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
Does Drosophila sechellia escape parasitoid attack by feeding on a toxic resource?
Host shifts can drastically change the selective pressures that animals experience from their environment. Drosophila sechellia is a species restricted to the Seychelles islands, where it specializes on the fruit Morinda citrifolia (noni). This fruit is known to be toxic to closely related Drosophila species, including D. melanogaster and D. simulans, releasing D. sechellia from interspecific competition when breeding on this substrate. Previously, we showed that larvae of D. sechellia are unable to mount an effective immunological response against wasp attack, while larvae of closely-related species can defend themselves from parasitoid attack by melanotic encapsulation. We hypothesized that this inability constitutes a trait loss due to a reduced risk of parasitoid attack in noni. Here we present a lab experiment and field survey aimed to test the hypothesis that specialization on noni has released D. sechellia from the antagonistic interaction with its larval parasitoids. Our results from the lab experiment suggest that noni may be harmful to parasitoid wasps. Our results from the field survey indicate that D. sechellia was found in ripe noni, whereas another Drosophila species, D. malerkotliana, was present in unripe and overripe stages. Parasitic wasps of the species Leptopilina boulardi emerged from overripe noni, where D. malerkotliana was the most abundant host, but not from ripe noni. These results indicate that the specialization of D. sechellia on noni has indeed drastically altered its ecological interactions, leading to a relaxation in the selection pressure to maintain parasitoid resistance.
Salazar-Jaramillo et al. (2021) Does Drosophila sechellia escape parasitoid attack by feeding on a toxic resource?. PeerJ 9:e10528 https://doi.org/10.7717/peerj.10528
Genomic diversity of Escherichia coli from healthy children in rural Gambia
Little is known about the genomic diversity of Escherichia coli in healthy children from sub-Saharan Africa, even though this is pertinent to understanding bacterial evolution and ecology and their role in infection. We isolated and whole-genome sequenced up to five colonies of faecal E. coli from 66 asymptomatic children aged three-to-five years in rural Gambia (n = 88 isolates from 21 positive stools). We identified 56 genotypes, with an average of 2.7 genotypes per host. These were spread over 37 seven-allele sequence types and the E. coli phylogroups A, B1, B2, C, D, E, F and Escherichia cryptic clade I. Immigration events accounted for three-quarters of the diversity within our study population, while one-quarter of variants appeared to have arisen from within-host evolution. Several isolates encode putative virulence factors commonly found in Enteropathogenic and Enteroaggregative E. coli, and 53% of the isolates encode resistance to three or more classes of antimicrobials. Thus, resident E. coli in these children may constitute reservoirs of virulence- and resistance-associated genes. Moreover, several study strains were closely related to isolates that caused disease in humans or originated from livestock. Our results suggest that within-host evolution plays a minor role in the generation of diversity compared to independent immigration and the establishment of strains among our study population. Also, this study adds significantly to the number of commensal E. coli genomes, a group that has been traditionally underrepresented in the sequencing of this species.
Foster-Nyarko et al. (2021) Genomic diversity of Escherichia coli from healthy children in rural Gambia. PeerJ 9:e10572 https://doi.org/10.7717/peerj.10572
A novel similarity score based on gene ranks to reveal genetic relationships among diseases
Knowledge of similarities among diseases can contribute to uncovering common genetic mechanisms. Based on ranked gene lists, a couple of similarity measures were proposed in the literature. Notice that they may suffer from the determination of cutoff or heavy computational load, we propose a novel similarity score SimSIP among diseases based on gene ranks. Simulation studies under various scenarios demonstrate that SimSIP has better performance than existing rank-based similarity measures. Application of SimSIP in gene expression data of 18 cancer types from The Cancer Genome Atlas shows that SimSIP is superior in clarifying the genetic relationships among diseases and demonstrates the tendency to cluster the histologically or anatomically related cancers together, which is analogous to the pan-cancer studies. Moreover, SimSIP with simpler form and faster computation is more robust for higher levels of noise than existing methods and provides a basis for future studies on genetic relationships among diseases. In addition, a measure MAG is developed to gauge the magnitude of association of anindividual gene with diseases. By using MAG the genes and biological processes significantly associated with colorectal cancer are detected.
Luo et al. (2021) A novel similarity score based on gene ranks to reveal genetic relationships among diseases. PeerJ 9:e10576 https://doi.org/10.7717/peerj.10576
Health status of Polychrus gutturosus based on physical examination, hematology and biochemistry parameters in Costa Rica
Studies evaluating the health status and characteristics of free-ranging wildlife populations are scarce or absent for most species. Saurian health assessments are usually performed in species that have conservation issues or that are kept in captivity. The Berthold’s bush anole (Polychrus guturossus) is one of eight species belonging to the genus Polychrus, the only representative of the family Polychrotidae. Only a handful of studies have been reported concerning these lizard’s morphological variation, ecology, and natural history, probably because P. gutturosus is a canopy dweller and it can be difficult to locate individuals. It is believed that deforestation and habitat modification could pose a threat for this species, although to date no health assessment has been done. The aim of this study was to generate health baseline data on P. gutturosus. Forty Berthold’s bush anoles (20 males and 20 females) were sampled at the Pacific versant in Costa Rica, where physical examination, skin and cloacal temperatures, and blood samples were obtained from individuals immediately after capture. Animals from the studied population were all healthy (body condition 2.5–3.0/5.0). No lesions or ectoparasites were detected, but hemoparasites were found in nine individuals. Hematological and biochemical values were obtained, and the morphology of leukocytes were found to be similar to other iguanians. A positive correlation was found between the tissue enzymes aspartate aminotransferase (AST) and creatinine kinase (CK) and a negative correlation was found between skin and cloacal temperatures and AST and CK. There were positive correlations between female weight and total protein, calcium, and the calcium and phosphorus ratio. No significant inter-sex differences were found in biochemical values, despite females being larger than males. This is the first health assessment performed on a free-ranging canopy dwelling lizard. These findings provide baseline data that may be useful for future monitoring if the species faces changes in health status due to anthropogenic causes or natural disturbances.
Arguedas et al. (2021) Health status of Polychrus gutturosus based on physical examination, hematology and biochemistry parameters in Costa Rica. PeerJ 9:e10649 https://doi.org/10.7717/peerj.10649
miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths worldwide. Currently, efficient genetic markers for diagnosis and treatment of ESCC are lacking. MicroRNAs (miRNAs) are global genetic regulators that control cancer gene expression by binding to the 3′untranslated regions (3′UTRs) of targeting mRNAs. In addition, miRNAs function as oncogenes or tumor suppressors in the progression of tumors. In the current study, we found that hsa-miR-875-5p (miR-875-5p) exhibited amplification in ESCC according to the TCGA database. Then, xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony formation assays were employed to detect cell proliferationand colony formationability. The results showed that miR-875-5p promoted the proliferation ESCC cells. Subsequently, transwell results indicated that miR-875-5p promoted the invasion and migration of ESCC cells. Furthermore, we showed that miR-875-5p was able to bind to CAPZA13’UTR, which contains the single nucleotide polymorphism (SNP), rs373245753, as reported in our previous study involving WGS and WES on ESCC. Subsequently, mRNA affinity pull-down assays verifiedthat the SNP disrupts miR-875-5p binding to CAPZA1. The current study is the first demonstration that miR-875-5p may function as an oncogene via down-regulation of CAPZA1 expression in ESCC.
Kang et al. (2021) miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma. PeerJ 9:e10020 https://doi.org/10.7717/peerj.10020
The reliability and validity of the weight-bearing lunge test in a Congenital Talipes Equinovarus population (CTEV)
Question What is the intra and inter-rater reliability and concurrent validity of the weight-bearing lunge test within a Congenital Talipes Equinovarus population? Design Test retest design for reliability and validity. The measure was taken, following preconditioning of the participants, using distance from wall, angle at distal posterior tibia using a digital inclinometer and the iPhone level function, twice by each rater. The raters included a clinician, clinician in training and a parent/carer. Outcome measures Weight bearing lunge test as a measure of ankle dorsiflexion. Results Twelve children aged 5–10 years were eligible to participate and consented, along with their parents. Intra-reliability of distance measures for all raters were good to excellent (ICC clinician 0.95, ICC training clinician 0.98 and ICC parent 0.89). Intra-rater reliability of the iPhone for all raters was good (ICCs > 0.751) and good to excellent for the inclinometer (ICC clinician 0.87, ICC training clinician 0.90). Concurrent validity between the clinician’s and parents distance measure was also high with ICC of 0.899. Inter-rater reliability was excellent for distance measure (ICC = 0.948), good for the inclinometer (ICC = 0.801) and moderate for the iPhone (ICC = 0.68). Standard error of measurement ranged from 0.70–2.05, whilst the minimal detectable change ranged from 1.90–5.70. Conclusion The use of the WBLT within this CTEV population has demonstrated good to excellent reliability and validity amongst clinicians, clinicians in training and parents/carers, supporting its use as an assessment measure of dorsiflexion range of motion. There is support for parents/carers to use the WBLT at home as a monitoring assessment measure which may assist with early detection of a relapse. Trial registration University of South Australia’s ethics committee (ID: 201397); Women’s and Children’s Hospital ethics committee (AU/1/4BD7310).
Gosse et al. (2021) The reliability and validity of the weight-bearing lunge test in a Congenital Talipes Equinovarus population (CTEV). PeerJ 9:e10253 https://doi.org/10.7717/peerj.10253