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International Journal of Molecular... Jun 2024Abscisic acid (ABA) plays a crucial role in plant defense mechanisms under adverse environmental conditions, but its metabolism and perception in response to heavy...
Abscisic acid (ABA) plays a crucial role in plant defense mechanisms under adverse environmental conditions, but its metabolism and perception in response to heavy metals are largely unknown. In exposed to CdCl, an accumulation of free ABA was detected in leaves at different developmental stages (A, youngest, unexpanded; B1, youngest, fully expanded; B2, mature; C, old), with the highest content found in A and B1 leaves. In turn, the content of ABA conjugates, which was highest in B2 and C leaves under control conditions, increased only in A leaves and decreased in leaves of later developmental stages after Cd treatment. Based on the expression of , (9-cis-epoxycarotenoid dioxygenase), (aldehyde oxidase) and (ABA-UDP-glucosyltransferase), and the activity of PsAOγ, B2 and C leaves were found to be the main sites of Cd-induced de novo synthesis of ABA from carotenoids and ABA conjugation with glucose. In turn, β-glucosidase activity and the expression of genes encoding ABA receptors (, , , ) suggest that in A and B1 leaves, Cd-induced release of ABA from inactive ABA-glucosyl esters and enhanced ABA perception comes to the forefront when dealing with Cd toxicity. The distinct role of leaves at different developmental stages in defense against the harmful effects of Cd is discussed.
Topics: Abscisic Acid; Pisum sativum; Plant Leaves; Cadmium; Gene Expression Regulation, Plant; Plant Proteins; Dioxygenases; beta-Glucosidase
PubMed: 38928288
DOI: 10.3390/ijms25126582 -
International Journal of Molecular... Jun 2024Paraformaldehyde (PFA) fixation is the preferred method for preserving tissue architecture for anatomical and pathological observations. Meanwhile, PFA reacts with the...
Paraformaldehyde (PFA) fixation is the preferred method for preserving tissue architecture for anatomical and pathological observations. Meanwhile, PFA reacts with the amine groups of biomolecules to form chemical cross-linking, which preserves RNA within the tissue. This has great prospects for RNA sequencing to characterize the molecular underpinnings after anatomical and pathological observations. However, RNA is inaccessible due to cross-linked adducts forming between RNA and other biomolecules in prolonged PFA-fixed tissue. It is also difficult to perform reverse transcription and PCR, resulting in low sequencing sensitivity and reduced reproducibility. Here, we developed a method to perform RNA sequencing in PFA-fixed tissue, which is easy to use, cost-effective, and allows efficient sample multiplexing. We employ cross-link reversal to recover RNA and library construction using random primers without artificial fragmentation. The yield and quality of recovered RNA significantly increased through our method, and sequencing quality metrics and detected genes did not show any major differences compared with matched fresh samples. Moreover, we applied our method for gene expression analysis in different regions of the mouse brain and identified unique gene expression profiles with varied functional implications. We also find significant dysregulation of genes involved in Alzheimer's disease (AD) pathogenesis within the medial septum (MS)/vertical diagonal band of Broca (VDB) of the 5×FAD mouse brain. Our method can thus increase the performance of high-throughput RNA sequencing with PFA-fixed samples and allows longitudinal studies of small tissue regions isolated by their in situ context.
Topics: Formaldehyde; Animals; Mice; Brain; Tissue Fixation; Sequence Analysis, RNA; Alzheimer Disease; Polymers; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; RNA
PubMed: 38928210
DOI: 10.3390/ijms25126504 -
International Journal of Molecular... Jun 2024Most reported breast cancer-associated deaths are directly correlated with metastatic disease. Additionally, the primary goal of treating metastatic breast cancer is to...
Most reported breast cancer-associated deaths are directly correlated with metastatic disease. Additionally, the primary goal of treating metastatic breast cancer is to prolong life. Thus, there remains the need for more effective and safer strategies to treat metastatic breast cancer. Recently, more attention has been given to natural products (or phytochemicals) as potential anticancer treatments. This study aimed to investigate the synergistic effects of the combination of the phytochemicals chlorogenic acid and cinnamaldehyde (CGA and CA) toward inhibiting metastasis. The hypothesis was that CGA and CA in combination decrease the metastatic potential of breast cancer cells by inhibiting their invasive and migratory abilities as well as the induction of apoptosis via the downregulation of the Akt, disrupting its signal transduction pathway. To test this, wound-healing and Transwell™ Matrigel™ assays were conducted to assess changes in the migration and invasion properties of the cells; apoptosis was analyzed by fluorescence microscopy for Annexin V/propidium iodide; and immunoblotting and FACSort were performed on markers for the epithelial-to-mesenchymal transition status. The results show that CGA and CA significantly downregulated Akt activation by inhibiting phosphorylation. Consequently, increased caspase 3 and decreased Bcl2-α levels were observed, and apoptosis was confirmed. The inhibition of metastatic behavior was demonstrated by the attenuation of N-cadherin, fibronectin, vimentin, and MMP-9 expressions with concomitant increased expressions of E-cadherin and EpCAM. In summary, the present study demonstrated that CGA and CA in combination downregulated Akt activation, inhibited the metastatic potential, and induced apoptosis in different breast cancer cell lines.
Topics: Humans; Chlorogenic Acid; Proto-Oncogene Proteins c-akt; Acrolein; Breast Neoplasms; Apoptosis; Female; Cell Movement; Cell Line, Tumor; Down-Regulation; Epithelial-Mesenchymal Transition; Signal Transduction; Gene Expression Regulation, Neoplastic; Neoplasm Metastasis
PubMed: 38928123
DOI: 10.3390/ijms25126417 -
Biology Jun 2024The proliferation of large green macroalgae in marine environments has led to the occurrence of green tides, particularly in the South Yellow Sea region of China, where... (Review)
Review
The proliferation of large green macroalgae in marine environments has led to the occurrence of green tides, particularly in the South Yellow Sea region of China, where has been identified as the primary species responsible for the world's largest green tide events. Allelopathy among plants is a critical factor influencing the dynamics of green tides. This review synthesizes previous research on allelopathic interactions within green tides, categorizing four extensively studied allelochemicals: fatty acids, aldehydes, phenols, and terpenes. The mechanisms by which these compounds regulate the physiological processes of green tide algae are examined in depth. Additionally, recent advancements in the rapid detection of allelochemicals are summarized, and their potential applications in monitoring green tide events are discussed. The integration of advanced monitoring technologies, such as satellite observation and environmental DNA (eDNA) analysis, with allelopathic substance detection is also explored. This combined approach addresses gaps in understanding the dynamic processes of green tide formation and provides a more comprehensive insight into the mechanisms driving these phenomena. The findings and new perspectives presented in this review aim to offer valuable insights and inspiration for researchers and policymakers.
PubMed: 38927336
DOI: 10.3390/biology13060456 -
Biology Jun 2024KT2440 is a popular platform for bioremediation due to its robust tolerance to environmental stress and strong biodegradation capacity. Limited research on the salt...
KT2440 is a popular platform for bioremediation due to its robust tolerance to environmental stress and strong biodegradation capacity. Limited research on the salt tolerance of KT2440 has hindered its application. In this study, the strain KT2440 was tested to tolerate a maximum of 4% / NaCl cultured with minimal salts medium. Transcriptomic data in a high-salinity environment showed significant expression changes in genes in membrane components, redox processes, chemotaxis, and cellular catabolic processes. -encoding betaine-aldehyde dehydrogenase was identified from the transcriptome data to overexpress and enhance growth profile of the strain KT2440 in minimal salts medium containing 4% / NaCl. Meanwhile, screening for exogenous salt-tolerant genes revealed that the Na/H antiporter from significantly increased the growth of the strain KT2440 in 4% / NaCl. Then, co-expression of and (KT2440-) increased the maximum salt tolerance of strain KT2440 to 5% / NaCl. Further addition of betaine and proline improved the salt tolerance of the engineered strain to 6% / NaCl. Finally, the engineered strain KT2440- was able to degrade 56.70% of benzoic acid and 95.64% of protocatechuic acid in minimal salt medium containing 4% / NaCl in 48 h, while no biodegradation was observed in the normal strain KT2440 in the same conditions. However, the strain KT2440- failed to degrade catechol in minimal salt medium containing 3% / NaCl. This study illustrated the improvement in the salt tolerance performance of KT2440 and the feasibility of engineered strain KT2440 as a potential salt-tolerant bioremediation platform.
PubMed: 38927284
DOI: 10.3390/biology13060404 -
Journal of Nanobiotechnology Jun 2024As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of...
As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu, 3,3'-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.
Topics: Copper; Animals; Carcinoma, Hepatocellular; Photochemotherapy; Liver Neoplasms; Mice; Humans; Photosensitizing Agents; Mice, Inbred BALB C; Cell Line, Tumor; Reactive Oxygen Species; Angiogenesis Inhibitors; Porphyrins; Chlorophyllides; Glutathione; Nanoparticles; Catalysis; Metal Nanoparticles; Drug Liberation; Mice, Nude; Antineoplastic Agents
PubMed: 38926721
DOI: 10.1186/s12951-024-02626-x -
Scientific Reports Jun 2024Biginelli-type heterocyclic compounds are particularly important due to their several chemical reactivities and various range of pharmacological activity. Therefore...
Synthesis of 3,4-dihydropyrimidines and octahydroquinazolinones by SBA-15 supported schiff-base iron (III) complex as durable and reusable catalyst under ultrasound irradiation.
Biginelli-type heterocyclic compounds are particularly important due to their several chemical reactivities and various range of pharmacological activity. Therefore Biginelli reaction has witnessed several modification and numerous investigations are continuing in this field to develop more effective and efficient methodologies. In this research, Iron (III) schiff base immobilized SBA-15 has been prepared as a valuable, efficient, and recoverable catalyst for the Biginelli reaction. The morphology of the prepared catalyst was identified by spectroscopic characterization techniques and structural microscopic analysis including Fourier transform infrared (FT-IR) patterns, X-ray diffraction (XRD) by powder crystal method, Energy-dispersive X-ray spectroscopy (EDS) study, Thermogravimetric-Differential thermal analysis (TGA-DTA), Transmission electron microscopy (TEM) and Field emission scanning electron microscopy (FE-SEM) images. Biginelli compounds containing 3,4-dihydropyrimidines and octahydroquinazolinones were conveniently synthesized by this catalyzed protocol from the cycloaddition of aromatic aldehydes with the 1,3-dicarbonyl substrates and urea via ultrasonic waves. The several advantages of the presented approach are high yields and easy isolation of products, shorter reaction times, and milder conditions, structural stability and reusable catalyst. The combination of heterogeneous catalyst and ultrasonic radiation can make catalytic reactions more efficient than traditional ways attractive for academic researchers and application scholars in the industry.
PubMed: 38926512
DOI: 10.1038/s41598-024-65519-x -
Nature Communications Jun 2024Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a...
Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the approximately 600 human E3 ligases are currently amenable to this strategy. This limits the actionable target space and clinical opportunities and thus establishes the necessity to expand to additional ligases. Here we identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12. SP3N features a minimal design, where a known FKBP12 ligand is appended with a flexible alkylamine tail that conveys degradation properties. We found that SP3N is a precursor and that the alkylamine is metabolized to an active aldehyde species that recruits the SCF ligase for FKBP12 degradation. Target engagement occurs via covalent adduction of Cys326 in the FBXO22 C-terminal domain, which is critical for ternary complex formation, ubiquitylation and degradation. This mechanism is conserved for two recently reported alkylamine-based degraders of NSD2 and XIAP, thus establishing alkylamine tethering and covalent hijacking of FBXO22 as a generalizable TPD strategy.
Topics: Humans; Proteolysis; Ubiquitination; F-Box Proteins; HEK293 Cells; Tacrolimus Binding Protein 1A; Ubiquitin-Protein Ligases; Amines; Proteasome Endopeptidase Complex; Ligands; Receptors, Cytoplasmic and Nuclear
PubMed: 38926334
DOI: 10.1038/s41467-024-49739-3 -
Marine Drugs May 2024Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an cluster from sp. MYA5, derived from the...
Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an cluster from sp. MYA5, derived from the Arctic plant , is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F () and six known clavatols (-), were isolated from sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds -. Compounds and demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound exhibited antibacterial activity against and with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds , , and also showed potential iron-binding ability.
Topics: Penicillium; Anti-Bacterial Agents; Staphylococcus aureus; Genomics; Escherichia coli; Microbial Sensitivity Tests; Transcriptome; Arctic Regions; Siderophores; Aldehyde Reductase
PubMed: 38921547
DOI: 10.3390/md22060236 -
Insects Jun 2024Microorganisms within insects play a vital role in maintaining the basal physiological functions of the insects, with olfactory signals as critical components of insect...
Microorganisms within insects play a vital role in maintaining the basal physiological functions of the insects, with olfactory signals as critical components of insect survival strategies. (), an invasive alien pest inflicting significant damage to eucalyptus trees, harbors a rich and varied bacterial community within its body. However, the impact of its endogenous bacteria and their microbial Volatile Organic Compounds (mVOCs) on the behavioral preferences of remains unexplored to date. This study focused on nine cultivable and dominant endogenous bacterial strains within . Using a Y-tube olfactometer, we investigated the behavioral responses of female to the mVOCs emitted by these bacteria. Concurrently, gas chromatography-mass spectrometry (GC-MS) was employed to quantify the mVOCs produced by these endogenous bacteria. Our findings revealed that sp. exhibited the highest attractiveness of , whereas sp. and exerted the most significant avoidance effects. The analysis of the mVOCs further highlighted the significance of aldehyde compounds, notably 2,3,6-trichlorobenzaldehyde, and alkane compounds, such as eicosane, in mediating the repellency and attraction effects. These results contribute to a deeper understanding of the invasion mechanism of and provide a scientific basis for developing novel biopesticides or elicitors.
PubMed: 38921169
DOI: 10.3390/insects15060455