Metabolism Signaling Research Articles

The context-dependent epigenetic and organogenesis programs determine 3D vs. 2D cellular fitness of MYC-driven murine liver cancer cells.

3D cellular-specific epigenetic and transcriptomic reprogramming is critical to organogenesis and tumorigenesis. Here we dissect the distinct cell fitness in 2D (normoxia vs. chronic hypoxia) vs 3D (normoxia) culture conditions for a MYC-driven murine liver cancer model. We identify over 600 shared essential genes and additional context-specific fitness genes and pathways. Knockout of the VHL-HIF1 pathway results in incompatible fitness defects under normoxia vs. 1% oxygen or 3D culture conditions. Moreover, deletion of each of the mitochondrial respiratory electron transport chain complex has distinct fitness outcomes. Notably, multicellular organogenesis signaling pathways including TGFb-SMAD specifically constrict the uncontrolled cell proliferation in 3D while inactivation of epigenetic modifiers (Bcor, Kmt2d, Mettl3 and Mettl14) has opposite outcomes in 2D vs. 3D. We further identify a 3D-dependent synthetic lethality with partial loss of Prmt5 due to a reduction of Mtap expression resulting from 3D-specific epigenetic reprogramming. Our study highlights unique epigenetic, metabolic and organogenesis signaling dependencies under different cellular settings.

A discovery in traditional Chinese medicine compatibility: Cinnabaris suppresses the Strychni Semen-induced neurotoxicity in Shang-Ke-Jie-Gu tablet

BackgroundCinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. Shang-Ke-Jie-Gu tablet is a famous Chinese patent medicine with Cinnabaris, However, the function of Cin in the prescription hasn't been clarified. PurposeOur study evaluated the toxicity of Shang-Ke-Jie-Gu tablet (SK) with or without Cinnabaris, and illuminate the related mechanisms that why cinnabaris is necessary. MethodsThe toxicity of SK and Cin free Shang-Ke-Jie-Gu tablet (CFSK) was evaluated by physical and behavioral tests and histological examinations. The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS. ResultsCin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12‑hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae_NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed. ConclusionAs a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines.

189 Association of the liver phosphoproteome with divergent dry matter intake in finishing beef steers

Abstract As the need for improving the sustainability of the beef industry increases, optimizing feed efficiency is of the utmost importance. The liver has a central role in nutrient metabolism, and for ruminants particularly, it is essential for providing glucose through gluconeogenesis via substrates such as propionate, lactate, and glycerol. Further, through cell signaling and vagal afferent signals, the liver acts to stimulate and inhibit dry matter intake (DMI). Thus, the objective of this study was to investigate alterations in the phosphoproteome of finishing beef steers in relation to divergent DMI to identify changes in the abundance of signaling proteins. Angus steers [n = 57; initial body weight (BW) = 518 ± 27 kg] underwent a 63-d intake trial utilizing an Insentec Roughage Intake Control System (Hokofarm Group, Emmeloord, The Netherlands). Prior to beginning the trial, liver biopsy samples were collected from all steers. Samples from steers with the greatest and least DMI (n = 8 each) were utilized for phosphoproteomic analysis. Liver protein was isolated and labeled with isobaric tandem mass tagging reagents. Samples were enriched for phosphopeptides using immobilized metal affinity chromatography and subsequently analyzed using high-performance liquid chromatography tandem mass spectrometry. Spectral data were searched in the National Center for Biotechnology Information Bos taurus protein database using MaxQuant (version 2.2.0.0; Max Planck Inst., Munich, Germany), and the data were analyzed using Perseus (version 2.0.10.0; Max Planck Inst.). Two sample t-tests were conducted to determine the difference in phosphopeptide abundance between steers with high and low DMI. A total of 16,365 phosphopeptides were identified, and 287 were differentially expressed (False Discovery Rate < 0.05). In addition, 2,777 phosphopeptides were differentially expressed based on an unadjusted P < 0.05 which were used for enrichment analysis of Gene Ontology processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the Database for Annotation, Visualization, and Integrated Discovery. The background for this analysis was all identified phosphopeptides. Gene ontology terms enriched included processes related to phosphorylation activity, intracellular signal transduction, response to insulin, kinase activity, and signaling protein binding. Enriched KEGG pathways included pathways related to insulin signaling, such as AMPK signaling, mTOR signaling, and MAPK signaling. Further, pathways related to glycolysis and gluconeogenesis, glucagon signaling, insulin resistance, carbon metabolism, and various other signaling pathways were also enriched. These results suggest a link between the liver phosphoproteome and DMI, indicating that divergent DMI is associated with alterations in signaling pathways related to nutrient uptake and metabolic processes.

Fermentation broth of a novel endophytic fungus enhanced maize salt tolerance by regulating sugar metabolism and phytohormone biosynthesis or signaling

Soil salinization is a major environmental factor that severely affects global agriculture. Root endophytes can enter root cells, and offer various ecological benefits, such as promoting plant growth, improving soil conditions, and enhancing plant resistance. Su100 is a novel strain of endophytic fungus that was characterized from blueberry roots. In this study, we focused on evaluating the effects of Su100 secretion on maize growth. The results demonstrated that maize treated with Su100 fermentation broth (SFB) exhibited significantly stronger salt tolerance than the control. It is worth mentioning that the treated root system not only had an advantage in terms of biomass but also a change in root structure with a significant increase in lateral roots (LRs) compared to the control. Transcriptome analysis combined with hormone content measurements indicated that SFB upregulated the auxin signaling pathway, and also caused alterations in brassinosteroids (BR) and jasmonic acid (JA) biosynthesis and signaling pathways. Transcriptome analyses also indicated that SFB caused significant changes in the sugar metabolism of maize roots. The major changes included: enhancing the conversion and utilization of sucrose in roots; increasing carbon flow to uridine diphosphate glucose (UDPG), which acted as a precursor for producing more cell wall polysaccharides, mainly pectin and lignin; accelerating the tricarboxylic acid cycle, which were further supported by sugar content determinations. Taken together, our results indicated that the enhanced salt tolerance of maize treated with SFB was due to the modulation of sugar metabolism and phytohormone biosynthesis or signaling pathways. This study provided new insights into the mechanisms of action of endophytic fungi and highlighted the potential application of fungal preparations in agriculture.

Exogenous strigolactone alleviates post-waterlogging stress in grapevine

With global climate change, the frequent occurrence of intense rainfall and aggravation of waterlogging disasters have severely threatened the plant growth and fruit quality of grapevines, which are commercially important fruit crops worldwide. There is accordingly an imperative to clarify the responses of grapevine to waterlogging and to propose appropriate remedial measures. Strigolactone (SL) is a phytohormone associated with plant abiotic stress tolerance, while, its function in plant responses to waterlogging stress remain undetermined. In this study, systematic analyses of the morphology, physiology, and transcriptome changes in grapevine leaves and roots under post-waterlogging and GR24 (a synthetic analog of SL) treatments were performed. Morphological and physiological changes in grapevines in response to post-waterlogging stress, including leaf wilting and yellowing, leaf senescence, photosynthesis inhibition, and increased anti-oxidative systems, could be alleviated by the application of GR24. Moreover, transcriptome analysis revealed that the primary gene functions induced by post-waterlogging stress changed over time; however, they were consistently associated with carbohydrate metabolism. The GR24-induced leaf genes were closely associated with carbohydrate metabolism, photosynthesis, antioxidant systems, and hormone signal transduction, which were considered vital aspects that were influenced by GR24 in grapevine to induce post-waterlogging tolerance. Concerning the roots, an enhancement of microtubules and cytoskeleton for cell construction in GR24 application was proposed to facilitate root system recovery after waterlogging. With this study, we comprehend the knowledge regarding the responses of grapevines to post-waterlogging and the ameliorative effect of GR24 with the insight to the transcriptome changes during these processes.

Pisolithus microcarpus isolates with contrasting abilities to colonise Eucalyptus grandis exhibit significant differences in metabolic signalling

Biotic factors in fungal exudates impact plant-fungal symbioses establishment. Mutualistic ectomycorrhizal fungi play various ecological roles in forest soils by interacting with trees. Despite progress in understanding secreted fungal signals, dynamics of signal production in situ before or during direct host root contact remain unclear. We need to better understand how variability in intra-species fungal signaling at these stages impacts symbiosis with host tissues. Using the ECM model Pisolithus microcarpus, we selected two isolates (Si9 and Si14) with different abilities to colonize Eucalyptus grandis roots. Hypothesizing that distinct early signalling and metabolite profiles between these isolates would influence colonization and symbiosis, we used microdialysis to non-destructively collect secreted metabolites from either the fungus, host, or both, capturing the dynamic interplay of pre-symbiotic signalling over 48 hours. Our findings revealed significant differences in metabolite profiles between Si9 and Si14, grown alone or with a host root. Si9, with lower colonization efficiency than Si14, secreted a more diverse range of compounds, including lipids, oligopeptides, and carboxylic acids. In contrast, Si14's secretions, similar to the host's, included more aminoglycosides. This study emphasizes the importance of intra-specific metabolomic diversity in ectomycorrhizal fungi, suggesting that early metabolite secretion is crucial for establishing successful mutualistic relationships.

PHGDH/SYK: a hub integrating anti-fungal immunity and serine metabolism.

Immune cells modify their metabolic pathways in response to fungal infections. Nevertheless, the biochemical underpinnings need to be better understood. This study reports that fungal infection drives a switch from glycolysis to the serine synthesis pathway (SSP) and one-carbon metabolism by inducing the interaction of spleen tyrosine kinase (SYK) and phosphoglycerate dehydrogenase (PHGDH). As a result, PHGDH promotes SYK phosphorylation, leading to the recruitment of SYK to C-type lectin receptors (CLRs). The CLR/SYK complex initiates signaling cascades that lead to transcription factor activation and pro-inflammatory cytokine production. SYK activates SSP and one-carbon metabolism by inducing PHGDH activity. Then, one-carbon metabolism supports S-adenosylmethionine and histone H3 lysine 36 trimethylation to drive the production of pro-inflammatory cytokines and chemokines. These findings reveal the crosstalk between amino acid metabolism, epigenetic modification, and CLR signaling during fungal infection.

The AMPK/cAMP Metabolic Signaling Axis as a Possible Therapeutic Target for Diabetes.

Diabetes is a complex disease, despite the availability of numerous treatments, its progression and complications can only be mitigated and managed to a certain extent. After the onset, diabetes cannot be reversed. Its global expansion makes it challenging for governments to control the considerable costs of treating people with diabetes. Many studies have been carried out by widely recognized pharmaceutical companies that are considering the development of new drugs for diabetic treatments. Diets, sedentary habits, and lifestyles that are currently prevalent have an enormous influence on the global spread of diabetes. The tools available to clinicians for therapy do not solve the problem. It is known that a patient, when diagnosed, would already have had diabetes for more than three years. Studies on diabetes signaling consider the effects of hyperglycemia but also highlight the roles of insulin receptor activation and resistance. Understanding the intricate signaling network and its interactions with hyperglycemiainduced pathways is crucial. In this context, the cyclic AMP/AMPK axis emerges as a promising therapeutic target for diabetes. However, there is a noticeable lack of literature exploring the metabolic network induced by hyperglycemia and its interconnected pathways. Therefore, investigating the cyclic cAMP/AMPK axis could provide valuable insights, given its complex connections with various metabolic pathways. This mini-review aims to delve into the metabolic signaling of the AMPK/cAMP axis in the context of diabetes, highlighting its metabolic interactions and potential implications.

The NF-κB Factor Relish maintains blood progenitor homeostasis in the developing Drosophila lymph gland.

Post-larval hematopoiesis in Drosophila largely depends upon the stockpile of progenitors present in the blood-forming organ/lymph gland of the larvae. During larval stages, the lymph gland progenitors gradually accumulate reactive oxygen species (ROS), which is essential to prime them for differentiation. Studies have shown that ROS triggers the activation of JNK (c-Jun Kinase), which upregulates fatty acid oxidation (FAO) to facilitate progenitor differentiation. Intriguingly, despite having ROS, the entire progenitor pool does not differentiate simultaneously in the late larval stages. Using expression analyses, genetic manipulation and pharmacological approaches, we found that the Drosophila NF-κB transcription factor Relish (Rel) shields the progenitor pool from the metabolic pathway that inducts them into the differentiation program by curtailing the activation of JNK. Although ROS serves as the metabolic signal for progenitor differentiation, the input from ROS is monitored by the developmental signal TAK1, which is regulated by Relish. This developmental circuit ensures that the stockpile of ROS-primed progenitors is not exhausted entirely. Our study sheds light on how, during development, integrating NF-κB-like factors with metabolic pathways seem crucial to regulating cell fate transition during development.

Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies.

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host-pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host-pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.

Enabling SENSE accelerated 2D CSI for hyperpolarized carbon-13 imaging

As hyperpolarized (HP) carbon-13 (13C) metabolic imaging is clinically translated, there is a need for easy-to-implement, fast, and robust imaging techniques. However, achieving high temporal resolution without decreasing spatial and/or spectral resolution, whilst maintaining the usability of the imaging sequence is challenging. Therefore, this study looked to accelerate HP 13C MRI by combining a well-established and robust sequence called two-dimensional Chemical Shift Imaging (2D CSI) with prospective under sampling and SENSitivity Encoding (SENSE) reconstruction. Due to the low natural abundance of 13C, the sensitivity maps cannot be pre-acquired for the reconstruction. As such, the implementation of sodium (23Na) sensitivity maps for SENSE reconstructed 13C CSI was demonstrated in a phantom and in vivo in the pig kidney. Results showed that SENSE reconstruction using 23Na sensitivity maps corrected aliased images with a four-fold acceleration. With high temporal resolution, the kidney spectra produced a detailed metabolic arrival and decay curve, useful for further metabolite kinetic modelling or denoising. Metabolic ratio maps were produced in three pigs demonstrating the technique’s ability for repeat metabolic measurements. In cases with unknown metabolite spectra or limited HP MRI specialist knowledge, this robust acceleration method ensures comprehensive capture of metabolic signals, mitigating the risk of missing spectral data.

Potential mechanisms and modifications of dietary antioxidants on the associations between co-exposure to plastic additives and diabetes

BackgroundThe association of plastic additive mixture exposure with diabetes and the modifying effects of dietary antioxidants are unclear.MethodsThe data from the NHANES 2011–2018 were retrieved, and phthalates and organophosphate esters (OPEs) were selected as exposures. The coexposure effect was analyzed by the environmental risk score (ERS) and quantile g-computation. To mitigate any potential bias caused by using the internal weights, another version of ERS was constructed using the cross-validation approach. The level of dietary antioxidant intake was measured by the composite dietary antioxidant index (CDAI). The biological mechanism underlying the association was studied by the adverse outcome pathway (AOP) framework.ResultsFifteen chemicals (ten phthalates and five OPEs) were measured in 2824 adult participants. A higher ERS was significantly associated with an increased risk of diabetes (OR per 1-SD increment of ERS: 1.25, 95% CI: 1.13–1.39). This association apparently interacted with the CDAI level (ORlow: 1.83, 95% CI: 1.37–2.55; ORhigh: 1.28, 95% CI: 1.15–1.45; Pinteraction = 0.038). Moreover, quantile g-computation also revealed higher level of combined exposure was positively associated with diabetes (OR: 1.27, 95% CI: 1.05–2.87), and the addition of dietary antioxidants showed a null association (OR: 1.09, 95% CI: 0.85–2.34). The AOP study identified TCPP and TCEP as key chemicals that cause aberrant glucose metabolism and insulin signaling pathways and result in diabetes.ConclusionsCoexposure to phthalates and OPEs is positively associated with diabetes, where an antioxidative diet plays a modifying role. Several potential mechanisms have been proposed by AOP framework.

Association Between Type 2 Diabetes Mellitus and Alzheimer's Disease: Common Molecular Mechanism and Therapeutic Targets.

Diabetes mellitus (DM) and Alzheimer's disease (AD) rates are rising, mirroring the global trend of an aging population. Numerous epidemiological studies have shown that those with Type 2 diabetes (T2DM) have an increased risk of developing dementia. These degenerative and progressive diseases share some risk factors. To a large extent, the amyloid cascade is responsible for AD development. Neurofibrillary tangles induce neurodegeneration and brain atrophy; this chain reaction begins with hyperphosphorylation of tau proteins caused by progressive amyloid beta (Aβ) accumulation. In addition to these processes, it seems that alterations in brain glucose metabolism and insulin signalling lead to cell death and reduced synaptic plasticity in AD, before the onset of symptoms, which may be years away. Due to the substantial evidence linking insulin resistance in the brain with AD, researchers have coined the name "Type 3 diabetes" to characterize the condition. We still know little about the processes involved, even though current animal models have helped illuminate the links between T2DM and AD. This brief overview discusses insulin and IGF-1 signalling disorders and the primary molecular pathways that may connect them. The presence of GSK-3β in AD is intriguing. These proteins' association with T2DM and pancreatic β-cell failure suggests they might be therapeutic targets for both disorders.

SCGB1A1 as a novel biomarker and promising therapeutic target for the management of HNSCC.

Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-β and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC.

Exploring Fatty Acid β-Oxidation Pathways in Bacteria: From General Mechanisms to DSF Signaling and Pathogenicity in Xanthomonas.

Fatty acids (FAs) participate in extensive physiological activities such as energy metabolism, transcriptional control, and cell signaling. In bacteria, FAs are degraded and utilized through various metabolic pathways, including β-oxidation. Over the past ten years, significant progress has been made in studying FA oxidation in bacteria, particularly in E. coli, where the processes and roles of FA β-oxidation have been comprehensively elucidated. Here, we provide an update on the new research achievements in FAs β-oxidation in bacteria. Using Xanthomonas as an example, we introduce the oxidation process and regulation mechanism of the DSF-family quorum sensing signal. Based on current findings, we propose the specific enzymes required for β-oxidation of several specific FAs. Finally, we discuss the future outlook on scientific issues that remain to be addressed. This paper supplies theoretical guidance for further study of the FA β-oxidation pathway with particular emphasis on its connection to the pathogenicity mechanisms of bacteria.

Multiomics analysis reveal the impact of 17α-Ethinylestradiol on mortality in juvenile zebrafish

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity.

Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach.

Cardiac glycosides (CGs), traditionally used for heart failure, have shown potential as anti-cancer agents. This study aims to explore their multifaceted mechanisms in cancer cell biology using proteome integral solubility alteration (PISA), focusing on the interaction with key proteins implicated in cellular metabolism and mitochondrial function. We conducted lysate-based and intact-cell PISA assays on cancer cells treated with CGs (Digoxin, Digitoxin, Ouabain) to analyze protein solubility changes. This was followed by mass spectrometric analysis and bioinformatics to identify differentially soluble proteins (DSPs). Molecular docking simulations were performed to predict protein-CG interactions. Public data including gene expression changes upon CG treatment were re-analyzed for validation. The PISA assays revealed CGs' broad-spectrum interactions, particularly affecting proteins like PKM2, ANXA2, SLC16A1, GOT2 and GLUD1. Molecular docking confirmed stable interactions between CGs and these DSPs. Re-analysis of public data supported the impact of CGs on cancer metabolism and cell signaling pathways. Our findings suggest that CGs could be repurposed for cancer therapy by modulating cellular processes. The PISA data provide insights into the polypharmacological effects of CGs, warranting further exploration of their mechanisms and clinical potential.

Sex-specific alterations in pulmonary metabolic, xenobiotic and lipid signalling pathways after e-cigarette aerosol exposure during adolescence in mice

BackgroundE-cigarette use is now prevalent among adolescents and young adults, raising concerns over potential adverse long-term health effects. Although it is hypothesised that e-cigarettes promote inflammation, studies have yielded conflicting...

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective: To evaluate the effect of asiaticoside on streptozotocin (STZ) and nicotinamide (NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats. Methods: Asiaticoside (50 and 100 mg/kg body weight) was administered to STZ-NAD-induced diabetic rats for 45 days, and its effects on hyperglycaemic, carbohydrate metabolic, and insulin signaling pathway markers were examined. Results: Asiaticoside increased insulin production, lowered blood glucose levels, and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities. Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity. Furthermore, asiaticoside upregulated the mRNA expressions of IRS-1, IRS-2, and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal. Conclusions: Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis, gluconeogenesis, and insulin signaling pathways.

Elucidating light and temperature-dependent signalling pathways from shoot to root in rice plants: Implications for stress responses.

The main aim of this work was to better understand how the low temperature signal from the leaves may affect the stress responses in the roots, and how the light conditions modify certain stress acclimation processes in rice plants. Rice plants grown at 27°C were exposed to low temperatures (12°C) with different light intensities, and in the case of some groups of plants, only the leaves received the cold, while the roots remained at control temperature. RNA sequencing focusing on the roots of plants grown under normal growth light conditions found 525 differentially expressed genes in different comparisons. Exposure to low temperature led to more down-regulated than up-regulated genes. Comparison between roots of the leaf-stressed plants and whole cold-treated or control plants revealed that nitrogen metabolism and nitric oxide-related signalling, as well as the phenylpropanoid-related processes, were specifically affected. Real-time PCR results focusing on the COLD1 and polyamine oxidase genes, as well as metabolomics targeting hormonal changes and phenolic compounds also showed that not only cold exposure of the leaves, either alone or together with the roots, but also the light conditions may influence certain stress responses in the roots of rice plants.