Identification of proteins related to SIS3 by iTRAQ and PRM-based comparative proteomic analysis in cisplatin-induced acute kidney injury
Background Cisplatin is a commonly used nephrotoxic drug and can cause acute kidney injury (AKI). In the present study, isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM)-based comparative proteomics were used to analyze differentially expressed proteins (DEPs) to determine the key molecular mechanism in mice with cisplatin-induced AKI in the presence or absence of SIS3, a specific p-smad3 inhibitor, intervention. Methods The cisplatin-induced AKI mouse model was established and treated with SIS3. We used iTRAQ to search for DEPs, PRM to verify key DEPs and combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for bioinformatics analysis. We then assessed lipid deposition, malondialdehyde (MDA) and reactive oxygen species (ROS) and detected the expression of SREBF1, SCD1, CPT1A, PPARα and NDRG1 in vitro. Results Proteomic analysis showed that the identified DEPs were mainly enriched in energy metabolism pathways, especially in lipid metabolism. When SIS3 was applied to inhibit the phosphorylation of Smad3, the expression of NDRG1 and fatty acid oxidation key proteins CPT1A and PPARα increased, the expression of lipid synthesis related proteins SREBF1 and SCD1 decreased and the production of lipid droplets, MDA and ROS decreased. Conclusion SIS3 alleviates oxidative stress, reduces lipid accumulation and promotes fatty acid oxidation through NDRG1 in cisplatin-induced AKI. Our study provides a new candidate protein for elucidating the molecular mechanisms of fatty acid metabolism disorders in cisplatin-induced acute kidney injury.
Huang et al. (2024) Identification of proteins related to SIS3 by iTRAQ and PRM-based comparative proteomic analysis in cisplatin-induced acute kidney injury. PeerJ 12:e17485 https://doi.org/10.7717/peerj.17485
Role of the transient receptor potential melastatin 4 in inhibition effect of arsenic trioxide on the tumor biological features of colorectal cancer cell
Background To investigate the effects of arsenic trioxide (ATO) on human colorectal cancer cells (HCT116) growth and the role of transient receptor potential melastatin 4 (TRPM4) channel in this process. Methods The viability of HCT116 cells was assessed using the CCK-8 assay. Western blot analysis was employed to examine the protein expression of TRPM4. The apoptosis of HCT116 cells was determined using TUNEL and Flow cytometry. Cell migration was assessed through the cell scratch recovery assay and Transwell cell migration assay. Additionally, Transwell cell invasion assay was performed to determine the invasion ability of HCT116 cells. Results ATO suppressed the viability of HCT116 cells in a dose-dependent manner, accompanied by a decline in cell migration and invasion, and an increase in apoptosis. 9-phenanthroline (9-Ph), a specific inhibitor of TRPM4, abrogated the ATO-induced upregulation of TRPM4 expression. Additionally, blocking TRPM4 reversed the effects of ATO on HCT116 cells proliferation, including restoration of cell viability, migration and invasion, as well as the inhibition of apoptosis. Conclusion ATO inhibits CRC cell growth by inducing TRPM4 expression, our findings indicate that ATO is a promising therapeutic strategy and TRPM4 may be a novel target for the treatment of CRC.
Gao et al. (2024) Role of the transient receptor potential melastatin 4 in inhibition effect of arsenic trioxide on the tumor biological features of colorectal cancer cell. PeerJ 12:e17559 https://doi.org/10.7717/peerj.17559
The role of attention bias malleability in experiencing pain and associated disability
Background Attentional processing of pain has been theorized to play a key role in the severity of pain and associated disability. In particular attentional bias towards pain information, resulting in poor pain outcomes, has been extensively researched. Recently, the idea was put forward that attention bias malleability (AM), i.e., the readiness to acquire an attentional bias irrespective of its direction, may be key in predicting poor pain outcomes. We tested this hypothesis in two studies. Methods In Study 1, 55 healthy participants completed an AM paradigm, followed by an experimental heat pain paradigm probing pain experience and pain-related task interference. In Study 2, 71 people with chronic pain completed an AM paradigm and questionnaires probing pain experience and associated disability. Results In Study 1, including healthy participants, no relationship was found between AM indices and experimental pain outcomes. In Study 2, including chronic pain patients, results indicated that higher levels of overall AM were related to higher levels of pain experience and disability. Conclusion This study partially supports the hypotheses that the degree to which individuals can adapt their attentional preference in line with changing environmental conditions is associated with poor pain outcomes. However, future research is needed to clarify inconsistent findings between healthy volunteers and chronic pain patients as well as to determine the causal status of AM in poor pain outcomes.
Mac Goris et al. (2024) The role of attention bias malleability in experiencing pain and associated disability. PeerJ 12:e17430 https://doi.org/10.7717/peerj.17430
Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study
Objective The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson’s correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P < 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P < 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P < 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P < 0.05); a similar trend was observed with the NLR values (P < 0.05). Conclusion Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.
Wang et al. (2024) Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study. PeerJ 12:e17499 https://doi.org/10.7717/peerj.17499
Effect of oral tryptamines on the gut microbiome of rats—a preliminary study
Background Psilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota. Methods To address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition. Results We found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in Verrucomicrobia and Actinobacteria, and decreases in Proteobacteria. Conclusion and Implications These preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.
Xu et al. (2024) Effect of oral tryptamines on the gut microbiome of rats—a preliminary study. PeerJ 12:e17517 https://doi.org/10.7717/peerj.17517
Characteristics and evolution of hemagglutinin and neuraminidase genes of Influenza A(H3N2) viruses in Thailand during 2015 to 2018
Background Influenza A(H3N2) virus evolves continuously. Its hemagglutinin (HA) and neuraminidase (NA) genes have high genetic variation due to the antigenic drift. This study aimed to investigate the characteristics and evolution of HA and NA genes of the influenza A(H3N2) virus in Thailand. Methods Influenza A positive respiratory samples from 2015 to 2018 were subtyped by multiplex real-time RT-PCR. Full-length HA and NA genes from the positive samples of influenza A(H3N2) were amplified and sequenced. Phylogenetic analysis with the maximum likelihood method was used to investigate the evolution of the virus compared with the WHO-recommended influenza vaccine strain. Homology modeling and N-glycosylation site prediction were also performed. Results Out of 443 samples, 147 (33.18%) were A(H1N1)pdm09 and 296 (66.82%) were A(H3N2). The A(H3N2) viruses circulating in 2015 were clade 3C.2a whereas sub-clade 3C.2a1 and 3C.2a2 dominated in 2016–2017 and 2018, respectively. Amino acid substitutions were found in all antigenic sites A, B, C, D, and E of HA but the majority of the substitutions were located at antigenic sites A and B. The S245N and N329S substitutions in the NA gene affect the N-glycosylation. None of the mutations associated with resistance to NA inhibitors were observed. Mean evolutionary rates of the HA and NA genes were 3.47 × 10−3 and 2.98 × 10−3 substitutions per site per year. Conclusion The influenza A(H3N2) virus is very genetically diverse and is always evolving to evade host defenses. The HA and NA gene features including the evolutionary rate of the influenza A(H3N2) viruses that were circulating in Thailand between 2015 and 2018 are described. This information is useful for monitoring the genetic characteristics and evolution in HA and NA genes of influenza A(H3N2) virus in Thailand which is crucial for predicting the influenza vaccine strains resulting in high vaccine effectiveness.
Anoma et al. (2024) Characteristics and evolution of hemagglutinin and neuraminidase genes of Influenza A(H3N2) viruses in Thailand during 2015 to 2018. PeerJ 12:e17523 https://doi.org/10.7717/peerj.17523
Metabolite analysis reveals flavonoids accumulation during flower development in Rhododendron pulchrum sweet (Ericaceae)
The azalea (Rhododendron simsii Planch.) is an important ornamental woody plant with various medicinal properties due to its phytochemical compositions and components. However little information on the metabolite variation during flower development in Rhododendron has been provided. In our study, a comparative analysis of the flavonoid profile was performed in Rhododendron pulchrum sweet at three stages of flower development, bud (stage 1), partially open flower (stage 2), and full bloom (stage 3). A total of 199 flavonoids, including flavone, flavonol, flavone C-glycosides, flavanone, anthocyanin, and isoflavone were identified. In hierarchical clustering analysis (HCA) and principal component analysis (PCA), the accumulation of flavonoids displayed a clear development stage variation. During flower development, 78 differential accumulated metabolites (DAMs) were identified, and most were enriched to higher levels at the full bloom stage. A total of 11 DAMs including flavone (chrysin, chrysoeriol O-glucuronic acid, and chrysoeriol O-hexosyl-O-pentoside), isoflavone (biochanin A), and flavonol (3,7-di-O-methyl quercetin and isorhamnetin) were significantly altered at three stages. In particular, 3,7-di-O-methyl quercetin was the top increased metabolite during flower development. Furthermore, integrative analyses of metabolomic and transcriptomic were conducted, revealing that the contents of isoflavone, biochanin A, glycitin, and prunetin were correlated with the expression of 2-hydroxyisoflavanone dehydratase (HIDH), which provide insight into the regulatory mechanism that controls isoflavone biosynthesis in R. pulchrum. This study will provide a new reference for increasing desired metabolites effectively by more accurate or appropriate genetic engineering strategies.
Yang et al. (2024) Metabolite analysis reveals flavonoids accumulation during flower development in Rhododendron pulchrum sweet (Ericaceae). PeerJ 12:e17325 https://doi.org/10.7717/peerj.17325
Association between yoga and related contextual factors with moderate-to-vigorous physical activity among children and youth aged 5 to 17 years across five Indian states
Physical inactivity is one of the four key preventable risk factors, along with unhealthy diet, tobacco use, and alcohol consumption, underlying most noncommunicable diseases. Promoting physical activity is particularly important among children and youth, whose active living behaviours often track into adulthood. Incorporating yoga, an ancient practice that originated in India, can be a culturally-appropriate strategy to promote physical activity in India. However, there is little evidence on whether yoga practice is associated with moderate-to-vigorous physical activity (MVPA) accumulation. Thus, this study aims to understand how yoga practice is associated with MVPA among children and youth in India. Data for this study were obtained during the coronavirus disease lockdown in 2021. Online surveys capturing MVPA, yoga practice, contextual factors, and sociodemographic characteristics, were completed by 5 to 17-year-old children and youth in partnership with 41 schools across 28 urban and rural locations in five states. Linear regression analyses were conducted to assess the association between yoga practice and MVPA. After controlling for age, gender, and location, yoga practice was significantly associated with MVPA among children and youth (β = 0.634, p < 0.000). These findings highlight the value of culturally-appropriate activities such as yoga, to promote physical activity among children and youth. Yoga practice might have a particularly positive impact on physical activity among children and youth across the world, owing to its growing global prevalence.
Patel et al. (2024) Association between yoga and related contextual factors with moderate-to-vigorous physical activity among children and youth aged 5 to 17 years across five Indian states. PeerJ 12:e17369 https://doi.org/10.7717/peerj.17369
Current and future scenarios of suitability and expansion of cassava brown streak disease, Bemisia tabaci species complex, and cassava planting in Africa
Cassava (Manihot esculenta) is among the most important staple crops globally, with an imperative role in supporting the Sustainable Development Goal of ‘Zero hunger’. In sub-Saharan Africa, it is cultivated mainly by millions of subsistence farmers who depend directly on it for their socio-economic welfare. However, its yield in some regions has been threatened by several diseases, especially the cassava brown streak disease (CBSD). Changes in climatic conditions enhance the risk of the disease spreading to other planting regions. Here, we characterise the current and future distribution of cassava, CBSD and whitefly Bemisia tabaci species complex in Africa, using an ensemble of four species distribution models (SDMs): boosted regression trees, maximum entropy, generalised additive model, and multivariate adaptive regression splines, together with 28 environmental covariates. We collected 1,422 and 1,169 occurrence records for cassava and Bemisia tabaci species complex from the Global Biodiversity Information Facility and 750 CBSD occurrence records from published literature and systematic surveys in East Africa. Our results identified isothermality as having the highest contribution to the current distribution of cassava, while elevation was the top predictor of the current distribution of Bemisia tabaci species complex. Cassava harvested area and precipitation of the driest month contributed the most to explain the current distribution of CBSD outbreaks. The geographic distributions of these target species are also expected to shift under climate projection scenarios for two mid-century periods (2041–2060 and 2061–2080). Our results indicate that major cassava producers, like Cameron, Ivory Coast, Ghana, and Nigeria, are at greater risk of invasion of CBSD. These results highlight the need for firmer agricultural management and climate-change mitigation actions in Africa to combat new outbreaks and to contain the spread of CBSD.
Sikazwe et al. (2024) Current and future scenarios of suitability and expansion of cassava brown streak disease, Bemisia tabaci species complex, and cassava planting in Africa. PeerJ 12:e17386 https://doi.org/10.7717/peerj.17386
Gut microbiota alterations in postmenopausal women with osteoporosis and osteopenia from Shanghai, China
Background The importance of the gut microbiota in maintaining bone homeostasis has been increasingly emphasized by recent research. This study aimed to identify whether and how the gut microbiome of postmenopausal women with osteoporosis and osteopenia may differ from that of healthy individuals. Methods Fecal samples were collected from 27 individuals with osteoporosis (OP), 44 individuals with osteopenia (ON), and 23 normal controls (NC). The composition of the gut microbial community was analyzed by 16S rRNA gene sequencing. Results No significant difference was found in the microbial composition between the three groups according to alpha and beta diversity. At the phylum level, Proteobacteria and Fusobacteriota were significantly higher and Synergistota was significantly lower in the ON group than in the NC group. At the genus level, Roseburia, Clostridia_UCG.014, Agathobacter, Dialister and Lactobacillus differed between the OP and NC groups as well as between the ON and NC groups (p < 0.05). Linear discriminant effect size (LEfSe) analysis results showed that one phylum community and eighteen genus communities were enriched in the NC, ON and OP groups, respectively. Spearman correlation analysis showed that the abundance of the Dialister genus was positively correlated with BMD and T score at the lumbar spine (p < 0.05). Functional predictions revealed that pathways relevant to amino acid biosynthesis, vitamin biosynthesis, and nucleotide metabolism were enriched in the NC group. On the other hand, pathways relevant to metabolites degradation and carbohydrate metabolism were mainly enriched in the ON and OP groups respectively. Conclusions Our findings provide new epidemiologic evidence regarding the relationship between the gut microbiota and postmenopausal bone loss, laying a foundation for further exploration of therapeutic targets for the prevention and treatment of postmenopausal osteoporosis (PMO).
Ji et al. (2024) Gut microbiota alterations in postmenopausal women with osteoporosis and osteopenia from Shanghai, China. PeerJ 12:e17416 https://doi.org/10.7717/peerj.17416