Identification of new subtypes and potential genetic signatures in triple-negative breast cancer using weighted gene co-expression network analysis.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Here, we used gene expression profiling to define new subtypes of TNBC, which may improve prevention and treatment through personalized medicine. MATERIALS AND METHODS: Gene expression profiles from the public datasets GSE76250, GSE61724, GSE61723, and GES76275 were subjected to co-expression analysis to identify differentially expressed genes (DEGs) between TNBC and non-TNBC tissues. Consistency clustering was used to define TNBC subtypes, whose correlation with gene modules was analyzed. Enrichment analysis was used to identify module genes' biological functions and pathways. Single-sample gene set enrichment analysis was used to assess immune cell infiltration in the different TNBC subtypes, and the ChAMP package was used to examine methylation sites in TNBC. RESULTS: A total of 4,958 DEGs in TNBC were identified, which showed the same expression differences across all datasets as in the dataset GSE76250 and clustered into 9 co-expression modules. TNBC samples clustered into two subtypes based on nine hub genes from the modules. Class I showed the most significant correlation with module 1, whose genes were related mainly to interleukin-1 response, while class II showed the most significant correlation with module 6, whose genes were related mainly to the transforming growth factor-ß pathway. Class I was significantly enriched in cell cycle and DNA replication, and tumors of this subtype showed lower immune cell infiltration than class II tumors. Tumor infiltration by Th2 cells correlated positively with the expression of MCM10 and negatively with the expression of PREX2. A greater methylation of CIDEC, DLC1, EDNRB, EGR2 and SRPK1 correlated with better prognosis. CONCLUSIONS: Class I TNBC, for which a useful biomarker is MCM10, may be associated with a worse prognosis than class II TNBC, for which PREX2 may serve as a biomarker.

Temperature management of intraoperative cardiopulmonary bypass in valve replacement surgery: a retrospective analysis of the impact on postoperative organ function.

OBJECTIVE: This study aimed to systematically analyze the effects of cardiopulmonary bypass (CPB) at different temperatures on the function of different organs in patients after heart valve replacement and to investigate its safety and feasibility. PATIENTS AND METHODS: The data of 275 heart valve replacement surgery patients who underwent static suction compound anesthesia under CPB between February 2018 and October 2019 were retrospectively analyzed and divided into normothermic CPB anesthesia group (group 0), shallow hypothermic CPB anesthesia group (group 1), medium hypothermic CPB anesthesia group (group 2), and deep hypothermic CPB anesthesia group (group 3) according to the different intraoperative CPB temperatures. The basic preoperative conditions, cardiac resuscitation, number of defibrillations, postoperative ICU stay, postoperative hospital stay, and postoperative evaluation of different organ functions, such as heart, lung, and kidney functions, were analyzed and studied in each group. RESULTS: The comparison of preoperative and postoperative pulmonary artery pressure and left ventricular internal diameter (LVD) was statistically significant in each group (p < 0.05), and the postoperative pulmonary function pressure was statistically significant in group 0 compared with groups 1 and 2 (p < 0.05). The preoperative glomerular filtration rate (eGFR) and the eGFR on the first postoperative day were statistically significant in all the groups (p < 0.05), and the eGFR on the first postoperative day in groups 1 and 2 were statistically significant (p < 0.05). CONCLUSIONS: The control of appropriate temperature during CPB was associated with the recovery of organ function in patients after valve replacement. Intravenous compound general anesthesia with superficial hypothermic CPB might be more beneficial in recovering cardiac, pulmonary, and renal functions.

Asperosaponin VI Protects Against Bone Loss Due to Hindlimb Unloading in Skeletally Growing Mice Through Regulating Microbial Dysbiosis Altering the 5-HT Pathway.

Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.

Acupuncture combined with exercise training at different time points on nerve repair of cerebral ischemia-reperfusion injury in rats and its effects on the expressions of Nestin, bFGF and EGF.

OBJECTIVE: The aim of the study was to observe the neuroreparative effect of electroacupuncture in rats with cerebral ischemia-reperfusion injury, and to explore the difference in the therapeutic effect of acupuncture on different acupoint groups after cerebral ischemia-reperfusion. MATERIALS AND METHODS: Experimental rats were randomly divided into: sham operation group, model group, electroacupuncture group, rehabilitation group, and Diankang group (electroacupuncture + rehabilitation training). There were 24 rats in each group, and the focal cerebral ischemia-reperfusion model was established by Zea-Longa suture method. After modeling, it took 4 hours to electroacupuncture at Baihui and Dazhui points, which was used to observe the changes of nerve function in rats with signs of keel nerve function defect. Protein expression was detected by immunohistochemistry. RESULTS: Compared with the model group, the EA 3d, 7d, 10d groups and the rehabilitation group had no significant difference in promoting the expression of Nestin (p>0.05). There was a significant difference (p<0.01). After cerebral ischemia-reperfusion injury, the expression of bFGF and EGF on the ischemic side was stronger. The peak of bFGF expression appeared earlier, and the peak of EGF expression appeared later. The expression of bFGF and EGF in cerebral ischemic cortex at different time points of ischemia in electroacupuncture group, rehabilitation group and Diankang group was increased, and the response was enhanced. The effect of Diankang group on the upregulation of bFGF and EGF was more significant (p<0.01, p<0.05). CONCLUSIONS: Under the influence of different effects, Diankang is superior to simple treatment in improving ischemic neurological dysfunction. This may be related to the fact that Diankang can promote the proliferation of neural stem cells and the expression of neurotrophic factors on the ischemic side of the rat brain.

The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment.

The article "The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment, by C.-J. Zhang, Y.-Z. Deng, Y.-H. Lei, J.-B. Zhao, W. Wei, Y.-H. Li, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 2169-2174-DOI: 10.26355/eurrev_201804_14751-PMID: 29687877" has been withdrawn from the authors due to some technical reasons (the authors still have not figured out how to address them). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14751.

Long-chain non-coding RNA Linc00888 promotes the proliferation and migration of esophageal cancer cells by downregulating miR-34a expression.

OBJECTIVE: To explore the role and potential mechanism of long-chain non-coding RNA 00888 in esophageal cancer (EC). PATIENTS AND METHODS: The expression level of Linc00888 in esophageal cancer tissues and adjacent ones, as well as corresponding cell lines, was measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Survival prognosis information of patients was collected, and KM survival analysis was performed to determine the prognostic value of Linc00888. To better understand the effect of Linc00888 on the proliferative and migration ability of EC cells, Cell Counting Kit-8 (CCK-8), clone formation, and transwell assays were performed after Linc00888 was knocked down in EC cell lines. Furthermore, bioinformatics prediction website was used to discover the potential target of Linc00888. Then, Dual-Luciferase reporter gene assay was performed to verify the binding relationship between Linc00888 and the downstream gene miR-34a. Then, the expression relationship between the two was measured both in cell lines and tissues. Finally, to clarify the regulation between Linc00888 and miR-34a, a recovery experiment was performed using co-transfection technology. RESULTS: Linc00888 was aberrantly upregulated in esophageal cancer tissues. The survival analysis showed that the higher expression of Linc00888 was significantly correlated with shorter overall survival. Cell functional experiment results suggested that Linc00888 played a role in promoting tumor proliferative and migration ability in EC cells. Besides, Dual-Luciferase reporter genes assay indicated that miR-34a and Linc00888 had binding sites. Meanwhile, we confirmed that there was a negative correlation between the expression levels of miR-34a and Linc00888 in cells and tissues. Cellular functional recovery experiments revealed that Linc00888 could modulate the progression of EC by miR-34a. CONCLUSIONS: Linc00888 promotes the proliferative and migration ability of EC through miR-34a.

Chi3l1 regulates APAP-induced liver injury by promoting macrophage infiltration.

The article "Chi3l1 regulates APAP-induced liver injury by promoting macrophage infiltration, by Y. Wang, M. Zhong, W. Wang, Y.-H. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4996-5003-DOI: 10.26355/eurrev_201906_18091-PMID: 31210337" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18091.

LncRNA HAGLR exacerbates hepatocellular carcinoma through negatively regulating miR-6785-5p.

OBJECTIVE: The purpose of this study was to explore the role of long non-coding RNA (lncRNA) HAGLR in exacerbating the development of hepatocellular carcinoma (HCC) by targeting microRNA-6785-5p (miR-6785-5p). PATIENTS AND METHODS: HAGLR levels in 46 HCC tissues and paracancerous tissues were detected. The relationship between HAGLR level and clinical features of HCC patients was analyzed. After knockdown of HAGLR, proliferative, and metastatic potential changes in Bel-7402 and Hub7 cells were assessed. Thereafter, the interaction between HAGLR and miR-6785-5p, as well as the involvement of miR-6785-5p in HAGLR-regulated HCC phenotypes were finally determined. RESULTS: It was found that HAGLR level was higher in HCC tissues than paracancerous ones and correlated with rates of lymphatic metastasis and distant metastasis but not with age, gender, and tumor staging in HCC patients. Survival analysis uncovered that HAGLR level was negatively linked to overall survival in HCC. After knockdown of HAGLR, proliferative, and metastatic potentials in Bel-7402 and Hub7 cells were attenuated. MiR-6785-5p was proven as the target gene binding to HAGLR. It was lowly expressed in HCC species, and negatively correlated with HAGLR level. Moreover, rescue experiments demonstrated that miR-6785-5p was responsible for HAGLR-regulated HCC phenotypes. CONCLUSIONS: LncRNA HAGLR stimulates proliferative and metastatic potentials in HCC via negatively regulating miR-6785-5p level, thus exacerbating the development of HCC.

LncRNA FAM83A-AS1 aggravates the malignant development of esophageal cancer by binding to miR-495-3p.

OBJECTIVE: It is of significance to screen out differentially expressed long non-coding RNAs (lncRNAs) that can be utilized as tumor biomarkers in esophageal cancer. This study aims to uncover the effect of lncRNA FAM83A-AS1 on regulating migratory potential in esophageal cancer and the underlying mechanism. PATIENTS AND METHODS: Tumor tissues and adjacent normal ones were collected from 62 esophageal cancer patients for detecting FAM83A-AS1 levels. Correlations of FAM83A-AS1 with clinical indexes and overall survival of esophageal cancer patients were analyzed. Thereafter, regulatory effects of FAM83A-AS1 on migratory potential in OE19 and OE33 cells were examined by transwell and wound healing assay. Then, the target genes of FAM83A-AS1 were predicted and functionally analyzed, and a protein interaction network was constructed. Finally, the mechanism of FAM83A-AS1 in regulating the downstream gene miR-495-3p was analyzed through Luciferase assay and rescue experiments. RESULTS: It was found that FAM83A-AS1 was upregulated in esophageal cancer tissues and cell lines. Higher rates of lymphatic and distant metastasis and worse survival were observed in esophageal cancer patients expressing higher level of FAM83A-AS1. Besides, the knockdown of FAM83A-AS1 suppressed migratory potential in OE19 cells, while the overexpression of FAM83A-AS1 yielded the opposite trend in OE33 cells. Moreover, miR-495-3p was indicated to be the target gene binding FAM83A-AS1, and it was lowly expressed in esophageal cancer and negatively regulated by FAM83A-AS1. Furthermore, the overexpression of miR-495-3p partially abolished the regulatory effect of FAM83A-AS1 on migratory potential in esophageal cancer. CONCLUSIONS: FAM83A-AS1 is upregulated in esophageal cancer, and it stimulates migratory potential in esophageal cancer by negatively regulating miR-495-3p.

The function and molecular mechanism of CEP55 in anaplastic thyroid cancer.

OBJECTIVE: The purpose of this study was to determine the role of centrosomal protein of 55 kDa (CEP55) in anaplastic thyroid cancer (ATC) and to further explore the mechanism, which might provide a new molecular marker for treatment of ATC. PATIENTS AND METHODS: The expression level of CEP55 in clinical cases was tested by fluorescence quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Also, qRT-PCR assay was performed in different TC cell lines. The relationship between CEP55 expression and clinicopathological characteristics was statistically analyzed. Kaplan-Meier curve and Cox's proportional hazards regression model were performed in survival analysis. Further, Western blot assay was used to analyze the protein expression changes in PI3K/Akt pathway. RESULTS: The expression level of CEP55 in TC tissues showed a noticeable upgrade, especially in ATC. In vitro, CEP55 expression was also increased in four kinds of TC cells, in which, the highest expression was found in ATC (TA-K) cells. The clinicopathological features, including lymph node metastasis, distant metastasis, and prognostic index were found to be correlated with the expression level of CEP55. Besides, the ATC patients with higher expression of CEP55 had a statistically worse overall survival (OS) time. In univariate analyses and multivariate analyses, the CEP55 level was an independent prognosis index of patients with ATC. In vitro study, CEP55 protein expression level was significantly reduced in si-CEP55-transfected TA-K cells. Notably, the downregulation of CEP55 could suppress the phosphorylation of PI3K and AKT. CONCLUSIONS: This study found that CEP55 could promote ATC progression, and PI3K/AKT pathway might be the downstream target of its action. These results provided a new therapeutic direction for the treatment of ATC.

MicroRNA-597 inhibits NSCLC progression through negatively regulating CDK2 expression.

OBJECTIVE: Previous studies have shown that microRNA-597 serves as a tumor suppressor gene. However, the role of microRNA-597 in non-small cell lung cancer (NSCLC) has not been fully elucidated. Therefore, the aim of this study was to investigate the expression of microRNA-597 in NSCLC, and to further explore the possible underlying mechanism. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (qPCR) was performed to examine microRNA-597 level in tumor tissues and para-cancerous normal tissues collected from 50 patients with NSCLC. The interplay between microRNA-597 expression and clinical indicators, as well as prognosis of NSCLC patients, was analyzed. Meanwhile, qPCR was used to verify microRNA-59 level in NSCLC cell lines. Subsequently, microRNA-597 overexpression and knockdown models were constructed using lentivirus in NSCLC cell lines (including H1299 and PC-9). The impacts of microRNA-597 on the biological functions of NSCLC cells were evaluated using cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assay, respectively. Finally, luciferase reporter gene assay and recovery experiment were performed to investigate the underlying molecular mechanism. RESULTS: QPCR results indicated that microRNA-597 level in NSCLC tissues was remarkably lower than that of adjacent normal tissues, and the difference was statistically significant (p<0.05). Compared with patients with high expression of microRNA-597, patients with low expression of microRNA-597 exhibited significantly higher incidence of pathological stage and lower overall survival rate (p<0.05). Similarly, compared with NC group, the proliferation ability of NSCLC cells was remarkably weakened in microRNA-597 overexpression group (p<0.05). However, the opposite results were observed in microRNA-597 inhibitor group (p<0.05). CDK2 expression was found remarkably elevated in NSCLC cell lines as well as in tissue samples CDK2 expression. Meanwhile, CDK2 expression was negatively correlated with microRNA-597 expression. Luciferase reporter gene assay demonstrated that overexpression of CDK2 could significantly attenuate the luciferase activity of wild-type microRNA-597 vector without attenuating that of mutant vector CDK2 expression. This further suggested that microRNA-597 could target bind to CDK2. Furthermore, cell recovery experiment revealed that CDK2 could reverse the impact of microRNA-597 on the malignant progression of NSCLC. CONCLUSIONS: MicroRNA-597 expression was significantly down-regulated in NSCLC tissues, as well as cell lines. Meanwhile, microRNA-597 expression was associated with the pathological staging and poor prognosis of patients with NSCLC. In addition, microRNA-597 might suppress the malignant progression of NSCLC through the regulation of CDK2.

Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury.

The article "Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury, by Y.-M. Yang, Y.-H. Li, L.-L. Ding, Y. Fu, N. Li, published in Eur Rev Med Pharmacol Sci 2019; 23(18):8011-8017. DOI: 10.26355/eurrev_201909_19017. PMID: 31599426" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.

MiR-20a ameliorates diabetic angiopathy in streptozotocin-induced diabetic rats by regulating intracellular antioxidant enzymes and VEGF.

OBJECTIVE: We evaluated the beneficial effect of miR-20a mimic against diabetic angiopathy (DA) in rats by regulating intracellular antioxidant enzymes and vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: Diabetes was induced by intraperitoneal administration of streptozotocin (STZ; 65 mg/kg). Rats were then treated with miR-20a mimic (250 nmol/kg orally) for 8 weeks after STZ administration. The effect of miR-20a mimic against DA in rats was evaluated by estimating serum glucose concentration, lipid profile, Lp-a, kidney function test, inflammatory mediators, and markers of endothelial cell function. Markers of oxidative stress in the aortic tissue were estimated in rats treated with miR-20a mimic. Western blot assay, RT-PCR, and histopathology of kidney and myocardial tissues were also performed. RESULTS: Serum levels of blood glucose and markers of renal function were significantly lower, and the lipid profile improved in the miR-20a mimic group compared to the DA group. Treatment with miR-20a mimic ameliorated the altered markers of endothelial function and oxidative stress, as well as mediators of inflammation, in the DA rats. Protein expressions of ERK1/2, JNK, and p38 MAPK, as well as mRNA expressions of TLR-4 and NF-κB, in aortic tissues were lower in the miR-20a mimic group than in the DA group. The miR-20a mimic group had fewer histopathological changes in kidney and myocardial tissues than the DA group. CONCLUSIONS: MiR-20a mimic can protect against DA in rats by regulating vascular endothelial function and oxidative stress.

Molecular tagging of biocontrol fungus Trichoderma asperellum and its colonization in soil.

AIMS: To conduct molecular tagging of the biocontrol fungus Trichoderma asperellum strain T4 and elucidate its colonization patterns in soil. METHODS AND RESULTS: We constructed an expression vector harbouring a hygromycin B-resistant gene (hph) and an efficient green fluorescent protein (egfp) gene. By applying Agrobacterium AGL-1-mediated genetic transformation technology, we conducted molecular tagging of T. asperellum and monitored the colonization dynamics of T. asperellum in soil. The results of tracking five independent transformants of T. asperellum indicated that its expansion rates ranged from 4·7 to 6·8 cm week-1 . After inoculation in soil, the quantities of T. asperellum could be maintained at over 10 × 104  CFU per gram soil in the first year. In the third year after inoculation, the quantities of T. asperellum in soil were still higher than 1 × 103  CFU per gram soil. In addition, molecularly tagged T. asperellum in soil in the second year (i.e. 12 months) after inoculation could still reach the biocontrol effect on cucumber Rhizoctonia rot by more than 74%. CONCLUSION: Trichoderma asperellum strain T4 is capable of effectively colonizing in soil and surviving for more than 1 year. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has provided the scientific basis for applying T. asperellum as the biocontrol fungus for prevention and control of plant diseases.

Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury.

OBJECTIVE: The aim of this study was to investigate the regulatory effect of long non-coding RNA (lncRNA) NKILA on autophagy in sepsis-induced kidney injury. MATERIALS AND METHODS: Sepsis model was successfully established in rats by cecal ligation and puncture (CLP). Hematoxylin and eosin (HE) staining was performed to evaluate the pathological lesions in rat kidney tissues. Subsequently, serum samples of sepsis rats were collected. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were determined. Western blot and quantitative real time-polymerase chain reaction (qRT-PCR) were conducted to detect the protein and mRNA expression levels of LC3, Beclin-1, activated caspase-3, p-Akt (308), p-Akt (472), Akt and NKILA in kidney tissues of sepsis rats at different time points, respectively. Subsequently, HK-2 cells were induced with different doses of lipopolysaccharide (LPS) for different time points. The expression levels of the above genes in cells were detected as well. Finally, changes in autophagy and apoptosis in LPS-induced HK-2 cells with the treatment of PI3K pathway inhibitor or Akt inhibitor were observed. RESULTS: Typical pathological lesions were observed in kidney tissues of sepsis rats, with increased serum levels of BUN and SCr. This indicated the successful construction of the sepsis model in rats. The expression levels of LC3, Beclin-1, and NKILA/Akt significantly increased in kidney tissues of sepsis rats. In vitro experiments revealed that NKILA expression in HK-2 cells gradually up-regulated with the increase of LPS dose and prolongation of LPS induction. The expressions of LC3 and NKILA/Akt were higher at 10 mg/L LPS treatment, and 8 h of LPS induction. Furthermore, the treatment of PI3K pathway inhibitor or Akt inhibitor remarkably down-regulated LPS-induced LC3 expression, while it accelerated cell apoptosis and up-regulated NKILA expression. CONCLUSIONS: Autophagy occurs at sepsis-induced kidney injury, which can be regulated by NKILA/Akt pathway.

LncRNA FBXL19-AS1 promotes proliferation and metastasis via regulating epithelial-mesenchymal transition in non-small cell lung cancer.

OBJECTIVE: To detect the relative expression of long non-coding ribonucleic acid (lncRNA) F-box and leucine-rich repeat protein 19-antisense RNA 1 (FBXL19-AS1) in tissues and cells of non-small-cell lung cancer (NSCLC), and investigate the mechanism of lncRNA FBXL19-AS1 in promoting NSCLC cell proliferation and metastasis by regulating epithelial-mesenchymal transition (EMT) via in vitro experiments. PATIENTS AND METHODS: The relative expression of lncRNA FBXL19-AS1 in NSCLC tissues and cells was detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The colony formation assay was performed to study the impact of interference with lncRNA FBXL19-AS1 expression on NSCLC cell proliferation. The flow cytometry was applied to determine the influence of si-FBXL19-AS1 on the cycle distribution of NSCLC cells. After the interference with lncRNA FBXL19-AS1 expression, the transwell assay was utilized to measure the changes in the migratory and invasive abilities of NSCLC cells, while the expression changes in EMT-related molecular markers was detected via Western blotting. RESULTS: The results of qRT-PCR showed that the expression of lncRNA FBXL19-AS1 in NSCLC tissues and cells was up-regulated. According to the results of the colony formation assay, the proliferative capacity of NSCLC cells was decreased after the interference with lncRNA FBXL19-AS1 expression. In flow cytometry, it was indicated that the cell cycle was arrested at the G0/G1 phase in the experimental group compared with that in the control group. The transwell assay results showed that the migratory and invasive abilities of NSCLC cells were weakened after the interference with lncRNA FBXL19-AS1 expression. The results of the Western blotting assay revealed that the expressions of EMT-related molecular markers (E-cadherin, N-cadherin, etc.) were changed. CONCLUSIONS: The expression of lncRNA FBXL19-AS1 in NSCLC tissues and cells is up-regulated, and the highly expressed lncRNA FBXL19-AS1 can promote NSCLC cell proliferation and metastasis by regulating the EMT.

Chi3l1 regulates APAP-induced liver injury by promoting macrophage infiltration.

OBJECTIVE: This study aims to investigate the role of Chi3l1 in Acetaminophen (APAP)-induced liver injury. MATERIALS AND METHODS: In vivo model of liver injury was established in mice administrated with APAP (250 mg/kg) or equivalent phosphate-buffered saline (PBS). Mouse liver tissues were collected at 1 h, 3 h, 6 h, 12 h, and 24 h after treatment, respectively. ALT levels and apoptosis were evaluated. Additionally, we established APAP-induced acute liver injury model in wild-type (WT) mice and Chi3l1-deficient (Chi3l1-/-) mice. Pathological changes of liver tissue were observed by hematoxylin and eosin (HE) staining. Mononuclear cells (MNCs) were isolated from mouse liver, and the amounts of infiltrating macrophages and neutrophils were then counted by flow cytometry. Serum levels of cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Bone marrow-derived macrophages (BMDMs) were extracted from each mouse. RESULTS: After APAP stimulation, Chi3l1-/- mice showed more severe liver injury than that of WT mice, which was manifested as higher ALT levels and more necrotic or apoptotic cells. Compared with WT mice, Chi3l1-/- mice expressed higher levels of inflammatory cytokines (MCP-1 and IL-6), macrophage-associated molecules (CD68 and CD86), as well as the amounts of infiltrating macrophages and neutrophils. In addition, higher expressions of inflammatory cytokines were found in BMDMs extracted from WT mice treated with those BMDM lysates derived from Chi3l1-/- mice than those of non-treated cells. APAP-treated Chi3l1-/- mice exhibited more severe liver injury than that of WT mice. CONCLUSIONS: Our study confirmed that Chi3l1 protects the liver function from APAP-induced injury by inhibiting the secretion of inflammatory factors and macrophage infiltration.

Effects of epidural infusion of morphine combined with small-dose naloxone on gastrointestinal interstitial cells of Cajal in rabbits.

OBJECTIVE: To study the effect of epidural infusion of morphine combined with small-dose naloxone on gastrointestinal interstitial cells of Cajal (ICC) in rabbits. MATERIALS AND METHODS: A total of 80 healthy New Zealand rabbits were selected as objects of study, and divided into normal saline control group (Group NS, n=20), morphine group (Group M, n=20), naloxone group (Group N, n=20), and morphine + naloxone group (Group NM, n=20). Rabbits in four the groups received epidural catheterization for continuous drug infusion for 7 d, and epidural analgesia pump was connected. Visual analogue scale (VAS) score, intestinal propulsion rate, c-kit expression, and ICC count were detected and compared among four groups of rabbits. RESULTS: No statistical differences of occurrence rates regarding constipation as well as expressions of c-kit and ICC count in the proximal colon were shown among rabbits in Group NS, Group N, and Group NM during drug administration (p>0.05). However, the occurrence rates of constipation of rabbits in Group M at 3-7 d were statistically higher than those in Group NS, Group N, and Group NM, and the differences were statistically significant (p<0.05). Moreover, the VAS scores in Group NS and Group N were significantly higher than those in Group M and Group NM, while the scores in Group M were also significantly increased compared to that in Group NM (p<0.05). The intestinal propulsion rates, expressions of c-kit and ICC counts of rabbits in Group NS, Group N, and Group NM were statistically higher than that in Group M (p<0.05). CONCLUSIONS: Epidural infusions of morphine combined with small-dose naloxone effectively inhibit the gastrointestinal motility of rabbits via the reduction of ICC in the proximal colon of the gastrointestinal tract of rabbits. Moreover, small-dose of naloxone enhances the analgesic effect and reduces the risk of adverse reactions.