Identification of key genes and crucial pathways for major depressive disorder using peripheral blood samples and chronic unpredictable mild stress rat models
Background Accurate diagnosis of major depressive disorder (MDD) remains difficult, and one of the key challenges in diagnosing MDD is the lack of reliable diagnostic biomarkers. The objective of this study was to explore gene networks and identify potential biomarkers for MDD. Methods In the present study, we performed a comprehensive analysis of the mRNA expression profiles using blood samples of four patients with MDD and four controls by RNA sequencing. Differentially expressed genes (DEGs) were screened, and functional and pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery. All DEGs were inputted to the STRING database to build a PPI network, and the top 10 hub genes were screened using the cytoHubba plugin of the Cytoscape software. The relative expression of 10 key genes was identified by quantitative real-time polymerase chain reaction (qRT-PCR) of blood samples from 50 MDD patients and 50 controls. Plasma levels of SQSTM1 and TNFα were measured using an enzyme-linked immunosorbent assay in blood samples of 44 MDD patients and 44 controls. A sucrose preference test was used to evaluate depression-like behavior in chronic unpredictable mild stress (CUMS) model rats. Immunofluorescence assay and western blotting were performed to study the expression of proteins in the brain samples of CUMS model rats Results We identified 247 DEGs that were closely associated with MDD. Gene ontology analyses suggested that the DEGs were mainly enriched in negative regulation of transcription by RNA polymerase II promoter, cytoplasm, and protein binding. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the DEGs were significantly enriched in the MAPK signaling pathway. Ten hub genes were screened through the PPI network, and qRT-PCR assay revealed that one and six genes were downregulated and upregulated, respectively; however, SMARCA2, PPP3CB, and RAB5C were not detected. Pathway enrichment analysis for the 10 genes showed that the mTOR signaling pathway was also enriched. A strong positive correlation was observed between SQSTM1 and TNFα protein levels in patients with MDD. LC3 II and SQSTM1 protein levels were increased in the CUMS rat model; however, p-mTOR protein levels were decreased. The sucrose preference values decreased in the CUMS rat model. Conclusions We identified 247 DEGs and constructed an MDD-specific network; thereafter, 10 hub genes were selected for further analysis. Our results provide novel insights into the pathogenesis of MDD. Moreover, SQSTM1, which is related to autophagy and inflammatory reactions, may play a key role in MDD. SQSTM1 may be used as a promising therapeutic target in MDD; additionally, more molecular mechanisms have been suggested that should be focused on in future in vivo and in vitro studies.
He et al. (2021) Identification of key genes and crucial pathways for major depressive disorder using peripheral blood samples and chronic unpredictable mild stress rat models. PeerJ 9:e11694 https://doi.org/10.7717/peerj.11694
Cellulose aerogel composites as oil sorbents and their regeneration
Background With every oil tanker comes the risk of an accident and oil spill. Sorbents are the most suitable means to remove oil spills. Aerogels as sorbents have high porosity and can be made from cellulose from paper waste. The literature does not distinguish between paper and cardboard as sources of cellulose aerogels and little is known about composites of cellulose aerogels consisting of cellulose fibres and chemically untreated, unprocessed fibres or particles of straw, wool, macroalgae or cellulose acetate from cigarette butts. In this study, the sorption properties for marine diesel oil and biodiesel of such aerogels and their regenerative capacity with bioethanol were investigated. Methods Cellulose aerogels were prepared from office paper and cardboard waste without and with chemically untreated algae, straw, wool and cellulose acetate as a composite by freeze drying. All samples were hydrophobised with methylsilane. The density to calculate the porosity and the contact angle were determined. Then the sorption capacity was determined over five cycles of sorption of oil and regeneration with bioethanol. Results The average contact angle of all samples was 125°, indicating hydrophobicity. Paper-based aerogels were found to consistently have higher sorption capacities for biodiesel, marine diesel oil and bioethanol than cardboard-based aerogels. In particular, the wool/cellulose aerogel composite was found to have better sorption capacity for biodiesel, marine diesel oil and bioethanol than all other samples. The cellulose acetate/cellulose aerogel composite showed significantly higher sorption capacities than the paper and cardboard control samples (highest value is 32.25 g g−1) only when first used as a sorbent for biodiesel, but with a rapid decrease in the following cycles.
Environmental Contamination and Remediation
Paulauskiene et al. (2021) Cellulose aerogel composites as oil sorbents and their regeneration. PeerJ 9:e11795 https://doi.org/10.7717/peerj.11795
Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression
Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Considering the important association between cellular immunity and PTC progression, it is worth exploring the biological significance of immune-related signaling in PTC. Methods Several bioinformatics tools, such as R software, WEB-based Gene SeT AnaLysis Toolkit (WebGestalt), Database for Annotation, Visualization and Integrated Discovery (DAVID), Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape were used to identify the immune-related hub genes in PTC. Furthermore, in vitro experiments were adopted to identify the proliferation and migration ability of PROS1 knockdown groups and control groups in PTC cells. Results The differentially expressed genes (DEGs) of five datasets from Gene Expression Omnibus (GEO) contained 154 upregulated genes and 193 downregulated genes, with Protein S (PROS1) being the only immune-related hub gene. Quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) have been conducted to prove the high expression of PROS1 in PTC. Moreover, PROS1 expression was significantly correlated with lymph nodes classification. Furthermore, knockdown of PROS1 by shRNAs inhibited the cell proliferation and cell migration in PTC cells. Conclusions The findings unveiled the clinical relevance and significance of PROS1 in PTC and provided potential immune-related biomarkers for PTC development and prognosis.
Wang et al. (2021) Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression. PeerJ 9:e11813 https://doi.org/10.7717/peerj.11813
A comparative study on knowledge towards COVID-19 prevention among undergraduate students in Macao and Zhuhai, China
In order to develop the strategy more suitable campus-based coronavirus disease 2019 (COVID-19) prevention programs for undergraduate students, it is critical to identify discrepancies in knowledge of COVID-19 prevention among students from different campuses in China. The present study examined the difference in preventive knowledge about COVID-19 pandemic in undergraduate students from two cities of Guangdong-Hong Kong-Macao Greater Bay Area (GBA), Macao Special Administrative Region (SAR), which had very few cases of COVID-19 patients, and Zhuhai, which is borders Macao SAR. In August 2020, two cohorts of undergraduate students from universities in Macao (n = 977) and Zhuhai (n = 2,818) were recruited for online. The self-rating questionnaire was used to gain information about their knowledge in COVID-19 prevention. Macao and Zhuhai students had similar correct rates in terms of heat inactivation conditions of SARS-CoV-2, (76.8% vs. 76.9%, P = 0.950), etiquette when coughing and sneezing (75.9% vs. 75.0%, P = 0.562), and use of disposable masks (92.2% vs. 90.6%, P = 0.126). However, students from Macao had significantly higher rates in correct use of disinfectants against SARS-CoV-2 (24.6% vs. 17.5%, P < 0.001) and in the route of transmission of SARS-CoV-2 (84.5% vs. 79.6%, P < 0.001) than those from Zhuhai. In conclusion, the knowledge level of COVID-19 prevention differs among undergraduate students from Macao and Zhuhai, which warrants an appropriate region-specific health education strategie for COVID-19 prevention.
Tao et al. (2021) A comparative study on knowledge towards COVID-19 prevention among undergraduate students in Macao and Zhuhai, China. PeerJ 9:e11833 https://doi.org/10.7717/peerj.11833
Influenza A virus infects pulmonary microvascular endothelial cells leading to microvascular leakage and release of pro-inflammatory cytokines
Objective To investigate the replication of influenza A virus A/Puerto Rico/8/34 (H1N1) in pulmonary microvascular endothelial cells and its effect on endothelial barrier function. Methods Human pulmonary microvascular endothelial cells were infected with influenza A/Puerto Rico/8/34 (H1N1) virus. Plaque reduction assay, real-time quantitative PCR, immunofluorescence staining, and western blot were used to elucidate the replication process of virus-infected endothelial cells. In addition, real-time quantitative PCR was used to detect the relative expression levels of mRNA of some inflammatory factors. The endothelial resistance assay was used to determine the permeability of the endothelial monolayer. Excavation and analysis of data from open databases, such as the GeneCards database, DAVID Bioinformatics Resources, STRING search tool, and DGIdb database determined the genes, proteins, and signal pathways related to microvascular leakage caused by the H1N1 virus, and predicted the drugs that could be effective for treatment. Results In vitro experiments showed that the influenza virus can infect endothelial cells, leading to a significant increase in the permeability of pulmonary microvascular endothelial cells and the release of pro-inflammatory cytokines, but does not efficiently replicate in endothelial cells. A total of 107 disease-related target genes were obtained from the Gene-cards database. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these genes mainly affected the pathways related to “Inflammatory bowel disease” (IBD), “Chagas disease” (American trypanosomiasis), “Influenza A”, and also played a key role in anti-inflammation and regulation of immunity. After enrichment analysis, 46 hub genes were screened. A total of 42 FDA-approved drugs corresponding to the hub genes were screened from the DGIdb database, and these could be formulated for topical application. In addition, these drugs can be used to treat other diseases, including cancer, inflammatory diseases, immune system disorders, and cardiovascular diseases. Conclusion H1N1 influenza virus affects the barrier function of endothelial cells indirectly. Combined with bioinformatics tools, we can better understand the possible mechanism of action of influenza A (H1N1) virus causing pulmonary microvascular leakage and provide new clues for the treatment of pulmonary microvascular leakage.
Han et al. (2021) Influenza A virus infects pulmonary microvascular endothelial cells leading to microvascular leakage and release of pro-inflammatory cytokines. PeerJ 9:e11892 https://doi.org/10.7717/peerj.11892
DOG1 is commonly expressed in pancreatic adenocarcinoma but unrelated to cancer aggressiveness
Background DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. Methods DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. Results DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.
Jansen et al. (2021) DOG1 is commonly expressed in pancreatic adenocarcinoma but unrelated to cancer aggressiveness. PeerJ 9:e11905 https://doi.org/10.7717/peerj.11905
DLFF-ACP: prediction of ACPs based on deep learning and multi-view features fusion
An emerging type of therapeutic agent, anticancer peptides (ACPs), has attracted attention because of its lower risk of toxic side effects. However process of identifying ACPs using experimental methods is both time-consuming and laborious. In this study, we developed a new and efficient algorithm that predicts ACPs by fusing multi-view features based on dual-channel deep neural network ensemble model. In the model, one channel used the convolutional neural network CNN to automatically extract the potential spatial features of a sequence. Another channel was used to process and extract more effective features from handcrafted features. Additionally, an effective feature fusion method was explored for the mutual fusion of different features. Finally, we adopted the neural network to predict ACPs based on the fusion features. The performance comparisons across the single and fusion features showed that the fusion of multi-view features could effectively improve the model’s predictive ability. Among these, the fusion of the features extracted by the CNN and composition of k-spaced amino acid group pairs achieved the best performance. To further validate the performance of our model, we compared it with other existing methods using two independent test sets. The results showed that our model’s area under curve was 0.90, which was higher than that of the other existing methods on the first test set and higher than most of the other existing methods on the second test set. The source code and datasets are available at https://github.com/wame-ng/DLFF-ACP.
Cao et al. (2021) DLFF-ACP: prediction of ACPs based on deep learning and multi-view features fusion. PeerJ 9:e11906 https://doi.org/10.7717/peerj.11906
Impact of the the COVID-19 pandemic on a queen conch (Aliger gigas) fishery in The Bahamas
The onset of the coronavirus (COVID-19) pandemic in early 2020 led to a dramatic rise in unemployment and fears about food-security throughout the Caribbean region. Subsistence fisheries were one of the few activities permitted during emergency lockdown in The Bahamas, leading many to turn to the sea for food. Detailed monitoring of a small-scale subsistence fishery for queen conch was undertaken during the implementation of coronavirus emergency control measures over a period of twelve weeks. Weekly landings data showed a surge in fishing during the first three weeks where landings were 3.4 times higher than subsequent weeks. Overall 90% of the catch was below the minimum legal-size threshold and individual yield declined by 22% during the lockdown period. This study highlights the role of small-scale fisheries as a ‘natural insurance’ against socio-economic shocks and a source of resilience for small island communities at times of crisis. It also underscores the risks to food security and long-term sustainability of fishery stocks posed by overexploitation of natural resources.
Higgs (2021) Impact of the the COVID-19 pandemic on a queen conch (Aliger gigas) fishery in The Bahamas. PeerJ 9:e11924 https://doi.org/10.7717/peerj.11924
DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma
Background Dual specificity protein phosphatase (DUSP)12 is an atypical member of the protein tyrosine phosphatase family, which are overexpressed in multiple types of malignant tumors. This protein family protect cells from apoptosis and promotes the proliferation and motility of cells. However, the pathological role of DUSP12 in hepatocellular carcinoma (HCC) is incompletely understood. Methods We analyzed mRNA expression of DUSP12 between HCC and normal liver tissues using multiple online databases, and explored the status of DUSP12 mutants using the cBioPortal database. The correlation between DUSP12 expression and tumor-infiltrating immune cells was demonstrated using the Tumor Immune Estimation Resource database and the Tumor and Immune System Interaction Database. Loss of function assay was utilized to evaluate the role of DUSP12 in HCC progression. Results DUSP12 had higher expression along with mRNA amplification in HCC tissues compared with those in normal liver tissues, which suggested that higher DUSP12 expression predicted shorter overall survival. Analyses of functional enrichment of differentially expressed genes suggested that DUSP12 regulated HCC tumorigenesis, and that knockdown of DUSP12 expression by short hairpin (sh)RNA decreased the proliferation and migration of HCC cells. Besides, DUSP12 expression was positively associated with the infiltration of cluster of differentiation (CD)4+ T cells (especially CD4+ regulatory T cells), macrophages, neutrophils and dendritic cells. DUSP12 expression was positively associated with immune-checkpoint moieties, and was downregulated in a C3 immune-subgroup of HCC (which had the longest survival). Conclusion These data suggest that DUSP12 may have a critical role in the tumorigenesis, infiltration of immune cells, and prognosis of HCC.
Ju et al. (2021) DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma. PeerJ 9:e11929 https://doi.org/10.7717/peerj.11929
Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer
Background Ovarian cancer is the most common gynecological malignancy and is difficult to manage due to the emergence of resistance to various chemotherapeutic drugs. New efforts are urgently awaited. Aspirin, which is traditionally considered a nonsteroidal anti-inflammatory drug (NSAID), has been reported to exert potential chemopreventive effects. Therefore, we aimed to investigate the anticancer effect and explore the underlying molecular mechanisms of aspirin on epithelial ovarian cancer (EOC) cells. Methods We conducted wound healing, transwell migration, EdU cell proliferation, colony formation and apoptosis detection assays to observe the effects of aspirin on the migration, proliferation and apoptosis of EOC cells (A2870, Caov-3, and SK-OV-3). EOC cells were treated with a combination of aspirin and cisplatin (CDDP) to observe the effect of aspirin on enhancing CDDP sensitivity. Orthotopic xenograft models of ovarian cancer established with A2780-Luciferase-GFP cells were applied to compare tumor growth inhibition in the control, CDDP and CDDP plus aspirin groups through in vivo imaging, which can be used to continuously monitor tumor growth. The expression and acetylation levels of p53 in EOC cells treated with aspirin were determined using western blotting, and p53 acetylation levels were examined in tumors harvested from the transplanted mice. Quantitative real-time PCR was used to assess the mRNA expression of p53 target genes. Results Aspirin inhibited migration and proliferation and induced apoptosis in EOC cell lines in a concentration-dependent manner. In vitro, aspirin enhanced the sensitivity of EOC cells to CDDP by increasing its inhibitory effect on proliferation and its effect on inducing apoptosis. In vivo, the differences in the tumor growth inhibition rates among the different CDDP experimental groups were statistically significant (p < 0.05). Aspirin did not affect p53 protein expression but increased the p53 acetylation level in a concentration-dependent manner. In addition, the mRNA levels of CDKN1A, BAX, FOXF1, PUMA, and RRAD in EOC cells were significantly increased by the aspirin treatment. Conclusions Aspirin inhibits tumor progression and enhances the CDDP sensitivity of EOC cells. These antitumor effects of aspirin might be mediated by p53 acetylation and subsequent activation of p53 target genes.
Guo et al. (2021) Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer. PeerJ 9:e11591 https://doi.org/10.7717/peerj.11591