MicroRNA-196b promotes gastric cancer progression by targeting ECRG4.

Gastric cancer is one of the most common malignant tumors. MicroRNA-196b (miR-196b) has been demonstrated to play important roles in human cancers. However, its functions in gastric cancer progression were still largely unknown. In this study, the expression of miR-196b was determined by quantitative real-time PCR. Esophageal cancer-related gene 4 (ECRG4) level was examined by western blot assay and immunohistochemistry staining assay. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were analyzed by transwell assay. The association between miR-196b and ECRG4 was analyzed by dual-luciferase reporter assay. The functional role of miR-196b in vivo was analyzed by murine xenograft assay. As a result, we found the expression of miR-196b was elevated and the protein expression of ECRG4 was reduced in gastric cancer tissues and cells. MiR-196b inhibition suppressed gastric cancer cell proliferation, migration and invasion. ECRG4 was a target of miR-196b and its protein expression was negatively regulated by miR-196b. Moreover, ECRG4 overexpression showed similar effects with miR-196b inhibition on the malignant behaviors of GC cells and ECRG4 knockdown reversed the effects of miR-196b inhibition on gastric cancer cell proliferation, migration and invasion. In addition, miR-196b inhibition suppressed tumor volume and weight in vivo. In conclusion, downregulation of miR-196b inhibited gastric cancer progression by modulating ECRG4 expression, indicating that miR-196b might be a potential therapeutic target for gastric cancer.

Identification of metabolism-associated pathways and genes involved in male and female liver cancer patients.

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is influenced by sex and multiple metabolic abnormalities. The present study aimed to compare the overall metabolic changes between male and female HCC patients and identify key metabolic genes. Metabolic genes and pathways were identified based on analyses of publicly available data. Differential expression analysis, gene set enrichment analysis, survival analysis and transcriptional regulation analysis were employed to explore sex differences and identify key metabolic genes in HCC. The results suggested that female patients had more severe metabolic gene expression abnormalities and pathway deregulation than male patients. This study identified 9 key metabolic genes, and only upregulated ALDH1A2 independently increased overall survival risk in patients. Bioinformatic analyses suggest that upregulated GATA3 and TAL1 activate ALDH1A2 and then disrupt amino acid and carbohydrate metabolism, which may increase the risk of HCC. This study identified a novel contribution of upregulated ALDH1A2 to HCC. Future studies are needed to elucidate the potential metabolic mechanism of the role of ALDH1A2 in HCC.

How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane.

Antimicrobial peptides (AMPs), as a key component of the immune defense systems of organisms, are a promising solution to the serious threat of drug-resistant bacteria to public health. As one of the most representative and extensively studied AMPs, melittin has exceptional broad-spectrum activities against microorganisms, including both Gram-positive and Gram-negative bacteria. Unfortunately, the action mechanism of melittin with bacterial membranes, especially the underlying physics of peptide-induced membrane poration behaviors, is still poorly understood, which hampers efforts to develop melittin-based drugs or agents for clinical applications. In this mini-review, we focus on recent advances with respect to the membrane insertion behavior of melittin mostly from a computational aspect. Membrane insertion is a prerequisite and key step for forming transmembrane pores and bacterial killing by melittin, whose occurrence is based on overcoming a high free-energy barrier during the transition of melittin molecules from a membrane surface-binding state to a transmembrane-inserting state. Here, intriguing simulation results on such transition are highlighted from both kinetic and thermodynamic aspects. The conformational changes and inter-peptide cooperation of melittin molecules, as well as melittin-induced disturbances to membrane structure, such as deformation and lipid extraction, are regarded as key factors influencing the insertion of peptides into membranes. The associated intermediate states in peptide conformations, lipid arrangements, membrane structure, and mechanical properties during this process are specifically discussed. Finally, potential strategies for enhancing the poration ability and improving the antimicrobial performance of AMPs are included as well.

Morusin suppresses the stemness characteristics of gastric cancer cells induced by hypoxic microenvironment through inhibition of HIF-1α accumulation.

Gastric cancer (GC) is a common, life-threatening malignancy that contributes to the global burden of cancer-related mortality, as conventional therapeutic modalities show limited effects on GC. Hence, it is critical to develop novel agents for GC therapy. Morusin, a typical prenylated flavonoid, possesses antitumor effects against various cancers. The present study aimed to demonstrate the inhibitory effect and mechanism of morusin on the stemness characteristics of human GC in vitro under hypoxia and to explore the potential molecular mechanisms. The effects of morusin on cell proliferation and cancer stem cell-like properties of the human GC cell lines SNU-1 and AGS were assessed by MTT assay, colony formation test, qRT-PCR, flow cytometry analysis, and sphere formation test under hypoxia or normoxia condition through in vitro assays. The potential molecular mechanisms underlying the effects of morusin on the stem-cell-like properties of human GC cells in vitro were investigated by qRT-PCR, western blotting assay, and immunofluorescence assay by evaluating the nuclear translocation and expression level of hypoxia-inducible factor-1α (HIF-1α). The results showed that morusin exerted growth inhibitory effects on SNU-1 and AGS cells under hypoxia in vitro. Moreover, the proportions of CD44+/CD24- cells and the sphere formation ability of SNU-1 and AGS reduced in a dose-dependent manner following morusin treatment. The expression levels of stem cell-related genes, namely Nanog, OCT4, SOX2, and HIF-1α, gradually decreased, and the nuclear translocation of the HIF-1α protein was apparently attenuated. HIF-1α overexpression partially reversed the abovementioned effects of morusin. Taken together, morusin could restrain stemness characteristics of GC cells by inhibiting HIF-1α accumulation and nuclear translocation and could serve as a promising compound for GC treatment.

An empirical analysis of the factors driving customers' purchase intention of green smart home products.

With the improvement of consumers' environmental awareness and the popularity of the Internet of Things, green smart home products (GSHPs) are becoming the dominant trend of future home life. This shift not only makes tedious home life easier and more convenient but also helps families save energy and reduce carbon emissions. However, given the impact of the current technological level, the proportion of users who actually purchase GSHPs remains small. Thus, seeking ways to promote the consumption of GSHPs has become an urgent issue. Hence, this study seeks to fill the gap in the existing research on green consumption behavior and obtain a full understanding of the factors influencing the purchase intention of GSHPs. To do so, this work uses task-technology fit theory and considers the actual situation of green smart home consumption to add social-technology fit into the original theoretical basis. In particular, this research focuses on middle- and high-end Chinese consumers who have experience in purchasing GSHPs. Moreover, it aims for an in-depth exploration of the formation mechanism of Chinese consumers' purchase intention for GSHPs through structural equation modeling. Using survey data collected from 331 green smart home product users in China, the study empirically examines the relationships among autonomy, environmental agility, sense of belonging, and self-actualization, and both task-technology fit and social-technology fit, which are expected to shape the purchase intention of GSHP users. The empirical results provide broad support for our hypotheses. The results of this study offer important contributions to the increasing research on GSHPs consumption and shed light on the importance of both technology characteristics and the needs of users in achieving both task-technology fit and social-technology fit and, ultimately enhancing the users' intention to purchase GSHPs.

A Moral Cleansing Process: How and When Does Unethical Pro-organizational Behavior Increase Prohibitive and Promotive Voice.

In this study, we draw on moral cleansing theory to investigate the consequence of unethical pro-organizational behavior (UPB) from the perspective of the actors. Specifically, we hypothesize that after conducting UPB, people may feel guilty and tend to cleanse their wrongdoings by providing suggestions or identifying problems at work (i.e., prohibitive and promotive voice). We further hypothesize that the above relationship is moderated by the actor's moral identity symbolization. We conducted three studies, including experiment and surveys, to test our hypotheses. Results of these studies show consistent support to our hypotheses. In particular, individuals reported more felt guilt after conducting UPB, and they tended to compensate with more prohibitive and promotive voice subsequently. In addition, the indirect relationship from UPB acting to both voice behaviors via felt guilt was stronger for people with a high level of moral identity symbolization. Theoretical and practical implications are discussed.

What Drives Employees' Innovative Behaviors in Emerging-Market Multinationals? An Integrated Approach.

The coronavirus disease 2019 (COVID-19) pandemic has severely damaged the global industrial supply chain and accelerated the digital transformation of the global economy. In such rapidly changing environments, multinational corporations (MNCs) should encourage employees to be more innovative in various fields than ever before. With the onset of the COVID-19 pandemic, employees have become psychologically anxious, their working conditions have deteriorated, and they are in danger of losing their jobs. In this study, we aim to address the question of whether servant leadership facilitates the innovative behavior of employees working in emerging-market MNCs when servant leadership is adopted within the firms. In addition, we explore the mediating roles of work-life balance and psychological stability perceived by employees, and the moderating role of organizational climate in the relationship between servant leadership and MNC employees' innovative behavior. In doing so, we collected data from a sample of 307 Chinese employees who are employed by five different Chinese MNCs from the Internet, information technology, electronics, and e-commerce industries. Based on a sample of survey data collected from employees of Chinese MNCs, we empirically test these ideas by specifically examining how servant leadership may shape the innovation behavior of employees in these MNCs. The results suggest that servant leadership positively influences employees' innovative behavior, and that the contribution of servant leadership to employees' innovative behavior is mediated by work-life balance and psychological stability as well as moderated by the degree of organizational climate. Moreover, the different organizational climates of these MNC employees are also expected to significantly shape the relationship between servant leadership and employees' innovative behavior. This study enriches our understanding of the importance of servant leadership in driving the innovative behaviors of employees in emerging-market MNCs and provides new insights into the mechanisms through which emerging-market MNCs can motivate their employees to be more innovative in their jobs. Thus, this study contributes to the research on human resource management by offering important implications vis-à-vis how MNCs manage their employees more effectively in addressing and responding to the dramatically changing global landscape in the post COVID-19 era.

Swertiamarin suppresses proliferation, migration, and invasion of hepatocellular carcinoma cells via negative regulation of FRAT1.

Studies have shown that swertiamarin (STM) has multiple biological activities, but its anti-tumour effects and molecular mechanisms are still unclear. The present research aimed to validate the STM's impacts on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and to study its potential mechanism. Two HCC cell lines were treated with STM. Tumour growth was observed by the mouse tumour xenografts model. HCC cell lines stably expressing T-cell lymphomas 1 (FRAT1) were generated by lentivirusmediated overexpression. Cell viability, proliferation, migration, and invasion were observed using Cell Counting Kit-8 (CCK8), the xCELLigence Real-Time Cell Analyzer system (RTCA), and transwell analysis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to observe the expression of FRAT1 and proteins related to the Wnt/ß-catenin signalling pathway. Tumour growth was inhibited by STM in vivo. STM suppressed the proliferation, migration, and invasion of HCC cells. STM negatively regulated FRAT1 expression, whereas overexpressed FRAT1 blocked the anti-tumour function of STM. The results revealed that STM suppressed the FRAT1/Wnt/ß-catenin signalling pathway. The findings of this study provide new insights into investigation of therapeutic strategies against HCC.

Long non-coding RNA snaR is involved in the metastasis of liver cancer possibly through TGF-ß1.

It was previously demonstrated that the long non-coding RNA (lncRNA) small NF90-associated RNA (snaR) served an oncogenic role in human colon cancer, although its roles in other types of cancer remain unknown. To investigate the potential involvement of lncRNA snaR in hepatocellular carcinoma (HCC), expression of snaR in liver biopsies and plasma of patients with HCC and healthy controls was detected by reverse transcription-quantitative polymerase chain reaction. ELISA was used to determine the protein expression levels of transforming growth factor-ß1 (TGF-ß1). A snaR expression vector was transfected into HCC cells, and the effects on cell migration and invasion were analyzed by Transwell migration and Matrigel invasion assays, respectively. The protein expression levels of TGF-ß1 in HCC cells were detected by western blotting. The expression of snaR and TGF-ß1 was significantly increased in the patients with HCC compared with the healthy controls. The plasma expression levels of snaR and TGF-ß1 were positively correlated in patients with HCC; however, not in healthy controls. snaR overexpression significantly promoted cancer cell migration and invasion, and additionally increased TGF-ß1 expression. Treatment with TGF-ß1 did not significantly affect snaR expression. A TGF-ß1 inhibitor attenuated the effects of snaR overexpression in cancer cell migration and invasion. snaR may promote the metastasis of liver cancer through TGF-ß1.

Bioinformatics analysis of differentially expressed genes in hepatocellular carcinoma cells exposed to Swertiamarin.

Aim: To explore gene expression profiling in hepatocellular carcinoma (HCC) cells exposed to swertiamarin. Methods: Cell viability, apoptosis and invasion were examined in HepG2 cells after swertiamarin treatment. Tumor growth of SK-Hep-1 cells xenografted in nude mice was monitored after swertiamarin treatment. Total RNA was isolated from HepG2 cells treated with swertiamarin for microarray analysis. The data of microarray were analyzed by bioinformatics. Results: Swertiamarin treatment decreased the viability and invasion while increased the apoptosis of HepG2 cells, and significantly inhibited the growth of SK-Hep-1 cells xenografted in nude mice. Pathway and biological process analysis of differentially expressed genes (DEGs) in swertiamarin treated HepG2 cells showed that PI3k-Akt was the most significant regulated pathway. 47 targets of swertiamarin were predicted by CGBVS while 21 targets were predicted by 3NN. Notably, 8 targets were predicted as the targets of swertiamarin by both programs, including two prominent targets JUN and STAT3. A large range of DEGs induced by swertiamarin could be regulated by JUN and STAT3. Conclusion: Swertiamarin treatment led to significant changes in the expression of a variety of genes that modulate cell survival, cell cycle progression, apoptosis, and invasion. Moreover, most of these genes can be clustered into pathway networks such as PI3K, JUN, STAT3, which are predicted targets of swertiamarin. Further confirmation of these targets will reveal the anti-tumor mechanisms of swertiamarin and facilitate the development of swertiamarin as a novel agent for cancer prevention and treatment.

Co-expression analysis and ceRNA network reveal eight novel potential lncRNA biomarkers in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world, with a high degree of malignancy and recurrence. The influence of the ceRNA network in tumor on the biological function of liver cancer is very important, It has been reported that many lncRNA play a key role in liver cancer development. In our study, integrated data analysis revealed potential eight novel lncRNA biomarkers in hepatocellular carcinoma. METHODS: Transcriptome data and clinical data were downloaded from the The Cancer Genome Atlas (TCGA) data portal. Weighted gene co-expression network analysis was performed to identify the expression pattern of genes in liver cancer. Then, the ceRNA network was constructed using transcriptome data. RESULTS: The integrated analysis of miRNA and RNAseq in the database show eight novel lncRNAs that may be involved in important biological pathways, including TNM and disease development in liver cancer. We performed function enrichment analysis of mRNAs affected by these lncRNAs. CONCLUSIONS: By identifying the ceRNA network and the lncRNAs that affect liver cancer, we showed that eight novel lncRNAs play an important role in the development and progress of liver cancer.

Study of Recellularized Human Acellular Arterial Matrix Repairs Porcine Biliary Segmental Defects.

Background: With the popularity of laparoscopic cholecystectomy, common bile duct injury has been reported more frequently. There is no perfect method for repairing porcine biliary segmental defects. Methods: After the decellularization of human arterial blood vessels, the cells were cultured with GFP+ (carry green fluorescent protein) porcine bile duct epithelial cells. The growth and proliferation of porcine bile duct epithelial cells on the human acellular arterial matrix (HAAM) were observed by hematoxylin-eosin (HE) staining, electron microscopy, and immunofluorescence. Then, the recellularized human acellular arterial matrix (RHAAM) was used to repair biliary segmental defects in the pig. The feasibility of it was detected by magnetic resonance cholangiopancreatography, liver function and blood routine changes, HE staining, immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blot. Results: After 4 weeks (w) of co-culture of HAAM and GFP+ porcine bile duct epithelial cells, GFP+ porcine bile duct epithelial cells grew stably, proliferated, and fused on HAAM. Bile was successfully drained into the duodenum without bile leakage or biliary obstruction. Immunofluorescence detection showed that GFP-positive bile duct cells could still be detected after GFP-containing bile duct cells were implanted into the acellular arterial matrix for 8 w. The implanted bile duct cells can successfully resist bile invasion and protect the acellular arterial matrix until the newborn bile duct is formed. Conclusion: The RHAAM can be used to repair biliary segmental defects in pigs, which provides a new idea for the clinical treatment of common bile duct injury.

Molecular details on the intermediate states of melittin action on a cell membrane.

Antimicrobial peptides (AMPs) provide a promising solution to the serious threat of multidrug-resistant bacteria or superbugs to public healthcare, due to their unique disruption to bacterial membrane such as perforation. Unfortunately, the underlying action mechanism of AMPs, especially the possible transition between the membrane binding and perforation states of peptides (i.e., the classical two-state model), is still largely unknown. Herein, by combining experimental techniques with pertinent membrane models and molecular dynamic (MD) simulations, new insights into the intermediate states of the AMP melittin-membrane interaction process are obtained. Specifically, it is demonstrated that, after the initial binding, the accumulated melittin on the bilayer triggers vigorous fluctuation of the membrane and even extracts some lipid molecules exclusively from the deformed outer leaflet of the bilayer. Such a distinctive mass removal manner and the resultant local asymmetry in lipid number between the two leaflets change the mechanical status of the membrane and in turn reduce the free energy barrier for the melittin insertion. Finally, the formation of the transmembrane pores is facilitated significantly. These findings provide new insights into the complicated antimicrobial mechanisms of AMPs.

Using Tree Shrews (Tupaia belangeri) as a Novel Animal Model of Liver Transplantation.

Liver transplantation (LT) is most effective and promising approach for end-stage liver disease. However, there remains room for further improvement and innovation, for example, to reduce ischemic reperfusion injury, transplant rejection and immune tolerance. A good animal model of LT is essential for such innovation in transplant research. Although rat LT model has been used since the last century, it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other. In this study, we for the first time performed LT using the tree shrew (Tupaia belangeri), a species in the Order Scandentia which is closely related with primates, and evaluated the possibility to adopt this species as a new model of LT. We performed LT on 30 animals using the two-cuff technique, examining the success rate, the survival rate and the immunological reaction. The recipient operation time was 60 min averagely, and we limited the time of the anhepatic phase within 20 min. Twenty-seven (90%) of the animals survived for at least 3 days after the transplantation. Thirteen animals that did not receive any immunosuppressive drug died in 8 days mostly because of acute rejection effect (n=9), similar to the reaction in human but not in experimental rat. The rest 14 animals that were given rapamycin survived significantly longer (38 days) and half of them survived for 60 days until the end of the study. Our results suggest that performing LT in tree shrews can yield high success rate and high survival rate. More importantly, the tree shrews share similar immunological reaction with human. In addition, previous genomics study found that the tree shrews share more proteins with human. In sum, the tree shrews may outperform the experimental rats and could be used as a better and cost-effective animal model for LT.