Identification of potential anti-tumor targets and mechanisms of HuaChanSu injection using network pharmacology and cytological experiments in Breast cancer.

HuaChanSu (HCS) or Cinobufacini injection is an aqueous extract of the dried skin of Bufo bufo gargarigans, and has anti-tumor effects. The aim of this study was to evaluate the possible therapeutic effect of HCS against breast cancer (BRCA) using cytology, network pharmacology, and molecular biology approaches. The half-inhibitory concentration (IC50) of HCS in the BRCA cells was determined by cytotoxicity assay, and were accordingly treated with high and low doses HCS in the TUNEL and scratch assays. The potential targets of HCS in the BRCA cells were identified through functional enrichment analysis and protein-protein interaction (PPI) networks, and verified by molecular docking. The expression levels of key signaling pathways-related proteins in HCS-treated BRCA cells by western blotting. HCS inhibited the proliferation and migration of MCF-7 and MDA-MB-231 cells, and induced apoptosis in a dose-dependent manner. Furthermore, we screened 289 core HCS targets against BRCA, which were primarily enriched in the PI3K-AKT, MAPK chemokines, and other. signaling pathways. In addition, PIK3CA, PIK3CD, and MTOR were confirmed as HCS targets by molecular docking. Consistent with this, we observed a reduction in the expression levels of phosphorylated PI3K, AKT, and MTOR in the HCS-treated BRCA cells. Taken together, our findings suggest that HCS inhibits the growth of BRCA cells by targeting the PI3K-AKT pathway, and warrants further investigation as a therapeutic agent for treating patients with BRCA.

Progress of evapotranspiration research based on VOSviewer: A review.

Evapotranspiration (ET) is a key link between atmospheric processes and land surface hydrological processes. With the impact of global warming and human activities, research on ET has become a hot topic. Supported by a total of 1,222 Chinese and English literatures from China National Knowledge Infrastructure and the Web of Science Core Collection from 2013 to 2022, this paper adopts the bibliometric visualization method to review the current research progress and future trend of ET with respect to the time of publication, countries, institutions, journals, and research hotspots. The results show that the number of related research articles is increasing rapidly and the journals with high citations are Journal of Hydrology, Agricultural and Forest Meteorology and Agricultural Water Management. The research hotspots have been focused on prototype observation, remote sensing inversion, mechanism equation, model simulation, spatial-temporal analysis, and attribution identification. In the future, there is an urgent need to integrate algorithms such as machine learning and artificial intelligence, to develop higher resolution remote sensing products, to improve the mechanism equations based on precise observations, and to clarify the impact of synergistic effects on ET among the driving factors.

Uncoordinated sleep replay across hemispheres in the zebra finch.

Bilaterally organized brain regions are often simultaneously active in both humans1,2,3 and animal models,4,5,6,7,8,9 but the extent to which the temporal progression of internally generated dynamics is coordinated across hemispheres and how this coordination changes with brain state remain poorly understood. To address these issues, we investigated the zebra finch courtship song (duration: 0.5-1.0 s), a highly stereotyped complex behavior10,11 produced by a set of bilaterally organized nuclei.12,13,14 Unilateral lesions to these structures can eliminate or degrade singing,13,15,16,17 indicating that both hemispheres are required for song production.18 Additionally, previous work demonstrated broadly coherent and symmetric bilateral premotor signals during song.9 To precisely track the temporal evolution of activity in each hemisphere, we recorded bilaterally in the song production pathway. We targeted the robust nucleus of the arcopallium (RA) in the zebra finch, where population activity reflects the moment-to-moment progression of the courtship song during awake vocalizations19,20,21,22,23,24 and sleep, where song-related network dynamics reemerge in "replay" events.24,25 We found that activity in the left and right RA is synchronized within a fraction of a millisecond throughout song. In stark contrast, the two hemispheres displayed largely independent replay activity during sleep, despite shared interhemispheric arousal levels. These findings demonstrate that the degree of bilateral coordination in the zebra finch song system is dynamically modulated by behavioral state.

Encoding of dynamic facial information in the middle dorsal face area.

Faces in motion reveal a plethora of information through visual dynamics. Faces can move in complex patterns while transforming facial shape, e.g., during the generation of different emotional expressions. While motion and shape processing have been studied extensively in separate research enterprises, much less is known about their conjunction during biological motion. Here, we took advantage of the discovery in brain-imaging studies of an area in the dorsal portion of the macaque monkey superior temporal sulcus (STS), the middle dorsal face area (MD), with selectivity for naturalistic face motion. To gain mechanistic insights into the coding of facial motion, we recorded single-unit activity from MD, testing whether and how MD cells encode face motion. The MD population was highly sensitive to naturalistic facial motion and facial shape. Some MD cells responded only to the conjunction of facial shape and motion, others were selective for facial shape even without movement, and yet others were suppressed by facial motion. We found that this heterogeneous MD population transforms face motion into a higher dimensional activity space, a representation that would allow for high sensitivity to relevant small-scale movements. Indeed, we show that many MD cells carry such sensitivity for eye movements. We further found that MD cells encode motion of head, mouth, and eyes in a separable manner, requiring the use of multiple reference frames. Thus, MD is a bona fide face-motion area that uses highly heterogeneous cell populations to create codes capturing even complex facial motion trajectories.

Mechanism of CAV and CAVIN Family Genes in Acute Lung Injury based on DeepGENE.

BACKGROUND: The fatality rate of acute lung injury (ALI) is as high as 40% to 60%. Although various factors, such as sepsis, trauma, pneumonia, burns, blood transfusion, cardiopulmonary bypass, and pancreatitis, can induce ALI, patients with these risk factors will eventually develop ALI. The rate of developing ALI is not high, and the outcomes of ALI patients vary, indicating that it is related to genetic differences between individuals. In a previous study, we found multiple functions of cavin-2 in lung function. In addition, many other studies have revealed that CAV1 is a critical regulator of lung injury. Due to the strong relationship between cavin-2 and CAV1, we suspect that cavin-2 is also associated with ALI. Furthermore, we are curious about the role of the CAV family and cavin family genes in ALI. METHODS: To reveal the mechanism of CAV and CAVIN family genes in ALI, we propose DeepGENE to predict whether CAV and CAVIN family genes are associated with ALI. This method constructs a gene interaction network and extracts gene expression in 84 tissues. We divided these features into two groups and used two network encoders to encode and learn the features. RESULTS: Compared with DNN, GBDT, RF and KNN, the AUC of DeepGENE increased by 7.89%, 16.84%, 20.19% and 32.01%, respectively. The AUPR scores increased by 8.05%, 15.58%, 22.56% and 23.34%. DeepGENE shows that CAVIN-1, CAVIN-2, CAVIN-3 and CAV2 are related to ALI. CONCLUSION: DeepGENE is a reliable method for identifying acute lung injury-related genes. Multiple CAV and CAVIN family genes are associated with acute lung injury-related genes through multiple pathways and gene functions.

Attenuation of the Severity of Acute Respiratory Distress Syndrome by Pomiferin through Blocking Inflammation and Oxidative Stress in an AKT/Foxo1 Pathway-Dependent Manner.

Acute respiratory distress syndrome (ARDS) gives rise to uncontrolled inflammatory response and oxidative stress, causing very high mortality globally. Pomiferin is a kind of prenylated isoflavonoid extracted from Maclura pomifera, owning anti-inflammatory and antioxidant properties. However, the functions and possible mechanisms of pomiferin in lipopolysaccharide- (LPS-) induced ARDS remain unknown. C57BL/6 mice were injected with LPS (5 mg/kg) intratracheally to induce an in vivo ARDS model while RAW264.7 macrophages were stimulated with LPS (100 ng/ml) to induce an in vitro model. Our data demonstrated that pomiferin (20 mg/kg) significantly improved pulmonary function and lung pathological injury in mice with ARDS, apart from increasing survival rate. Meanwhile, pomiferin treatment also inhibited LPS-induced inflammation as well as oxidative stress in lung tissues. LPS stimulation significantly activated AKT/Foxo1 signal pathway in lung tissues, which could be reversed after pomiferin treatment. In vitro experiments further showed that 10, 20, and 50 µM of pomiferin could enhance cell viability of RAW264.7 macrophages stimulated with LPS. What is more, 3-deoxysappanchalcone (3-DE), one AKT agonist, was used to active AKT in RAW264.7 macrophages. The results further showed that 3-DE could abolish pomiferin-elicited protection in LPS-treated RAW264.7 macrophages, evidenced by activated inflammation and oxidative stress. Taken together, our study showed that pomiferin could exert an ARDS-protective effect by blocking the AKT/Foxo1 signal pathway to inhibit LPS-induced inflammatory response and oxidative injury, which may serve as a potential candidate for the treatment of ARDS in the future.

The mechanism and biomarker function of Cavin-2 in lung ischemia-reperfusion injury.

BACKGROUND: Lung Ischemia Reperfusion injury(LIRI) is one of the most predominant complications of ischemic lung disease. Cavin-2 emerged as a regulator of a variety of cellular processes, including endocytosis, lipid homeostasis, signal transduction and tumorigenesis, but the function of Cavin-2 in LIRI is unknown. The purpose of this study was to determine the predictive potential of Cavin-2 in protecting lung ischemia-reperfusion injury and its corresponding mechanisms. METHODS: We found the strong relationship between Cavin-2 and multiple immune-related genes by deep learning method. To reveal the mechanism of Cavin-2 in LIRI, the LIRI SD rat model was constructed to detect the expression of Cavin-2 in the lung tissue of SD rats after LIRI, and the expression of Cavin-2 in lung cell lines was also detected. The expression of IL-6, IL-10 and MDA in cells after Cavin-2 over-expression or knockdown was examined under hypoxic conditions. The expression levels of p-AKT, p-STAT3 and p-ERK1/2 were measured in over-expressing Cavin-2 cells under hypoxic-ischemia conditions, and then the corresponding blockers of AKT, STAT3 and ERK1/2 were given to verify, whether they play a protective role in LIRI. RESULTS: After hypoxia, the expression of Cavin-2 in rat lung tissues was significantly increased, and the cellular activity and IL-10 in Cavin-2 over-expressing cells were significantly higher than that of the control group, while IL-6 and MDA were significantly lower than that of the control group, while the above results were reversed in Cavin-2 knockdown cells; Meanwhile, the phosphorylation levels of AKT, STAT3, and ERK1/2 were significantly increased in Cavin-2 over-expression cells after hypoxia. When AKT, STAT3, and ERK1/2 specific blockers were given, they lost their protective effect against LIRI. CONCLUSIONS: Cavin-2 shows biomarker potential in protecting lung from ischemia-reperfusion injury through the survivor activating factor enhancement (SAFE) and reperfusion injury salvage kinase (RISK) pathway.

Dermcidin Enhances the Migration, Invasion, and Metastasis of Hepatocellular Carcinoma Cells In Vitro and In Vivo.

Background and Aims: Hepatocellular carcinoma (HCC) is a common primary liver neoplasm with high mortality. Dermcidin (DCD), an antimicrobial peptide, has been reported to participate in oncogenesis. This study assessed the effects and underlying molecular events of DCD overexpression and knockdown on the regulation of HCC progression in vitro and in vivo. Methods: The serum DCD level was detected using enzyme-linked immunosorbent assay. DCD overexpression, knockdown, and Ras-related C3 botulinum toxin substrate 1 (Rac1) rescue were performed in SK-HEP-1 cells using plasmids. Immunofluorescence staining, quantitative PCR, and Western blotting were used to detect the expression of different genes and proteins. Differences in HCC cell migration and invasion were detected by Transwell migration and invasion assays. A nude mouse HCC cell orthotopic model was employed to verify the in vitro data. Results: The level of serum DCD was higher in patients with HCC and in SK-HEP-1 cells. DCD overexpression caused upregulation of DCD, fibronectin, Rac1, and cell division control protein 42 homologue (Cdc42) mRNA and proteins as well as actin-related protein 2/3 (Arp2/3) protein (but reduced Arp2/3 mRNA levels) and activated Rac1 and Cdc42. Phenotypically, DCD overexpression induced HCC cell migration and invasion in vitro, whereas knockout of DCD expression had the opposite effects. A Rac1 rescue experiment in DCD-knockdown HCC cells increased HCC cell migration and invasion and increased the levels of active Rac1/total Rac1, Wiskott-Aldrich syndrome family protein (WASP), Arp2/3, and fibronectin. DCD overexpression induced HCC cell metastasis to the abdomen and liver in vivo. Conclusions: DCD promotes HCC cell migration, invasion, and metastasis through upregulation of noncatalytic region of tyrosine kinase adaptor protein 1 (Nck1), Rac1, Cdc42, WASP, and Arp2/3, which induce actin cytoskeletal remodeling and fibronectin-mediated cell adhesion in HCC cells.

Protein Arginine Methylation: An Emerging Modification in Cancer Immunity and Immunotherapy.

In recent years, protein arginine methyltransferases (PRMTs) have emerged as new members of a gene expression regulator family in eukaryotes, and are associated with cancer pathogenesis and progression. Cancer immunotherapy has significantly improved cancer treatment in terms of overall survival and quality of life. Protein arginine methylation is an epigenetic modification function not only in transcription, RNA processing, and signal transduction cascades, but also in many cancer-immunity cycle processes. Arginine methylation is involved in the activation of anti-cancer immunity and the regulation of immunotherapy efficacy. In this review, we summarize the most up-to-date information on regulatory molecular mechanisms and different underlying arginine methylation signaling pathways in innate and adaptive immune responses during cancer. We also outline the potential of PRMT-inhibitors as effective combinatorial treatments with immunotherapy.

MicroRNA-762 Modulates Lipopolysaccharide-induced Acute Lung Injury via SIRT7.

BACKGROUND: Inflammation and oxidative stress contribute to the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MicroRNA-762 (miR-762) has been implicated in the progression of inflammation and oxidative stress; however, its role in ALI remains unclear. In this study, we aim to investigate the role and underlying mechanisms of miR-762 in LPS-induced ALI. METHODS: Mice were intravenously injected with miR-762 antagomir, agomir or the negative controls for 3 consecutive days and then received a single intratracheal instillation of LPS (5 mg/kg) for 12 h to establish ALI model. Adenoviral vectors were used to knock down the endogenous SIRT7 expression. RESULTS: An increased miR-762 expression was detected in LPS-treated lungs. miR-762 antagomir significantly reduced inflammation, oxidative stress and ALI in mice, while the mice with miR-762 agomir treatment exhibited a deleterious phenotype. Besides, we found that SIRT7 upregulation was essential for the pulmonoprotective effects of miR-762 antagomir, and that SIRT7 silence completely abolished the anti-inflammatory and anti-oxidant capacities of miR-762 antagomir. CONCLUSION: miR-762 is implicated in the pathogenesis of LPS-induced ALI via modulating inflammation and oxidative stress, which depends on its regulation of SIRT7 expression. It might be a valuable therapeutic target for the treatment of ALI.

The function and mechanism of microRNA-92a-3p in lipopolysaccharide-induced acute lung injury.

OBJECTIVES: Sepsis-associated acute lung injury (ALI) is a clinically severe respiratory disorder and remains the leading cause of multiple organ failure and mortality. Herein, we used lipopolysaccharide (LPS) to generate sepsis-induced ALI and try to explore the role and mechanism of microRNA-92a-3p (miR-92a-3p) in this process. METHODS: Mice were intravenously injected with miR-92a-3p agomir, antagomir and negative controls for 3 consecutive days and then were intratracheally instillated by LPS (5 mg/kg) for 12 h. To knock down the endogenous A-kinase anchoring protein 1 (AKAP1), mice were intratracheally injected with recombinant adenovirus carrying the short hairpin RNA targeting AKAP1 (shAkap1) at 1 week before LPS administration. RESULTS: miR-92a-3p level was significantly upregulated in the lungs by LPS injection. miR-92a-3p antagomir reduced LPS-induced intrapulmonary inflammation and oxidative stress, thereby preventing pulmonary injury and dysfunction. In contrast, miR-92a-3p agomir aggravated LPS-induced intrapulmonary inflammation, oxidative stress, pulmonary injury and dysfunction. Moreover, we reported that AKAP1 upregulation was required for the beneficial effects of miR-92a-3p antagomir, and that AKAP1 knockdown completely abolished the anti-inflammatory and antioxidant capacities of miR-92a-3p antagomir. CONCLUSION: Our data identify that miR-92a-3p modulates LPS-induced intrapulmonary inflammation, oxidative stress and ALI via AKAP1 in mice.

Recent Advances in Self-Powered Piezoelectric and Triboelectric Sensors: From Material and Structure Design to Frontier Applications of Artificial Intelligence.

The development of artificial intelligence and the Internet of things has motivated extensive research on self-powered flexible sensors. The conventional sensor must be powered by a battery device, while innovative self-powered sensors can provide power for the sensing device. Self-powered flexible sensors can have higher mobility, wider distribution, and even wireless operation, while solving the problem of the limited life of the battery so that it can be continuously operated and widely utilized. In recent years, the studies on piezoelectric nanogenerators (PENGs) and triboelectric nanogenerators (TENGs) have mainly concentrated on self-powered flexible sensors. Self-powered flexible sensors based on PENGs and TENGs have been reported as sensing devices in many application fields, such as human health monitoring, environmental monitoring, wearable devices, electronic skin, human-machine interfaces, robots, and intelligent transportation and cities. This review summarizes the development process of the sensor in terms of material design and structural optimization, as well as introduces its frontier applications in related fields. We also look forward to the development prospects and future of self-powered flexible sensors.

Joint encoding of facial identity, orientation, gaze, and expression in the middle dorsal face area.

The last two decades have established that a network of face-selective areas in the temporal lobe of macaque monkeys supports the visual processing of faces. Each area within the network contains a large fraction of face-selective cells. And each area encodes facial identity and head orientation differently. A recent brain-imaging study discovered an area outside of this network selective for naturalistic facial motion, the middle dorsal (MD) face area. This finding offers the opportunity to determine whether coding principles revealed inside the core network would generalize to face areas outside the core network. We investigated the encoding of static faces and objects, facial identity, and head orientation, dimensions which had been studied in multiple areas of the core face-processing network before, as well as facial expressions and gaze. We found that MD populations form a face-selective cluster with a degree of selectivity comparable to that of areas in the core face-processing network. MD encodes facial identity robustly across changes in head orientation and expression, it encodes head orientation robustly against changes in identity and expression, and it encodes expression robustly across changes in identity and head orientation. These three dimensions are encoded in a separable manner. Furthermore, MD also encodes the direction of gaze in addition to head orientation. Thus, MD encodes both structural properties (identity) and changeable ones (expression and gaze) and thus provides information about another animal's direction of attention (head orientation and gaze). MD contains a heterogeneous population of cells that establish a multidimensional code for faces.

Diagnostic Value of Multislice Spiral CT Cardiothoracic Combined with Angiography in Acute Chest Pain.

Acute chest pain is a common clinical emergency condition with a variety of causes, including acute coronary syndrome, pulmonary embolism, aortic coarctation, and pneumothorax. It is essential for emergency physicians to quickly and accurately understand the cause of acute chest pain. 64-slice spiral CT combined cardiothoracic angiography is an accurate and rapid way to diagnose and differentiate the cause of acute chest pain. 64-slice combined cardiothoracic angiography can accurately and rapidly display the thoracic aorta, both pulmonary arteries, the main trunk of the coronary artery and its major branches, and also provide a comprehensive view of both lungs and mediastinum, which is an effective test for the diagnosis and differential diagnosis of acute chest pain. Based on this, this study further investigated the value of 64-slice spiral CT triplex examination in the diagnosis of acute chest pain. The results showed that 64-slice spiral CT has the advantages of fast scanning speed, high resolution, and advanced postprocessing technology, and combined cardiothoracic angiography can quickly and accurately help emergency physicians analyze the cause of acute chest pain, which plays a very important role in formulating the correct treatment plan in a timely manner. At the same time, with the continuous development of CT technology, the temporal and spatial resolution has improved the quality of CT images, giving us more options to reduce the effective radiation dose and reduce the total amount of contrast, making the 64-row spiral CT cardiothoracic imaging more perfect.

Corilagin Inhibits Esophageal Squamous Cell Carcinoma by Inducing DNA Damage and Down-Regulation of RNF8.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC), the most prevalent histologic subtype of esophageal cancer, is an aggressive malignancy with poor prognosis and a high incidence in the East. Corilagin, an active component present in Phyllanthus niruri L., has been shown to suppress tumor growth in various cancers. However, the effects of corilagin on ESCC and the mechanisms for its tumor suppressive function remain unknown. METHODS: Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assays. Annexin V/PI double-staining was performed to assess cell apoptosis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. A xenograft mice model was used to assess the in vivo antitumor effects of corilagin alone or in combination with cisplatin. RESULTS: We for the first time showed that corilagin was effectively able to inhibit ESCC cell proliferation and induce cell apoptosis. Additionally, our results validated its antitumor effects in vivo using a xenograft mouse model. Mechanistically, we found that corilagin caused significant DNA damage in ESCC cells. We found that corilagin could significantly attenuate the expression of the E3 ubiquitin ligase RING finger protein 8 (RNF8) through ubiquitin-proteasome pathway, leading to the inability of DNA damage repair response and eventually causing cell apoptosis. Furthermore, we also showed that corilagin substantially enhanced the antitumor effects of chemotherapy drug cisplatin both in vitro and in vivo. CONCLUSION: Our results not only provided novel and previously unrecognized evidences for corilagin-induced tumor suppression through inducing DNA damage and targeting RNF8 in ESCC, but also highlighted that corilagin might serve as an adjunctive treatment to conventional chemotherapeutic drugs in ESCC patients.

Co-expression network analysis identified KIF2C in association with progression and prognosis in lung adenocarcinoma.

Lung cancer is a malignant tumor with high morbidity and mortality, of which 80% is non-small cell lung cancer (NSCLC). And lung adenocarcinoma (LUAD) is the most important and common subtype in the NSCLC. In current study, the microarray data GSE31210 containing LUAD (n= 226) and normal lung tissue (n= 20) was analyzed to identify 965 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Finally, it was confirmed that there was a significant correlation between brown module and LUAD stage. In the significant module, a total of 54 network hub genes were identified, and six of them were also identified as hub genes of the protein-protein interaction network. In validation, KIF2C showed a higher correlation with disease stage than other hub genes (p< 0.001, R2 = 0.955). Functional enrichment suggests that KIF2C is associated with cell mitosis and cell cycle. Combined with clinicopathological parameters, we found that the high expression of KIF2C is closely related to the relapse and tumor stage of LUAD. Survival analysis showed a significant reduction in overall survival in LUAD patients with high expression of KIF2C. Gene set enrichment analysis (GSEA) also showed that the "cell cycle signaling pathway" and "P53 related pathway" were significantly enriched in LUAD samples with high expression of KIF2C (FDR < 0.05). In conclusion, based on the co-expression analysis, KIF2C was identified in the association with progression and prognosis of LUAD, which might refer a poor prognosis probably by regulating cell cycle signaling pathway.

Overexpression of Ulk2 inhibits proliferation and enhances chemosensitivity to cisplatin in non-small cell lung cancer.

The aim of the present study was to examine the function of unc-51 like autophagy activating kinase 2 (Ulk2) in non-small cell lung cancer (NSCLC). Western blotting was used to analyze the protein expression of Ulk2 in seven pairs of cancerous and adjacent non-cancerous NSCLC specimens. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to determine the mRNA expression of Ulk2 in 20 pairs of tumor and adjacent normal tissues. Two NSCLC cell lines, A549 and H460, were transfected with an Ulk2 overexpression plasmid or empty vector; cell proliferation and chemosensitivity were measured using an MTT assay, and flow cytometry and western blotting were used to evaluate apoptosis. A nude mouse tumorigenesis experiment was used to assess tumor volume in vivo, using A549 cells stably overexpressing Ulk2 and control cells. The protein expression levels of Ulk2 were significantly lower in 6/7 (85.7%) cases of NSCLC compared with in non-cancerous tissues, as determined by western blotting (P<0.05). The mRNA expression levels of Ulk2 were significantly lower in 16/20 (70.0%) NSCLC specimens compared with in non-cancerous tissues, as revealed by RT-qPCR (P<0.05). Overexpression of Ulk2 significantly inhibited the proliferation of A549 and H460 cells (P<0.05) and sensitized the NSCLC cell lines to cisplatin- and etoposide-induced inhibition of proliferation, and to cisplatin-induced apoptosis, with a significant difference identified compared with the control group (P<0.05). Overexpression of Ulk2 significantly increased basal autophagy levels in A549 and H460 cells (P<0.05). Thus, Ulk2-induced enhanced chemosensitivity was suggested to be partly mediated through increased autophagy. The overexpression of Ulk2 significantly suppressed tumor volume in vivo (P<0.05). Overexpression of Ulk2 inhibits cancer cell proliferation and enhances chemosensitivity to cisplatin in NSCLC.

To compare the efficacy between fixation with tightrope and screw in the treatment of syndesmotic injuries: A meta-analysis.

BACKGROUND: To compare the efficacy between fixation with suture-button and screw in the treatment of syndesmotic injuries: a meta-analysis. METHODS: We comprehensively searched PubMed, Embase, and the Cochrane Library and performed a meta-analysis of randomized controlled trials (RCTs) and retrospective comparative studies (RTCs). We performed using Review Manager 5.2. RESULTS: Three RCTs and six retrospective studies were conducted, including a total of 397 patients. The significant differences of the fixation of suture-button were reported for AOFAS scores (at 3, 6 and 12 months follow-up), full-weight time, reoperation, malreduction and the rate of failure of fixation. There were no significant differences between the groups regarding complications of infection, VAS, OMAS, range of motion, TFCS, TFO and MCS. CONCLUSIONS: Neither the functional outcome nor complications significantly differed between the fixation methods, but suture-button might lead to a quicker return to work. This analysis needs to be confirmed and updated by larger sample data and rigorously designed RCTs.

Neuregulin1 acts as a suppressor in human lung adenocarcinoma via AKT and ERK1/2 pathway.

BACKGROUND: Neuregulin1 (NRG1) is critical signaling protein that mediates the activation of downstream signaling pathways associated with malignancies. Multiple gene fusions related to NRG1 have been found in lung cancer. However, the underlying role NRG1 in lung cancer is yet unclear. Therefore, the present study investigated the biological functions on human lung adenocarcinoma (LUAD). METHODS: The expression of NRG1 was detected in LUAD tissues by Western blot (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The expression of NRG1 was upregulated by the addition of exogenous NRG1 and downregulated by small interfering RNA (siRNA), and the biological behaviors of LUAD cells were assessed: cell proliferation by MTT assay, cell cycle and apoptosis by flow cytometry analysis, and migration and invasion using Transwell system. Finally, the pathway underlying the cellular function was analyzed by WB. RESULTS: A lower expression of NRG1 was observed in LUAD cancer tissues (P<0.05). Moreover, the addition of exogenous NRG1 reduced the cell proliferation, migration, and invasion (P<0.001), while the downregulation of endogenous NRG1 promoted the three kinds of biological behaviors of LUAD cell lines (P<0.001); however, these manifestations did no effect on the distribution of cell cycle and apoptosis status (P>0.05). Furthermore, the deficiency of NRG1 reduced the expression of p-ERK1/2 and p-AKT at the protein level (P<0.001). CONCLUSIONS: The current results suggested that NRG1 might be a suppressor in the development of LUAD, and its function was related to AKT and ERK1/2 pathway.

Oestrogen receptor ß5 and epidermal growth factor receptor synergistically promote lung cancer progression.

Oestrogen receptor beta (ERß) and epidermal growth factor receptor (EGFR) pathway can synergistically promote the proliferation, invasion, and metastasis of non-small-cell lung cancer (NSCLC) cells. ERß has five subtypes, and the selective splicing of exon 8 in ERß5 transcription translational phase makes its biological function different from other subtypes. The following study investigates whether ERß5 interacts with EGFR pathway in lung cancer. Briefly, we found that the overexpression of ERß5 and EGFR is associated with poor prognosis and decreased overall survival in NSCLC patients. Furthermore, the effects of ERß5 and EGFR on cell biological behaviour were investigated in vitro. These results indicated that the combination of ERß5 and EGF induces cell proliferation and invasion, while the combination of ERß5 and Gefitinib (EGFR inhibitors, Gef) induces cell apoptosis and promotes cell mitosis in A549 cell line. In addition, the combination of ERß5 and EGF increases the expression of ERß5, EGFR, and p-ERK1/2 in lung cancer cells. To sum up, the obtained results suggest that ERß5 and EGFR synergistically promote the progression of lung cancer by activating MEK/ERK signalling pathway, which provides a theoretical basis for more accurate combined targeted therapy.