Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma
MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.
Li et al. (2021) Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma. PeerJ 9:e10470 https://doi.org/10.7717/peerj.10470
Perfluorooctane sulfonate exerts inflammatory bowel disease-like intestinal injury in rats
Background Perfluorooctane sulfonate (PFOS), a type of perfluorinated compounds (PFCs), can induce various organ toxicity, including hepatomegaly, immunotoxicity, and gut microbiota disorder. PFCs have been associated with inflammatory bowel disease (IBD). Yet, whether PFOS exposure causes IBD-like disorder and the underlying mechanism remains undefined. Here, we investigated the influence of PFOS exposure on the development of IBD-like disorder in rats. Methods Sprague-Dawley rats were intraperitoneally injected with PFOS (1 or 10 mg/kg) or normal saline (NS) every other day for 15 days. Body weight, serum concentrations of serum amyloid A (SAA) and high sensitivity C reactive protein (hsCRP) were measured. Pathological assessments of villi height and crypt depth in the proximal duodenum and jejunum were performed using H&E staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to assay cell apoptosis in the jejunum. The infiltration of inflammatory cells and cytokines in the jejunum were detected by immunohistochemistry analysis. Results PFOS (10 mg/kg) significantly increased the body weight, SAA and hsCRP, whereas no significant differences were observed in PFOS 1 mg/kg group of rats. The villi height and crypt depth in the proximal duodenum and jejunum were significantly reduced upon PFOS exposure. PFOS induced higher histopathological score in intestinal tissues compared to NS. Notably, TUNEL-positive cells were significantly higher in the jejunum upon PFOS exposure. Further, neutrophil and macrophage accumulated, and inflammatory cytokines infiltration were also remarkably increased in rats exposed to PFOS. Conclusion PFOS induces IBD-like phenotypes in rats, with associated inflammatory infiltration to intestinal.
Liang et al. (2021) Perfluorooctane sulfonate exerts inflammatory bowel disease-like intestinal injury in rats. PeerJ 9:e10644 https://doi.org/10.7717/peerj.10644
Microbial community structure in aquifers associated with arsenic: analysis of 16S rRNA and arsenite oxidase genes
The microbiomes of deep and shallow aquifers located in an agricultural area, impacted by an old tin mine, were explored to understand spatial variation in microbial community structures and identify environmental factors influencing microbial distribution patterns through the analysis of 16S rRNA and aioA genes. Although Proteobacteria, Cyanobacteria, Actinobacteria, Patescibacteria, Bacteroidetes, and Epsilonbacteraeota were widespread across the analyzed aquifers, the dominant taxa found in each aquifer were unique. The co-dominance of Burkholderiaceae and Gallionellaceae potentially controlled arsenic immobilization in the aquifers. Analysis of the aioA gene suggested that arsenite-oxidizing bacteria phylogenetically associated with Alpha-, Beta-, and Gamma proteobacteria were present at low abundance (0.85 to 37.13%) and were more prevalent in shallow aquifers and surface water. The concentrations of dissolved oxygen and total phosphorus significantly governed the microbiomes analyzed in this study, while the combination of NO3--N concentration and oxidation-reduction potential significantly influenced the diversity and abundance of arsenite-oxidizing bacteria in the aquifers. The knowledge of microbial community structures and functions in relation to deep and shallow aquifers is required for further development of sustainable aquifer management.
Environmental Contamination and Remediation
Sonthiphand et al. (2021) Microbial community structure in aquifers associated with arsenic: analysis of 16S rRNA and arsenite oxidase genes. PeerJ 9:e10653 https://doi.org/10.7717/peerj.10653
DNA profiling and assessment of genetic diversity of relict species Allium altaicum Pall. on the territory of Altai
Analysis of the genetic diversity of natural populations of threatened and endangered species of plants is a main aspect of conservation strategy. The endangered species Allium altaicum is a relict plant of the Ice Age and natural populations are located in extreme climatic conditions of Kazakstan’s Altai Mountains. Mobile genetic elements and other interspersed repeats are basic components of a eukaryote genome, which can activate under stress conditions and indirectly promote the survival of an organism against environmental stresses. Detections of chromosomal changes related to recombination processes of mobile genetic elements are performed by various PCR methods. These methods are based on interspersed repeat sequences and are an effective tool for research of biological diversity of plants and their variability. In our research, we used conservative sequences of tRNA primer binding sites (PBS) when initializing the retrotransposon replication as PCR primers to research the genetic diversity of 12 natural populations of A. altaicum found in various ecogeographic conditions of the Kazakhstani Altai. High efficiency of the PBS amplification method used was observed already at the intrapopulation level. Unique amplicons representative of a certain population were found at the intrapopulation level. Analysis of molecular dispersion revealed that the biodiversity of populations of mountainous and lowland A. altaicum is due to intrapopulation differences for climatic zones of habitation. This is likely conditional upon predominance of vegetative reproduction over seed reproduction in some populations. In the case of vegetative reproduction, somatic recombination related to the activity of mobile genetic elements are preserved in subsequent generations. This leads to an increase of intrapopulation genetic diversity. Thus, high genetic diversity was observed in populations such as A. altaicum located in the territory of the Kalbinskii Altai, whereas the minimum diversity was observed in the populations of the Leninororsk ecogeographic group. Distinctions between these populations were also identified depending on the areas of their distribution. Low-land and mid-mountain living environments are characterized by a great variety of shapes and plasticity. This work allowed us to obtain new genetic data on the structure of A. altaicum populations on the territory of the Kazakhstan Altai for the subsequent development of preservation and reproduction strategies for this relict species.
Khapilina et al. (2021) DNA profiling and assessment of genetic diversity of relict species Allium altaicum Pall. on the territory of Altai. PeerJ 9:e10674 https://doi.org/10.7717/peerj.10674
Synergism between calcium nitrate applications and fungal endophytes to increase sugar concentration in Festuca sinensis under cold stress
Epichloë endophytes have been shown to increase tolerance to biotic and abiotic stresses in many cool-season grasses. We investigated the impact of endophyte infection of Festuca sinensis, on root metabolic activity, photosynthetic pigments, leaf relative water content (RWC) and soluble carbohydrates in a field experiment carried out during chilling and irrigation with Ca(NO3)2. A highly significant (P < 0.001) correlation for Epichloë endophytes was observed for root metabolic activity. Ca(NO3)2 affected very significantly root metabolic activity and total chlorophyll (P < 0.001). Low temperature led to highly significant (P < 0.001) reductions in root metabolic activity, RWC, total chlorophyll, chlorophyll a/b ratio, and carotenoid contents. In addition, the fructose concentrations of shoots were greater on the 14th day than on the 28th day and before treatment, whilst the glucose concentration of roots was much higher on the 28th day than before and after 14 days treatment. Moreover, our results indicated that the addition of calcium nitrate contributed to higher levels of total chlorophylls, soluble sugars, sucrose, fructose or glucose in the shoots and roots in both E+ and E- plants during long periods of chilling. These results suggest that Epichloë endophyte infection and/or exogenous calcium nitrate can confer better tolerance to cold stress.
Zhou et al. (2021) Synergism between calcium nitrate applications and fungal endophytes to increase sugar concentration in Festuca sinensis under cold stress. PeerJ 9:e10568 https://doi.org/10.7717/peerj.10568
Strategies for recovery of imbalanced full-scale biogas reactor feeding with palm oil mill effluent
Background Full-scale biogas production from palm oil mill effluent (POME) was inhibited by low pH and highly volatile fatty acid (VFA) accumulation. Three strategies were investigated for recovering the anaerobic digestion (AD) imbalance on biogas production, namely the dilution method (tap water vs. biogas effluent), pH adjustment method (NaOH, NaHCO3, Ca(OH)2, oil palm ash), and bioaugmentation (active methane-producing sludge) method. The highly economical and feasible method was selected and validated in a full-scale application. Results The inhibited sludge from a full-scale biogas reactor could be recovered within 30–36 days by employing various strategies. Dilution of the inhibited sludge with biogas effluent at a ratio of 8:2, pH adjustment with 0.14% w/v NaOH, and 8.0% w/v oil palm ash were considered to be more economically feasible than other strategies tested (dilution with tap water, or pH adjustment with 0.50% w/v Ca(OH)2, or 1.25% NaHCO3 and bioaugmentation) with a recovery time of 30–36 days. The recovered biogas reactor exhibited a 35–83% higher methane yield than self-recovery, with a significantly increased hydrolysis constant (kH) and specific methanogenic activity (SMA). The population of Clostridium sp., Bacillus sp., and Methanosarcina sp. increased in the recovered sludge. The imbalanced full-scale hybrid cover lagoon reactor was recovered within 15 days by dilution with biogas effluent at a ratio of 8:2 and a better result than the lab-scale test (36 days). Conclusion Dilution of the inhibited sludge with biogas effluent could recover the imbalance of the full-scale POME-biogas reactor with economically feasible and high biogas production performance.
Wongfaed et al. (2021) Strategies for recovery of imbalanced full-scale biogas reactor feeding with palm oil mill effluent. PeerJ 9:e10592 https://doi.org/10.7717/peerj.10592
Reversine, a selective MPS1 inhibitor, induced autophagic cell death via diminished glucose uptake and ATP production in cholangiocarcinoma cells
Reversine is a selective inhibitor of mitotic kinase monopolar spindle 1 (MPS1) and has been reported as an anticancer agent in various cancers. The effects of reversine on bile duct cancer, cholangiocarcinoma (CCA), a lethal cancer in Northeastern Thailand, were investigated. This study reports that reversine inhibited cell proliferation of CCA cell lines in dose- and time-dependent manners but had less inhibitory effect on an immortalized cholangiocyte cell line. Reversine also triggered apoptotic cell death by decreasing anti-apoptotic proteins, Bcl-XL and Mcl-1, increasing Bax pro-apoptotic protein and activating caspase-3 activity. Moreover, reversine induced autophagic cell death by increasing LC3-II and Beclin 1 while decreasing p62. Reversine activated autophagy via the AKT signaling pathway. Additionally, this study demonstrated for the first time that reversine could diminish the expression of Hypoxia-Inducible Factor 1- alpha (HIF-1α) and glucose transporter 1 (GLUT1), resulting in a reduction of glucose uptake and energy production in CCA cell lines. These findings suggest that reversine could be a good candidate as an alternative or supplementary drug for CCA treatment.
Prajumwongs et al. (2021) Reversine, a selective MPS1 inhibitor, induced autophagic cell death via diminished glucose uptake and ATP production in cholangiocarcinoma cells. PeerJ 9:e10637 https://doi.org/10.7717/peerj.10637
Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis
Background Ulcerative colitis (UC) is one of the most challenging human diseases. Natural shikonin (SK) and its derivatives (with have higher accumulation) isolated from the root of Lithospermum erythrorhizon have numerous beneficial effects, such as wound healing and anti-inflammatory activities. Some researchers have reported that hydroxynaphthoquinone mixture (HM) and SK attenuate the acute UC induced by dextran sulfate sodium (DSS). However, no existing study has systemically investigated the effectiveness of SK and other hydroxynaphthoquinone natural derivative monomers on UC. Methods In this study, mice were treated with SK and its derivatives (25 mg/kg) and mesalazine (200 mg/kg) after DSS administration daily for one week. Disease progression was monitored daily by observing the changes in clinical signs and body weight. Results Intragastric administration natural single naphthoquinone attenuated the malignant symptoms induced by DSS. SK or its derivatives remarkably suppressed the serum levels of pro-inflammatory cytokines while increasing the inflammatory cytokine interleukin (IL)-10 . Additionally, both SK and alkanin restrained the activities of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) in serum and colonic tissues. SK and its derivatives inhibited the activation of nucleotide binding oligomerization domain-like receptors (NLRP3) inflammasome and NF-κB signaling pathway, thereby relieving the DSS-induced disruption of epithelial tight junction (TJ) in colonic tissues. Conclusions Our findings shed more lights on the pharmacological efficacy of SK and its derivatives in UC against inflammation and mucosal barrier damage.
Han et al. (2021) Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis. PeerJ 9:e10675 https://doi.org/10.7717/peerj.10675
Reproducing country-wide COVID-19 dynamics can require the usage of a set of SIR systems
This work shows that simple compartmental epidemiological models may not reproduce actually reported country-wide statistics since the latter reflects the cumulative amount of infected persons, which in fact is a sum of outbreaks within different patched. It the same time, the multilogistic decomposition of such epidemiological curves reveals components, which are quite close to the solutions of the SIR model in logistic approximations characterised by different sets of parameters including time shifts. This line of reasoning is confirmed by processing data for Spain and Russia in details and, additionally, is illustrated for several other countries.
Postnikov (2021) Reproducing country-wide COVID-19 dynamics can require the usage of a set of SIR systems. PeerJ 9:e10679 https://doi.org/10.7717/peerj.10679
Biochemical characterization and inhibition of thermolabile hemolysin from Vibrio parahaemolyticus by phenolic compounds
Vibrio parahaemolyticus (Vp), a typical microorganism inhabiting marine ecosystems, uses pathogenic virulence molecules such as hemolysins to cause bacterial infections of both human and marine animals. The thermolabile hemolysin VpTLH lyses human erythrocytes by a phospholipase B/A2 enzymatic activity in egg-yolk lecithin. However, few studies have been characterized the biochemical properties and the use of VpTLH as a molecular target for natural compounds as an alternative to control Vp infection. Here, we evaluated the biochemical and inhibition parameters of the recombinant VpTLH using enzymatic and hemolytic assays and determined the molecular interactions by in silico docking analysis. The highest enzymatic activity was at pH 8 and 50 °C, and it was inactivated by 20 min at 60 °C with Tm = 50.9 °C. Additionally, the flavonoids quercetin, epigallocatechin gallate, and morin inhibited the VpTLH activity with IC50 values of 4.5 µM, 6.3 µM, and 9.9 µM, respectively; while phenolics acids were not effective inhibitors for this enzyme. Boltzmann and Arrhenius equation analysis indicate that VpTLH is a thermolabile enzyme. The inhibition of both enzymatic and hemolytic activities by flavonoids agrees with molecular docking, suggesting that flavonoids could interact with the active site’s amino acids. Future research is necessary to evaluate the antibacterial activity of flavonoids against Vp in vivo.
Vazquez-Morado et al. (2021) Biochemical characterization and inhibition of thermolabile hemolysin from Vibrio parahaemolyticus by phenolic compounds. PeerJ 9:e10506 https://doi.org/10.7717/peerj.10506