Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology
Background Septic cardiomyopathy (SC) is a common complication of sepsis that leads to an increase in mortality. The pathogenesis of septic cardiomyopathy is unclear, and there is currently no effective treatment. EGCG (epigallocatechin gallate) is a polyphenol that has anti-inflammatory, antiapoptotic, and antioxidative stress effects. However, the role of EGCG in septic cardiomyopathy is unknown. Methods Network pharmacology was used to predict the potential targets and molecular mechanisms of EGCG in the treatment of septic cardiomyopathy, including the construction and analysis of protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and molecular docking. The mouse model of septic cardiomyopathy was established after intraperitoneal injection of LPS (lipopolysaccharide). The myocardial protective effect of EGCG on septic mice is observed by cardiac ultrasound and HE staining. RT-PCR is used to verify the expression level of the EGCG target in the septic cardiomyopathy mouse model. Results A total of 128 anti-SC potential targets of EGCGareselected for analysis. The GO enrichment analysis and KEGG pathway analysis results indicated that the anti-SC targets of EGCG mainly participate in inflammatory and apoptosis processes. Molecular docking results suggest that EGCG has a high affinity for the crystal structure of six targets (IL-6 (interleukin-6), TNF (tumor necrosis factor), Caspase3, MAPK3 (Mitogen-activated protein kinase 3), AKT1, and VEGFA (vascular endothelial growth factor)), and the experimental verification result showed levated expression of these 6 hub targets in the LPS group, but there is an obvious decrease in expression in the LPS + EGCG group. The functional and morphological changes found by echocardiography and HE staining show that EGCG can effectively improve the cardiac function that is reduced by LPS. Conclusion Our results reveal that EGCG may be a potentially effective drug to improve septic cardiomyopathy. The potential mechanism by which EGCG improves myocardial injury in septic cardiomyopathy is through anti-inflammatory and anti-apoptotic effects. The anti-inflammatory and anti-apoptotic effects of EGCG occur not only through direct binding to six target proteins (IL-6,TNF-α, Caspase3, MAPK3, AKT1, and VEGFA) but also by reducing their expression.
Wu et al. (2022) Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology. PeerJ 10:e12994 https://doi.org/10.7717/peerj.12994
Optimizing seawater temperature conditions to increase the productivity of ex situ coral nurseries
Large scale ex situ propagation of coral colonies for reef restoration is a relatively new and developing field. One of the many advantages of utilizing ex situ coral nurseries is the ability to optimize water quality conditions for coral health and survival. Slight alterations in environmental parameters (light, pH, temperature etc.) can affect the health and grow-out time of cultured coral, ultimately influencing production rates. However, corals are also subjected to pests associated with culture facilities such as ciliates, cyanobacterial blooms, and infectious diseases. Therefore, adjusting environmental parameters to optimize coral growth for a shorter ex situ residency time will lead to greater survival and faster restoration. Studies indicate that some coral species demonstrate parabolic tissue growth in response to increasing sea-surface temperatures until the maximum temperature tolerance is reached, whereafter they bleach. To maximize coral growth in Mote Marine Laboratory’s ex situ system, we tested the effect of two water temperature treatments (high temperature: 29.5 ± 0.03 °C; control: 25.2 ± 0.08 °C) on two coral species commonly used in reef restoration. To quantify this, we used four replicates of three genotypes each of Montastraea cavernosa (n = 12) and Acropora palmata (n = 12). Two-dimensional tissue area was recorded monthly using ImageJ and survival rates within each treatment were documented for 7 months. Results found that M. cavernosa had greater growth rates and equal survivorship in the high temperature treatment compared to the control treatment. A. palmata grew faster and had equal survivorship in the control treatment compared with the high temperature treatment. These results suggest that temperature preferences exist among coral species within ex situ systems and restoration practitioners should consider species-specific temperature regimes to maximize ex situ coral growth rates. This information is critical for optimizing production when corals are in the grow-out stage and should also be considered when designing ex situ systems to ensure temperature regulation can be controlled on a species-specific basis.
Merck et al. (2022) Optimizing seawater temperature conditions to increase the productivity of ex situ coral nurseries. PeerJ 10:e13017 https://doi.org/10.7717/peerj.13017
Perfluoroalkyl acids in sediment and water surrounding historical fire training areas at Barksdale Air Force Base
Perfluoroalkyl acids (PFAAs) are environmentally persistent components of surfactants that consist of fully fluorinated carbon chains and a terminal sulfonate or carboxylate polar head moiety. Due to their unique amphiphilic properties, PFAAs are used in the manufacturing of products such as aqueous film forming foams (AFFF). There is cause for concern for PFAA contamination resulting from runoff and groundwater infiltration of AFFF that were used during fire training. This study analyzed water and sediment samples that were collected over a 13-month sampling period from bayous upstream and downstream of two former fire training areas located near Barksdale Air Force Base (BAFB); the occurrence and magnitude of PFAAs supported an aquatic ecological risk assessment of potential impacts of PFAAs at the site. Liquid chromatography coupled with mass spectrometry was used for determination of 6 PFAAs listed under the third Unregulated Contaminant Monitoring Rule (UCMR 3). Total PFAA concentrations in surface water and sediment samples ranged from 0 (ND) −7.1 ng/mL and 0 (ND) −31.4 ng/g, respectively. Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were the predominant PFAAs detected. In general, perfluorosulfonates were quantified more frequently and at higher concentrations than perfluorocarboxylates. The perfluoroalkyl chain length of PFAAs also showed significant influence on PFAA concentrations when analyzed by Spearman’s rank correlation analysis. Some contamination we observed in surface water and sediment samples from reference locations could be a result of local runoff from the use of commercial products containing per- and poly-fluoroalkyl substances (PFAS), but AFFF appears to be the primary source given the close proximity of the historical fire training areas.
Environmental Contamination and Remediation
Wilkinson et al. (2022) Perfluoroalkyl acids in sediment and water surrounding historical fire training areas at Barksdale Air Force Base. PeerJ 10:e13054 https://doi.org/10.7717/peerj.13054
Expression of connexin-43 in surgical resections of primary tumor and lymph node metastases of squamous cell carcinoma and adenocarcinoma of the lung: a retrospective study
Background Connexins are transmembrane proteins forming gap junctions between the cells, which allow intercellular communication. Significance of gap junctions and connexins in lung carcinoma is not yet understood. The objective of the study was to investigate immunohistochemical expression and the localization of connexin-43 (Cx43) in primary lung carcinoma and its lymphatic metastases. Methods Surgical specimens of excised tumors from 88 patients (45 men and 43 women, 61.9 ± 7.4 years) with lung carcinoma (52 adenocarcinoma (AC), 36 squamous cell carcinoma (SqCC)) who were operated on at the University Hospital “Bezanijska Kosa” in a five-year period (2012–2016) were used. We conducted immunohistochemical staining for Cx43 and measured the degree of expression (percentage of positive cells and staining intensity) as well as localization of Cx43 in primary tumor and in lymphatic metastases. Results Immunohistochemical analysis of the primary tumors revealed that SqCC showed significantly higher percentage of tumor cells expressing Cx43 as well as higher staining intensity than AC (p < 0.001). Almost 70% of samples with SqCC showed high Cx43 expression, whereas AC showed no expression in more than 50% of cases. Localization of Cx43 expression was most often cytoplasmic (AC and SqCC) and combined membranous and cytoplasmic (SqCC) with very rare instances of nuclear localization (AC). Almost the same pattern in distribution, intensity, and localization of Cx43 expression was observed in the lymph node metastases; however, almost a third of AC cases changed the pattern of Cx43 expression in the metastasis compared to primary tumor. Conclusion The results of this study showed that lung carcinomas express Cx43 in more than 65% of cases and that it was aberrantly localized (not membranous localization). We highlighted that SqCC expressed Cx43 more than did AC, both in primary tumor and lymphatic metastases. Further research is needed to establish whether Cx43 could be used as a prognostic biomarker in lung carcinoma.
Savic et al. (2022) Expression of connexin-43 in surgical resections of primary tumor and lymph node metastases of squamous cell carcinoma and adenocarcinoma of the lung: a retrospective study. PeerJ 10:e13055 https://doi.org/10.7717/peerj.13055
Environmental enrichment changes rabbits’ behavior, serum hormone level and further affects cecal microbiota
Many studies have shown that stress is associated with gut microbiota. Environmental enrichment (EE) could reduce stress in farm animals; however, limited information is available on the microbial community composition in rabbits raised with or without EE. This study aimed to identify EE influences on the behavior, serum hormonal levels, and cecal microbiota of rabbits. Two hundred Rex rabbits were segregated randomly within four cohorts (n = 50); reared for 76 d within standardized enclosures (non-enriched) or within cages containing a willow-stick (WS), rubber-duck (RD), or a can of beans (CB). The rabbits’ ingestive, rest, locomotion, exploratory, grooming, and abnormal behavior were observed. The serum hormone levels for rabbits were measured, and cecal specimens were sequencedfrom the V3–V4 region using 16S rRNA amplicons. Environmental enrichment increased feeding and drinking time, promoted exploratory behavior, and reduced abnormal behavior in rabbits. Insulin-like growth factor 1(IGF-1) levels of the enriched cohorts were elevated in comparison to the control cohort. Serum cortisol level for CB cohort was markedly reduced in comparison to the control cohort (p < 0.05), while dopamine levels for CB cohort peaked. Further, we found that EE mainly affected the dominant microbiota. Several families, such as Erysipelotrichaceae, Tannerellaceae, Enterobacteriaceae, Burkholderiaceae, and Prevotellaceae were markedly reduced within the CB cohort. Bacteria such as Alloprevotella, Bifidobacterium, Enterobacteriaceae, Parabacteroides, and Erysipelatoclostridium were identified as having negative associations with the presence of serum cortisol. EE influenced rabbit behavior and serum hormonal levels, and CB enrichment was the most suitable for rabbits. Further, cecal microbiota composition and diversity were affected by CB enrichment. These findings suggested that CB could be considered for use in rabbit husbandry.
Feng et al. (2022) Environmental enrichment changes rabbits’ behavior, serum hormone level and further affects cecal microbiota. PeerJ 10:e13068 https://doi.org/10.7717/peerj.13068
Long-term consumption of artificial sweeteners does not affect cardiovascular health and survival in rats
Background Recent epidemiological cohort studies have suggested that consumption of artificial sweeteners (AS) is associated with adverse cardiovascular events and mortality. However, these population association studies cannot establish a causal relationship. In this study we investigated the effect of long-term (1-year) consumption of AS (Equal and Splenda, two commonly used AS) on cardiovascular health and survival in rats. Methods Adult Sprague-Dawley rats (both sexes, 4–5 months old) were randomized into the following 3 groups: control (n = 21), AS Equal (n = 21) and Splenda (n = 18). In the AS groups, Equal or Splenda was added to the drinking water (2-packets/250 ml), while drinking water alone was used in the control rats. The treatment was administered for 12 months. Cardiovascular function and survival were monitored in all animals. Results It was found that rats in the AS groups consistently consumed more sweetened water than those in the control group. AS did not affect body weight, non-fasting blood cholesterol, triglycerides, blood pressure or pulse wave velocity. There were no significant differences in left ventricular wall thicknesses, chamber dimension, cardiac function or survival. AS did not affect heart rate or atrial effective refractory period. However, rats in both Equal and Splenda groups had prolonged PR intervals (63 ± 5ms in Equal, 68 ± 6 ms in Splenda, vs 56 ± 8 ms in control, p < 0.05) and a tendency of increased atrial fibrillation inducibility. Conclusion Long-term consumption of AS does not affect cardiovascular structure, function or survival but may cause some electrophysiological abnormalities with prolonged PR intervals and a tendency of increased atrial fibrillation inducibility in rats.
Guru et al. (2022) Long-term consumption of artificial sweeteners does not affect cardiovascular health and survival in rats. PeerJ 10:e13071 https://doi.org/10.7717/peerj.13071
Full-length transcriptome analysis of Adiantum flabellulatum gametophyte
Ferns are important components of plant communities on earth, but their genomes are generally very large, with many redundant genes, making whole genome sequencing of ferns prohibitively expensive and time-consuming. This means there is a significant lack of fern reference genomes, making molecular biology research difficult. The gametophytes of ferns can survive independently, are responsible for sexual reproduction and the feeding of young sporophytes, and play an important role in the alternation of generations. For this study, we selected Adiantum flabellulatum as it has both ornamental and medicinal value and is also an indicator plant of acidic soil. The full-length transcriptome sequencing of its gametophytes was carried out using PacBio three-generation sequencing technology. A total of 354,228 transcripts were obtained, and 231,705 coding sequences (CDSs) were predicted, including 5,749 transcription factors (TFs), 2,214 transcription regulators (TRs) and 4,950 protein kinases (PKs). The transcripts annotated by non-redundant protein sequence database (NR), Kyoto encyclopedia of genes and genomes (KEGG), eukaryotic ortholog groups (KOG), Swissprot, protein family (Pfma), nucleotide sequence database (NT) and gene ontology (GO) were 251,501, 197,474, 193,630, 194,639, 195,956, 113,069 and 197,883, respectively. In addition, 138,995 simple sequence repeats (SSRs) and 111,793 long non-coding RNAs (lncRNAs) were obtained. We selected nine chlorophyll synthase genes for qRT-PCR, and the results showed that the full-length transcript sequences and the annotation information were reliable. This study can provide a reference gene set for subsequent gene expression quantification.
Cai et al. (2022) Full-length transcriptome analysis of Adiantum flabellulatum gametophyte. PeerJ 10:e13079 https://doi.org/10.7717/peerj.13079
Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, hundreds of millions of people have been infected worldwide. There have been unprecedented efforts in acquiring effective vaccines to confer protection against the disease. mRNA vaccines have emerged as promising alternatives to conventional vaccines due to their high potency with the capacity for rapid development and low manufacturing costs. In this review, we summarize the currently available vaccines against SARS-CoV-2 in development, with the focus on the concepts of mRNA vaccines, their antigen selection, delivery and optimization to increase the immunostimulatory capability of mRNA as well as its stability and translatability. We also discuss the host immune responses to the SARS-CoV-2 infection and expound in detail, the adaptive immune response upon immunization with mRNA vaccines, in which high levels of spike-specific IgG and neutralizing antibodies were detected after two-dose vaccination. mRNA vaccines have been shown to induce a robust CD8+T cell response, with a balanced CD4+ TH1/TH2 response. We further discuss the challenges and limitations of COVID-19 mRNA vaccines, where newly emerging variants of SARS-CoV-2 may render currently deployed vaccines less effective. Imbalanced and inappropriate inflammatory responses, resulting from hyper-activation of pro-inflammatory cytokines, which may lead to vaccine-associated enhanced respiratory disease (VAERD) and rare cases of myocarditis and pericarditis also are discussed.
Salleh et al. (2022) Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2. PeerJ 10:e13083 https://doi.org/10.7717/peerj.13083
Distinct metabolic profiling is correlated with bisexual flowers formation resulting from exogenous ethephon induction in melon (Cucumis melo L.)
Melon (Cucumis melo L.) is an agronomically important vegetable. Most cultivars of melon are andromonoecious and bisexual flowers only emerged from the leaf axil of lateral branches. However, the regulatory mechanism contributing to the occurrence of bisexual flowers were still obscure. In this study, ethephon was applied in two common cultivars of melon. In control without ethephon treatment, no bisexual flower was made in the main stem. However, 6.56 ± 1.42 and 6.63 ± 0.55 bisexual flowers were respectively induced in main stem of ‘Yangjiaocui-QX’ and ‘Lvbao’ after ethephon treatment, and induced bisexual flowers distributed in 12–20 nodes of main stem. During the formation of bisexual flowers, 41 metabolites were significantly up-regulated and 98 metabolites were significantly down-regulated. According to the KEGG enrichment analysis of 139 different metabolites, a total of 30 pathways were mapped and KEGG terms of “Phenylalanine, tyrosine and tryptophan biosynthesis”, “Phenylalanine metabolism” and “Flavone and flavonol biosynthesis” were significantly enriched. In three significantly enriched KEGG terms, shikimic acid, L-tryptophan, L-phenylalanine, and kaempferol were significantly up-regulated while L-tyrosine, 4-hydroxycinnami acid and luteolin were significantly down-regulated in ET compared to CK. Different metabolites were also classified depend on major class features and 14 classes were acquired. The results of metabonomics and endogenous hormone identification indicated that ethylene could enhance the concentration of salicylic acid, methyl jasmonate, ABA and IAA. This study provided an important theoretical foundation for inducing bisexual flowers in main stem and breeding new varieties of melon in future.
Fang et al. (2022) Distinct metabolic profiling is correlated with bisexual flowers formation resulting from exogenous ethephon induction in melon (Cucumis melo L.). PeerJ 10:e13088 https://doi.org/10.7717/peerj.13088
A bZIP transcription factor, PqbZIP1, is involved in the plant defense response of American ginseng
American ginseng (Panax quinquefolius L.) is a perennial medicinal plant that has a long usage history in China. However, root rot, which is mainly caused by Fusarium solani can severely reduce the yield and quality of American ginseng, but no disease-resistant variety of American ginseng exists, and the resistance against this disease is not yet well understood. Thus, it is very urgent to analyze the interaction mechanism regulating the interactions between American ginseng and F. solani to mine disease resistance genes. Using transcriptome data and quantitative polymerase chain reaction (qPCR), we screened the transcription factor PqbZIP1 in response to induction by chitin. Yeast self-activation and subcellular localization experiments proved that PqbZIP1 showed transcriptional activity and was localized in the plant nucleus. In addition, qPCR showed that the highest relative expression level was in the roots, wherein chitin and F. solani inhibited and activated the expression of PqbZIP1, respectively, in American ginseng. Additionally, PqbZIP1 significantly inhibited the growth of the Pseudomonas syringae pv. tomato D36E strain in Nicotiana benthamiana, where expressing PqbZIP1 in N. benthamiana increased the jasmonic acid, salicylic acid, and abscisic acid content. Furthermore, PqbZIP1 expression was continually increased upon inoculation with F. solani. Hence, this study revealed that the PqbZIP1 transcription factor might mediate multiple hormonal signaling pathway to modulate root rot disease resistance in American ginseng, and provided important information to breed disease-resistant American ginseng.
Yang et al. (2022) A bZIP transcription factor, PqbZIP1, is involved in the plant defense response of American ginseng. PeerJ 10:e12939 https://doi.org/10.7717/peerj.12939