Nonintubated spontaneous ventilation versus intubated mechanical ventilation anesthesia for video-assisted thoracic surgery in terms of perioperative complications and practitioners' workload assessments: a pilot randomized control study.

BACKGROUND: The use of nonintubated video-assisted thoracoscopic surgery (NI-VATS) has been increasingly reported to yield favourable outcomes. However, this technology has not been routinely used because its advantages and safety have not been fully confirmed. The aim of this study was to assess the safety and feasibility of nonintubated spontaneous ventilation (NI-SV) anesthesia compared to intubated mechanical ventilation (I-MV) anesthesia in VATS by evaluating of perioperative complications and practitioners' workloads. METHODS: Patients who underwent uniportal VATS were randomly assigned at a 1:1 ratio to receive NI-SV or I-MV anesthesia. The primary outcome was the occurrence of intraoperative airway intervention events, including transient MV, conversion to intubation and repositioning of the double-lumen tube. The secondary outcomes included perioperative complications and modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) scores from anesthesiologists and surgeons. RESULTS: Thirty-five patients in each group were enrolled in the intention-to-treat analysis. The incidence of intraoperative airway intervention events was greater in the NI-SV group than in the I-MV group (12 [34.3%] vs. 3 [8.6%]; OR = 0.180; 95% CI = 0.045-0.710; p = 0.009). No significant difference was found in the postoperative pulmonary complications between the groups (p > 0.05). The median of the anesthesiologists' overall NASA-TLX score was 37.5 (29-52) when administering the NI-SV, which was greater than the 25 (19-34.5) when the I-MV was administered (p < 0.001). The surgeons' overall NASA-TLX score was comparable between the two ventilation strategies (28 [21-38.5] vs. 27 [20.5-38.5], p = 0.814). CONCLUSION: The NI-SV anesthesia was feasible for VATS in the selected patients, with a greater incidence of intraoperative airway intervention events than I-MV anesthesia, and with more surgical effort required by anesthesiologists. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055427. https://www.chictr.org.cn/showproj.html?proj=147872 was registered on January 09, 2022.

Development of a prognostic signature of patients with esophagus adenocarcinoma by using immune-related genes.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor prognosis. The immune-related genes (IRGs) are crucial to immunocytes tumor infiltration. This study aimed to construct a IRG-related prediction signature in EAC. METHODS: The related data of EAC patients and IRGs were obtained from the TCGA and ImmPort database, respectively. The cox regression analysis constructed the prediction signature and explored the transcription factors regulatory network through the Cistrome database. TIMER database and CIBERSORT analytical tool were utilized to explore the immunocytes infiltration analysis. RESULTS: The prediction signature with 12 IRGs (ADRM1, CXCL1, SEMG1, CCL26, CCL24, AREG, IL23A, UCN2, FGFR4, IL17RB, TNFRSF11A, and TNFRSF21) was constructed. Overall survival (OS) curves indicate that the survival rate of the high-risk group is significantly shorter than the low-risk group (P = 7.26e-07), and the AUC of 1-, 3- and 5- year survival prediction rates is 0.871, 0.924, and 0.961, respectively. Compared with traditional features, the ROC curve of the risk score in the EAC patients (0.967) is significant than T (0.57), N (0.738), M (0.568), and Stage (0.768). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are accurate by the combined analysis of the risk score, Sex, M stage, and Stage (The AUC of 1- and 3-years are 0.911, and 0.853). CONCLUSION: The 12 prognosis-related IRGs might be promising therapeutic targets for EAC.

Post-Translational Modification of Adiponectin Affects Lipid Accumulation, Proliferation and Migration of Vascular Smooth Muscle Cells.

BACKGROUND/AIMS: Adiponectin (Apn) is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. Previous reports showed that several conserved lysine residues within the N-terminal collagenous domain of Apn are modified by hydroxylation and glycosylation. Here, we investigated the potential roles of post-translational modifications of Apn on the function of human vascular smooth muscle cells (VSMCs). METHODS: Blood samples of 92 coronary artery disease (CAD) patients and 20 healthy volunteers were collected and total and high molecular weight (HMW) Apn concentration and glycosylation were analyzed. RESULTS: The results revealed that total and HMW Apn derived from blood samples of CAD patients with severe stenosis significantly increased, however the glycosylation of HMW Apn significantly decreased. Functional studies of human VSMCs revealed that glycosylated Apn significantly inhibited the oxidized LDL-induced lipid accumulation, proliferation and migration of VSMCs, whereas non-glycosylated Apn had no inhibitory effects. CONCLUSION: Taken together, these data suggest that glycosylation of Apn is critically involved in regulating function against atherosclerosis by inhibiting lipid accumulation and proliferation and migration of VSMCs.

The clinicopathological parameters significance of CD133 and Nestin in epithelial ovarian cancer: a meta-analysis.

This meta-analysis was conducted to evaluate the association of CD133 and Nestin with epithelial ovarian cancer. Databases (PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang) were searched for relevant studies updated in August 2017. CD133 and Nestin expression were estimated by immunohistochemistry. Statistical analysis was performed by RevMan. A total of 18 studies were included in this meta-analysis. High expression of both CD133 and Nestin was associated with late International Federation of Gynecology and Obstetrics stage (p < 0.00001), larger size of residual cancer (p < 0.05). CD133 overexpression was also associated with higher histological grade (p = 0.0006) and lymph node metastases (p < 0.00001). Nestin overexpression was associated with a higher rate of treatment resistance (p = 0.0007). Positive expression of CD133 and Nestin may be associated with aggressive biological behaviors in epithelial ovarian cancer.

SLC39A6: a potential target for diagnosis and therapy of esophageal carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer, and its underlying molecular mechanisms are poorly understood. Recent large-scale genome-wide association studies in Chinese Han populations have identified an ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the expression and biological function of SLC39A6 in ESCC. METHODS: Multiethnic validation of SLC39A6 protein expression was performed in different cohorts of patients from Chinese Han and Kazakh populations in the Xinjiang region by immunohistochemistry. The associations among SLC39A6 expression, clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied. RESULTS: SLC39A6 protein expression increased progressively from normal esophageal epithelium (NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly, SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared with that in NEE. Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II. High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression was an independent prognostic factor for poor OS in ESCC. Experimentally, the suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated proliferation and invasion, and induced an EMT phenotype that included enhanced expression of E-cadherin, loss of vimentin, and morphological changes in ESCC cells in vitro. CONCLUSIONS: Combined, our findings highlight a tumor-promoting role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6 might be a potential therapeutic strategy for blocking ESCC.

Secretion of adipocytes and macrophages under conditions of inflammation and/or insulin resistance and effect of adipocytes on preadipocytes under these conditions.

The purpose of the present study was to examine changes in preadipocytes following the coculture of preadipocytes and adipocytes and the effects on the secretion of adipocytes and macrophages following induction of inflammation and insulin resistance. Mature adipocytes and RAW264.7 macrophages were treated with lipopolysaccharide and insulin to establish models of inflammation and insulin resistance, respectively. The mRNA expression levels of IL-6, MCP-1, and TNF-α in all adipocyte treatment groups were significantly greater compared with the control, and that of adiponectin was less (P<0.05). In the RAW264.7 macrophages, the mRNA expression levels of IL-6 and TNF-α were greater than those in the control group (P<0.05). Moreover, the results of this study confirmed that adipocytes and macrophages increased the secretion of inflammatory factors under conditions of induced inflammation and insulin resistance. In addition, 3T3-L1 adipocytes inhibited the proliferation and differentiation of preadipocytes when cocultured with adipocytes under conditions of inflammation and/or insulin resistance, and the phenotype of preadipocytes did not change.

The microRNAs as prognostic biomarkers for survival in esophageal cancer: a meta-analysis.

OBJECTIVES: We performed this meta-analysis to summarize all the results from available studies, aiming delineating the prognostic role of miRNA in esophageal cancer. DESIGN AND METHODS: We searched the electronic databases PubMed, EMBASE, and ISI Web of Science without time restrictions for the correlative literature to aggregate the survival results. Relevant data were extracted from studies investigating the relationship between miRNAs expression and survival in esophageal cancer patients. Pooled hazard ratios of miR-21 and miR-375 for OS in ESCC were calculated. RESULTS: A total of 25 studies involving 2,258 subjects analyzed the relationship between miRNA and prognosis of EC. In all, thirty-nine miRNAs associated with prognosis were reported in these studies. The pooled HR of higher miR-21 expression compared with lower miR-21 expression in ESCC was 1.84 (95% CI: 1.41-2.40, P < 0.001), which could significantly predict poorer OS in ESCC. Besides, higher miR-375 was also a significant predictor for OS in ESCC, with a pooled HR of 0.55 (95% CI: 0.42-0.72, P < 0.001). CONCLUSIONS: Our results support that miR-21 and miR-375 have a prognostic role in ESCC and may be useful therapeutic targets for the treatment of ESCC and meticulous follow-up for early detection of recurrence.

Prognostic value of tumor­associated CD177+ neutrophils in lung adenocarcinoma.

The aim of the present study was to detect CD177+ neutrophils in tumor tissues and analyze their association with the clinical characteristics and prognosis of patients with lung adenocarcinoma (LUAD). Immunohistochemistry was used to detect CD177+ neutrophils in tumors and adjacent tissues of 16 patients with LUAD who underwent curative surgical resection. A total of 120 patients with LUAD were recruited, and their clinical data were collected; survival follow-up was performed. CD177+ neutrophils in tumor tissues were detected via immunohistochemistry, and the association between CD177+ neutrophils and clinical characteristics was analyzed. The density of CD177+ neutrophils in tumor tissues and adjacent tissues of patients with LUAD was analyzed using t-test, and the association between CD177+ neutrophils and clinical characteristics was analyzed through the Chi-square test. Survival was calculated using the Kaplan-Meier survival rate curve. Finally, the association between these indicators and the survival of LUAD patients was evaluated using Cox regression analysis. CD177+ neutrophil infiltration was significantly higher in LUAD tumor tissues, and the high density of CD177+ neutrophils was associated with the clinical characteristics of TNM stage, tumor differentiation and poor progression-free and overall survival in LUAD. In conclusion, tumor-associated CD177+ neutrophils associated with malignant progression and poor prognosis may be independent and unfavorable prognostic biomarkers for LUAD.

Thoracoscopic treatment of primary spontaneous pneumothorax without a drainage tube in male patients.

OBJECTIVE: To propose a treatment approach for primary spontaneous pneumothorax (PSP) in male patients with a smaller incision and less pain. METHODS: We retrospectively studied 29 patients with PSP who underwent areola-port video-assisted thoracoscopic surgery (VATS) and 21 patients who underwent single-port VATS. The areola-port VATS technique was performed as follows. First, an arc incision was made along the lower edge of the areola, and a 5-mm-diameter thoracoscope was placed. The bullae were completely removed, and the absence of air leaks and other bullae was confirmed. A drainage tube was placed in the chest with negative pressure and then quickly pulled out, and the reserved suture line was knotted. RESULTS: All patients were male, and their mean age was 19.07 ± 2.43 years. The mean intraoperative hemorrhage volume and postoperative pain score were significantly lower in the areola-port than single-port group. The mean operative time and mean postoperative hospital stay were also shorter in the areola-port group, but without statistical significance. The incidence of complications and the 1-year postoperative recurrence rate were 0% in both groups. CONCLUSION: Our method is clinically feasible and inexpensive, has a traceless effect, and is especially suitable for adolescents.

Identification and Validation of Cyclin A2 and Cyclin E2 as Potential Biomarkers in Small Cell Lung Cancer.

INTRODUCTION: Small cell lung cancer (SCLC) is a special type of lung cancer sensitive to radiotherapy and chemotherapy but is prone to drug resistance and recurrence and has a very poor prognosis. This study aimed to explore the potential biomarkers and therapeutic targets for SCLC. METHODS: After batch normalization of GSE40275, GSE1037, and GSE44447 datasets, R was used to screen SCLC's differentially expressed genes (DEGs) and hub genes. We used immunohistochemistry (IHC) to assess the tissue's expression level of the hub gene. The clinical value of the hub gene was further evaluated based on the collected clinical-pathological data. RESULTS: In this study, a total of 230 DEGs (133 upregulated and 97 downregulated) were screened by the R package. The IHC showed that the expression of CCNA2 and CCNE2 in SCLC tissues was significantly higher than that in normal tissues (p < 0.01). Overexpression of CCNA2 was closely associated with the extensive period of NCCN (p = 0.004), tumor position (p = 0.046), and clinical stage (p = 0.002). The high expression levels of CCNE2 were related to high survival in chemotherapy patients (p = 0.019). CONCLUSION: CCNA2 and CCNE2 may serve as potential biomarkers of diagnosis and treatment for SCLC.

Two-rope method for dissecting esophagus in McKeown MIE.

Objective: Minimally invasive McKeown esophagectomy (McKeown MIE) is performed at many hospitals in esophageal cancer(EC) treatment. However, secure and quick methods for dissecting the esophagus and dissecting lymph nodes in this surgery are lacking. This study introduces a simple, secure and feasible esophagus dissecting technique named two-rope method. Two mobile traction ropes are placed around the esophagus and we tow these ropes to free the esophagus, dissect the lymph nodes, and decrease the operative trauma. Materials and Methods: Retrospective analysis was performed on 112 patients who underwent McKeown MIE in our center from January 2019 to September 2021. They were assigned into two groups based on the method of dissecting the esophagus: Group A (two-rope method, 45 cases) and Group B (regular method, 67 cases). Operation time, thoracic operation time, the number of dissected thoracic lymph nodes, and postoperative complications were compared between the two groups after propensity score matching. Results: Using 1:1 nearest neighbor matching, we successfully matched 41 pairs of patients. Operation time, thoracic operation time, and the duration (ac to as) was significantly shorter and the size of the abdominal incision was significantly smaller in the Group A than Group B (p < 0.05). There was no statistically significant difference in the number of dissected thoracic lymph nodes, pulmonary infection, anastomotic leak, recurrent laryngeal (RLN) injury, and chylothorax between the two groups (p > 0.05). Conclusions: Two-rope method to free the esophagus and dissect thoracic lymph nodes in McKeown MIE has significant advantages compared with the regular method. The technique is, therefore suitable for widespread adoption by surgeons.

Corrigendum: DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

[This corrects the article DOI: 10.3389/fonc.2021.629974.].

Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease.

BACKGROUND: Disorders of endocrine substances in epicardial adipose tissue are known causes of coronary artery disease (CAD). Adiponectin is associated with cardiovascular disease. However, expression of adiponectin in epicardial adipose tissue and its function in CAD pathogenesis is unclear. This study investigates adiponectin expression in epicardial adipose tissue in CAD patients. METHODS: Vessels or adipose tissue samples collected from CAD patients and non-CAD controls were examined after immunochemical staining. Adiponectin, cytokines of interleukin-6 (IL-6) and necrosis factor-α (TNF-α) and toll-like receptor 4 (TLR4) expression level in adipose tissue were measured using real-time quantitative RT-PCR. Adiponectin concentrations in peripheral and coronary sinus vein plasma were measured with enzyme-linked immunosorbent assay. Peripheral vein plasma biochemistries were performed with routine laboratory techniques. Monocytes were collected from blood using lymphocyte separation medium. Expression level of cytokines and transcription factor NF-κB were measured to learn the effect of adiponectin on stearic acid-stimulated monocytes. Percentage of TLR4 positive monocytes was analyzed using flow cytometry. RESULTS: Histological examination revealed increased macrophage infiltration into epicardial adipose tissue of CAD patients. Decreased adiponectin displayed by real-time quantitative RT-PCR was associated with enhanced cytokines of IL-6 and TNF-α or TLR4 expression level in epicardial adipose tissue, suggesting decreased circulating adiponectin may be useful as a more sensitive predictor for coronary atherosclerosis than routine laboratory examinations. Adiponectin suppressed secretion of IL-6 and TNF-α in stimulated monocytes and TLR4 was expressed on cell surfaces. CONCLUSIONS: Endocrine disorders in epicardial adipose tissue are strongly linked to CAD, and adiponectin has a protective effect by inhibiting macrophage-mediated inflammation.

MicroRNA-3614 regulates inflammatory response via targeting TRAF6-mediated MAPKs and NF-κB signaling in the epicardial adipose tissue with coronary artery disease.

OBJECTIVE: The inflammatory status of epicardial adipose tissue (EAT) is one of the factors leading to the development of related diseases such as coronary artery disease (CAD). The thickness of CAD EAT increases and is accompanied with increased macrophage infiltration and heightened inflammatory responses. However, microRNAs (miRNAs) regulating the inflammatory responses of macrophages in CAD EAT remain unclear. METHOD: miRNA expression profiles of CAD EATs and non-CAD EATs were determined by miRNA microarrays. Quantitative real-time reverse transcription-polymerase chain reaction, Western blotting, immunohistochemical assay, and fluorescence in-situ hybridization were adopted to detect miR-3614 expression and function in EATs and macrophages. The interaction between miR-3614 and tumor necrosis factor receptor-associated factor 6 (TRAF6) was identified using an online website combined with a dual-luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the expression of inflammatory cytokines. RESULTS: The decreased expression of miR-3614 was identified in CAD EAT. The level of miR-3614 was down-regulated by lipopolysaccharide (LPS) in macrophages, whereas LPS-induced inflammatory injury can be reduced by miR-3614 overexpression. TRAF6 was predicted and verified to be a target of miR-3614. The phosphorylated levels of kinases in the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways were inhibited by miR-3614 overexpression. Importantly, the knockdown of TRAF6 inhibited the LPS-induced inflammatory cytokine expressions in cells. CONCLUSION: A novel negative feedback loop by miR-3614 possibly contribute to the regulation of inflammatory processes via targeting the TRAF6/MAPK/NF-κB pathway in EATs and prevents an overwhelming inflammatory response.

Perioperative safety and short-term efficacy of functional minimally invasive esophagectomy.

BACKGROUND: Standard minimally invasive McKeown three-field esophagectomy (SMIE) results in high perioperative risk and poor postoperative quality of life owing to considerable surgical damage and numerous postoperative complications. We created a modified procedure, functional minimally invasive esophagectomy (FMIE), which preserves the azygos arch, bronchial artery, pulmonary branch of the vagus nerve, and the mediastinal pleura. Our aim was to evaluate the efficacy and safety of FMIE and to determine whether it has limited invasiveness. METHODS: Between 2018 and 2020, FMIE was performed for 48 patients who were compared with 76 SMIE cases; 44 paired cases were matched using propensity score matching. RESULTS: Operation time, extubation time, and postoperative hospital stay were significantly lower in the FMIE group. FMIE was also associated with fewer pulmonary infections. Postoperative drainage volume on postoperative day (POD) 1 and POD 2, and white blood cell counts on POD 2 and POD 4 were also significantly lower in the FMIE group. There was no statistically significant difference in the number of dissected lymph nodes, short-term recurrence, metastasis rates, or survival rate between the two groups. CONCLUSIONS: FMIE is a less invasive procedure and may be a suitable alternative for lower and early middle esophageal carcinoma.

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.

Roles of human epicardial adipose tissue in coronary artery atherosclerosis.

This study examined the adipocytokine-vascular interactions and link between epicardial adipose tissue and coronary artery atherosclerosis. Thirty-four patients undergoing open heart surgery were chosen randomly, and divided into group I (non-coronary artery disease group) and group II (coronary artery disease group). Blood samples were taken through peripheral vein prior to surgery. Plasma levels of a panel of proteins (adiponectin, IL-10, TNF-α) were detected by using ELISA. Epicardial adipose tissue was taken near the proximal tract of the right coronary artery and subcutaneous adipose was taken from the leg before cardiopulmonary bypassing, adiponectin and CD68 + were detected by using RT-PCR and immunohistochemistry. Our results showed that plasma adiponectin level was significantly lower in the group II as compared with group I (P<0.05). There were no differences in plasma concentration (IL-10, TNF-α, tatal-chol, HDL-chol, LDL-chol) between group I and group II. The number of CD68+ cells in epicardial adipose tissue of group II was significantly higher than that in subcutaneous adipose tissue. Adiponectin mRNA expression was 6 fold higher in subcutaneous adipose tissue than in epicardial adipose tissue of group II (P<0.01). Furthermore, the level of adiponectin mRNA in the epicardial adipose tissue in group II was also significantly lower than in group I (P<0.05). We are led to conclude that inflammation that occurs locally in epicardial adipose tissue of CAD contributes to the pathogenesis of coronary artery disease.

Next-Generation Sequencing of Synchronous Multiple Primary Lung Cancers in a Patient with Squamous Cell Carcinoma and Small Cell Lung Cancer.

The incidence of synchronous multiple primary malignancies is low. The presence of different lung tumor types in one patient is rare. Here, we report a rare case of synchronous lung squamous cell cancer and small cell lung cancer in a 60-year-old man. Because of the presence of two different tumor types, the proper treatment must be determined. To identify treatment targets, the genetic features of primary tumor tissues from the lungs were analyzed by next-generation sequencing (NGS). The objective was to analyze the origin and evolution of multiple primary lung cancers. NGS can find the genetic mutation sites of patients to guide treatment and promote the advancement of precision medicine. The effects of standard treatments were evaluated by response evaluation criteria in solid tumors. The results suggest that early treatment of synchronous multiple primary malignancies is a favorable outcome.

Adiponectin promotes preadipocyte differentiation via the PPARγ pathway.

According to the results of a preliminary study, it was hypothesized that the effects of adiponectin (APN) on the improvement of atherosclerosis may be associated with adipocyte differentiation and peroxisome proliferator­activated receptor γ (PPARγ). The present study simulated the inflammatory environment of epicardial adipose tissue by stimulating mature adipocytes with lipopolysaccharide (LPS); subsequently, the differentiation of 3T3­L1 preadipocytes was observed. 3T3­L1 preadipocytes were infected with an adenovirus containing the human adiponectin gene apM1 (Ad­apM1) and were co­cultured with mature adipocytes stimulated with LPS. Differentiation into mature adipocytes was initiated using differentiation medium. After 8 days, an MTT assay was used to examine cell viability and oil red O staining was used to observe preadipocyte differentiation. In addition, the mRNA expression levels of monocyte chemoattractant protein­1 (MCP­1), interleukin (IL)­6, IL­8 and tumor necrosis factor α (TNF­α) were examined by quantitative polymerase chain reaction, and the protein expression levels of PPARγ, CCAAT/enhancer binding protein α (C/EBPα) and preadipocyte factor­1 (Pref­1) were measured by western blotting. The results indicated that APN overexpression significantly increased preadipocyte differentiation and cell viability, inhibited MCP­1, IL­6, IL­8 and TNF­α expression, upregulated PPARγ and C/EBPα expression, and downregulated Pref­1 under LPS stimulation. In addition, inhibition of PPARγ activity by T0070907 markedly attenuated the effects of APN overexpression. Taken together, the present study demonstrated that the effects of APN on the promotion of preadipocyte differentiation under inflammatory conditions may involve the PPARγ signaling pathway, and at least partly depends on upregulation of PPARγ expression.

A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway.

Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is considered a key transcriptional regulator of arsenic­induced apoptosis. Due to a few controversial issues about arsenic­mediated extracellular signal­regulated MAP kinases (ERK) signaling, a meta­analysis was performed. Subgroup analyses demonstrated that high doses (≥2 µmol/l) of arsenic increased the expression of Ras, ERK, ERK1, ERK2, phosphorylated (p)­ERK, p­ERK1, and p­ERK2, while low doses (<2 µmol/l) decreased the expression of Ras, ERK1, p­ERK, and p­ERK2 when compared to control groups. Long term exposure (>24 h) to arsenic led to inhibition of expression of ERK1, p­ERK1, and p­ERK2, whereas short­term exposure (≤24 h) triggered the expression of ERK1, ERK2, p­ERK, p­ERK1, and p­ERK2. Furthermore, normal cells exposed to arsenic exhibited higher production levels of Ras and p­ERK. Conversely, exposure of cancer cells to arsenic showed a lower level of production of Ras and p­ERK as well as higher level of p­ERK1 and p­ERK2 as compared to control group. Short­term exposure of normal cells to high doses of arsenic may promote ERK signaling pathway. In contrast, long­term exposure of cancer cells to low doses of arsenic may inhibit ERK signaling pathway. This study may be helpful in providing a theoretical basis for the diverging result of arsenic adverse effects on one hand and therapeutic mechanisms on the other concerning arsenic­induced apoptosis.