ABSTRACT
BACKGROUND AND PURPOSE: Gastrointestinal tumours overexpress voltage-gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti-tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. EXPERIMENTAL APPROACH: Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch-clamp experiments. The anti-tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. KEY RESULTS: High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration- and use-dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down-regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. CONCLUSION AND IMPLICATIONS: Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.
ABSTRACT
INTRODUCTION: Aerobic physical training (APT) reduces eosinophilic airway inflammation, but its effects and mechanisms in severe asthma remain unknown. METHODS: An in vitro study employing key cells involved in the pathogenesis of severe asthma, such as freshly isolated human eosinophils, neutrophils, and bronchial epithelial cell lineage (BEAS-2B) and lung fibroblasts (MRC-5 cells), was conducted. Additionally, an in vivo study using male C57Bl/6 mice, including Control (Co; n = 10), Trained (Exe; n = 10), house dust mite (HDM; n = 10), and HDM + Trained (HDM + Exe; n = 10) groups, was carried out, with APT performed at moderate intensity, 5x/week, for 4 weeks. RESULTS: HDM and bradykinin, either alone or in combination, induced hyperactivation in human neutrophils, eosinophils, BEAS-2B, and MRC-5 cells. In contrast, IL-10, the primary anti-inflammatory molecule released during APT, inhibited these inflammatory effects, as evidenced by the suppression of numerous cytokines and reduced mRNA expression of the B1 receptor and ACE-2. The in vivo study demonstrated that APT decreased bronchoalveolar lavage levels of bradykinin, IL-1ß, IL-4, IL-5, IL-17, IL-33, TNF-α, and IL-13, while increasing levels of IL-10, klotho, and IL-1RA. APT reduced the accumulation of polymorphonuclear cells, lymphocytes, and macrophages in the peribronchial space, as well as collagen fiber accumulation, epithelial thickness, and mucus accumulation. Furthermore, APT lowered the expression of the B1 receptor and ACE-2 in lung tissue and reduced bradykinin levels in the lung tissue homogenate compared to the HDM group. It also improved airway resistance, tissue resistance, and tissue damping. On a systemic level, APT reduced total leukocytes, eosinophils, neutrophils, basophils, lymphocytes, and monocytes in the blood, as well as plasma levels of IL-1ß, IL-4, IL-5, IL-17, TNF-α, and IL-33, while elevating the levels of IL-10 and IL-1RA. CONCLUSION: These findings indicate that APT inhibits the severe asthma phenotype by targeting kinin signaling.
Subject(s)
Asthma , Bradykinin , Humans , Animals , Mice , Male , Interleukin-10 , Interleukin 1 Receptor Antagonist Protein , Interleukin-17 , Interleukin-33 , Interleukin-4 , Interleukin-5 , Tumor Necrosis Factor-alphaABSTRACT
Salinity stress is a prominent environmental factor that presents obstacles to the growth and development of plants. When the soil contains high salt concentrations, the roots face difficulties in absorbing water, resulting in water deficits within the plant tissues. Consequently, plants may experience inhibited growth, decreased development, and a decline in biomass accumulation. The use of nanoparticles has become a popular amendment in recent times for the alleviation of salinity stress. The study investigated the biological approach for the preparation of Se nanoparticles (NP) and their effect on the growth of wheat plants under saline conditions. The leaf extract of lemon (Citrus limon L.) was used for the green synthesis of selenium nanoparticles (Se-NPs). The synthesized NPs were characterized by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) and were applied foliar in the range of 0.01%, 0.05% and 0.1% on wheat plants. Results showed that 0.1% SeNP alone exhibited a significantly higher yield per plant, biomass per plant, 1000 grains weight, chlorophyll a, chlorophyll b and total chlorophyll over the SS (salt stress) control. A significant decline in MDA and H2O2 also validated the effectiveness of 0.1% SeNP over the SS control.
Subject(s)
Citrus , Nanoparticles , Selenium , Triticum , Chlorophyll A , Hydrogen Peroxide , Salt Stress , WaterABSTRACT
Seed quality (i.e., emergence energy, viability, physical purity, size, weight) is a critical factor that influences the yield of crops. Poor seed quality can lead to reduced germination rates, lower plant populations, and, ultimately, lower crop yields. On the other hand, seed priming is suggested to be an effective technique for improving seeds germination and plant population. In this study, we investigated the effect of seed priming with polyethylene glycol (PEG) on the germination, growth, and yield of two varieties of canola, super canola, and sandal canola. The treatment plan includes five concentrations of PEG (i.e., 5, 10, 15, 20%), distilled water priming, and control (no priming). All of the treatments were applied in 3 replications following a completely randomized design. Our results showed that seed priming with 5%PEG (T2) significantly improved radicle length (50 and 36%), plant height (43 and 34%), chlorophyll a (44 and 43%), chlorophyll b (120 and 208%), and total chlorophyll (83 and 111%) compared to control in super canola and sandal canola, respectively. In particular, seed priming with 5%PEG resulted in the highest increase in protein contents (25 and 1.40%), oleic acid (26 and 40%), and linolenic acid (6 and 6%) compared to control in super canola and sandal canola, respectively. It is concluded that seed priming with 5%PEG is an effective treatment to improve the performance of canola crops in terms of seedling growth, yield, chlorophyll, protein, and oil content. More investigations are recommended as future perspectives using other canola varieties to declare 5% PEG as an effective treatment for canola for improvement in growth, oil, protein, and chlorophyll contents.
ABSTRACT
Flame retardants (FRs) are chemical substances used to inhibit the spread of fire in numerous industrial applications, and their abundance in modern manufactured products in the indoor and outdoor environment leads to extensive direct and food chain exposure of humans. Although once considered relatively non-toxic, FRs are demonstrated by recent literature to have disruptive effects on many biological processes, including signaling pathways, genome stability, reproduction, and immune system function. This review provides a summary of research investigating the impact of major groups of FRs, including halogenated and organophosphorus FRs, on animals and humans in vitro and/or in vivo. We put in focus those studies that explained or referenced the modes of FR action at the level of cells, tissues and organs. Since FRs are highly hydrophobic chemicals, their biophysical and biochemical modes of action usually involve lipophilic interactions, e.g. with biological membranes or elements of signaling pathways. We present selected toxicological information about these molecular actions to show how they can lead to damaging membrane integrity, damaging DNA and compromising its repair, changing gene expression, and cell cycle as well as accelerating cell death. Moreover, we indicate how this translates to deleterious bioactivity of FRs at the physiological level, with disruption of hormonal action, dysregulation of metabolism, adverse effects on male and female reproduction as well as alteration of normal pattern of immunity. Concentrating on these subjects, we make clear both the advances in knowledge in recent years and the remaining gaps in our understanding, especially at the mechanistic level.
Subject(s)
Fires , Flame Retardants , Animals , Female , Male , Humans , Flame Retardants/toxicity , Organophosphorus Compounds/analysis , Halogenated Diphenyl Ethers/analysis , Dust/analysisABSTRACT
Lead (Pb) toxicity is a significant environmental issue, especially in areas with a past of industrial activities and mining. The existence of Pb in the soil can have negative impacts on plant growth and development, and it can also pose a risk to human health through the food chain. Acidified carbon has shown promise as an effective management technology for mitigating Pb toxicity. This study provides important insights into the potential of acidified biochar as a low-cost and eco-friendly method for managing Pb-contaminated soils. The current study explores the effectiveness of acidified biochar (AB) in alleviating Pb stress in mint. The study involved two levels of Pb (0 = control and 200 mg/kg Pb) and four levels of AB as treatments (0, 0.45, 0.90, and 1.20%). Results indicate that 1.20% AB was the most effective treatment, significantly decreasing root and shoot Pb concentration while enhancing shoot and root fresh and dry weight, shoot and root length, and shoot and root N, P, and K concentration. Moreover, a significant decrease in MDA (0.45AB, 0.90AB, and 1.20AB caused a decline in MDA content by 14.3%, 27.8%, and 40.2%, respectively) and an increase in ascorbic acid (0.45AB, 0.90AB, and 1.20AB led to an increase in ascorbic acid content of 1.9%, 24.8%, and 28.4%, respectively) validated the effectiveness of 1.20% AB compared to the control. Adding 0.45AB, 0.90AB, and 1.20AB led to an increase in soluble sugar content of 15.6%, 27.5%, and 32.1%, respectively, compared to the treatment without AB. Further investigations at the field level are suggested to confirm the efficacy of 1.20% AB as the best treatment against Pb toxicity in saline soil conditions.
Subject(s)
Mentha , Soil Pollutants , Humans , Soil/chemistry , Lead/toxicity , Charcoal/pharmacology , Ascorbic Acid , Saline Solution , Soil Pollutants/analysisABSTRACT
Water deficit stress exposure frequently constrains plant and agri-food production globally. Biostimulants (BSs) can be considered a new tool in mitigating water deficit stress. This study aimed to understand how BSs influence water deficit stress perceived by savory plants (Satureja hortensis L.), an important herb used for nutritional and herbal purposes in the Middle East. Three BS treatments, including bio-fertilizers, humic acid and foliar application of amino acid (AA), were implemented. Each treatment was applied to savory plants using three irrigation regimes (low, moderate and severe water deficit stress FC100, FC75 and FC50, respectively). Foliar application of AA increased dry matter yield, essential oil (EO) content and EO yield by 22%, 31% and 57%, respectively. The greatest EO yields resulted from the moderate (FC75) and severe water deficit stress (FC50) treatments treated with AA. Primary EO constituents included carvacrol (39-43%), gamma-terpinene (27-37%), alpha-terpinene (4-7%) and p-cymene (2-5%). Foliar application of AA enhanced carvacrol, gamma-terpinene, alpha-terpinene and p-cymene content by 6%, 19%, 46% and 18%, respectively. Physiological characteristics were increased with increasing water shortage and application of AA. Moreover, the maximum activities of superoxide dismutase (3.17 unit mg-1 min-1), peroxidase (2.60 unit mg-1 min-1) and catalase (3.08 unit mg-1 min-1) were obtained from plants subjected to severe water deficit stress (FC50) and treated with AA. We conclude that foliar application of AA under water deficit stress conditions would improve EO quantity and quality in savory.
Subject(s)
Oils, Volatile , Satureja , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Dehydration , Satureja/chemistry , WaterABSTRACT
Contact sites between the endoplasmic reticulum (ER) and mitochondria play a pivotal role in cell signaling, and the interaction between these organelles is dynamic and finely regulated. We have studied the role of ER Ca2+ concentration ([Ca2+]ER) in modulating this association in HeLa and HEK293 cells and human fibroblasts. According to Manders' coefficient, ER-mitochondria colocalization varied depending on the ER marker; it was the highest with ER-Tracker and the lowest with ER Ca2+ indicators (Mag-Fluo-4, erGAP3, and G-CEPIA1er) in both HeLa cells and human fibroblasts. Only GEM-CEPIA1er displayed a high colocalization with elongated mitochondria in HeLa cells, this ER Ca2+ indicator reveals low Ca2+ regions because this ion quenches its fluorescence. On the contrary, the typical rounded and fragmented mitochondria of HEK293 cells colocalized with Mag-Fluo-4 and, to a lesser extent, with GEM-CEPIA1er. The ablation of the three IP3R isoforms in HEK293 cells increased mitochondria-GEM-CEPIA1er colocalization. This pattern of colocalization was inversely correlated with the rate of ER Ca2+ leak evoked by thapsigargin (Tg). Moreover, Tg and Histamine in the absence of external Ca2+ increased mitochondria-ER colocalization. On the contrary, in the presence of external Ca2+, both Bafilomycin A1 and Tg reduced the mitochondria-ER interaction. Notably, knocking down MCU decreased mitochondria-ER colocalization. Overall, our data suggest that the [Ca2+] is not homogenous within the ER lumen and that mitochondria-ER interaction is modulated by the ER Ca2+ leak and the [Ca2+]i.
Subject(s)
Endoplasmic Reticulum , Mitochondria , Humans , HeLa Cells , HEK293 Cells , Endoplasmic Reticulum/metabolism , Mitochondria/metabolism , Thapsigargin/pharmacology , Calcium/metabolism , Calcium SignalingABSTRACT
The overexpression of the Orai1 channel inhibits SOCE when using the Ca2+ readdition protocol. However, we found that HeLa cells overexpressing the Orai1 channel displayed enhanced Ca2+ entry and a limited ER depletion in response to the combination of ATP and thapsigargin (TG) in the presence of external Ca2+. As these effects require the combination of an agonist and TG, we decided to study whether the phosphorylation of Orai1 S27/S30 residues had any role using two different mutants: Orai1-S27/30A (O1-AA, phosphorylation-resistant) and Orai1-S27/30D (O1-DD, phosphomimetic). Both O1-wt and O1-AA supported enhanced Ca2+ entry, but this was not the case with O1-E106A (dead-pore mutant), O1-DD, and O1-AA-E106A, while O1-wt, O1-E106A, and O1-DD inhibited the ATP and TG-induced reduction of ER [Ca2+], suggesting that the phosphorylation of O1 S27/30 interferes with the IP3R activity. O1-wt and O1-DD displayed an increased interaction with IP3R in response to ATP and TG; however, the O1-AA channel decreased this interaction. The expression of mCherry-O1-AA increased the frequency of ATP-induced sinusoidal [Ca2+]i oscillations, while mCherry-O1-wt and mCherry-O1-DD decreased this frequency. These data suggest that the combination of ATP and TG stimulates Ca2+ entry, and the phosphorylation of Orai1 S27/30 residues by PKC reduces IP3R-mediated Ca2+ release.
Subject(s)
Calcium Channels , Calcium , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Calcium/metabolism , Calcium Channels/metabolism , HeLa Cells , Humans , ORAI1 Protein/metabolism , Phosphorylation , Protein Kinase C/metabolism , Thapsigargin/pharmacologyABSTRACT
The study investigated the effect of organic/biofertilizers in intercropping patterns on seed yield and yield components and essential oil, fatty acid, and phenolic compounds of fennel (Foeniculum vulgare L.) and fenugreek (Trigonella foenum-graecum L.). Experimental treatments included the application of humic acid (HA), biofertilizers (BFS), and the unfertilized control in five planting patterns [1 row fennel + 2 rows fenugreek intercropping (1F:2FG), 2 rows fennel + 2 rows fenugreek intercropping (2F:2FG), 2 rows fennel + 4 rows fenugreek intercropping (2F:4FG), and sole cropping of each species]. Sole cropping with BFS produced the highest seed yields for fennel (2233 kg ha-1) and fenugreek (1240 kg ha-1). In contrast, the 2F:2FG intercropping ratio with BFS yielded the maximum fixed oil content for fennel (17.4%) and fenugreek (8.3%). Application of HA and BFS enhanced oil yields by 66% and 75% in fennel and 40% and 57% in fenugreek, respectively. The 2F:2FG intercropping ratio with BFS produced the maximum essential oil constituents [(E)-anethole, estragole, and fenchone] in fennel. In addition, 2F:4FG with BFS and 1F:1FG with HA produced the highest unsaturated fatty acid (oleic and linoleic acids) concentration in both species. The 2F:2FG intercropping ratio with BFS and HA produced the highest chlorogenic acid and quercetin contents, respectively, in fennel. In contrast, the 2F:4FG intercropping ratio with HA produced the highest chlorogenic acid and caffeic acid contents in fenugreek. Intercropping fennel/fenugreek with BFS or HA improved the essential oil content (fennel only), fixed oil quality and quantity, and phenolic compounds and created a more sustainable cultivation system than sole cropping systems for both species under low-input conditions.
Subject(s)
Foeniculum , Oils, Volatile , Trigonella , Chlorogenic Acid , Humic Substances , PhenolsABSTRACT
High lead (Pb) concentration in soils is becoming a severe threat to human health. It also deteriorates plants, growth, yield and quality of food. Although the use of plant growth-promoting rhizobacteria (PGPR), biochar and compost can be effective environment-friendly amendments for decreasing Pb stress in crop plants, the impacts of their simultaneous co-application has not been well documented. Thus current study was carried, was conducted to investigate the role of rhizobacteria and compost mixed biochar (CB) under Pb stress on selected soil properties and agronomic parameters in mint (Mentha piperita L.) plants. To this end, six treatments were studied: Alcaligenes faecalis, Bacillus amyloliquefaciens, CB, PGPR1 + CB, PGPR2 + CB and control. Results showed that the application A. faecalis + CB significantly decreased soil pH and EC over control. However, OM, nitrogen, phosphorus and potassium concentration were significantly improved in the soil where A. faecalis + CB was applied over control. The A. faecalis + CB treatment significantly improved mint plant root dry weight (58%), leaves dry weight (32%), chlorophyll (37%), and N (46%), P (39%) and K (63%) leave concentration, while also decreasing the leaves Pb uptake by 13.5% when compared to the unamended control. In conclusion, A. faecalis + CB has a greater potential to improve overall soil quality, fertility and mint plant productivity under high Pb soil concentration compared to the sole application of CB and A. faecalis.
Subject(s)
Charcoal/metabolism , Composting/methods , Lead/toxicity , Mentha/drug effects , Rhizosphere , Soil Pollutants/toxicity , Alcaligenes faecalis/enzymology , Alcaligenes faecalis/metabolism , Aminohydrolases/metabolism , Bacillus amyloliquefaciens/enzymology , Bacillus amyloliquefaciens/metabolism , Bacterial Proteins/metabolism , Biodegradation, Environmental , Fruit/chemistry , Lead/metabolism , Mentha/microbiology , Soil Pollutants/metabolism , Stress, Physiological , Vegetables/chemistryABSTRACT
Drought stress, being the inevitable factor that exists in various environments without recognizing borders and no clear warning thereby hampering plant biomass production, quality, and energy. It is the key important environmental stress that occurs due to temperature dynamics, light intensity, and low rainfall. Despite this, its cumulative, not obvious impact and multidimensional nature severely affects the plant morphological, physiological, biochemical and molecular attributes with adverse impact on photosynthetic capacity. Coping with water scarcity, plants evolve various complex resistance and adaptation mechanisms including physiological and biochemical responses, which differ with species level. The sophisticated adaptation mechanisms and regularity network that improves the water stress tolerance and adaptation in plants are briefly discussed. Growth pattern and structural dynamics, reduction in transpiration loss through altering stomatal conductance and distribution, leaf rolling, root to shoot ratio dynamics, root length increment, accumulation of compatible solutes, enhancement in transpiration efficiency, osmotic and hormonal regulation, and delayed senescence are the strategies that are adopted by plants under water deficit. Approaches for drought stress alleviations are breeding strategies, molecular and genomics perspectives with special emphasis on the omics technology alteration i.e., metabolomics, proteomics, genomics, transcriptomics, glyomics and phenomics that improve the stress tolerance in plants. For drought stress induction, seed priming, growth hormones, osmoprotectants, silicon (Si), selenium (Se) and potassium application are worth using under drought stress conditions in plants. In addition, drought adaptation through microbes, hydrogel, nanoparticles applications and metabolic engineering techniques that regulate the antioxidant enzymes activity for adaptation to drought stress in plants, enhancing plant tolerance through maintenance in cell homeostasis and ameliorates the adverse effects of water stress are of great potential in agriculture.
ABSTRACT
Gamma radiation produces DNA instability and impaired phenotype. Previously, we observed negative effects on phenotype, DNA methylation, and gene expression profiles, in offspring of zebrafish exposed to gamma radiation during gametogenesis. We hypothesize that previously observed effects are accompanied with changes in the expression profile of non-coding RNAs, inherited by next generations. Non-coding RNA expression profile was analysed in F1 offspring (5.5 h post-fertilization) by high-throughput sequencing 1 year after parental irradiation (8.7 mGy/h, 5.2 Gy total dose). Using our previous F1-γ genome-wide gene expression data (GSE98539), hundreds of mRNAs were predicted as targets of differentially expressed (DE) miRNAs, involved in pathways such as insulin receptor, NFkB and PTEN signalling, linking to apoptosis and cancer. snRNAs belonging to the five major spliceosomal snRNAs were down-regulated in the F1-γ group, Indicating transcriptional and post-transcriptional alterations. In addition, DEpiRNA clusters were associated to 9 transposable elements (TEs) (LTR, LINE, and TIR) (p = 0.0024), probable as a response to the activation of these TEs. Moreover, the expression of the lincRNAs malat-1, and several others was altered in the offspring F1, in concordance with previously observed phenotypical alterations. In conclusion, our results demonstrate diverse gamma radiation-induced alterations in the ncRNA profiles of F1 offspring observable 1 year after parental irradiation.
Subject(s)
Gamma Rays/adverse effects , RNA, Untranslated/genetics , Zebrafish/genetics , Animals , DNA Damage/genetics , DNA Damage/radiation effects , DNA Methylation/genetics , DNA Methylation/radiation effects , Gametogenesis/genetics , Gametogenesis/radiation effects , Signal Transduction/genetics , Signal Transduction/radiation effects , Transcriptome/genetics , Transcriptome/radiation effectsABSTRACT
There is a need for a more innovative fertilizer approach that can increase the productivity of agricultural systems and be more environmentally friendly than synthetic fertilizers. In this article, we reviewed the recent development and potential benefits derived from the use of nanofertilizers (NFs) in modern agriculture. NFs have the potential to promote sustainable agriculture and increase overall crop productivity, mainly by increasing the nutrient use efficiency (NUE) of field and greenhouse crops. NFs can release their nutrients at a slow and steady pace, either when applied alone or in combination with synthetic or organic fertilizers. They can release their nutrients in 40-50 days, while synthetic fertilizers do the same in 4-10 days. Moreover, NFs can increase the tolerance of plants against biotic and abiotic stresses. Here, the advantages of NFs over synthetic fertilizers, as well as the different types of macro and micro NFs, are discussed in detail. Furthermore, the application of NFs in smart sustainable agriculture and the role of NFs in the mitigation of biotic and abiotic stress on plants is presented. Though NF applications may have many benefits for sustainable agriculture, there are some concerns related to the release of nanoparticles (NPs) from NFs into the environment, with the subsequent detrimental effects that this could have on both human and animal health. Future research should explore green synthesized and biosynthesized NFs, their safe use, bioavailability, and toxicity concerns.
ABSTRACT
Global warming promotes soil calcification and salinization processes. As a result, soil phosphorus (P) is becoming deficient in arid and semiarid areas throughout the world. In this pot study, we evaluated the potential of phosphate-solubilizing bacteria (PSB) for enhancing the growth and P uptake in maize under varying levels of lime (4.8%, 10%, 15% and 20%) and additional P supplements (farmyard manure, poultry manure, single super phosphate and rock phosphate) added at the rate of 45 mg P2O5 kg-1. Inoculation and application of P as organic manures (Poultry and farm yard manures) improved maize growth and P uptake compared to the control and soils with P applied from mineral sources. Liming adversely affected crop growth, but the use of PSB and organic manure significantly neutralized this harmful effect. Mineral P sources combined with PSB were as effective as the organic sources alone. Furthermore, while single supper phosphate showed better results than Rock phosphate, the latter performed comparably upon PSB inoculation. Thus, PSB plus P application as organic manures is an eco-friendly option to improve crop growth and P nutrition in a calcareous soil under changing climate.
ABSTRACT
BACKGROUND: A primary underlying cause of postoperative complications is related to the surgical stress response, which may be mitigated by hyperbaric oxygen therapy (HBOT), the intermittent administration of oxygen at a pressure higher than the atmospheric pressure at sea level. Promising clinical studies have emerged suggesting HBOT's efficacy for reducing some postoperative complications. Notwithstanding, the effectiveness (if any) of HBOT across a range of procedures and postoperative outcomes has yet to be clearly quantified. OBJECTIVE: This systematic review aimed to summarise the existing literature on peri-operative HBOT to investigate its potential to optimise surgical patient outcome. DESIGN: A systematic review of randomised controlled trials (RCTs) with narrative summary of results. DATA SOURCES: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials were searched without language restrictions through to 19 June 2018. ELIGIBILITY CRITERIA: Studies were included if they involved patients of any age undergoing any surgical procedure and provided with at least one HBOT session in the peri-operative period. Two independent reviewers screened the initial identified trials and determined those to be included. Risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. RESULTS: The search retrieved 775 references, of which 13 RCTs were included (627 patients). Ten RCTs (546 patients) reported treatment was effective for improving at least one of the patient outcomes assessed, while two studies (55 patients) did not find any benefit and one study (26 patients) found a negative effect. A wide range of patient outcomes were reported, and several other methodological limitations were observed among the included studies, such as limited use of sham comparator and lack of blinding. CONCLUSION: Peri-operative preventive HBOT may be a promising intervention to improve surgical patient outcome. However, future work should consider addressing the methodological weaknesses identified in this review. TRIAL REGISTRATION: The protocol (CRD42018102737) was registered with the International ProspectiveRegister of Systematic Reviews (PROSPERO).
Subject(s)
Hyperbaric Oxygenation , Humans , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Treatment OutcomeABSTRACT
INTRODUCTION: Evidence from many areas of healthcare suggests that skills learned during simulation transfer to clinical settings; however, this has not yet been investigated in hyperbaric medicine. This systematic review aimed to identify, summarize, and assess the impact of simulation-based education in hyperbaric medicine. METHODS: Eligible studies investigated the effect of simulation-based education for learning in hyperbaric medicine, used any design, and were published in English in a peer-reviewed journal. Learning outcomes across all Kirkpatrick levels were included. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched. Pairs of independent reviewers assessed references for study eligibility. RESULTS: We found no article assessing the impact of simulation-based education in hyperbaric medicine published in English. Only one potentially relevant paper published in German was found. CONCLUSIONS: More research is needed to determine how the hyperbaric medicine community and their patients may benefit from simulation-based education to optimize both practice and patient care.
Subject(s)
Clinical Competence , Computer Simulation , Education, Medical, Continuing , Hyperbaric Oxygenation , HumansABSTRACT
Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.
Subject(s)
Gamma Rays/adverse effects , Genetic Loci/radiation effects , Histone Code/radiation effects , Salmo salar/genetics , Zebrafish/genetics , Animals , Embryonic Development/genetics , Embryonic Development/radiation effects , Gametogenesis/radiation effects , Genetic Loci/genetics , Histones/chemistry , Histones/metabolism , Lysine/metabolism , Methylation/radiation effects , Salmo salar/embryology , Salmo salar/physiology , Zebrafish/embryology , Zebrafish/physiologyABSTRACT
The Golgi apparatus (GA) is a bona fide Ca2+ store; however, there is a lack of GA-specific Ca2+ mobilizing agents. Here, we report that emetine specifically releases Ca2+ from GA in HeLa and HL-1 atrial myocytes. Additionally, it has become evident that the trans-Golgi is a labile Ca2+ store that requires a continuous source of Ca2+ from either the external milieu or from the ER, to enable it to produce a detectable transient increase in cytosolic Ca2+. Our data indicates that the emetine-sensitive Ca2+ mobilizing mechanism is different from the two classical Ca2+ release mechanisms, i.e. IP3 and ryanodine receptors. This newly discovered ability of emetine to release Ca2+ from the GA may explain why chronic consumption of ipecac syrup has muscle side effects.
Subject(s)
Antinematodal Agents/pharmacology , Calcium/metabolism , Emetine/pharmacology , Epithelial Cells/drug effects , Myocytes, Cardiac/drug effects , trans-Golgi Network/drug effects , Cell Line , Epithelial Cells/metabolism , Humans , Myocytes, Cardiac/metabolism , trans-Golgi Network/metabolismABSTRACT
Ionizing radiation is known to cause DNA damage, yet the mechanisms underlying potential transgenerational effects of exposure have been scarcely studied. Previously, we observed effects in offspring of zebrafish exposed to gamma radiation during gametogenesis. Here, we hypothesize that these effects are accompanied by changes of DNA methylation possibly inherited by subsequent generations. We assessed DNA methylation in F1 embryos (5.5 hours post fertilization) with whole genome bisulfite sequencing following parental exposure to 8.7 mGy/h for 27 days and found 5658 differentially methylated regions (DMRs). DMRs were predominantly located at known regulatory regions, such as gene promoters and enhancers. Pathway analysis indicated the involvement of DMRs related to similar pathways found with gene expression analysis, such as development, apoptosis and cancers, which could be linked to previous observed developmental defects and genomic instability in the offspring. Follow up of 19 F1 DMRs in F2 and F3 embryos revealed persistent effects up to the F3 generation at 5 regions. These results indicate that ionizing radiation related effects in offspring can be linked to DNA methylation changes that partly can persist over generations. Monitoring DNA methylation could serve as a biomarker to provide an indication of ancestral exposures to ionizing radiation.