in cancer recurrence and metastasis, leading to poor prognosis of HER2+ BC. In the present study, we found that non-structural maintenance of chromosome condensin 1 complex subunit G (NCAPG) expression was highly upregulated in trastuzumab-resistant HER2+ BC. Ectopic NCAPG was positively correlated with tumor relapse and shorter survival in HER2+ BC patients. Moreover, overexpression of NCAPG promoted, while silencing of NCAPG reduced, the proliferative and anti-apoptotic capacity of HER2+ BC cells both in vitro and in vivo, indicating NCAPG reduces the sensitivity of HER2+ BC cells to trastuzumab and may confer trastuzumab resistance. Furthermore, our results suggest that NCAPG triggers a series of biological cascades by phosphorylating SRC and enhancing nuclear localization and activation of STAT3. To summarize, our study explores a crucial role for NCAPG in trastuzumab resistance and its underlying mechanisms in HER2+ BC, and suggests that NCAPG could be both a potential prognostic marker as well as a therapeutic target to effectively overcome trastuzumab resistance.

Potential risk of hyperuricemia: leading cardiomyocyte hypertrophy by inducing autophagy.

BACKGROUND: Clinical studies have shown that hyperuricemia is associated with many cardiovascular diseases; however, the mechanisms involved remain unclear. In this study, we investigated the effect of uric acid on cardiomyocytes and the underlying mechanism. METHODS AND RESULTS: H9c2 cardiomyocytes were treated with various concentrations of uric acid. 3-Methyladenine (3-MA) or Compound C was added before treatment with uric acid. The expression of myocardial hypertrophy-related genes was measured using polymerase chain reaction (PCR). The cell surface area was calculated using ImageJ Software. Western blotting was used to measure the protein levels. Uric acid increased the gene expression of Nppa, Nppb, and Myh5, which are involved in myocardial hypertrophy, and the relative cell surface area of cardiomyocytes in a dose-dependent manner. Consistently, the ratio of LC3II/I, which is a biomarker of autophagy, increased dose-dependently, whereas the protein level of p62, a protein that is degraded by autophagy, decreased. 3-MA, an autophagy inhibitor, rescued uric acid-induced myocardial hypertrophy. Treatment with uric acid increased the level of phosphorylated adenosine monophosphate kinase (AMPK), as well as its downstream effector unc-51-like kinase (ULK1). Pharmacological inhibition of AMPK by Compound C attenuated the uric acid-induced activation of autophagy and myocardial hypertrophy. CONCLUSIONS: Uric acid induces myocardial hypertrophy by activating autophagy via the AMPK-ULK1 signaling pathway. Decreasing the serum uric acid level may therefore be clinically beneficial in alleviating cardiac hypertrophy.

Hepatic HuR modulates lipid homeostasis in response to high-fat diet.

Lipid transport and ATP synthesis are critical for the progression of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) forms complexes with NAFLD-relevant transcripts. It associates with intron 24 of Apob pre-mRNA, with the 3'UTR of Uqcrb, and with the 5'UTR of Ndufb6 mRNA, thereby regulating the splicing of Apob mRNA and the translation of UQCRB and NDUFB6. Hepatocyte-specific HuR knockout reduces the expression of APOB, UQCRB, and NDUFB6 in mice, reducing liver lipid transport and ATP synthesis, and aggravating high-fat diet (HFD)-induced NAFLD. Adenovirus-mediated re-expression of HuR in hepatocytes rescues the effect of HuR knockout in HFD-induced NAFLD. Our findings highlight a critical role of HuR in regulating lipid transport and ATP synthesis.

HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling.

AIMS: The elevated expression of phospholamban (PLB) has been observed in heart failure and cardiac remodelling, inhibiting the affinity of Ca2+ pump to Ca2+ thereby impairing heart relaxation. However, the mechanisms underlying the regulation of PLB remains to be further studied. The present study aims to test the role of RNA-binding protein HuR in the regulation of PLB and the impact of this regulatory process in cardiac remodelling. METHODS AND RESULTS: A mouse model specifically deleted HuR in cardiomyocytes were used for testing the role of HuR in regulating PLB during isoproterenol (ISO)-induced cardiac remodelling. HuR deficiency did not significantly influence the phenotype and function of mouse heart under static status. However, deletion of HuR in cardiomyocytes mitigated the effect of ISO in inducing PLB expression and reducing ß1-AR expression, in turn aggravating ISO-induced myocardial hypertrophy and cardiac fibrosis. In H9C2 cells, association of HuR with PLB and ß1-AR mRNAs stabilized PLB mRNA and destabilized ß1-AR mRNA, respectively. CONCLUSION: HuR stabilizes PLB mRNA and destabilizes ß1-AR mRNA. The HuR-PLB and HuR-ß1-AR regulatory processes impact on ISO-induced cardiac remodelling.

Genetic polymorphism of SLC31A1 is associated with clinical outcomes of platinum-based chemotherapy in non-small-cell lung cancer patients through modulating microRNA-mediated regulation.

SLC31A1 is the major transporter for platinum drug intake, its expression correlates with drug disposition and response. In 1004 Chinese NSCLC patients with platinum-based chemotherapy, we investigated the association between SLC31A1 polymorphisms and clinical outcomes. Heterozygotes of rs10759637 at 3'UTR was associated with severe thrombocytopenia (odds ratio [OR]: 2.69; P = 0.012) and shorter overall survival (hazard ratio [HR]: 1.24; P = 0.005). Variant homozygote of rs2233914 was correlated with longer overall survival (hazard ratio [HR]: 0.73; P = 0.008). Haplotype and diplotype of these linked SNPs were associated with hematologic toxicities. In stratification analyses, rs10759637 and rs2233914 consistently correlated with overall survival in specific subgroups such as men, smoker, patients older than 58 years, or with ECOG PS 0-1, or with squamous cell carcinoma. rs10759637 could change the local structure of 3'UTR harboring putative binding sites for hsa-miR-29, whose transfection into 16HBE cells resulted in remarkable suppression of gene expression. The rs10759637 variant significantly correlated with lowered luciferase activity in reporter assays and decreased expression of SLC31A1 transcript in tumorous tissues. The study thereby identified functional polymorphism of SLC31A1 that modulates miRNA-3'UTR interaction and gene expression as potential pharmacogenetic biomarker for clinical outcomes of platinum-based chemotherapy in NSCLC patients.

Value of three-dimensional speckle tracking echocardiography to assess left ventricular function in hyperuricemia patients.

To assess the value of three-dimensional speckle tracking echocardiography (3D STE) in evaluating the left ventricular (LV) function in hyperuricemia patients. We enrolled 15 healthy controls and 40 hyperuricemia patients and collected and analyzed full-volume 3D STE images of the left ventricle in the apical four-chamber heart view. Laboratory tests and 3D STE parameters, including left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, stroke volume (SV), global longitudinal strain (GLS), and global circumferential strain (GCS), were compared between hyperuricemia patients and healthy controls. Hyperuricemia patients exhibited higher body mass index (24.70 ± 2.9 vs. 21.83 ± 2.4 kg/m2, p = 0.001), C-reactive protein (5.82 ± 9.4 vs. 1.12 ± 1.8 g/L, p = 0.012), alanine transaminase (34.26 ± 26.6 vs. 17.60 ± 13.0 U/L, p = 0.011), aspartate transaminase (24.90 ± 11.3 vs. 17.70 ± 4.1 U/L, p = 0.001), blood urea nitrogen (5.11 ± 1.6 vs. 4.18 ± 0.6 mmol/L, p = 0.046), and serum creatinine (90.25 ± 14.6 vs. 77.93 ± 10.8 µmol/L, p = 0.006) levels, as well as a lower estimated glomerular filtration rate (87.87 ± 16.5 vs. 103.64 ± 11.3 mL/min/1.73m2, p = 0.002). The 3D STE parameters reflecting LV function, including SV (54.71 ± 9.6 vs. 61.92 ± 14.4 mL, p = 0.024), GLS (- 20.51 ± 4.0 vs. - 23.20 ± 4.0%, p = 0.019), and GCS (- 31.30 ± 5.0 vs. - 35.65 ± 2.5%, p = 0.000), were significantly decreased in hyperuricemia patients. Furthermore, GCS was significantly correlated with the serum uric acid (sUA) level even after adjustment of confounding variables like age, body mass index, and serum creatinine. 3D STE is a novel technique for recognizing the early decline in LV function, with GLS and GCS serving as reliable indicators, in hyperuricemia patients. Moreover, the degree of decline in LV function may be correlated with the sUA level in hyperuricemia patients.

New urate depositions on dual-energy computed tomography in gouty arthritis during urate-lowering therapy.

Reduction of urate depositions in the joints, on dual-energy computed tomography (DECT), in patients with gout during urate-lowering therapy (ULT) was demonstrated in previous studies. The aim of this study was to further investigate the changes in distribution of urate deposits during ULT. This randomized controlled trial enrolled 46 patients diagnosed with gout from Zhongshan Hospital, China, between October 2013 and June 2014. Epidemiological data, serum uric acid level, and arthritis attacks were recorded at monthly follow-up visits. DECT of bilateral feet and ankles was performed at baseline and after 6 months of ULT. Overall, 163 areas of urate deposition were found in the 46 patients; of these, 133/163 (81.6%) areas were associated with former arthritis attacks. On DECT at 6 months, the number of urate deposits decreased to 126, with 68 areas disappearing and 31 new deposits areas. The mean volume of urate deposits at baseline was 1.3 ± 3.8 cm3, decreasing to 0.6 ± 2.1 cm3 at the end of 6 months (P = 0.01), with 3/46 (6.5%) patients showing complete disappearance of urate deposits. New urate depositions were found in 21/46 (45.7%) patients, while urate depositions in some joints disappeared in some joints in 31/46 (67.4%) patients. High-sensitivity C-reactive protein was significantly lower in patients with new deposits (4.6 ± 9.3 vs. 7.1 ± 7.6 mg/dL; P = 0.01). There is dynamic redistribution of urate depositions in gout patients receiving ULT.

The critical role of IL-6 in the pathogenesis of Takayasu arteritis.

OBJECTIVES: To investigate T cell subsets and immune cytokine profiles in untreated Takayasu arteritis (TAK) patients and the underlying immunopathological mechanism. METHODS: We enrolled 50 untreated TAK patients and 40 age-matched controls (20 healthy controls, 20 untreated SLE patients). Enzyme-linked immunosorbent assays (ELISAs) were used to define cytokine profiles in all patients, and flow cytometry was performed for 9 TAK patients and 12 healthy controls. Hematoxylin and eosin (Handamp;E) staining and immunohistochemistry (IHC) were performed in aortic tissues of 9 TAK and 9 atherosclerosis patients; clinical data were also collected. RESULTS: Circulating CD4(+) T cells were more frequent in TAK patients (p<0.05). Frequencies of Th1, Th2, and Th17 cells were higher, whereas Treg cells were reduced in TAK. Significantly higher levels of IL-6 and lower levels of IFN-γ, IL-4, and IL-17 were detected in TAK patients (p<0.05). By H & E staining, thickened vascular walls with proliferation of collagen fibre were observed in most patients. Inflammatory sites with infiltrating macrophages, lymphocytes, and neutrophils were located in adventitia. IHC revealed T cells (mainly CD4(+) T cells) in vascular lesions. Additionally, IL-6 was positive throughout the vascular wall in most specimens, whereas IFN-γ, IL-12, and IL-17 were detected in inflammatory sites of active patients. IL-6 levels were positively related to ESR, CRP, and Kerr scores (p<0.05). CONCLUSIONS: Significantly increased levels of IL-6 were detected in peripheral blood and aortic tissues of untreated patients. IL-6 might be a sensitive biomarker to assess disease activity and could be critical in the immunopathogenesis of TAK.

Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.

Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.

[Morphology of lymph vessels in human gastric carcinoma tissues and its association with cancer metastasis].

OBJECTIVE: To investigate the morphology of the lymph vessels in human gastric carcinoma tissues and the relationship to cancer metastasis. METHODS: Morphological changes of the lymph vessels and capillaries in 32 cases of gastric carcinoma tissues and adjacent tissue of the tumor. RESULTS: Numerous lymph vessels and capillaries were seen with opened lumen in the adjacent tissues of the tumor, and fasciculated lymph capillaries were most frequent in gastric carcinoma. The maximal lumen area, perimeter and diameter of lymph vessels and capillaries in gastric carcinoma and the adjacent tissues were significantly different between metastatic group and non-metastatic group (P<0.05). CONCLUSIONS: Dilation of lymph vessels and capillaries due to interstitial edema of the adjacent tissues of gastric carcinoma facilitates tumor metastasis, and lymph metastasis of carcinoma cells occurs through mature lymph capillaries in the adjacent tissues.