Leisure television watching exerts a causal effect on gastroesophageal reflux disease: evidence from a two-step mendelian randomization study.

BACKGROUND: Previous studies have shown that physical activity (PA) and leisure sedentary behaviors (LSB, including leisure television watching) are linked to gastroesophageal reflux disease (GERD). However, the associations between PA/LSB and GERD remain controversial. In this study, we aimed to reveal whether these associations reflect causal relationships and reveal the potential mechanisms of these relationships using bidirectional and two-step Mendelian randomization (MR) analyses. METHODS: We obtained genome-wide association study (GWAS) summary statistics for PA/LSB, four common risk factors (including cigarettes smoked per day, alcoholic drinks per week, triglycerides, total cholesterol) and GERD from published GWASs. A bidirectional MR analysis was performed to identify causal relationships between PA/LSB and GERD. Then, a series of sensitivity analyses were performed to verify the robustness of the results. Finally, a mediation analysis via two-step MR was conducted to investigate any effects explained by common risk factors in these relationships. RESULTS: Genetically predicted per 1-SD increase in leisure time television watching significantly increased the risk of GERD in the bidirectional MR analysis (OR = 1.33; 95% CI: 1.14-1.56; P = 2.71 × 10- 4). Sensitivity analyses successfully verified the robustness of the causal relationship. Further mediation analysis showed that this effect was partly mediated by increasing cigarettes smoked per day, with mediated proportions of 18.37% (95% CI: 11.94-39.79%). CONCLUSION: Our findings revealed a causal relationship between leisure television watching and an increased risk of GERD, notably, the causal effect was partially mediated by cigarettes smoked per day. These findings may inform prevention and management strategies directed toward GERD.

Matrin-3 acts as a potential biomarker and promotes hepatocellular carcinoma progression by interacting with cell cycle-regulating genes.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The oncogenic role of Matrin-3 (MATR3), an a nuclear matrix protein, in HCC remains largely unknown. Here, we document the biological function of MATR3 in HCC based on integrated bioinformatics analysis and functional studies. According to the TCGA database, MATR3 expression was found to be positively correlated with clinicopathological characteristics in HCC. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve displayed the diagnostic and prognostic potentials of MATR3 in HCC patients, respectively. Pathway enrichment analysis represented the enrichment of MATR3 in various molecular pathways, including the regulation of the cell cycle. Functional assays in HCC cell lines showed reduced proliferation of cells with stable silencing of MATR3. At the same time, the suppressive effects of MATR3 depletion on HCC development were verified by xenograft tumor experiments. Moreover, MATR3 repression also resulted in cell cycle arrest by modulating the expression of cell cycle-associated genes. In addition, the interaction of MATR3 with cell cycle-regulating factors in HCC cells was further corroborated with co-immunoprecipitation and mass spectrometry (Co-IP/MS). Furthermore, CIBERSORT and TIMER analyses showed an association between MATR3 and immune infiltration in HCC. In general, this study highlights the novel oncogenic function of MATR3 in HCC, which could comprehensively address how aberrant changes in the cell cycle promote HCC development. MATR3 might serve as a prognostic predictor and therapeutic target for HCC patients.

Sex hormone-binding globulin exerts sex-related causal effects on lower extremity varicose veins: evidence from gender-stratified Mendelian randomization.

Background: The association between serum sex hormones and lower extremity varicose veins has been reported in observational studies. However, it is unclear whether the association reflects a causal relationship. Besides, serum sex hormone-binding globulin (SHBG) has been rarely studied in lower extremity varicose veins. Here, we aim to investigate the association between serum levels of SHBG, testosterone, and estradiol and the risk of lower extremity varicose veins using Mendelian randomization (MR). Methods: We obtained genome-wide association study summary statistics for serum SHBG levels with 369,002 European participants, serum testosterone levels with 424,907 European participants, serum estradiol levels with 361,194 European participants, and lower extremity varicose veins with 207,055 European participants. First, a univariable MR was performed to identify the causality from SHBG and sex hormone levels to lower extremity varicose veins with several sensitivity analyses being performed. Then, a multivariable MR (MVMR) was performed to further assess whether the causal effects were independent. Finally, we performed a gender-stratified MR to understand the role of genders on lower extremity varicose veins. Results: Genetically predicted higher serum SHBG levels significantly increased the risk of lower extremity varicose veins in the univariable MR analysis (OR=1.39; 95% CI: 1.13-1.70; P=1.58×10-3). Sensitivity analyses and MVMR (OR=1.50; 95% CI:1.13-1.99; P=5.61×10-3) verified the robustness of the causal relationships. Gender-stratified MR revealed that higher serum SHBG levels were associated with lower extremity varicose veins in both sexes. However, the OR of serum SHBG levels on lower extremity varicose veins risk in females (OR=1.51; 95% CI: 1.23-1.87; P=1.00×10-4) was greater than in males (OR=1.26; 95% CI: 1.04-1.54; P=1.86×10-2). Conclusions: Serum SHBG levels are positively related to lower extremity varicose veins risk in both sexes, especially in females. This may partly explain the higher prevalence of varicose vines among females.

MEGF6 prevents sepsis-induced acute lung injury in mice.

OBJECTIVE: Acute lung injury (ALI) is featured as excessive inflammatory response and oxidative damage, and results in high death rate of septic patients. This research intends to determine the function of multiple EGF like domains 6 (MEGF6) in sepsis-induced ALI. METHODS: Mice were intratracheally treated with adenovirus to knock down or overexpress MEGF6 in lung tissues, and then were subjected to cecum ligation and puncture (CLP) operation to induce ALI. Primary peritoneal macrophages were isolated, and were knocked down or overexpressed with MEGF6, and then, were stimulated with lipopolysaccharide (LPS) to confirm its role in vitro. RESULTS: Serum and lung MEGF6 levels were significantly elevated in septic mice. MEGF6 knockdown exacerbated, while MEGF6 overexpression prevented inflammation, oxidative damage and ALI in CLP mice. Meanwhile, LPS-elicited inflammatory response and oxidative damage in primary macrophages were reduced by MEGF6 overexpression, but were further aggravated by MEGF6 knockdown. Mechanistic studies revealed that MEGF6 reduced cluster of differentiation 38 (CD38) expression and subsequently elevated intracellular nicotinamide adenine dinucleotide levels, thereby activating sirtuin 1 (SIRT1) without affecting the protein expression. SIRT1 suppression or CD38 overexpression with either genetic or pharmacologic methods remarkably blunted the lung protective effects of MEGF6 in CLP mice. CONCLUSION: MEGF6 prevents CLP-induced ALI through CD38/SIRT1 pathway, and it might be a valuable therapeutic candidate for the management of sepsis-induced ALI.

Limonin, a novel AMPK activator, protects against LPS-induced acute lung injury.

AMP-activated protein kinase (AMPK) activation plays crucial roles in the treatment of many oxidative stress- and inflammation-induced diseases, including acute lung injury (ALI). Limonin is a naturally occurring tetracyclic triterpenoid extracted from the plants of Rutaceae and Meliaceae. Limonin also serves as an AMPK activator with anti-inflammatory and anti-oxidation effects. However, the potential beneficial effects of limonin on ALI and the possible mechanisms have never been disclosed till now. Here, the effects of limonin on lipopolysaccharide (LPS)-induced ALI in C57 BL/6 mice, plus bone marrow-derived macrophages (BMDM) stimulated with LPS to induce in vitro ALI model were investigated. Limonin significantly improved pulmonary function and alleviated lung pathological injury in LPS-induced mice. Meanwhile, limonin also markedly decreased inflammation and oxidative stress in lung tissues from LPS-treated mice. In vitro experiments also unveiled that limonin could decrease inflammation and oxidative stress in LPS-induced BMDM in a concentration-dependent manner. Mechanically, limonin could promote the activation of AMPKα and upregulate the expression of nuclear factor erythroid 2-related factor 2 (NRF2) in lung tissues and BMDM. Pharmacological inhibition of AMPKα by Compound C or AMPKα knockout could abolish the pulmonary protection from limonin during ALI. In conclusion, limonin mediates the activation of AMPKα/NRF2 pathway, providing an attractive therapeutic target for ALI in the future.

Nesfatin-1, a novel energy-regulating peptide, alleviates pulmonary fibrosis by blocking TGF-ß1/Smad pathway in an AMPKα-dependent manner.

Pulmonary fibrosis is a chronic progressive disease which steadily causes a critical public health concern. Nesfatin-1, a novel energy-regulating peptide discovered in 2006, could increase the level of AMPK phosphorylation. Previous studies have unveiled that Nesfatin-1 possessed many pharmacological effects including anti-inflammation, anti-oxidative stress, anti-fibrosis, and the regulation of lipid metabolism. Here, we investigated the impact of Nesfatin-1 on pulmonary fibrosis. Male C57BL/6J mice were intraperitoneally injected with Nesfatin-1 (10 µg·kg-1·day-1) for 21 days since mice were intratracheally administrated with bleomycin (BLM) (2 U/kg). Primary murine lung fibroblasts were stimulated with TGF-ß1 (10 ng/ml) for 48 h. The results showed that Nesfatin-1 treatment significantly improved pulmonary function and decreased the production of collagen in BLM-treated mice. Meantime, Nesfatin-1 treatment also inhibited oxidative stress and inflammation in lung tissues from BLM-treated mice. Mechanically, Nesfatin-1 blocked the activation of TGF-ß1/Smad2/3 signaling pathway in lung tissues challenged with BLM. In addition, we found that Nesfatin-1 enhanced the phosphorylation of AMPKα during pulmonary fibrosis. However, pharmacological inhibition or genetic deletion of AMPKα could both offset the pulmonary protection mediated by Nesfatin-1 during pulmonary fibrosis. Our experimental results firstly show Nesfatin-1 might serve as a novel treatment or adjuvant against pulmonary fibrosis by blocking TGF-ß1/Smad pathway in an AMPKα-dependent manner.

Panorama of Breakthrough Infection Caused by SARS-CoV-2: A Review.

Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in 2019, many countries have successively developed a variety of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, with the continuous spread of SARS-CoV-2, it has evolved several variants; as a result, prevention and control of the pandemic of SARS-CoV-2 has become more important. Among these variants, the Omicron variant has higher transmissibility and immune escape ability and is the main variant causing a large number of COVID-19 breakthrough infection, thus, presenting new challenges to pandemic prevention and control. Hence, we review the biological characteristics of the Omicron variant and discuss the current status and possible mechanism of breakthrough infection caused by the Omicron variant in order to provide insights into the prevention and control of the pandemic of SARS-CoV-2.

The Application of Two-Stage Operation for High-Risk Patients with Oesophageal Cancer Following Gastrectomy.

BACKGROUND: Oesophageal replacement by colonic interposition remains a major challenge due to its complexity and high incidence of complications; here we applied the two-stage operation strategy to oesophageal replacement by colonic interposition in high-risk oesophageal cancer patients following gastrectomy. METHODS: We performed a retrospective analysis on the data of patients with a history of distal gastrectomy who underwent one-stage and two-stage oesophageal replacement by colonic interposition from February 2012 to February 2020, and explored the relationship between the staging strategy and postoperative outcomes. RESULTS: The clinical data of 93 patients were collected and analysed. There were no significant differences in the patients' characteristics between the two groups (all p > 0.05), except for comorbidities and Charlson Comorbidity Index (all p < 0.05). The Clavien-Dindo score between the two groups was also not significantly different (p > 0.05). The logistic regression models revealed that patients who had received preoperative therapy had a higher Clavien-Dindo score (p < 0.05), but the stage strategy did not (p > 0.05). CONCLUSIONS: The two-stage operation is feasible in high-risk patients who need to undergo colonic interposition for oesophageal replacement. At the same time, it lowers the technical threshold of colonic interposition for oesophageal replacement, increasing this surgical technique's acceptability.

TTYH3, a potential prognosis biomarker associated with immune infiltration and immunotherapy response in lung cancer.

PURPOSE: The recognition of new diagnostic and prognostic biological markers for lung cancer is an essential and eager study. It's shown that ion channels play important roles in regulating various cellular processes and have been suggested to be associated with patient survival. However, tweety family member 3 (TTYH3), as a maxi-Cl- channel, its role in lung cancer remains elusive. METHODS: The expression, diagnostic and prognostic efficacy of TTYH3 were analyzed by public databases and clinical samples. Cell functional experiments were used to explore the effects of TTYH3 on cell viability. GO and KEGG enrichment analysis revealed underlying pathways that TTYH3 and its co-expressed genes were enriched in. TIMER, TIDE and R language analyses were used to detect the correlation between TTYH3 and immune infiltration cell and immunotherapy response. RESULTS: TTYH3 was up-regulated in lung cancer tissues compared to normal tissues and possessed a prominent diagnostic and prognostic value. TTYH3 knockdown significantly inhibited the proliferation of lung cancer cells. Enrichment analyses showed that TTYH3 and its co-expressed genes were mainly involved in immune related signaling pathways. Further investigation clarified that TTYH3 had a positive correlation with the infiltration of TAMs, Treg infiltration as well as T cell exhaustion and high TTYH3 expression indicated worse immunotherapy response and shorter survival after immune checkpoint blockade treatment. CONCLUSION: This study not only revealed the diagnostic and prognostic value of TTYH3 but also provided TTYH3-based estimation of immunotherapy response for lung cancer patients, which might provide new strategies like anti-TTYH3 combined with immune therapy for the treatment of lung cancer.

Insulin receptor substrate 1(IRS1) is related with lymph node metastases and prognosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related mortality globally with a high risk of lymph node metastasis (LNM). In this study, weighted gene co-expression network analysis (WGCNA) showed the identification of 10 modules among which the significant module (turquoise), including 1352 genes, was correlated with LNM. A group 52 overlapping differentially expressed genes (DEGs) was identified based on the comparison of turquoise module with GSE23400 and GSE20347 datasets. Using Ctyohubba plugin, we identified 7 hub genes (ACTG2, SORBS1, MYH11, CXCL12, CNN1, IRS1 and CXCL8). IRS1 displayed significant correlation with metastasis. The decreased expression of IRS1 was also a predictor of poor OS of ESCC patients whereas the hub genes namely ACTG2, MYH11, CXCL8, CXCL12, IRS1 and CNN1 were associated with RFS of ESCC patients. These findings suggest that the altered expression of these hub genes are associated with prognosis and thus can be used as potential biomarkers for ESCC. Moreover, immunohistochemical staining and cell functional experiments displayed that the overexpression of IRS1 was negatively associated with metastasis in ESCC. In general, our research revealed several novel genes in ESCC especially the association of IRS1 with LNM in ESCC, which could provide novel insights into the initiation and progression of ESCC.

MicroRNA-31-5p Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via Inactivating Cab39/AMPKα Pathway.

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPKα) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPKα to exert the protective effects that were abrogated by AMPKα inhibition. Further studies revealed that Cab39 was required for AMPKα activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPKα.

Placenta­derived mesenchymal stem cells ameliorate lipopolysaccharide­induced inflammation in RAW264.7 cells and acute lung injury in rats.

Acute lung injury (ALI) is a severe lung syndrome with high morbidity and mortality, due to its complex mechanism and lack of effective therapy. The use of placenta­derived mesenchymal stem cells (pMSCs) has provided novel insight into treatment options of ALI. The effects of pMSCs on lipopolysaccharide (LPS)­induced inflammation were studied using a co­culture protocol with LPS­stimulated RAW264.7 cells. An LPS­induced ALI Sprague­Dawley rat model was developed by intravenously injecting 7.5 mg/kg LPS, and intratracheal instillation of 1x105 pMSCs was performed after administration of LPS to investigate the therapeutic potential of these cells. pMSCs ameliorated LPS­induced ALI, as suggested by downregulated pro­inflammatory cytokine tumor necrosis factor­α and increased anti­inflammatory cytokine interleukin­10 in both cell and animal models. Moreover, the protein and leukocyte cells in bronchoalveolar lavage fluid decreased at a rapid rate after treatment with pMSCs. Histopathology demonstrated that pMSCs alleviated the infiltration of inflammatory cells, pulmonary hyperemia and hemorrhage, and interstitial edema. In addition, pMSC reduced the LPS­induced expression of C­X­C motif chemokine ligand 12 in RAW264.7 macrophages and in lung tissue of ALI rats. This demonstrated that pMSCs are therapeutically effective in LPS­induced ALI.

MicroRNA­375 prevents TGF­ß­dependent transdifferentiation of lung fibroblasts via the MAP2K6/P38 pathway.

Transdifferentiation of lung fibroblasts to myofibroblasts is a crucial pathophysiological process in pulmonary fibrosis. MicroRNA­375 (miR­375) was initially identified as a tumor­suppressive factor, and its expression was negatively associated with the severity of lung cancer; however, its role and potential mechanism in myofibroblast transdifferentiation and pulmonary fibrosis remain unclear. In the present study, human lung fibroblasts were stimulated with transforming growth factor­ß (TGF­ß) to induce myofibroblast transdifferentiation. A mimic and inhibitor of miR­375, and their negative controls, were used to overexpress or suppress miR­375 in lung fibroblasts, respectively. The mRNA expression levels of fibrotic markers, and protein expression of α­smooth muscle actin and periostin, were subsequently detected by reverse transcription­quantitative PCR and western blotting, to assess myofibroblast transdifferentiation. miR­375 was markedly upregulated in human lung fibroblasts after TGF­ß stimulation. The miR­375 mimic alleviated, whereas the miR­375 inhibitor aggravated TGF­ß­dependent transdifferentiation of lung fibroblasts. Mechanistically, miR­375 prevented myofibroblast transdifferentiation and collagen synthesis by blocking the P38 mitogen­activated protein kinases (P38) pathway, and P38 suppression abrogated the deleterious effect of the miR­375 inhibitor on myofibroblast transdifferentiation. Furthermore, the present study revealed that mitogen­activated protein kinase kinase 6 was involved in P38 inactivation by miR­375. In conclusion, miR­375 was implicated in modulating TGF­ß­dependent transdifferentiation of lung fibroblasts, and targeting miR­375 expression may help to develop therapeutic approaches for treating pulmonary fibrosis.

GDF-15 prevents lipopolysaccharide-mediated acute lung injury via upregulating SIRT1.

Inflammation and oxidative stress were involved in alveolar epithelial cells (AECs) damage and contributed to the progression of acute lung injury (ALI). Growth differentiation factor-15 (GDF-15) was reported to have important roles in pulmonary diseases, yet its role in AECs damage and ALI remains elusive. Herein, we found that GDF-15 was upregulated upon LPS stimulation in murine lungs and human AECs. GDF-15 treatment prevented, whereas Gdf-15 silence aggravated LPS-induced inflammation, oxidative stress and apoptosis. Moreover, we determined that GDF-15 alleviated AECs damage and ALI via upregulating SIRT1, and SIRT1 suppression completely abrogated the beneficial effects of GDF-15 in vivo and in vitro. GDF-15 protected against LPS-triggered AECs damage and ALI via upregulating SIRT1, and GDF-15 might be a valuable therapeutic candidate for treating ALI.

Minichromosome maintenance protein 10 as a marker for proliferation and prognosis in lung cancer.

DNA replication is a vital process in cell division where anomalies can lead to tumorigenesis. Minichromosome maintenance complex component 10 (MCM10) plays a crucial role in this process. However, the role of MCM10 in lung cancer pathogenesis remains to be elucidated. In current study, using the publicly available lung cancer Gene Expression Omnibus (GEO) datasets, and Oncomine and the Cancer Genome Atlas databases, an increased expression of MCM10 was found in lung cancer tissues compared to normal lung tissues. The high expression of MCM10 was subsequently validated in clinical specimens by reverse transcription­quantitative PCR and immunohistochemistry. Analysis of the GEO datasets revealed that the high MCM10 expression was significantly associated with early and late recurrence, pathological stage and worse overall survival (OS). Cox's proportional hazards regression analyses revealed that MCM10 expression was an independent risk factor for poor OS and worse recurrence­free survival both in univariate and multivariate analysis. Furthermore, the increased expression of MCM10 was enriched in cell cycle­related processes, while in vitro transfection with small interfering RNA targeting MCM10 significantly suppressed cell viability, clone formation and induced G1 phase arrest in A549 and H661 cell lines by regulating the expression of cyclin D1 (CCND1). In addition, the current results indicated a combined effect of MCM10­CCND1 in predicting the prognosis of lung cancer patients. Altogether, the present study provided a novel potential molecular mechanism of lung cancer progression and may aid in development of novel treatment strategies.

Uridine-cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer.

Lung cancer has the highest morbidity and mortality among all cancers. Discovery of early diagnostic and prognostic biomarkers of lung cancer can greatly facilitate the survival rate and reduce its mortality. In our study, by analyzing Gene Expression Omnibus and Oncomine databases, we found a novel potential oncogene uridine-cytidine kinase 2 (UCK2), which was overexpressed in lung tumor tissues compared to adjacent nontumor tissues or normal lung. Then we confirmed this finding in clinical samples. Specifically, UCK2 was identified as highly expressed in stage IA lung cancer with a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). We also found that high UCK2 expression was related to poorer clinicopathological features, such as higher T stage and N stage and higher probability of early recurrence. Furthermore, we found that patients with high UCK2 expression had poorer first progression survival and overall survival than patients with low UCK2 expression. Univariate and multivariate Cox regression analyses showed that UCK2 was an independent risk factor related with worse DFS and OS. By gene set enrichment analysis, tumor-associated biological processes and signaling pathways were enriched in the UCK2 overexpression group, which indicated that UCK2 might play a vital role in lung cancer. Furthermore, in cytology experiments, we found that knockdown of UCK2 could suppress the proliferation and migration of lung cancer cells. In conclusion, our study indicated that UCK2 might be a potential early diagnostic and prognostic biomarker for lung cancer.

Colon Interposition for Corrosive Esophageal Stricture: Single Institution Experience with 119 Cases.

The colon is an alternative graft organ for esophageal reconstruction. The present study reviewed our experience with the colon interposition for esophageal replacement following corrosive ingestion, to evaluate the outcomes of colon interposition based on our surgical experience. The clinical data of 119 patients who underwent colon interposition for esophageal replacement from January 2005 to March 2017 were retrospectively analyzed. The routes of the colon interposition were retrosternal in 119 (100%). The median operative time was 390 min (range: 290-610 min) and the median blood loss was 615 mL (range: 270-2500 mL). Of these 119 patients, the cervical anastomosis was performed at the hypopharynx (n=20, 16.8%), the larynx (n=3, 2.5%), and the cervical esophagus (n=96, 80.7%). Five patients experienced cervical anastomotic leakage (4 cases for esophagus-colon, and one for hypopharynx-colon). One patient experienced wound infection of the abdominal wall. Three patients had injury of recurrent laryngeal nerve and hoarseness. Three patients had stress ulcer with bleeding and treated with octreotide. Two patients suffered from incomplete intestinal obstruction. The postoperative follow-up was made for 12 months in all patients and all of them were alive. In conclusion, The colon is well-suited for esophageal reconstruction. The selection of the colon graft should be flexible and be based on the inspection of blood supply and the length needed. We must therefore make every effort to reduce the number of postoperative complications, and improve the quality of life for patients.

Knockdown of Sfrp4 attenuates apoptosis to protect against myocardial ischemia/reperfusion injury.

Secreted frizzled-related protein (Sfrp) 4 is a protein that involve in cardiac development and several cardiovascular diseases. However, the effect of Sfrp4 in mediating myocardial ischemia/reperfusion injury remains unknown. In this work, adenoviral (Ad)-shSfrp4 adenoviruses was used to knockdown of Sfrp4 in myocardium to examine the role of Sfrp4 in mediating myocardial I/R injury. Knockdown of Sfrp4 in mice attenuated myocardial I/R injury, as indicated by the decrease levels of lactate dehydrogenase and creatine kinase, and increment of ventricular function following I/R injury. Besides, knockdown of Sfrp4 led to a reduction in Bax, active caspase 3, and increase Bcl-2 and c-Myc in cardiac tissue. Knockdown of Sfrp4 lost its protection against I/R injury in mice infected with Ad-dn-AKT. In conclusion, knockdown of Sfrp4 in myocardium attenuated myocardial ischemia and reperfusion injury by AKT signaling pathway.

miR-210 promotes lung adenocarcinoma proliferation, migration, and invasion by targeting lysyl oxidase-like 4.

Accumulating evidence has revealed that various microRNAs are deregulated and involved in lung cancer development and metastasis. miR-210 is implicated in several cancer progression. However, the detailed biological function and role of miR-210 in lung adenocarcinoma remains unclear. Our current study was aimed to investigate the mechanism of miR-210 in lung adenocarcinoma progression. We observed that miR-210 was significantly upregulated in lung cancer cell lines (A549 and H1650) in comparison to BEAS-2B cells. In addition, we found that miR-210 was greatly elevated in lung adenocarcinoma tissues. Then, it was shown that overexpression of miR-210 was able to promote lung cancer cell proliferation and colony formation ability while inhibitors of miR-210 exhibited a reversed phenomenon. Subsequently, A549 and H1650 cell migration and invasion capacity were obviously restrained by miR-210 inhibition whereas induced by miR-210 mimics. Lysyl oxidase-like 4 (LOXL4), a member of the secreted copper-dependent amine oxidases has been found to be increased or decreased in different cancer types. Here, we confirmed that LOXL4 could serve as a downstream target of miR-210 and miR-210 promoted lung cancer progression via targeting LOXL4. In A549 and H1650 cells, knockdown of LOXL4 dramatically repressed lung cancer cell proliferation, migration, and invasion. In conclusion, our study implied that miR-210 might indicate a new perspective for lung cancer.