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Scientific Reports Jun 2024Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1...
Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.
Topics: Humans; Male; Prostatic Neoplasms; TOR Serine-Threonine Kinases; Gene Expression Regulation, Neoplastic; Disease Progression; Signal Transduction; Cell Line, Tumor; CDC2 Protein Kinase; DNA Methylation; Promoter Regions, Genetic; Cell Proliferation; Down-Regulation; Prognosis; Cell Movement
PubMed: 38942821
DOI: 10.1038/s41598-024-66020-1 -
Methods in Enzymology 2024Chemoenzymatic synthesis of non-natural terpenes using the promiscuous activity of terpene synthases allows for the expansion of the chemical space of terpenoids with...
Chemoenzymatic synthesis of non-natural terpenes using the promiscuous activity of terpene synthases allows for the expansion of the chemical space of terpenoids with potentially new bioactivities. In this report, we describe protocols for the preparation of a novel aphid attractant, (S)-14,15-dimethylgermacrene D, by exploiting the promiscuity of (S)-germacrene D synthase from Solidago canadensis and using an engineered biocatalytic route to convert prenols to terpenoids. The method uses a combination of five enzymes to carry out the preparation of terpenoid semiochemicals in two steps: (1) diphosphorylation of five or six carbon precursors (prenol, isoprenol and methyl-isoprenol) catalyzed by Plasmodium falciparum choline kinase and Methanocaldococcus jannaschii isopentenyl phosphate kinase to form DMADP, IDP and methyl-IDP, and (2) chain elongation and cyclization catalyzed by Geobacillus stearothermophilus (2E,6E)-farnesyl diphosphate synthase and S. canadensis (S)-germacrene D synthase to produce (S)-germacrene D and (S)-14,15-dimethylgermacrene D. Using this method, new non-natural terpenoids are readily accessible and the approach can be adopted to produce different terpene analogs and terpenoid derivatives with potential novel applications.
Topics: Terpenes; Alkyl and Aryl Transferases; Plasmodium falciparum; Animals; Biocatalysis; Substrate Specificity; Aphids
PubMed: 38942504
DOI: 10.1016/bs.mie.2024.03.015 -
Environmental Pollution (Barking, Essex... Jun 2024Bisphenols (BPs), including BPA, BPF, BPS, and BPAF, are synthetic phenolic organic compounds and endocrine-disrupting chemicals. These organics have been broadly... (Review)
Review
Bisphenols (BPs), including BPA, BPF, BPS, and BPAF, are synthetic phenolic organic compounds and endocrine-disrupting chemicals. These organics have been broadly utilized to produce epoxy resins, polycarbonate plastics, and other products. Mounting evidence has shown that BPs, especially BPA, may enter into the human body and participate in the development of human diseases mediated by nuclear hormone receptors. Moreover, BPA may negatively affect human health at the epigenetic level through processes such as DNA methylation and histone acetylation. Recent studies have demonstrated that, as part of epigenetics, noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs), have vital impacts on BP-related diseases, such as reproductive system diseases, nervous system diseases, digestive system diseases, endocrine system diseases, and other diseases. Moreover, based on the bioinformatic analysis, changes in ncRNAs may be relevant to normal activities and functions and BP-induced diseases. Thus, we conducted a meta-analysis to identify more promising ncRNAs as biomarkers and therapeutic targets for BP exposure and relevant human diseases. In this review, we summarize the regulatory functions of ncRNAs induced by BPs in human diseases and latent molecular mechanisms, as well as identify prospective biomarkers and therapeutic targets for BP exposure and upper diseases.
PubMed: 38942269
DOI: 10.1016/j.envpol.2024.124447 -
Chemosphere Jun 2024This study proposes a novel and eco-friendly approach for wastewater treatment using plasma jet technology under bubble condition. This method allows for the controlled...
This study proposes a novel and eco-friendly approach for wastewater treatment using plasma jet technology under bubble condition. This method allows for the controlled production of highly reactive hydroxyl radicals () while minimizing unwanted interactions with nitrogen in the air. The presence of bubbles in liquid significantly boosts the diffusion of within the wastewater, leading to a two-fold increase in degradation rate compared to normal condition. The effectiveness of the treatment was confirmed through ultraviolet-visible spectroscopy, which showed a significant decrease in rhodamine B and methyl orange absorbance peaks . Raman spectroscopy further revealed structural changes in both pollutants, indicating successful degradation. Additionally, plasma characteristics like power, electron temperature, and density were monitored to gain deeper insights into the underlying mechanism. Importantly, the process minimizes the formation of harmful secondary pollutants such as ozone and nitrogen oxides. These pollutants were found under concentration of 0.14 mg m which is below established safety thresholds, adhering to World Health Organization guidelines. This research demonstrates that plasma jet treatment in bubble condition not only enhances the degradation efficiency of pollutants in wastewater but also minimizes the formation of harmful byproducts. This represents a significant breakthrough in developing sustainable wastewater treatment technologies.
PubMed: 38942242
DOI: 10.1016/j.chemosphere.2024.142689 -
Bioorganic & Medicinal Chemistry Jun 2024This study explored the potential of perfumery compounds as sources of transient receptor potential ankyrin 1 (TRPA1) inhibitors that could be formulated for effective...
This study explored the potential of perfumery compounds as sources of transient receptor potential ankyrin 1 (TRPA1) inhibitors that could be formulated for effective delivery to the skin and airways. A highly potent, small, and selective TRPA1 inhibitor, 2-methyl-4-phenyl-1-pentanol (1), was discovered in perfumery compounds. Compound 1 demonstrated promising inhibitory activity against a broad range of TRPA1 agonists. A single stereoisomer of 1 was identified as the most effective TRPA1 inhibitor, indicating the potential for stereoselective synthesis to enhance its potency. Additionally, the structure-activity relationship of 1 was evaluated to elucidate the structural features of TRPA1 inhibitors within the fragrance-like compounds. Notably, the topical application of 1 alleviated sensory irritation in individuals with sensitive skin, while the inhalation of 1 resulted in a significant reduction in ammonia irritation, underscoring its efficacy in both skin and airway applications.
PubMed: 38941887
DOI: 10.1016/j.bmc.2024.117812 -
Journal of Hazardous Materials Jun 2024Nanoplastics (NPs, size <1000 nm) are ubiquitous plastic particles, potentially more abundant than microplastics in the environment; however, studies highlighting their...
Environmental nanoplastics quantification by pyrolysis-gas chromatography-mass spectrometry in the Pearl River, China: First insights into spatiotemporal distributions, compositions, sources and risks.
Nanoplastics (NPs, size <1000 nm) are ubiquitous plastic particles, potentially more abundant than microplastics in the environment; however, studies highlighting their distribution dynamics in freshwater are rare due to analytical limitations. Here, we investigated spatiotemporal levels of nine polymers of NPs in surface water samples (n = 30) from the full stretch of the Pearl River (sites, n = 15) using pyrolysis gas chromatography-mass spectrometry (Py-GC/MS). Six polymers were detected, including polystyrene (PS), polyvinyl chloride (PVC), nylon/polyamide 66 (PA66), polyester (PES), poly(methyl methacrylate) (PMMA) and polyethylene (PE), where three polymers showed high detection frequencies; PS (100 % in winter and summer), followed by PVC (73 % in winter and 87 % in summer) and PA66 (53 % in winter and 67 % in summer). The spatiotemporal distribution revealed the sites related to aquaculture (AQ) and shipping (SHP) showed higher NP levels than those of human settlement (HS) and wastewater treatment plants (WWTPs) (p = 0.004), and relatively high average levels of NPs in the urban sites compared to rural sites (p = 0.04), albeit showed no obvious seasonal differences (p = 0.78). For instance, the average PS levels in the Pearl River were in the following order: AQ 411.55 µg/L > SHP 81.75 µg/L > WWTP 56.66 µg/L > HS 47.75 µg/L in summer and HS 188.1 µg/L > SHP 103.55 µg/L > AQ 74.7 µg/L > WWTP 62.1 µg/L in winter. Source apportionment showed a higher contribution through domestic plastic waste emissions among urban sites, while rural sites showed an elevated contribution via aquaculture, agriculture, and surface run-off to the NP pollution. Risk assessment revealed that NPs at SHP and AQ sites posed a higher integrated risk in terms of pollution load index (PLI) than those at WWTP and HS sites. Regarding polymer hazard index (HI), 80 % of sampling sites in summer and 60 % of sampling sites in winter posed level III polymer risk, with PVC posing the highest risk. This study provides novel insights into the seasonal contamination and polymer risks of NP in the Pearl River, which will help to regulate the production and consumption of plastics in the region. ENVIRONMENTAL IMPLICATIONS: The contamination dynamics of field nanoplastics (NPs) in freshwater resources remain little understood, mainly attributed to analytical constraints. This study aims to highlight the spatiotemporal distribution of NPs in the Pearl River among various land use types, urban-rural comparison, seasonal comparison, their compositional profiles, potential sources, interaction with environmental factors, and ecological and polymer hazard assessments of investigated polymers in the full stretch of the Pearl River from Liuxi Reservoir to the Pearl River Delta (PRD) region. This study, with a comparatively large number of samples and NP polymers, will offer novel insights into the contamination profiles of nano-sized plastic particles in one of the important freshwater riverine systems in China.
PubMed: 38941826
DOI: 10.1016/j.jhazmat.2024.135055 -
Current Opinion in Plant Biology Jun 2024Flowering plants exhibit unique DNA methylation dynamics during development. Particular attention can be focused on seed development and the embryo, which represents the... (Review)
Review
Flowering plants exhibit unique DNA methylation dynamics during development. Particular attention can be focused on seed development and the embryo, which represents the starting point of the sporophytic life cycle. A build-up of CHH methylation is now recognized as highly characteristic of embryo development. This process is thought to occur in order to silence potentially harmful transposable element expression, though roles in promoting seed dormancy and dessication tolerance have also been revealed. Recent studies show that increased CHH methylation in embryos inhabits both novel loci, unmethylated elsewhere in the plant, as well as shared loci, exhibiting more dense methylation. The role of DNA methylation in cis-regulatory gene regulation in plants is less well established compared to mammals, and here we discuss both transposable element regulation and the potential role of DNA methylation in dynamic gene expression.
PubMed: 38941722
DOI: 10.1016/j.pbi.2024.102593 -
Bioorganic Chemistry Jun 2024Extracellular vesicles (EVs) appear to play an important role in intercellular communication in various physiological processes and pathological conditions such as...
Extracellular vesicles (EVs) appear to play an important role in intercellular communication in various physiological processes and pathological conditions such as cancer. Like enveloped viruses, EVs can transport their contents into the nucleus of recipient cells, and a new intracellular pathway has been described to explain the nuclear shuttling of EV cargoes. It involves a tripartite protein complex consisting of vesicle-associated membrane protein-associated protein A (VAP-A), oxysterol-binding protein (OSBP)-related protein-3 (ORP3) and late endosome-associated Rab7 allowing late endosome entry into the nucleoplasmic reticulum. Rab7 binding to ORP3-VAP-A complex can be blocked by the FDA-approved antifungal drug itraconazole. Here, we design a new series of smaller triazole derivatives, which lack the dioxolane moiety responsible for the antifungal function, acting on the hydrophobic sterol-binding pocket of ORP3 and evaluate their structure-activity relationship through inhibition of VOR interactions and nuclear transfer of EV and HIV-1 cargoes. Our investigation reveals that the most effective compounds that prevent nuclear transfer of EV cargo and productive infection by VSV-G-pseudotyped HIV-1 are those with a side chain between 1 and 4 carbons, linear or branched (methyl) on the triazolone region. These potent chemical drugs could find clinical applications either for nuclear transfer of cancer-derived EVs that impact metastasis or viral infection.
PubMed: 38941696
DOI: 10.1016/j.bioorg.2024.107589 -
Acta Pharmacologica Sinica Jun 2024C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in...
C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.
PubMed: 38942954
DOI: 10.1038/s41401-024-01310-y -
Pest Management Science Jun 2024Plant volatile organic compounds (VOCs) play a crucial role in mediating interactions between plants, herbivores and natural enemies. Among these VOCs, methyl salicylate...
BACKGROUND
Plant volatile organic compounds (VOCs) play a crucial role in mediating interactions between plants, herbivores and natural enemies. Among these VOCs, methyl salicylate and (E,E)-α-farnesene are emitted as herbivore-induced plant volatiles (HIPVs) by soybean plants in response to feeding by the brown stink bug Eushistus heros. These HIPVs function as synomones, influencing the foraging behaviour of the egg parasitoid, Telenomus podisi, the main natural enemy of E. heros, one of the major soybean pests in Brazil.
RESULTS
Laboratory experiments showed that two soybean cultivars, BRS 7580 and BRS 7880, produced similar qualitative blends of HIPVs, with methyl salicylate, (E,E)-α-farnesene and (Z)-3-hexenyl acetate being produced by both cultivars. Soybean cultivar BRS 7580 produced a significant lower amount of HIPVs compared to BRS 7880 but this difference did not affect the attractiveness of the egg parasitoid Telenomus podisi. Field experiments using these two cultivars and synthetic applications of methyl salicylate and (E,E)-α-farnesene showed a substantial increase in egg parasitism in all treated areas. Parasitism rates ranged from 50% to 80% in areas where these HIPVs were deployed, compared to only 10% in untreated control areas.
CONCLUSIONS
The egg parasitoid Telenomus podisi demonstrated an adept ability in recognising between HIPVs in soybean blends, even in the presence of significant quantitative differences. The results from the field experiment showed the potential of HIPVs in attracting natural enemies to specific target areas within fields. (E,E)-α-Farnesene showed an improved action during the later stages of soybean growth, notably at R6. In addition, this volatile attracted other families of natural enemies. © 2024 Society of Chemical Industry.
PubMed: 38942611
DOI: 10.1002/ps.8274