Surgical management of duodenal Crohn's disease.

BACKGROUND: The case of Crohn's disease involving the duodenum is rare, and its surgical management requires a thorough understanding. AIM: To investigate the surgical management of duodenal Crohn's disease. METHODS: We systematically reviewed patients diagnosed with duodenal Crohn's disease who underwent surgery in the Department of Geriatrics Surgery of the Second Xiangya Hospital of Central South University from January 1, 2004, to August 31, 2022. The general information, surgical procedures, prognosis, and other information of these patients were collected and summarized. RESULTS: A total of 16 patients were diagnosed with duodenal Crohn's disease, where 6 cases had primary duodenal Crohn's disease, and 10 had secondary duodenal Crohn's disease. Among patients with primary disease, 5 underwent duodenal bypass and gastrojejunostomy, and 1 received pancreaticoduodenectomy. Among those with a secondary disease, 6 underwent closure of duodenal defect and colectomy, 3 received duodenal lesion exclusion and right hemicolectomy, and 1 underwent duodenal lesion exclusion and double-lumen ileostomy. CONCLUSION: Crohn's disease involving the duodenum is a rare condition. Different surgical management should be applied for patients with Crohn's disease presenting with different clinical manifestations.

circ-PTK2 (hsa_circ_0008305) regulates the pathogenic processes of ovarian cancer via miR-639 and FOXC1 regulatory cascade.

BACKGROUND: Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. METHODS: CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial-mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. RESULTS: CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001). Inhibiting the level of CHD1L significantly decreased cell migration and invasion (P < 0.05), increased the expression of epithelial markers, and decreased the expression of mesenchymal markers. Following inhibition of CHD1L expression, RNA-seq was conducted and 82 circRNAs had significantly upregulated expression, while 247 had significantly downregulated expression. The circRNAs were validated by PCR, and hsa_circ_0008305 (circ-PTK2) was selected and further validated by Sanger sequencing, FISH, and RT-qPCR. Circ-PTK2 expression was significantly higher in the ovarian cancer tissues compared with normal ovary tissues (P < 0.001). By regulating the level of circ-PTK2 with siRNA and an overexpression vector, expression of circ-PTK2 was found to be positively correlated to cell migration and invasion. Overexpression of circ-PTK2 enhanced tumor formation and was correlated to expression of EMT pathway markers. Prediction of the target of circ-PTK2 was validated with dual luciferase assay and identified miR-639 and FOXC1 as the valid target of circ-PTK2 and miR-639, respectively. The RNA level of miR-639 was negatively correlated to cell proliferation and migration, whereas the mRNA level of FOXC1 was positively correlated to those processes. miR-639 mimics reversed the function of circ-PTK2 overexpression; however, interference of FOXC1 mRNA also reversed the function of circ-PTK2. CONCLUSIONS: circ-PTK2 is an important molecule in regulating the pathogenic processes of ovarian cancer via the miR-639 and FOXC1 regulatory cascade.

The C-terminal domain of the type III secretion chaperone HpaB contributes to dissociation of chaperone-effector complex in Xanthomonas campestris pv. campestris.

Many animal and plant pathogenic bacteria employ a type three secretion system (T3SS) to deliver type three effector proteins (T3Es) into host cells. Efficient secretion of many T3Es in the plant pathogen Xanthomonas campestris pv. campestris (Xcc) relies on the global chaperone HpaB. However, how the domain of HpaB itself affects effector translocation/secretion is poorly understood. Here, we used genetic and biochemical approaches to identify a novel domain at the C-terminal end of HpaB (amino acid residues 137-160) that contributes to virulence and hypersensitive response (HR). Both in vitro secretion assay and in planta translocation assay showed that the secretion and translocation of T3E proteins depend on the C-terminal region of HpaB. Deletion of the C-terminal region of HpaB did not affect binding to T3Es, self-association or interaction with T3SS components. However, the deletion of C-terminal region sharply reduced the mounts of free T3Es liberated from the complex of HpaB with the T3Es, a reaction catalyzed in an ATP-dependent manner by the T3SS-associated ATPase HrcN. Our findings demonstrate the C-terminal domain of HpaB contributes to disassembly of chaperone-effector complex and reveal a potential molecular mechanism underpinning the involvement of HpaB in secretion of T3Es in Xcc.

6-Gingerol attenuates ventilator-induced lung injury via anti-inflammation and antioxidative stress by modulating the PPARγ/NF-κBsignalling pathway in rats.

Although mechanical ventilation (MV) is indispensable to life-support therapy in critically ill patients, it may promote or aggravatelunginjury known asventilator-inducedlunginjury(VILI). 6-Gingerol is the principal ingredient of ginger with potential anti-inflammatory and antioxidant properties in various diseases. Nevertheless, the role and mechanism of 6-gingerol in the process of VILI has not been explicitly investigated. In the study, we found that pre-treatment with 6-gingerol significantly improved the histological changes and pulmonary oedema, inhibited neutrophil accumulation and the release of early pro-inflammatory cytokines and MPO, and reduced oxidative stress reactions after high MV. Moreover, 6-gingerol treatment also increased PPARγ expression and decreased NF-κB activation in rats subjected to high MV. Furthermore, GW9662, a specific PPARγ inhibitor, was demonstrated to activatethe NF-κB pathway and cancele the protective role of 6-gingerol in VILI. This indicates that 6-gingerol exerted anti-inflammatory and antioxidative stress effects in VILI by activating PPARγ and inhibiting the NF-κBsignalling pathway.

Validation of the 8th edition of the American Joint Committee on Cancer Pathological Prognostic Staging for young breast cancer patients.

PURPOSE: This study aimed to validate the newly proposed American Joint Committee on Cancer (AJCC) pathological prognostic staging system for young breast cancer patients (aged ≤40 years). RESULTS: We included 12811 women in this study. Overall, 52.8% of patients in the 7th AJCC stages were restaged to the 8th AJCC pathological staging system, including 10.7% upstaged and 42.1% downstaged. The receiver operating characteristics analysis showed that the new staging system had a better role in predicting breast cancer-specific survival (BCSS) compared with 7th edition staging (P<0.001). The results of the multivariate prognostic analysis showed that the hazard ratio of BCSS increased with the 8th AJCC stages, while the 7th anatomic stages had no significant difference in BCSS. CONCLUSIONS: The novel pathological staging system could provide more accurate prognostic stratification for young women with breast cancer because of the high proportion of stage migration. PATIENTS AND METHODS: Data for young breast cancer patients diagnosed between 2010 and 2014 were included from the Surveillance, Epidemiology, and End Results program. Chi-squared test, Kaplan-Meier method, receiver operating characteristics curve, and Cox proportional hazard analysis were applied to statistical analysis.

KIF11 Functions as an Oncogene and Is Associated with Poor Outcomes from Breast Cancer.

PURPOSE: The study aimed to search and identify genes that were differentially expressed in breast cancer, and their roles in cancer growth and progression. MATERIALS AND METHODS: The Gene Expression Omnibus (Oncomine) and The Cancer Genome Atlas databases (https://cancergenome.nih.gov/) were screened for genes that were expressed differentially in breast cancer and were closely related to a poor prognosis. Gene expressions were verified by quantitative real-time polymerase chain reaction, and genes were knocked down by a lentivirus-based system. Cell growth and motility were evaluated and in vivo nude mice were used to confirm the in vitro roles of genes. Markers of epithelial-to-mesenchymal transition and the associations of KIF11 with the classical cancer signaling pathways were detected by Western blot. RESULTS: A series of genes expressed differentially in patients with breast cancer. The prognosis associated with high KIF11 expression was poor, and the expression of KIF11 increased significantly in high stage and malignant tumor cells. Inhibiting KIF11 expression in lentivirus-suppressed cells revealed that KIF11 inhibition significantly reduced cell viability and colony formation, inhibited migration and invasion, but promoted apoptosis. The sizes and weights of KIF11-inhibited tumors in nude mice were significantly lower than in the negative controls. Western blot showed that E-cadherin in breast cancer was significantly upregulated in KIF-inhibited cells and tumor tissues, whereas N-cadherin and vimentin were significantly downregulated. BT549 and MDA231 cells with KIF11 knockdown exhibited decreased ERK, AMPK, AKT, and CREB phosphorylation. CONCLUSION: KIF11 acts as a potential oncogene that regulates the development and progression of breast cancer.

RpfC regulates the expression of the key regulator hrpX of the hrp/T3SS system in Xanthomonas campestris pv. campestris.

BACKGROUND: The Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris recruits the hrp/T3SS system to inject pathogenicity effector proteins into host cells and uses the rpf/DSF cell-cell signaling system to regulate the expression of virulence factors such as extracellular enzymes and polysaccharide. Whether these two systems have any connection is unknown. METHODS: Positive regulator candidates affecting hrpX expression were identified by sacB strategy. The transcriptional expression was determined by qRT-PCR and GUS activity analysis. Transcriptome analysis was performed by RNA deep-sequencing. The hypersensitive response (HR) was determined in the nonhost plant pepper ECW-10R and electrolyte leakage assay. RESULTS: Mutation of the gene encoding the sensor RpfC of the rpf/DSF system significantly reduced the expression of hrpX, the key regulator of the hrp/T3SS system, all of the genes in the hrp cluster and most reported type III effector genes. Mutation of rpfG did not affect the expression of hrpX. The rpfC mutant showed a delayed and weakened HR induction. CONCLUSIONS: RpfC positively regulates the expression of hrpX independent of RpfG, showing a complex regulatory network linking the rpf/DSF and hrp/T3SS systems.

Systematic Functional Analysis of Sigma (σ) Factors in the Phytopathogen Xanthomonas campestris Reveals Novel Roles in the Regulation of Virulence and Viability.

The black rot pathogen Xanthomonas campestris pv. campestris (Xcc) is a model organism for the study of plant bacterial pathogenesis mechanisms. In bacteria, σ factors serve as important regulatory elements that respond to various environmental signals and cues. Though Xcc encodes 15 putative σ factors little is known about their roles. As an approach to identify the potential role of each σ factor, we constructed mutations in each of the σ-factor genes as well as generating mutants deficient in multiple σ factors to assess these regulators potential additive functions. The work identified two σ70 factors essential for growth. Furthermore, the work discovered a third σ70 factor, RpoE1, important for virulence. Further studies revealed that RpoE1 positively regulates the expression of the hrp gene cluster that encodes the type III secretion system (T3SS) which determines the pathogenicity and hypersensitive response of Xcc on plants. In vivo and in vitro studies demonstrated that RpoE1 could bind to the promoter region and promote transcription of hrpX, a gene encoding a key regulator of the hrp genes. Overall, this systematic analysis reveals important roles in Xcc survival and virulence for previously uncharacterized σ70 factors that may become important targets for disease control.

The effect of dexmedetomidine on inflammatory inhibition and microglial polarization in BV-2 cells.

OBJECTIVE: Microglia have different phenotypic and functional states: M1 is associated with inflammatory responses, whereas M2 results in anti-inflammatory effects. The cellular state of microglia plays an important role in brain inflammation associating with many neuroinflammatory diseases. The purpose of this study was to detect the effect of dexmedetomidine (Dex) on inflammatory inhibition and microglial polarization in BV-2 cells. MATERIALS AND METHODS: Dex exerts anti-inflammatory effects in various experimental models. The BV-2 microglial cell line was treated with liposaccharide in the presence or absence of Dex. The M1 and M2 markers were evaluated by quantitative real-time PCR (qRT-PCR) and western blot. RESULTS: We found that Dex exerted a potent anti-inflammatory effect by reducing the expression of M1 marker genes such as tumor necrosis factor alpha (P < 0.05), interleukin-1ß (IL-1ß) (P < 0.001) and IL-6 (P < 0.001). Importantly, Dex improved the expression of microglia M2 markers arginase-1 (Arg-1) (P < 0.01), Flt3-interacting zinc finger protein 1 (Fizz-1) (P < 0.001) and CD206) (P < 0.001). Further, Dex enhanced the activation of Akt pathway. DISCUSSION: Our results indicated that Dex promotes microglia from the M1 phenotype to the M2 phenotype. Therefore, Dex may be a potential novel therapeutic drug for treating brain inflammation-associated diseases not only because of its anti-inflammatory property but also because it can remodel M1 phenotype microglia to M2 phenotype microglia.

Vernonia amygdalina Delile extract inhibits the hepatic gluconeogenesis through the activation of adenosine-5'monophosph kinase.

AIMS: It has been reported that Vernonia amygdalina Delile(VA) presents an anti-diabetic effect, and the effect of VA on lowering glucose is formulated via suppressing the expression of the key hepatic gluconeogenesis enzyme. Therefore, we further explored the probable mechanism of VA on dismissing hepatic gluconeogenesis through the activation of adenosine-5' monophosphate kinase (AMPK) in vivo and in vitro. METHODS: We developed type 2 diabetic mice with STZ and oral administration with VA (50 mg/kg, 100 mg/kg and 150 mg/kg) once a day for 6 weeks. Fasting blood glucose (FBG), fasting insulin (FINS) and oral glucose tolerance tests (OGTT) were conducted. The expression levels of AMPK, phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) proteins in live were evaluated by western blot. Then, we further explored the mechanism of VA on hepatic gluconeogenesis in vitro experiments. Glucose production and the expression of AMPK, PEPCK and G6Pase proteins were detected after VA treatment with the presence of the AMPK inhibitor Compound C. KEY FINDINGS: VA reduced FBG and caused a significant improvement in glucose tolerance and insulin resistance (HOMA-IR) in STZ-induced mice. VA inhibited the elevated expression of gluconeogenesis key enzymes (PEPCK and G6Pase) and up-regulated AMPK activity in liver. In palmitic acid (PA)-induced HepG2 cells, VA decreased glucose production and the expression of PEPCK and G6Pase proteins, also activated AMPK pathway. The effects of VA on gluconeogenesis could be reversed by Compound C. CONCLUSION: These results reveal that VA suppresses hepatic gluconeogenesis at least partially through activating the AMPK.

Moringa oleifera Seed Extract Alleviates Scopolamine-Induced Learning and Memory Impairment in Mice.

The extract of Moringa oleifera seeds has been shown to possess various pharmacological properties. In the present study, we assessed the neuropharmacological effects of 70% ethanolic M. oleifera seed extract (MSE) on cognitive impairment caused by scopolamine injection in mice using the passive avoidance and Morris water maze (MWM) tests. MSE (250 or 500 mg/kg) was administered to mice by oral gavage for 7 or 14 days, and cognitive impairment was induced by intraperitoneal injection of scopolamine (4 mg/kg) for 1 or 6 days. Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity and neurogenesis in the hippocampus. MSE pretreatment significantly ameliorated scopolamine-induced cognitive impairment and enhanced cholinergic system reactivity and neurogenesis in the hippocampus. Additionally, the protein expressions of phosphorylated Akt, ERK1/2, and CREB in the hippocampus were significantly decreased by scopolamine, but these decreases were reversed by MSE treatment. These results suggest that MSE-induced ameliorative cognitive effects are mediated by enhancement of the cholinergic neurotransmission system and neurogenesis via activation of the Akt, ERK1/2, and CREB signaling pathways. These findings suggest that MSE could be a potent neuropharmacological drug against amnesia, and its mechanism might be modulation of cholinergic activity via the Akt, ERK1/2, and CREB signaling pathways.

A novel PPARα/γ agonist, propane-2-sulfonic acid octadec-9-enyl-amide, ameliorates insulin resistance and gluconeogenesis in vivo and vitro.

Peroxisome proliferator-activated receptor alpha/gamma (PPARα/γ) agonists have emerged as important pharmacological agents for improving insulin action. Propane-2-sulfonic acid octadec-9-enyl-amide (N15) is a novel PPARα/γ dual agonist synthesized in our laboratory. The present study investigates the efficacy and safety of N15 on insulin resistance regulation in high fat diet (HFD)-and streptozotocin (STZ)-induced diabetic mice and in palmitic acid (PA)-induced HepG2 cells. Our results showed that N15 remarkably ameliorated insulin resistance and dyslipidemia in vivo, as well as rectified the glucose consumption and gluconeogenesis in vitro. Moreover, the glucose-lowering effect of N15 was associated with PPARγ mediated up-regulation of hepatic glucose consumption and down-regulation of gluconeogenesis. Meanwhile, N15 exerted advantageous effects on glucose and lipid metabolism without triggering weight gain and hepatotoxicity in mice. In conclusion, our data demonstrated that by alleviating glucose and lipid abnormalities, N15 could be used as a potential prophylactic and therapeutic agent against type 2 diabetes and related metabolic disorders.

Peptidoglycan hydrolysis mediated by the amidase AmiC and its LytM activator NlpD is critical for cell separation and virulence in the phytopathogen Xanthomonas campestris.

The essential stages of bacterial cell separation are described as the synthesis and hydrolysis of septal peptidoglycan (PG). The amidase, AmiC, which cleaves the peptide side-chains linked to the glycan strands, contributes critically to this process and has been studied extensively in model strains of Escherichia coli. However, insights into the contribution of this protein to other processes in the bacterial cell have been limited. Xanthomonas campestris pv. campestris (Xcc) is a phytopathogen that causes black rot disease in many economically important plants. We investigated how AmiC and LytM family regulators, NlpD and EnvC, contribute to virulence and cell separation in this organism. Biochemical analyses of purified AmiC demonstrated that it could hydrolyse PG and its activity could be potentiated by the presence of the regulator NlpD. We also established that deletion of the genes encoding amiC1 or nlpD led to a reduction in virulence as well as effects on colony-forming units and cell morphology. Moreover, further genetic and biochemical evidence showed that AmiC1 and NlpD affect the secretion of type III effector XC3176 and hypersensitive response (HR) induction in planta. These findings indicate that, in addition to their well-studied role(s) in cell separation, AmiC and NlpD make an important contribution to the type III secretion (T3S) and virulence regulation in this important plant pathogen.

Incorporation of the number of positive lymph nodes leads to better prognostic discrimination of node-positive early stage cervical cancer.

To determine the prognostic value of the number of positive lymph nodes (LNs) in cervical cancer and further stratify patients with positive LNs into multiple risk groups based on analysis of Surveillance Epidemiology and End Results (SEER) program. Patients with cervical cancer who undergo hysterectomy and had pathologically-confirmed positive LNs after lymphadenectomy were identified using the SEER database (1988-2012). Kaplan-Meier survival methods and Cox proportional hazards regression were performed. We included 2,222 patients with the median number of removed LNs and positive LNs was 22 and 2, respectively. Multivariable Cox analysis showed patients with > 2 positive LNs had poorer cause-specific survival (CSS) (hazard ratio [HR] 1.631, 95% confidence interval [CI] 1.382-1.926, P < 0.001) and overall survival (OS) (HR 1.570, 95% CI 1.346-1.832, P < 0.001) than patients with 1-2 positive LNs. Five-year CSS and OS were 78.9% vs. 65.5% (P < 0.001) and 76.7% vs. 62.7% (P < 0.001) for 1-2 positive LNs and > 2 positive LNs, respectively. The number of positive LNs had prognostic value in cervical squamous cell carcinoma or adenosquamous carcinoma, but not in cervical adenocarcinoma. The number of positive LNs is an independent risk factor for CSS and OS in cervical cancer. This new category might be helpful in better prognostic discrimination of node-positive early stage cervical cancer after hysterectomy.

Oleoylethanolamide attenuates apoptosis by inhibiting the TLR4/NF-κB and ERK1/2 signaling pathways in mice with acute ischemic stroke.

This study was carried out to investigate the exact mechanisms behind the neuroprotective effects of oleoylethanolamide (OEA) after acute cerebral ischemic injury. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. OEA (40 mg/kg, ip) was administered with a single injection upon reperfusion. The number of apoptotic cells was detected by TUNEL staining. The expression of Bax, Bcl-2, and TLR4, as well as the activities of NF-κB, Akt, and ERK1/2 were analyzed by western blot. Our data showed that OEA treatment alleviated cell apoptosis in a mouse model of ischemic stroke, accompanied by suppression of Bax, as well as upregulation of antiapoptotic protein Bcl-2 level. The changes of Bax and Bcl-2 could not be observed in PPARα knockout mice models with OEA administration. Importantly, OEA inhibited MCAO-induced TLR4 expression, NF-κB activation, IκBα degradation, and ERK1/2 phosphorylation. Our findings demonstrated that the neuroprotective effects of OEA on cerebral ischemia may be attributed to its antiapoptotic property achieved, at least in part, through the PPARα signaling and inhibition of both TLR4/NF-κB and ERK1/2 signaling pathways. These results provide new evidence indicating the neuroprotective effect of OEA on ischemic stroke.

Patterns of distant metastasis in Chinese women according to breast cancer subtypes.

To access possible relationships between breast cancer subtypes (BCS) and patterns of distant metastasis in advanced breast cancer. Breast cancer patients with distant metastasis at two academic centers from 2000-2015 were retrospectively reviewed. The breast cancer was classified into four subtypes: hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2) - (i.e., estrogen receptor [ER] + and/or progesterone receptor [PR] +, HER2-); HR+/HER2+ (ER+ and/or PR+, HER2+), HR-/HER2+ (ER- and PR-, and HER2+); and HR-/HER2- (ER- and PR-, and HER2-). A total of 679 patients were identified. The distribution of the BCS was 39.9% (271/679), 23.7% (161/679), 16.8% (114/679), and 19.6% (133/679) in HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-, respectively. Patients with HR+/HER2+ and HR-/HER2+ subtypes were prone to abdominal and pelvic metastasis, those with HR+/HER2- and HR+/HER2+ subtypes were prone to bone metastasis, while patients with the HR-/HER2- subtype were prone to lung/mediastinal and brain metastases. In patients with pleural, axillary and/or neck lymph node, and other distant soft tissue metastases, there was no significant difference in metastatic patterns among the BCS. There are different patterns of distant metastasis associated with different BCS. There should be a different focus in the postoperative follow-up and monitoring of breast cancer patients with different BCS.

A novel PPARα agonist propane-2-sulfonic acid octadec-9-enyl-amide inhibits inflammation in THP-1 cells.

Our group synthesized propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator activated receptor alpha (PPARα) agonist. Because PPARα activation is associated with inflammation control, we hypothesize that N15 may have anti-inflammatory effects. We investigated the effect of N15 on the regulation of inflammation in THP-1 cells stimulated with lipopolysaccharide (LPS). In particular, we assessed the production of chemokines, adhesion molecules and proinflammatory cytokines, three important types of cytokines that are released from monocytes and are involved in the development of atherosclerosis. The results showed that N15 remarkably reduced the mRNA expression of chemokines, such as monocyte chemotactic protein 1 (MCP-1 or CCL2), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10 or CXCL10), and proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). N15 also decreased the protein expression of vascular cell adhesion molecule (VCAM) and matrix metalloproteinase (MMP) 2 and 9. The reduction in the expression of cytokine mRNAs observed following N15 treatment was abrogated in THP-1 cells treated with PPARα siRNA, indicating that the anti-inflammatory effects of N15 are dependent on PPARα activation. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) inhibition, which are dependent on PPARα activation, were also involved in the mechanism underlying the anti-inflammatory effects of N15. In conclusion, the novel PPARα agonist, N15, exerts notable anti-inflammatory effects, which are mediated via PPARα activation and TLR4/NF-κB and STAT3 inhibition, in LPS-stimulated THP-1 cells. In our study, N15 exhibits promise for the treatment of atherosclerosis.

Use of CEA and CA15-3 to Predict Axillary Lymph Node Metastasis in Patients with Breast Cancer.

PURPOSE: The clinical significance of preoperative serum levels of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) in breast cancer is controversial. The purpose of this study was to assess the clinical value of preoperative serum levels of CEA and CA 15-3 on the risk of axillary lymph node metastasis (ALNM) in patients with breast cancer. METHODS: This retrospective study analyzed 1148 breast cancer patients whose preoperative CEA and CA 15-3 levels were measured. The association of these tumor markers and clinicopathologic parameters with ALNM was determined by univariate and multivariate analysis. RESULTS: A median of 15 lymph nodes were removed. Seven hundred seventy-eight (67.8%) patients had node-negative disease and 370 (32.2%) had ALNM. Univariate analysis showed that tumor location (P = 0.024), stage (P = 0.001), grade (P < 0.001), lymphovascular invasion (LVI) (P < 0.001), CEA level (P < 0.001), CA15-3 level (P < 0.001), and breast cancer subtype (BCS) (P < 0.001) were significantly associated with ALNM. ALNM was present in 4.5% of patients with normal CEA and 11.6% of patients with elevated CEA. ALNM was present in 8.0% of patients with normal CA15-3 and 17.0% of patients with high CA15-3. Multivariate logistic regression analysis showed that tumor location, stage, grade, LVI, CEA, CA15-3, and BCS were significantly and independently associated with ALNM (P < 0.05 for all). CONCLUSION: The probability of ALNM was greater in patients with elevated preoperative serum levels of CEA and CA15-3. CEA and CA15-3 appear to be independent predictors of ALNM in breast cancer.

Prognosis of patients with esophageal squamous cell carcinoma after esophagectomy using the log odds of positive lymph nodes.

To compare the log odds of positive lymph nodes (LODDS) with the number of positive lymph nodes (pN), lymph node ratio (LNR), removed lymph node (RLN) count, and negative lymph node (NLN) count in determining the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. The records of patients with ESCC who received esophagectomy were retrospectively reviewed. The log-rank test was used to compare curves for overall survival (OS), and Cox regression analysis was performed to identify prognostic factors. The prognostic performance of the different lymph node staging systems were compared using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion. A total of 589 patients were enrolled. Univariate Cox analysis showed that pN stage, LNR, RLN count, NLN count, and the LODDS were significantly associated with OS (p < 0.05 for all). Multivariate Cox analysis adjusted for significant factors indicated that LODDS was independent risk factor on overall survival (OS), and a higher LODDS was associated with worse OS (hazard ratio = 3.297, 95% confidence interval: 2.684-4.050, p < 0.001). The modified Tumor-LODDS-Metastasis staging system had better discriminatory ability, monotonicity, and homogeneity, and better optimistic prognostic stratification than the Tumor-Node-Metastasis staging system in determining the prognosis of patients with ESCC. The LODDS staging system was superior to other lymph node classifications in determining the prognosis of patients with ESCC after esophagectomy. LODDS may be incorporated into esophageal staging system if these results are eventually confirmed by other studies.

Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian Cancer.

PURPOSE: The impact of ABO blood group on the survival of patients with ovarian cancer remains uncertain. The aim of this study was to evaluate the prognostic value of the ABO blood group in ovarian cancer patients. METHODS: 256 ovarian cancer patients who received a cytoreductive surgery were retrospectively reviewed. The prognostic impact of the ABO blood group with respect to overall survival (OS) was analyzed. RESULTS: The median follow-up time was 57 months and the 5-year OS was 70.1%. The 5-year OS were 55.0%, 83.3%, 82.5%, and 70.0% in patients with A, B, AB, and O blood type, respectively (p = 0.003). Patients with blood type A had a poorer 5-year OS than patients with blood type non-A (55.0% vs. 75.0%, p = 0.001), especially in patients with age > 50 years (40.0% vs. 62.5%, p = 0.004). Univariate Cox analyses showed that blood type A was significantly associated with OS than those with non-A types (hazard ratio (HR) 2.210, 95% confidence interval (CI) 1.373-3.557, p = 0.001). Blood type A remained an independent prognostic factor for OS than those with non-A blood types in multivariate analyses (HR 2.235, 95% CI 1.360-3.674, p = 0.002). CONCLUSION: ABO blood group is associated with survival in patients with ovarian cancer, patients with blood type A had a significantly worse OS than patients with non-A blood types, especially in patients with age > 50 years.