Acute lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (II/R) injury and contributes to the associated high mortality rate. However, the underlying mechanism is poorly understood and treatments are limited. RNA interference (RNAi) has been demonstrated to provide a promising disease treatment strategy both in vitro and in vivo. Therefore, the present study aimed to test whether blocking the proinflammatory cytokine IL‑6 by RNAi may protect the lungs from remote organ injury following II/R, and to investigate the potential underlying mechanisms. A total of 176 adult healthy male Sprague‑Dawley rats were randomly divided into sham, II/R, negative‑control and IL‑6‑short hairpin (sh)RNA groups. The rats underwent II/R injury with occlusion of the superior mesenteric artery and coeliac artery to induce ischemia for 40 min, and were subsequently reperfused for 0‑48 h. The negative‑control group received a control lentiviral vector containing scrambled or non‑specific sequences, and the IL‑6‑shRNA groups were administered with a vector containing an IL‑6 shRNA sequence to affect RNAi‑mediated knockdown of IL‑6. ALI severity was determined by lung edema (lung wet/dry ratio) and histological analysis (lung injury scores). IL‑6 localization, and mRNA and protein expression levels, were detected by immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. IL‑10 expression induced by IL‑6 knockdown in lung tissues was additionally detected. IL‑6 RNAi was revealed to significantly reduce the expression of IL‑6, which was associated with upregulated IL‑10 expression in lung tissues. Consequently, the severities of ALI and edema induced by II/R were substantially improved. In conclusion, the present study demonstrated that IL‑6 RNAi may protect the lung from ALI induced by II/R, and that this protective role may be associated with upregulation of IL‑10. These findings may contribute to the development of an IL‑6‑RNAi‑based therapeutic strategy for the treatment of II/R‑induced ALI.

Visfatin, an adipocytokine and cytosolic enzyme with nicotinamide phosphoribosyltransferase (Nampt) activity, is involved in the pathogenesis of numerous metabolic disorders. In addition, the nuclear receptor peroxisome proliferator‑activated receptor‑γ (PPAR‑γ) serves important roles in anti‑inflammatory reactions and regulates glucose and lipid metabolism. The aim of the present study was to investigate the effect of interleukin‑6 (IL‑6) on the expression and secretion of visfatin in BeWo cells, and to determine whether the PPAR‑γ pathway is involved in the regulation of visfatin by IL‑6. Therefore, BeWo cells were stimulated with serial concentrations of IL‑6 or pioglitazone, and the expression levels of visfatin and PPAR‑γ were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. The results of the present study demonstrated that IL‑6 downregulated the mRNA levels of visfatin and PPAR‑γ, which were strongly associated. Activation of PPAR‑γ by pioglitazone resulted in significantly increased expression of visfatin, which abrogated the inhibitory effect of IL‑6 on visfatin in BeWo cells. Furthermore, treatment using pioglitazone alone increased the expression and secretion of the visfatin protein, compared with the control or IL‑6 alone group. In summary, the findings of the present study suggested that IL‑6 inhibited the expression of visfatin and PPAR‑γ at the transcriptional level; in addition, activation of PPAR‑γ upregulated visfatin at the mRNA and protein expression levels. Therefore, the PPAR‑γ signaling pathway may be involved in the regulation of visfatin by IL‑6 in BeWo cells. These results may provide novel insight into the roles of visfatin in trophoblastic cells. Furthermore, thiazolidinedione pioglitazone, by upregulating visfatin expression, may promote the energy metabolism of trophoblastic cells, maintain the function of the placenta and improve the outcome of pregnancy.

Interleukin (IL)‑1β is a key promotor in the pathogenesis of temporomandibular joint osteoarthritis. Differentiation of stem cells to cartilage is a crucial repair mechanism of articular cartilage damage, and IL‑1β has been reported to impede the differentiation by upregulating the secretion of IL‑6, an important inflammatory factor. Long non‑coding RNAs (lncRNAs) regulate a number of physiological and pathological processes, but whether lncRNA AK094629 contributes to the IL‑1β mediated induction of inflammation remains unclear. Therefore, the aim of the present study was to investigate the effect of AK094629 on IL‑1β‑induced IL‑6 expression in synovial‑derived mesenchymal stem cells (SMSCs) of the temporomandibular joints. The results of the present study demonstrated that the expression of AK094629 in the synovial tissue of patients with osteoarthritis was positively correlated with IL‑1β. In addition, IL‑1β upregulated the expression of AK094629 in the SMSCs in vitro, and AK094629 knockdown inhibited the IL‑1β mediated upregulation of IL‑6. The present study also demonstrated that AK094629 knockdown downregulated the expression of the mitogen‑activated protein kinase kinase kinase 4 (MAP3K4), which is upregulated by IL‑1β, whereas knockdown of MAP3K4 did not affect the expression of AK094629, but reversed the upregulation of IL‑6 in SMSCs. In conclusion, AK094629 knockdown attenuated the expression of IL‑1β‑regulated IL‑6 in the SMSCs of the temporomandibular joint by inhibiting MAP3K4. Therefore, AK094629 may be a potential novel therapeutic target for the treatment of temporomandibular joint osteoarthritis.

To investigate the effects of inflammatory factor interleukin (IL)‑6 on the expression of endothelial lipase (EL) and its potential signaling pathways in atherosclerosis, a primary culture of human umbilical vein endothelial cells (HUVECs) was established and treated as follows: i) Control group without any treatment; ii) recombinant human (rh)IL‑6 treatment (10 ng/ml) for 0, 4, 8, 12 and 24 h; iii) p38 mitogen‑activated protein kinases (MAPKs) inhibitor (SB203580, 10 µmol/l) pretreatment for 1 h prior to rhIL‑6 (10 ng/ml) treatment; iv) nuclear factor (NF)‑κB activation inhibitor (pyrrolidine dithiocarbamate, 10 mmol/l) pretreatment for 1 h prior to rhIL‑6 (10 ng/ml) treatment. EL levels were detected by immunocytochemical staining and western blot analysis. Proliferation of HUVECs was detected by immunostaining of proliferating cell nuclear antigen (PCNA) and an MTT assay. p38 MAPK and NF‑κB p65 levels were detected by western blotting. The results showed that rhIL‑6 treatment increased EL expression and proliferation of HUVECs. NF‑κB p65 and MAPK p38 protein levels also increased in a time‑dependent manner in HUVECs after rhIL‑6 treatment. NF‑κB inhibitor and MAPK p38 inhibitor prevented the effects of rhIL‑6 on EL expression. In conclusion, inflammatory factor IL‑6 may participate in the pathogenesis of atherosclerosis by increasing EL expression and the proliferation of endothelial cells via the p38 MAPK and NF-κB signaling pathways.

Total resection of adamantinomatous craniopharyngioma (ACP) is complex and often leads to postoperative recurrence. This is due to the tendency of the tumor to invade the surrounding brain tissue and the generation of a local inflammatory state between the tumor cells and parenchyma. While there is evidence to suggest that interleukin‑6 (IL‑6) induces craniopharyngioma (CP)‑associated inflammation, particularly in ACP, the role of IL‑6 in the progression of ACP remains unclear. The results of the present study demonstrated that CP inflammation was associated with pathological classification, extent of surgery, degree of calcification and postoperative hypothalamic status scale. Cytokine antibody arrays were conducted to measure the expression of IL‑6 and other inflammatory factors in tumor tissues in response to various levels of inflammatory exposure. IL‑6, IL‑6 receptor (IL‑6R) and glycoprotein 130 expression was detected by immunohistochemistry. In addition, an ELISA was performed to quantify the levels of soluble IL‑6R (sIL‑6R) in the cystic fluid and supernatants of ACP cells and tumor‑associated fibroblasts. These measurements demonstrated that ACP cells produce IL‑6 and its associated proteins. In addition, the results revealed that while the viability of ACP cells was not affected, the migration of ACP cells was promoted by IL‑6 treatment in a concentration‑dependent manner. Conversely, treatment with an IL‑6‑blocking monoclonal antibody significantly decreased the migration of ACP cells. In addition, IL‑6 treatment increased the expression of vimentin and decreased the expression of E‑cadherin in a dose‑dependent manner. The findings of the present study demonstrate that IL‑6 may promote migration in vitro via the classic‑ and trans‑signaling pathways by inducing epithelial‑mesenchymal transition in ACP cell cultures.

Obesity is a confirmed risk factor for hyperlipidemia, type‑II diabetes, hypertension, and cardiovascular disease. MicroRNAs (miRs) have emerged as an important field of study within energy metabolism and obesity. A previous study demonstrated miR‑1275 to be markedly down‑regulated during maturation of human preadipocytes. It has been reported that miR‑1275 dysregulates expression in several types of cancer and infections. Little is currently known about the regulation of miR‑1275 transcription. The aim of the current study was to explore the mechanism underlying the expression of miR‑1275 in mature human adipocytes. After differentiation, human adipocytes were incubated with tumor necrosis factor (TNF)‑α and interleukin‑6. The results of reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑1275 can be down‑regulated by TNF‑α and IL‑6, in human mature adipocytes. Bioinformatic analysis was used to predict nuclear factor (NF)‑κB binding sites of miR‑1275's promoter region. Luciferase assay and rescue experiments were performed in HEK293T cells. NF‑κB was involved in regulating miR‑1275 transcription by binding to its promoter. In response to TNF‑α, NF‑κB was bound to the promoter of miR‑1275 and inhibited its transcription. These results indicated that inflammatory factors could regulate miR‑1275 transcription through NF‑κB and influencing miR‑1275 effects on obesity.

Cerulein‑induced pancreatitis resembles human acute pancreatitis in terms of pathological events, such as enzymatic activation and inflammatory cell infiltration in the pancreas. Cerulein is a cholecystokinin analog that increases levels of reactive oxygen species (ROS) and interleukin‑6 (IL‑6) expression level in pancreatic acinar cells. Serum levels of resistin, which is secreted from adipocytes, are reportedly higher in patients with acute pancreatitis than in healthy individuals. Previously, it was shown that the adipokine resistin can aggravate the cerulein‑induced increase in ROS levels and IL‑6 expression level in pancreatic acinar cells. Peroxisome proliferator‑activated receptor‑gamma (PPAR‑γ) is a key regulator of the transcription and expression of antioxidant enzymes, including heme oxygenase 1 (HO‑1) and catalase. α‑lipoic acid, a naturally occurring dithiol antioxidant, can prevent cerulein‑induced pancreatic damage in rats. In the present study, it was aimed to investigate whether α‑lipoic acid can attenuate the cerulein/resistin‑induced increase in IL‑6 expression and ROS levels via PPAR‑γ activation in pancreatic acinar AR42J cells. The anti‑inflammatory mechanism of α‑lipoic acid was determined using reverse transcription‑quantitative PCR, western blot analysis, enzyme‑linked immunosorbent assay, immunofluorescence staining and fluorometry. Treatment with cerulein and resistin increased ROS levels and IL‑6 expression level, which were inhibited by α‑lipoic acid in pancreatic acinar cells. α‑lipoic acid increased the nuclear translocation and expression level of PPAR‑γ and the expression levels of its target genes: HO‑1 and catalase. The PPAR‑γ antagonist GW9662 and HO‑1 inhibitor zinc protoporphyrin reversed the inhibitory effect of α‑lipoic acid on cerulein/resistin‑induced increase in ROS and IL‑6 levels. In conclusion, α‑lipoic acid inhibits the cerulein/resistin‑induced increase in ROS production and IL‑6 expression levels by activating PPAR‑γ and inducing the expression of HO‑1 and catalase in pancreatic acinar cells.

Several circular RNAs (circRNAs) may have role important roles in biological processes, however, there is limited knowledge of circRNAs and their potential functions in RAW264.7 macrophages. The present study aimed to examine the expression of circRNAs and explore their effects on interleukin‑6 (IL‑6) expression induced by calcitonin gene‑related peptide (CGRP) in RAW264.7 macrophages. To identify circRNAs, the circRNA expression was measured in macrophages with or without CGRP stimulation. The interaction between circRNAs and microRNAs (miRs) were then identified using bioinformatic software and networks. In the current study, it was demonstrated that CGRP increased the expression of IL‑6 mRNA in a dose‑ and time‑dependent manner. Furthermore, mmu_circRNA_007893 was significantly increased in the CGRP‑stimulated macrophages. Silencing of mmu_circRNA_007893, IL‑6 mRNA expression was significantly decreased, whereas mmu‑miR‑485‑5p expression was markedly increased. Furthermore, when overexpression of mmu‑miR‑485‑5p, IL‑6 mRNA was markedly decreased. The results demonstrated that CGRP‑induced IL‑6 mRNA expression was mediated by mmu_circRNA_007893, and mmu_circRNA_007893 functioned as an endogenous mmu‑miR‑485‑5p sponge as part of induction of IL‑6 mRNA expression.

Resistance to epidermal growth factor receptor (EGFR) inhibitors is of primary concern in the treatment of non‑small‑cell lung cancer (NSCLC) with EGFR mutations. To investigate the effects of matrine on H1975 cells and to examine a novel, potential treatment option for NSCLC, the present study measured cell viability, apoptotic rate, interleukin 6 (IL‑6) expression and activation of the janus kinase (JAK) 1/signal transducer and activator of transcription (STAT)3 signaling pathway in cells treated with or without matrine, in the presence or absence of afatinib. The results demonstrated that matrine treatment inhibited cell growth, decreased B‑cell lymphoma 2 (Bcl‑2) expression and induced apoptosis. Matrine treatment additionally decreased the mRNA and protein levels of IL‑6 and inhibited activation of the JAK1/STAT3 signaling pathway in H1975 cells in a dose‑dependent manner. H1975 cells treated with IL‑6 small interfering RNA exhibited a decrease in Bcl‑2 expression levels and cell viability. Treatment with a combination of matrine and afatinib demonstrated increased inhibitory effects on the growth rate of H1975 cells. The findings of the present study suggested that matrine treatment decreases IL‑6 expression, inhibits activation of the JAK1/STAT3 signaling pathway, reduces the expression levels of Bcl‑2 and inhibits cell growth. Furthermore, matrine treatment was demonstrated to increase the inhibitory effects of afatinib on H1975 cells with the T790M EGFR mutation.

Acute pancreatitis is a severe inflammatory disease of the pancreas. In experimental acute pancreatitis, cerulein induces the expression of interleukin‑6 (IL‑6) by activating Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 in pancreatic acinar cells. Ligands of peroxisome proliferator activated receptor‑γ (PPAR‑γ) and suppressor of cytokine signaling (SOCS) 3 inhibit IL‑6 expression by suppressing JAK2/STAT3 in cerulein‑stimulated pancreatic acinar AR42J cells. Lutein, an oxygenated carotenoid, upregulates and activates PPAR‑γ to regulate inflammation in a renal injury model. The present study aimed to determine whether lutein activated PPAR‑γ and induced SOCS3 expression in unstimulated AR42J cells, and whether lutein inhibited activation of JAK2/STAT3 and IL‑6 expression via activation of PPAR‑γ and SOCS3 expression in cerulein‑stimulated AR42J cells. The anti‑inflammatory mechanism of lutein was determined using reverse transcription‑quantitative PCR, western blot analysis and enzyme‑linked immunosorbent assay in AR42J cells stimulated with or without cerulein. In another experiment, cells were treated with lutein and the PPAR‑γ antagonist GW9662 or the PPAR‑γ agonist troglitazone prior to cerulein stimulation to determine the involvement of PPAR‑γ activation. The results indicated that lutein increased PPAR‑γ and SOCS3 levels in unstimulated cells. Cerulein increased phospho‑specific forms of JAK2 and STAT3, and mRNA and protein expression of IL‑6, but decreased SOCS3 levels in AR42J cells. Cerulein‑induced alterations were suppressed by lutein or troglitazone. GW9662 alleviated the inhibitory effect of lutein on JAK2/STAT3 activation and IL‑6 expression in cerulein‑stimulated cells. In conclusion, lutein inhibited the activation of JAK2/STAT3 and reduced IL‑6 levels via PPAR‑γ‑mediated SOCS3 expression in pancreatic acinar cells stimulated with cerulein.

A limited number of studies have revealed that adding kidneys to liver perfusion may maintain an improved physiological balance; however, the underlying mechanism remains to be elucidated. The preset study confirmed the protective role of this new model and investigated the underlying mechanisms. Methods: A total of 12 rats were randomly assigned into two groups (n=6 for each group): The kidney‑liver perfusion (KL) group and liver perfusion (LP) group. Perfusate samples were collected during the perfusion process for the analysis of pH, K+ and liver function. Liver tissues were obtained for the evaluation of adenosine triphosphate (ATP), terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling and immunohistochemistry of Ki67. Cell cycle inhibitors, apoptosis‑associated genes and signal transducer and activator of transcription 3 (Stat3) were analyzed using quantitative polymerase chain reaction and western blot analysis. Results: Overall pH and K+ values of the KL group were significantly different from the LP group and more stable; aspartate aminotransferase, alanine transaminase and lactate dehydrogenase levels increased progressively over time in the LP group and were significantly different at different time points compared with pre‑perfusion levels and the KL group, which suggested the KL group was superior to the LP group. In addition, KL reduced portal vein resistance and was associated with lower ATP consumption compared with the LP group. Furthermore, liver proliferation was upregulated with the upregulation of the interleukin 6 (IL‑6)/Stat3 signaling pathway in KL compared with LP. The present study revealed for the first time that KL and hypothermic machine perfusion demonstrated a more proactive repair capability by maintaining liver regeneration via the upregulation of the IL‑6/Stat3 signaling pathway.

Tocotrienols, members of the vitamin E family, have been shown to possess anti-inflammatory properties and display activity against a variety of chronic diseases, such as cancer, cardiovascular and neurological diseases. However, whether tocotrienols contribute to the prevention of inflammatory responses in adipose tissue remains to be elucidated. In this study, we examined the effects of γ-tocotrienol, the most common tocotrienol isomer, on tumor necrosis factor-α (TNF-α)-induced inflammatory responses by measuring the expression of the adipokines, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and adiponectin in 3T3-L1 adipocytes. Exposure to TNF-α (10 ng/ml) for 24 h increased MCP-1 and IL-6 secretion, and decreased adiponectin secretion and peroxisome proliferator-activated receptor-γ (PPARγ) mRNA expression. γ-tocotrienol effectively improved the TNF-α-induced adverse changes in MCP-1, IL-6 and adiponectin secretion, and in MCP-1, IL-6, adiponectin and PPARγ mRNA expression. Furthermore, TNF-α-mediated IκB-α phosphorylation and nuclear factor-κB (NF-κB) activation were significantly suppressed by the γ-tocotrienol treatment. Our results suggest that γ-tocotrienol may improve obesity-related functional abnormalities in adipocytes by attenuating NF-κB activation and the expression of inflammatory adipokines.

Hepatitis B virus (HBV) infection can activate macrophages to accelerate liver disease progression, including inflammation and fibrosis. However, the exact mechanism remains undetermined. The present study assessed the effects of macrophage polarization and the related cytokines on Th‑17 differentiation in HBeAg positive individuals with a HBV infection, and also evaluated the potential association of Th‑17 cell frequency with the severity of liver injury. A cross‑sectional study design was used to collect the clinical parameters, blood samples and liver tissue samples of patients with alanine transaminase £2x upper limit of normal and confirmed hepatitis B who underwent liver puncture in Qishan Hospital between January 2019‑December 2021. Macrophage and Th‑17 cell related factors were assayed using ELISA. The expression and quantification of cell surface antigen and intracellular markers in cells were assessed using flow cytometry. Pathological staining, including hematoxylin and eosin, reticular fiber staining and immunohistochemical staining were used to assess inflammation and fibrosis in the liver tissue. In the peripheral blood of patients with HBV infection, the number of CD14+ macrophages was significantly increased compared with the healthy control, especially in the hepatitis B e antigen (HBeAg) positive group. CD14+ macrophages were predominantly of the M1 type based on the assessment of the phenotype using flow cytometry and cytokine secretion. Furthermore, the percentage of M1 phenotype and related cytokines were positively correlated with Th‑17 differentiation. IL‑17A secreted by Th‑17 was positively correlated with the degree of liver inflammation and fibrosis, as well as with the severity of liver disease, which indicated that the differentiation of Th‑17 may be involved in the progression of liver disease. HBeAg may promote Th‑17 differentiation and IL‑17A production by M1 macrophages to accelerate the pathogenesis of liver inflammation and fibrosis in CHB patients.

The present study aimed to assess the protective effects of tetramethylpyrazine (TMP) on the livers of mice fed a high fat diet. The mice were divided into five groups: Regular diet; high fat diet; simvastatin‑treated; and low and high dose TMP‑treated groups. The results demonstrated that, compared with the control group, serum glucose, total cholesterol (TC) and low‑density lipoprotein cholesterol levels were increased in the model group. Additionally, compared with the model group, simvastatin lowered the TC level, whereas TMP did not. Compared with the control group, the level of malondialdehyde (MDA) in the liver tissue was increased and the level of glutathione peroxidase (GSH‑pX) in the liver tissue was decreased in the model group. Furthermore, compared with the model group, TMP decreased the level of MDA and increased the level of GSH‑Px; however, simvastatin did not have these effects. Immunohistochemistry and western blotting were performed; the results showed that, compared with the control group, the levels of inflammatory factors (tumor necrosis factor‑α and interleukin‑6) in the liver tissue were increased, and the ratio of phosphorylated (p)‑nuclear factor κB (NF‑κB)/NF‑κB was also increased in the model group. The addition of TMP and simvastatin demonstrated that, compared with the model group, the inflammatory factor levels and the ratio of p‑NF‑κB/NF‑κB were decreased. In addition, liver lipid deposition was examined in the model group using hematoxylin and eosin staining and Oil Red O staining, and the results showed that TMP and simvastatin reduced liver lipid deposition. Furthermore, compared with the control group, the reactive oxygen species (ROS) level in the liver tissue was increased. Compared with that in the model group, TMP and simvastatin decreased the ROS level. In conclusion, TMP, similar to simvastatin, exerted a notable hepatoprotective effect on mice fed a high fat diet with non‑alcoholic fatty liver disease, by inhibiting inflammatory factors and the p‑NF‑κB/ROS signaling pathway.

Mesenchymal stem cells (MSCs) are a potential source of adult stem cells for cell-based therapeutics due to their substantial multilineage differentiation capacity and secretory functions. No information is presently available regarding the maintenance of immunosuppressive properties of this cell type with repeated passages. It was therefore the aim of the present study to analyze the biological properties, particularly the immunoregulatory effect, of MSCs from late passages. The differences between young and old MSCs in morphology, cell surface antigen phenotype, proliferation, gene expression and immunomodulatory ability were investigated. The results of the current study demonstrated that with the passage of cells, senescent MSCs displayed a characteristically enlarged and flattened morphology, different gene expression profiles and stronger immunosuppressive activities. Increased interleukin-6 production may be a possible underlying mechanism for this enhanced immunomodulatory ability of MSCs. These findings suggest that aged MSCs may provide a treatment option for patients with graft versus host disease and other diseases associated with dysregulation of the immune system.

(-)-Epigallocatechin-3-gallate (EGCG) is the most widely studied catechin in green tea and has been identified to regulate immune function. The objective of the present study was to explore the possible application of EGCG in the treatment of Parkinson's disease (PD) by examining its effects on the peripheral immune system in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)‑induced PD mouse model. The results demonstrated that EGCG treatment restored the movement behavior of the mice impaired by MPTP, and protected tyrosine hydroxylase‑positive cells in the substantia nigra pars compacta region from MPTP toxicity. Flow cytometric analysis indicated that the ratio of CD3+CD4+ to CD3+CD8+ T lymphocytes in the peripheral blood increased in MPTP‑treated mice following treatment with EGCG, and EGCG reduced expression of inflammatory factors tumor necrosis factor‑α and interleukin‑6 in serum. The present findings indicated that EGCG serves neuroprotective effects in an MPTP‑induced PD mice model and may exert this through modulating peripheral immune response.

Leukemia inhibitory factor (LIF) is a stem cell growth factor that maintains self‑renewal of mouse embryonic stem cells (mESCs). LIF is a cytokine in the interleukin‑6 family and signals via the common receptor subunit gp130 and ligand‑specific LIF receptor. LIF causes heterodimerization of the LIF receptor and gp130, activating the Janus kinase/STAT and MAPK pathways, resulting in changes in protein phosphorylation. The present study profiled LIF‑mediated protein phosphorylation changes in mESCs via proteomic analysis. mESCs treated in the presence or absence of LIF were analyzed via two‑dimensional differential in‑gel electrophoresis and protein and phosphoprotein staining. Protein identification was performed by matrix‑assisted laser desorption/ionization‑time of flight mass spectrophotometry. Increased phosphorylation of 16 proteins and decreased phosphorylation of 34 proteins in response to LIF treatment was detected. Gene Ontology terms enriched in these proteins included 'organonitrogen compound metabolic process', 'regulation of mRNA splicing via spliceosome' and 'nucleotide metabolic process'. The present results revealed that LIF modulated phosphorylation levels of nucleotide metabolism‑associated proteins, thus providing insight into the mechanism underlying LIF action in mESCs.

Long intergenic non-coding RNAs (lincRNAs) are long non‑coding transcripts from the intergenic regions of annotated protein‑coding genes. lincRNA cyclooxygenase 2 (Cox2) is an early‑primary response gene regulated by the NF‑κB signaling pathway in macrophages. It was found that lincRNACox2 was significantly increased in patients with the Mycobacterium tuberculosis (M. tuberculosis) H37Ra strain infection and macrophages, using reverse transcription-quantitative PCR (RT‑qPCR). ELISA, western blotting and RT‑qPCR results indicated that the inflammatory response factors tumor necrosis factor‑α, interferon‑γ, interleukin‑6, Cox2 and inducible nitric oxide synthase were significantly increased in H37Ra infected macrophages. In addition, the inflammatory regulating proteins NF‑κB and Stat3 were significantly increased in H37Ra infected macrophages but decreased in lincRNACox2 knockdown macrophages infected with H37Ra. Moreover, the knockdown of lincRNACox2 increased the apoptotic rate of H37Ra infected macrophages and facilitated the proliferation of H37Ra. Collectively, the present results suggested that lincRNACox2 may be required for the activation of NF‑κB and Stat3, in order to regulate inflammatory responses involved in resistance to M. tuberculosis infection.

The protective effect of taurine against inflammation, apoptosis and oxidative stress in traumatic brain injury was investigated in the present study. Taurine is a non‑proteogenic and essential amino acid in animals. It plays a critical nutritional role in brain cell growth, differentiation, and development. Taurine is involved in regeneration and neuroprotection in the injured nervous system, and is an effective antioxidant against lead‑, cadmium‑, and exercise‑induced oxidative stress. Astrocytes and neuron cells were co‑cultured and cells were treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72 h, and the levels of reactive oxygen species, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factor‑α, interleukin‑6, caspase‑3, p53, B‑cell lymphoma 2 and Bcl‑2‑associated X protein were determined. These inflammatory, apoptotic, and oxidative stress markers were substantially increased in injured cells, and returned to normal levels following taurine supplementation. Thus, taurine supplementation may be effective against oxidative stress, apoptosis, and inflammation in injured brain cells.

Ischemic stroke is a leading cause of mortality and permanent disability, with enormous financial repercussions on health systems worldwide. Ischemic brain injury results from a complex sequence of pathophysiological events that evolve over time. In order to examine the molecular mechanisms underlying middle cerebral artery occlusion (MCAO)-induced ischemic stroke, the GSE35338 affymetrix microarray data was obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) between samples from patients with MCAO-induced ischemic stroke and sham controls at various time points were identified. Furthermore, protein-protein interaction (PPI) networks were constructed by mapping the DEGs into PPI data to identify the pathways that these DEGS are involved in. The results revealed that the expression of 438 DEGs, which are mainly involved in cell death, oxidant reduction, cell cycle and cell-cell signaling, were altered in MCAO samples. The nodes of CXC motif chemokine 10 (CXCL10) and interleukin-6 (IL-6) were large, with degrees of >20. In conclusion, the results suggest that CXCL10 and IL-6 have important roles in the occurrence and progression of MCAO-induced ischemic stroke.