PubMed

Genes Dis. 2024 Jul 16;12(2):101377. doi: 10.1016/j.gendis.2024.101377. eCollection 2025 Mar.NO ABSTRACTPMID:39649842 | PMC:PMC11625321 | DOI:10.1016/j.gendis.2024.101377

Sports Med Health Sci. 2024 Mar 8;7(1):37-47. doi: 10.1016/j.smhs.2024.03.001. eCollection 2025 Jan.ABSTRACTExercise training in pulmonary arterial hypertension (PAH) has been gaining popularity with guidelines now recommending it as an important adjunct to medical therapy. Despite improvements in function and quality of life, an understanding of metabolic changes and their mechanisms remain unexplored. The objective of this study was therefore to understand the metabolic basis of exercise in a monocrotaline model of PAH. 24 male Wistar rats (age: 8-12 weeks and mean body weight: [262.16 ​± ​24.49] gms) were assigned to one of the four groups (i.e., Control, PAH, Exercise and PAH ​+ ​Exercise). The exercise groups participated in treadmill running at 13.3 ​m/min, five days a week for five weeks. Demographic and clinical characteristics were monitored regularly. Following the intervention, LC-MS based metabolomics were performed on blood samples from all groups at the end of five weeks. Metabolite profiling, peak identification, alignment and isotope annotation were also performed. Statistical inference was carried out using dimensionality reducing techniques and analysis of variance. Partial-least-squares discrimination analysis and variable importance in the projection scores showed that the model was reliable, and not over lifting. The analysis demonstrated significant perturbations to lipid and amino acid metabolism, arginine and homocysteine pathways, sphingolipid (p ​< ​0.05), glycerophospholipid (p ​< ​0.05) and nucleotide metabolism in PAH. Exercise, however, was seen to restore arginine (p ​< ​0.05) and homocysteine(p ​< ​0.000 1) levels which were independent effects, irrespective of PAH. Dysregulated arginine and homocysteine pathways are seen in PAH. Exercise restores these dysregulated pathways and could potentially impact severity and outcome in PAH.PMID:39649790 | PMC:PMC11624410 | DOI:10.1016/j.smhs.2024.03.001

World J Gastroenterol. 2024 Dec 7;30(45):4839-4843. doi: 10.3748/wjg.v30.i45.4839.ABSTRACTIn this editorial, we comment on Liu et al's article published in the recent issue of the World Journal of Gastroenterology. Biochemically and pathologically, Liu et al proved that the urate-lowering activity of leech total protein (LTP) was mainly attributed to the rectification of gut microbiota. Specifically, we noticed the change in Bacteroides and Akkermansia after LTP administration. Both bacteria have been reported to alleviate metabolic dysfunction-associated steatohepatitis and other chronic metabolic diseases. LTP was administrated through intragastric manners. Most possibly, LTP would be digested by the gut microbiota further. The anti-hyperuricemia effects should, to the most possible extent, be exerted by the peptides or their secondary metabolic products. Human gut microbiota communicates with other organs through metabolites generated by the microbes or co-metabolized with the host. Whether the anti-hyperuricemia effect could be partially ascribed to the microbiota metabolites also deserves to be discussed. Although metabolomics analysis was performed for serum samples, fecal metabolomics was highly advocated which could facilitate exact mechanism explanation. This study implied that gut microbiota contains many unexplored targets with different therapeutic potentials. It is foreseeable that utilizing these targets can avoid the impairment or side effects of directly using human targets to some extent.PMID:39649550 | PMC:PMC11606374 | DOI:10.3748/wjg.v30.i45.4839

Photosynthetica. 2023 Oct 10;61(4):451-460. doi: 10.32615/ps.2023.037. eCollection 2023.ABSTRACTCommon periwinkle (Catharanthus roseus L.) is an important medicinal plant used by the pharmaceutical industry. The present work aimed to determine the effect of low light intensity on the primary and secondary metabolic processes, using various photosynthesis and targeted and untargeted analytical techniques. Growth light had only limited effects on the photosynthetic electron transport processes, although membrane stability seemed slightly higher in plants growing under higher light conditions. The reduced growth light caused a reduction in certain primary metabolites, including amino acids and sugars, and it also reduced the contents of most of the phenolic compounds investigated in the present experiments. Interestingly, the differences in the growth light caused a much less pronounced difference in the alkaloid contents than that found in the flavonoid contents. However, besides the growth light, genotypic differences, most evident in flower colour, also affected some metabolic processes, including primary and secondary processes.PMID:39649484 | PMC:PMC11586840 | DOI:10.32615/ps.2023.037

Photosynthetica. 2023 Dec 19;61(4):398-404. doi: 10.32615/ps.2023.044. eCollection 2023.NO ABSTRACTPMID:39649483 | PMC:PMC11586841 | DOI:10.32615/ps.2023.044

Physiol Plant. 2024 Nov-Dec;176(6):e14646. doi: 10.1111/ppl.14646.ABSTRACTThe barley powdery mildew disease caused by the biotrophic fungus Blumeria hordei (Bh) poses enormous risks to crop production due to yield and quality losses. Plants and fungi can produce and release volatile organic compounds (VOCs) that serve as signals in plant communication and defense response to protect themselves. The present study aims to identify VOCs released by barley (Hordeum vulgare) during Bh-infection and to decipher VOC-induced disease resistance in receiver plants. VOC profiles of susceptible MLO wild type (MLO WT) and a resistant near-isogenic backcross line (mlo5) were characterized over time (one day or three days after Bh inoculation) using TD-GC/MS. Comparative analysis revealed genotype-dependent VOC profiles and significant differences in emission rates for β-caryophyllene, linalool, (Z)-3-hexenol, and methyl salicylate. Furthermore, susceptible barley plants were exposed to the complex VOC bouquet of MLO WT or mlo5 sender plants in plant-to-plant communication. We found that VOC-induced resistance in receiver plants depended on the sender genotype in a Bh susceptibility assay. Additionally, untargeted metabolomics and gene expression studies provide evidence toward an SA-dependent pathway mediating VOC-induced resistance against powdery mildew. The exogenous application of methyl salicylate resulted in the enhanced expression of the BARLEY CHEMICALLY INDUCED-4 marker gene and induced resistance in receiver plants. The findings suggest genotype-dependent alterations in barley VOC profiles during biotrophic plant-fungus interactions and show a VOC-mediated resistance that shares components with salicylic acid-related pathways. The VOC signals identified here could serve as non-invasive markers for disease progression in barley-powdery mildew interactions and as signals for resistance induction in recipient plants.PMID:39648862 | DOI:10.1111/ppl.14646

J Cereb Blood Flow Metab. 2024 Dec 9:271678X241305914. doi: 10.1177/0271678X241305914. Online ahead of print.ABSTRACTSingle-cell RNA sequencing (scRNA-seq) is a high-throughput transcriptomic approach with the power to identify rare cells, discover new cellular subclusters, and describe novel genes. scRNA-seq can simultaneously reveal dynamic shifts in cellular phenotypes and heterogeneities in cellular subtypes. Since the publication of the first protocol on scRNA-seq in 2009, this evolving technology has continued to improve, through the use of cell-specific barcodes, adoption of droplet-based systems, and development of advanced computational methods. Despite induction of the cellular stress response during the tissue dissociation process, scRNA-seq remains a popular technology, and commercially available scRNA-seq methods have been applied to the brain. Recent advances in spatial transcriptomics now allow the researcher to capture the positional context of transcriptional activity, strengthening our knowledge of cellular organization and cell-cell interactions in spatially intact tissues. A combination of spatial transcriptomic data with proteomic, metabolomic, or chromatin accessibility data is a promising direction for future research. Herein, we provide an overview of the workflow, data analyses methods, and pros and cons of scRNA-seq technology. We also summarize the latest achievements of scRNA-seq in stroke and acute traumatic brain injury, and describe future applications of scRNA-seq and spatial transcriptomics.PMID:39648853 | DOI:10.1177/0271678X241305914

Phytother Res. 2024 Dec 9. doi: 10.1002/ptr.8389. Online ahead of print.ABSTRACTCoptisine (COP), a naturally occurring alkaloid, is known for its diverse pharmacological effects and its supportive role in intestinal health. Despite this, the detailed mechanisms behind its therapeutic benefits are not yet fully understood. The objective of this study is to investigate the therapeutic potential of COP for the treatment of Ulcerative Colitis (UC) and to delineate the critical pathways by which it exerts its therapeutic effects. To assess COP's therapeutic effectiveness, mice were administered COP and monitored for clinical symptoms, activity, and disease activity index (DAI) changes. Intestinal histopathology, mucosal barrier function, and gut microbiota structure were evaluated, along with metabolic profiling, focusing on Prenol lipids in the colon to identify COP-induced metabolic shifts. Mice treated with COP exhibited significant relief from diarrhea and bleeding, along with increased activity and a marked reduction in DAI scores. Histopathological evaluation revealed a reduction in intestinal inflammation, and the intestinal mucosal barrier function was notably enhanced. The gut microbiota composition in COP-treated mice showed improvements. Additionally, the levels of Prenol lipids in the colon were elevated by COP treatment, which is crucial for the recovery of intestinal function. Our study demonstrates that COP effectively ameliorates colitis symptoms by modulating colon Prenol lipids metabolism, particularly under the influence of key bacterial species. The findings of this study provide novel insights into the therapeutic mechanisms of COP in the treatment of UC.PMID:39648789 | DOI:10.1002/ptr.8389

Br J Nutr. 2024 Dec 9:1-29. doi: 10.1017/S0007114524002812. Online ahead of print.ABSTRACTPrior observational studies have reported the potential protective effect of omega-3 fatty acids on the prognosis of acute pancreatitis. However, the causal impact of omega-3 fatty acids on acute pancreatitis is unclear. We aimed to investigate further the association of omega-3 fatty acids with acute pancreatitis. We performed a meta-analysis and Mendelian randomization (MR) to explore the association between omega-3 fatty acids and the prognosis of acute pancreatitis from clinical observation and genetics perspectives, respectively. 9 randomized controlled trials were included in this study. The result meta-analysis showed that complementary therapy of omega-3 fatty acids significantly decreased mortality (RR: 0.30; 95% CI 0.14 to 0.65, P＜0.05) and infectious complications in acute pancreatitis (RR: 0.45; 95% CI 0.27 to 0.77, P＜0.05). Compared to the control groups, the hospital stays (MD: -1.02; 95% CI -1.85 to -0.20, P＜0.05) in acute pancreatitis patients with omega-3 fatty acids treatment were statistically reduced. However, the ICU stay (MD: -0.49; 95% CI -1.29 to -0.31, P＞0.05) between control groups and acute pancreatitis patients with omega-3 fatty acids treatment was insignificant. Utilizing genetic susceptibility analysis in the Mendelian randomization (MR) approach, the MR showed omega-3 fatty acids have a significant causal effect on the acute pancreatitis risk (OR, 0.887; 95% CI, 0.797-0.986, P = 0.027, fixed-effect; OR, 0.887; 95% CI, 0.792-0.993, P = 0.037, random-effect). Omega-3 fatty acids complementary therapy may improve the prognosis of acute pancreatitis. Furthermore, genetically predicted serum levels of omega-3 fatty acids can significantly lower acute pancreatitis risk.PMID:39648710 | DOI:10.1017/S0007114524002812

Pharm Biol. 2024 Dec;62(1):341-355. doi: 10.1080/13880209.2024.2318791. Epub 2024 May 9.ABSTRACTCONTEXT: Cervicitis is a common gynecological inflammatory disease. The Chinese herbal prescription Kang-Gong-Yan (KGY) is clinically effective against cervicitis; however, the chemical constituents and therapeutic mechanism of KGY remain elusive.OBJECTIVE: To analyze the chemical constituents of KGY and explore the potential mechanism of KGY in treating cervicitis.MATERIALS AND METHODS: UHPLC-Q-Exactive Plus Orbitrap MS was used to identify the active compounds of KGY; Sprague-Dawley (SD) female rats were randomly divided into the control, model, and KGY groups. Phenol mucilage (25%) was slowly injected into the vagina and cervix of the rats to establish the cervicitis model. Then, rats in the KGY groups (low dose: 1 g/kg/d; medium dose: 5 g/kg/d; high dose: 10 g/kg/d) were continuously gavaged KGY for one week. HE staining was used to observe the cervical tissues of rats; ELISA was used to detect inflammatory factors in plasma; non-targeted metabolomics was used to analyze metabolites; 16S rRNA sequencing was used to analyze intestinal microorganisms.RESULTS: KGY exerted anti-cervicitis effects and decreased the levels of IL-6, IL-1β, and TNF-α. The mechanism of KGY in treating cervicitis is mainly associated with betaine, amino acid, pyrimidine, and phospholipid metabolism by regulating fifteen metabolites. Moreover, KGY reversed cervicitis-induced gut dysbiosis by mediating five bacteria.DISCUSSION AND CONCLUSIONS: The Chinese herbal prescription KGY may alleviate cervicitis by modulating metabolites and gut microbiota disorders. These findings provide a scientific basis for the clinical application of KGY and a new strategy for treating cervicitis in Chinese medicine.PMID:39648685 | DOI:10.1080/13880209.2024.2318791

Prep Biochem Biotechnol. 2024 Dec 8:1-13. doi: 10.1080/10826068.2024.2423665. Online ahead of print.ABSTRACTUsing an engineered Escherichia coli to produce lipase and can easily achieve high-level expression. The investigation of biochemical processes during lipase fermentation, approached from a metabolomics perspective, will yield novel insights into the efficient secretion of recombinant proteins. In this study, the lipase batch fermentation was carried out first with enzyme activity of 36.83 U/mg cells. Then, differential metabolites and metabolic pathways were identified using an untargeted metabolomics approach through comparative analysis of various fermentation periods. In total, 574 metabolites were identified: 545 were up-regulated and 29 were down-regulated, mainly in 153 organic acids and derivatives, 160 organoheterocyclic compounds, 64 lipids and lipid-like molecules, and 58 organic oxygen compounds. Through metabolic pathways and network analysis, it could be found that tryptophan metabolism was of great significance to lipase production, which could affect the secretion and synthesis of recombinant protein. In addition, the promotion effects of cell growth by varying concentrations of indole acetic acid serve to validate the results obtained from tryptophan metabolism. This study offers valuable insights into metabolic regulation of engineered E. coli, indicating that its fermentation bioprocess can be systematically designed according to metabolomics findings to enhance recombinant protein production.PMID:39648316 | DOI:10.1080/10826068.2024.2423665

Vet Comp Oncol. 2024 Dec 8. doi: 10.1111/vco.13034. Online ahead of print.ABSTRACTCanine lymphoma represents a biologically and metabolically heterogeneous group of neoplasms that arise from malignant transformation of lymphoid cells. An accurate diagnosis is crucial because of its impact on survival. Current diagnostic methods include clinical laboratory tests and imaging, most of which are invasive and lack sensitivity and specificity. Interestingly, recent work in cancer patients focuses on the search for biomarkers for diagnosis, investigation of treatment response mechanisms, treatment efficacy and prognosis and the discovery of tumour metabolic pathways using metabolomic analysis. In this study, we compare the metabolite profiles in serum from 37 dogs with multicentric lymphoma (22 B-cell lymphomas/LB, 9 CD45+ T-cell lymphomas/LTCD45+, 6 CD45- T-cell lymphomas/LTCD45-) and 25 healthy dogs using 1H nuclear magnetic resonance spectroscopy (NMR). 1H NMR-based metabolite profiling analysis recognised lipids and 22 metabolites, with 16 of them altered, and was shown to be an effective approach for differentiating samples from dogs with lymphoma and healthy controls based on principal component analysis of the NMR data. We also investigated variations in the serum metabolome between immunophenotypes and the control group through pairwise comparisons of the healthy against the LB, LTCD45+ and LTCD45- groups, respectively which showed similar metabolomic profiles. In addition, there were significant differences in the levels of five individual metabolites based on the univariate statistical analysis. Our results showed alterations in energy, protein and lipid metabolism, suggesting glucose, lactate, N-acetyl glycoproteins (NAGs), scyllo-inositol and choline as possible new candidate biomarkers in canine multicentric lymphoma.PMID:39648045 | DOI:10.1111/vco.13034

Bioresour Technol. 2024 Dec 6:131958. doi: 10.1016/j.biortech.2024.131958. Online ahead of print.ABSTRACTAtmospheric and room temperature plasma mutation and co-mutation with ethanol were employed to generate Haematococcus pluvialis mutants AV3 and AV8. These mutants were screened using multiple indices of chlorophyll fluorescence, quantum yield, lethality, growth rate, dry cell weight, and lipid content. Compared to the wild strain, the mutants demonstrated genetic stability (*p > 0.05) over three cultivation periods, with biomass, lipid content, and growth rate increasing by over 16 %, 55 %, and 45 %, respectively. Lipid accumulation was correlated with higher activities of key lipid biosynthesis enzymes, acetyl-CoA carboxylase, and diacylglycerol acyltransferases. Transcriptomic and metabolomic analyses revealed differentially expressed genes and differential metabolites, with significant changes in glutathione, arginine and Pyruvate metabolism pathways. This study provides new insights into the molecular mechanisms behind enhanced lipid synthesis and highlights the potential of plasma mutation for improving lipid production in microalgae, offering a promising avenue for biofuel production.PMID:39647716 | DOI:10.1016/j.biortech.2024.131958

J Am Acad Dermatol. 2024 Dec 6:S0190-9622(24)03328-0. doi: 10.1016/j.jaad.2024.11.052. Online ahead of print.NO ABSTRACTPMID:39647705 | DOI:10.1016/j.jaad.2024.11.052

J Nutr Biochem. 2024 Dec 6:109830. doi: 10.1016/j.jnutbio.2024.109830. Online ahead of print.ABSTRACTPoor intrauterine environments increase the prevalence for chronic metabolic diseases in offspring, whereas maternal exercise is an effective measure to break this vicious intergenerational cycle. Placenta is increasingly being studied to explore its role in maternal-fetal metabolic cross-talk. The association between placental miRNA and offspring development trajectories has been established, yet the specific role and mechanism thereof in maternal exercise-induced metabolic protection remain elusive. Here, C57BL/6 female mice were subjected to either a normal control or a high-fat diet (HFD), half of the HFD-fed dams were housed with voluntary wheel running for 3 weeks before and during gestation. At embryonic day 18.5, we sacrificed parturient mice and then conducted miRNA-seq, transcriptomic, and metabolomic profiling of the placenta. Our data revealed that maternal HFD resulted in significant alterations in both miRNA and gene expressions, as well as metabolic pathways of the placenta, whereas prenatal exercise negated these perturbations. The common differentially expressed transcripts among three groups were enriched in multiple critical pathways involving energy expenditure, signal transduction, and fetal development. Through integrated analysis of multi-omics data, we speculated that maternal exercise reversed the suppression of miR-495-5p induced by HFD, thereby inhibiting miR-495-5p-targeted Snx7 and modulating kynurenic acid production. These datasets provided novel mechanistic insight into how maternal exercise positively affects the metabolic homeostasis of offspring. The discovered important miRNAs, mRNAs, and metabolites could be promising predictive and therapeutic targets for protecting offspring metabolic health.PMID:39647668 | DOI:10.1016/j.jnutbio.2024.109830

Crit Rev Oncol Hematol. 2024 Dec 6:104590. doi: 10.1016/j.critrevonc.2024.104590. Online ahead of print.ABSTRACTCurrent therapeutic strategies for benign prostatic hyperplasia (BPH) and prostate cancer focus mainly on androgen receptors (AR) and 5-alpha reductase inhibition to suppress androgen-driven prostate growth. However, these methods often result in side effects and resistance. Recent research identifies novel targets like integrin and cadherin inhibitors, gene regulation, microRNAs, cellular senescence, and metabolomics pathways to overcome these limitations. These innovations offer more personalized approaches with potentially fewer adverse effects and reduced resistance compared to traditional androgen-focused therapies. Novel target sites and pathways, either suppressed or overexpressed, offer control points for modulating signaling in prostate diseases, suggesting future potential for treatment through innovative exogenous substances. Data was compiled from Google Scholar, PubMed, and Google to highlight the comparative potential of these emerging methods in enhancing treatment efficacy for prostate health.PMID:39647642 | DOI:10.1016/j.critrevonc.2024.104590

J Adv Res. 2024 Dec 6:S2090-1232(24)00559-9. doi: 10.1016/j.jare.2024.12.003. Online ahead of print.ABSTRACTINTRODUCTION: Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment, being implicated in enhancing tumor growth and fostering drug resistance. Nonetheless, the mechanisms underlying their function in prostate cancer (PCa) remain incompletely understood, which is essential for devising effective therapeutic strategies.OBJECTIVES: The main objective of this study was to explore the mechanisms by which CAFs mediate PCa growth and chemoresistance.METHODS: We validated through data analysis and experimentation that CAFs significantly impact PCa cell proliferation and chemoresistance. Subsequently, we conducted a comprehensive proteomic analysis of the conditioned media from CAFs and PCa cells and identified angiopoietin-like protein 4 (ANGPTL4) as a key factor. We employed ELISA and multiplex immunofluorescence assays, all of which indicated that ANGPTL4 was primarily secreted by CAFs.Next, we conducted metabolomics analysis, GST pull-down assays, Co-IP, and other experiments to explore the specific molecular mechanisms of ANGPTL4 and its precise effects on PCa cells. Through drug screening, we identified Quercetin 3-O-(6'-galactopyranosyl)-β-D-galactopyranoside (QGGP) as an effective inhibitor of CAFs function. Finally, we thoroughly assessed the therapeutic potential of QGGP both as a monotherapy and in combination with docetaxel in PCa cells RESULTS: We discovered that the extracrine factor ANGPTL4 is primarily expressed in CAFs in PCa. When ANGPTL4 binds to IQ motif-containing GTPase-activating protein 1 (IQGAP1) on the PCa cell membrane, it activates the Raf-MEK-ERK-PGC1α axis, promoting mitochondrial biogenesis and OXPHOS metabolism, and thereby facilitating PCa growth and chemoresistance. Furthermore, virtual and functional screening strategies identified QGGP as a specific inhibitor of IQGAP1 that promotes its degradation. Combined with docetaxel treatment, QGGP can reverse the effects of CAFs and improve the responsiveness of PCa to chemotherapy.CONCLUSIONS: This study uncovers a paracrine mechanism of chemoresistance in PCa and proposes that targeting the stroma could be a therapeutic choice.PMID:39647634 | DOI:10.1016/j.jare.2024.12.003

Phytomedicine. 2024 Nov 29;136:156306. doi: 10.1016/j.phymed.2024.156306. Online ahead of print.ABSTRACTBACKGROUND: Sleep deprivation (SLD) is a widespread condition that disrupts physiological functions and may increase mortality risk. Valeriana officinalis, a traditional medicinal herb known for its sedative and hypnotic properties, contains isobicyclogermacrenal (IG), a newly isolated active compound. However, research on the therapeutic potential of IG for treating SLD remains limited.METHODS: In this study, IG was extracted and characterized from Valeriana officinalis, and an SLD model was established in rats using p-chlorophenylalanine (PCPA). Behavioral tests and pathological studies were conducted to assess the effects of IG on SLD, and transcriptomic and metabolomic analyses were utilized to investigate its underlying mechanisms.RESULTS: IG administration significantly improved the cognitive performance of SLD rats in behavioral tests and ameliorated histological injuries in the hippocampus and cerebral cortex. IG treatment increased the levels of brain-derived neurotrophic factor (BDNF) and neurotransmitters such as serotonin (5-HT) in SLD rats. Additionally, IG directly targets TFRC, thereby improving iron metabolism in the hippocampus. Comprehensive transcriptomic and metabolomic analyses revealed that the improvements from IG stemmed from the mitigation of abnormalities in iron metabolism, cholesterol metabolism, and glutathione metabolism, leading to reduced oxidative stress, ferroptosis, and neuroinflammation in the hippocampus caused by SLD.CONCLUSIONS: Collectively, these findings suggest that IG has the potential to ameliorate neurological damage and cognitive impairment caused by SLD, offering a novel strategy for protection against the adverse effects of SLD.PMID:39647468 | DOI:10.1016/j.phymed.2024.156306

Arch Oral Biol. 2024 Oct 10;171:106107. doi: 10.1016/j.archoralbio.2024.106107. Online ahead of print.ABSTRACTOBJECTIVES: In this study, we explored the efficacy of methanolic extract of Thuja orientalis (TOME) as a novel antibacterial and antibiofilm agent against a cariogenic bacterium, Enterococcus faecalis ATCC 29212.DESIGN: Antibacterial susceptibility studies were conducted and surface morphology analysis was performed using field emission scanning electron microscopy (FESEM). Antibiofilm activity was evaluated through both qualitative and quantitative biofilm inhibition assays and validated by microscopic analysis. In-silico molecular docking studies were conducted using the EDock server. The effectiveness of TOME was substantiated by biofilm model on dentin discs and cytotoxicity towards the HaCaT cell line was assessed using the MTT assay.RESULTS: TOME exhibited significant bactericidal activity with minimum inhibitory concentration of 12.5 mg/mL and additionally, it effectively compromised bacterial cell wall integrity. Qualitative, quantitative and microscopic studies depicted the inhibition of biofilm formation. TOME significantly impacted the production of extracellular polymeric substance and extracellular DNA. Molecular docking studies identified beta-caryophyllene as a potent inhibitor of the Enterococcal surface protein (Esp). Biofilm model depicted the reduction of bacterial load on dentin discs. Additionally, TOME showed reduced cytotoxicity on HaCaT cells, indicating its potential as a safe therapeutic agent.CONCLUSION: These findings highlight TOME's promise for developing novel treatments for dental infections and biofilm-associated diseases. Further research should focus on isolating and characterizing the active compounds within TOME, particularly beta-caryophyllene, to elucidate their precise mechanisms of action.PMID:39647458 | DOI:10.1016/j.archoralbio.2024.106107

J Hazard Mater. 2024 Dec 4;484:136795. doi: 10.1016/j.jhazmat.2024.136795. Online ahead of print.ABSTRACTCadmium (Cd) is easily absorbed by rice and enters the food chain, posing a health risk to humans. Plant growth promoting bacteria (PGPB) can help the plant respond to Cd stress, but the mechanism of PGPB for Cd reduction is unclear. Therefore, this study was conducted and found inoculation with a newly isolated Pseudomonas koreensis promoted the growth of rice and reduced its Cd content. Fluorescent staining using PI and H2O2 probe indicated that PGPB attenuated oxidative damage in rice. Metabolomics revealed that 59 metabolites were upregulated after inoculation, with phenylpropanoids and flavonoids being significantly activated. Spectrophotometry analysis comfirmed the content of flavonoid, lignin, phenol, glutathione, proline and the activities of antioxidant enzymes were higher in the inoculated rice than in the control. Quantitative PCR showed the expression of genes related to phenylpropanoids (OsPAL, OsC4H, Os4CL) and flavonoids (OsCHS, OsCHI) was significantly increased by PGPB, while the genes of heavy metal transporters (OsNRAMP5, OsHMA2, OsIRT1) were significantly decreased. Overall, this study provides an insight into the PGPB-mediated detoxification mechanism in rice under Cd stress and emphasizes the role of phenylpropanoids and flavonoids in the production of low-Cd rice to ensure human health.PMID:39647335 | DOI:10.1016/j.jhazmat.2024.136795