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International Journal of Molecular... May 2024Abscisic acid (ABA) is a drought-stress-responsive hormone that plays an important role in the stomatal activity of plant leaves. Currently, ABA glycosides have been...
Abscisic acid (ABA) is a drought-stress-responsive hormone that plays an important role in the stomatal activity of plant leaves. Currently, ABA glycosides have been identified in apples, but their glycosyltransferases for glycosylation modification of ABA are still unidentified. In this study, the mRNA expression of glycosyltransferase gene was significantly up-regulated in mature apple leaves which were treated in drought stress by Real-Time PCR. It was hypothesised that might play an important role in drought stress. In order to further characterise the glycosylation modification substrate of glycosyltransferase MdUGT73AR4, we demonstrated through in vitro and in vivo functional validation that MdUGT73AR4 can glycosylate ABA. Moreover, the overexpression lines of significantly enhance its drought stress resistance function. We also found that the adversity stress transcription factor AREB1B might be an upstream transcription factor of by bioinformatics, EMSA, and ChIP experiments. In conclusion, this study found that the adversity stress transcription factor AREB1B was significantly up-regulated at the onset of drought stress, which in turn positively regulated the downstream glycosyltransferase MdUGT73AR4, causing it to modify ABA by mass glycosylation and promoting the ABA synthesis pathway, resulting in the accumulation of ABA content, and displaying a stress-resistant phenotype.
Topics: Abscisic Acid; Plant Stomata; Glycosyltransferases; Droughts; Gene Expression Regulation, Plant; Malus; Glycosylation; Plant Proteins; Stress, Physiological; Plant Leaves
PubMed: 38891859
DOI: 10.3390/ijms25115672 -
International Journal of Molecular... May 2024Tumor recurrence and drug resistance are responsible for poor prognosis in colorectal cancer (CRC). DNA mismatch repair (MMR) deficiency or elevated interleukin-8 (IL-8)...
Tumor recurrence and drug resistance are responsible for poor prognosis in colorectal cancer (CRC). DNA mismatch repair (MMR) deficiency or elevated interleukin-8 (IL-8) levels are characteristics of CRCs, which have been independently correlated with treatment resistance to common therapies. We recently demonstrated significantly impaired therapeutical response and increased IL-8 release of CRC cell lines with reduced expression of MMR protein MLH1 as well as cytoskeletal non-erythrocytic spectrin alpha II (SPTAN1). In the present study, decreased intratumoral MLH1 and SPTAN1 expression in CRCs could be significantly correlated with enhanced serum IL-8. Furthermore, using stably reduced SPTAN1-expressing SW480, SW620 or HT-29 cell lines, the RASmediated RAFMEKERK pathway was analyzed. Here, a close connection between low SPTAN1 expression, increased IL-8 secretion, enhanced extracellular-signal-regulated kinase (ERK) phosphorylation and a mesenchymal phenotype were detected. The inhibition of ERK by U0126 led to a significant reduction in IL-8 secretion, and the combination therapy of U0126 with FOLFOX optimizes the response of corresponding cancer cell lines. Therefore, we hypothesize that the combination therapy of FOLFOX and U0126 may have great potential to improve drug efficacy on this subgroup of CRCs, showing decreased MLH1 and SPTAN1 accompanied with high serum IL-8 in affected patients.
Topics: Humans; Colorectal Neoplasms; Interleukin-8; Fluorouracil; Butadienes; Nitriles; Cell Line, Tumor; Organoplatinum Compounds; Leucovorin; Antineoplastic Combined Chemotherapy Protocols; Female; Male; Extracellular Signal-Regulated MAP Kinases; HT29 Cells; MAP Kinase Signaling System; MutL Protein Homolog 1; Middle Aged; Aged; Gene Expression Regulation, Neoplastic; Phosphorylation
PubMed: 38891846
DOI: 10.3390/ijms25115658 -
International Journal of Molecular... May 2024Carotenoid cleavage oxygenases can cleave carotenoids into a range of biologically important products. Carotenoid isomerooxygenase (NinaB) and β, β-carotene 15,...
Carotenoid cleavage oxygenases can cleave carotenoids into a range of biologically important products. Carotenoid isomerooxygenase (NinaB) and β, β-carotene 15, 15'-monooxygenase (BCO1) are two important oxygenases. In order to understand the roles that both oxygenases exert in crustaceans, we first investigated () and () within the genome of Chinese mitten crab (). Their functions were then deciphered through an analysis of their expression patterns, an in vitro β-carotene degradation assay, and RNA interference. The results showed that both and contain an RPE65 domain and exhibit high levels of expression in the hepatopancreas. During the molting stage, exhibited significant upregulation in stage C, whereas showed significantly higher expression levels at stage AB. Moreover, dietary supplementation with β-carotene resulted in a notable increase in the expression of and in the hepatopancreas. Further functional assays showed that the expressed in underwent significant changes in its color, from orange to light; in addition, its β-carotene cleavage was higher than that of . After the knockdown of or in juvenile , the expression levels of both genes were significantly decreased in the hepatopancreas, accompanied by a notable increase in the redness () values. Furthermore, a significant increase in the β-carotene content was observed in the hepatopancreas when mRNA was suppressed, which suggests that plays an important role in carotenoid cleavage, specifically β-carotene. In conclusion, our findings suggest that and may exhibit functional co-expression and play a crucial role in carotenoid cleavage in crabs.
Topics: Animals; beta Carotene; Brachyura; beta-Carotene 15,15'-Monooxygenase; Hepatopancreas; Molting; Oxygenases; Phylogeny; Arthropod Proteins
PubMed: 38891781
DOI: 10.3390/ijms25115592 -
International Journal of Molecular... May 2024Neural tube defects (NTDs), which are caused by impaired embryonic neural tube closure, are one of the most serious and common birth defects. Peptidyl-prolyl cis/trans...
Neural tube defects (NTDs), which are caused by impaired embryonic neural tube closure, are one of the most serious and common birth defects. Peptidyl-prolyl cis/trans isomerase 1 (Pin1) is a prolyl isomerase that uniquely regulates cell signaling by manipulating protein conformation following phosphorylation, although its involvement in neuronal development remains unknown. In this study, we explored the involvement of Pin1 in NTDs and its potential mechanisms both in vitro and in vivo. The levels of Pin1 expression were reduced in NTD models induced by all-trans retinoic acid (Atra). Pin1 plays a significant role in regulating the apoptosis, proliferation, differentiation, and migration of neurons. Moreover, Pin1 knockdown significantly was found to exacerbate oxidative stress (OS) and endoplasmic reticulum stress (ERs) in neuronal cells. Further studies showed that the Notch1-Nrf2 signaling pathway may participate in Pin1 regulation of NTDs, as evidenced by the inhibition and overexpression of the Notch1-Nrf2 pathway. In addition, immunofluorescence (IF), co-immunoprecipitation (Co-IP), and GST pull-down experiments also showed that Pin1 interacts directly with Notch1 and Nrf2. Thus, our study suggested that the knocking down of Pin1 promotes NTD progression by inhibiting the activation of the Notch1-Nrf2 signaling pathway, and it is possible that this effect is achieved by disrupting the interaction of Pin1 with Notch1 and Nrf2, affecting their proteostasis. Our research identified that the regulation of Pin1 by retinoic acid (RA) and its involvement in the development of NTDs through the Notch1-Nrf2 axis could enhance our comprehension of the mechanism behind RA-induced brain abnormalities.
Topics: Tretinoin; NIMA-Interacting Peptidylprolyl Isomerase; Animals; Mice; Neural Tube Defects; Receptor, Notch1; NF-E2-Related Factor 2; Signal Transduction; Down-Regulation; Apoptosis; Oxidative Stress; Neurons; Female; Neural Tube; Endoplasmic Reticulum Stress; Cell Proliferation; Cell Differentiation; Cell Movement; Humans
PubMed: 38891776
DOI: 10.3390/ijms25115588 -
International Journal of Molecular... May 2024One useful technique for increasing the efficiency of organic dye-sensitized solar cells (DSSCs) is to extend the π-conjugated bridges between the donor (D) and the...
DFT and TD-DFT Investigations for the Limitations of Lengthening the Polyene Bridge between N,N-dimethylanilino Donor and Dicyanovinyl Acceptor Molecules as a D-π-A Dye-Sensitized Solar Cell.
One useful technique for increasing the efficiency of organic dye-sensitized solar cells (DSSCs) is to extend the π-conjugated bridges between the donor (D) and the acceptor (A) units. The present study used the DFT and TD-DFT techniques to investigate the effect of lengthening the polyene bridge between the donor N, N-dimethyl-anilino and the acceptor dicyanovinyl. The results of the calculated key properties were not all in line with expectations. Planar structure was associated with increasing the π-conjugation linker, implying efficient electron transfer from the donor to the acceptor. A smaller energy gap, greater oscillator strength values, and red-shifted electronic absorption were also observed when the number of polyene units was increased. However, some results indicated that the potential of the stated dyes to operate as effective dye-sensitized solar cells is limited when the polyene bridge is extended. Increasing the polyene units causes the HOMO level to rise until it exceeds the redox potential of the electrolyte, which delays regeneration and impedes the electron transport cycle from being completed. As the number of conjugated units increases, the terminal lobes of HOMO and LUMO continue to shrink, which affects the ease of intramolecular charge transfer within the dyes. Smaller polyene chain lengths yielded the most favorable results when evaluating the efficiency of electron injection and regeneration. This means that the charge transfer mechanism between the conduction band of the semiconductor and the electrolyte is not improved by extending the polyene bridge. The open circuit voltage (V) was reduced from 1.23 to 0.70 V. Similarly, the excited-state duration (τ) decreased from 1.71 to 1.23 ns as the number of polyene units increased from n = 1 to n = 10. These findings are incompatible with the power conversion efficiency requirements of DSSCs. Therefore, the elongation of the polyene bridge in such D-π-A configurations rules out its application in solar cell devices.
Topics: Solar Energy; Polyenes; Coloring Agents; Density Functional Theory; Aniline Compounds; Electron Transport
PubMed: 38891775
DOI: 10.3390/ijms25115586 -
Cells May 2024The future of drug delivery offers immense potential for the creation of nanoplatforms based on nanogels. Nanogels present a significant possibility for pharmaceutical... (Review)
Review
The future of drug delivery offers immense potential for the creation of nanoplatforms based on nanogels. Nanogels present a significant possibility for pharmaceutical advancements because of their excellent stability and effective drug-loading capability for both hydrophobic and hydrophilic agents. As multifunctional systems, composite nanogels demonstrate the capacity to carry genes, drugs, and diagnostic agents while offering a perfect platform for theranostic multimodal applications. Nanogels can achieve diverse responsiveness and enable the stimuli-responsive release of chemo-/immunotherapy drugs and thus reprogramming cells within the TME in order to inhibit tumor proliferation, progression, and metastasis. In order to achieve active targeting and boost drug accumulation at target sites, particular ligands can be added to nanogels to improve the therapeutic outcomes and enhance the precision of cancer therapy. Modern "immune-specific" nanogels also have extra sophisticated tumor tissue-editing properties. Consequently, the introduction of a multifunctional nanogel-based drug delivery system improves the targeted distribution of immunotherapy drugs and combinational therapeutic treatments, thereby increasing the effectiveness of tumor therapy.
Topics: Humans; Tumor Microenvironment; Drug Delivery Systems; Nanogels; Neoplasms; Animals; Polyethyleneimine
PubMed: 38891040
DOI: 10.3390/cells13110908 -
Cells May 2024Improving the drought resistance of rice is of great significance for expanding the planting area and improving the stable yield of rice. In our previous work, we found...
Improving the drought resistance of rice is of great significance for expanding the planting area and improving the stable yield of rice. In our previous work, we found that () protein promoted enhanced tolerance to drought stress by eliminating reactive oxygen species (ROS) levels and triggering the abscisic acid (ABA) response. However, the mechanism through which REL1 regulates drought tolerance by removing ROS is unclear. In this study, we identified REL1 interacting protein 5 (RIP5) and found that it directly combines with REL1 in the chloroplast. We found that was strongly expressed in ZH11 under drought-stress conditions, and that the mutants significantly improved the tolerance of rice plants to drought, whereas overexpression of resulted in greater susceptibility to drought. Further investigation suggested that negatively regulated drought tolerance in rice by decreasing the content of ascorbic acid (AsA), thereby reducing ROS clearance. RNA sequencing showed that the knockout of caused differential gene expression that is chiefly associated with ascorbate and aldarate metabolism. Furthermore, multiple experimental results suggest that is involved in regulating drought tolerance by inhibiting . Collectively, our findings reveal the importance of the inhibition of RIP5 by REL1 in affecting the rice's response to drought stress. This work not only explains the drought tolerance mechanism of rice, but will also help to improve the drought tolerance of rice.
Topics: Oryza; Plant Proteins; Droughts; Gene Expression Regulation, Plant; Reactive Oxygen Species; Stress, Physiological; Abscisic Acid; Chloroplasts; Adaptation, Physiological; Plants, Genetically Modified; Ascorbic Acid; Protein Binding; Drought Resistance
PubMed: 38891020
DOI: 10.3390/cells13110887 -
Foods (Basel, Switzerland) May 2024Four different concentrations of an aqueous extract of cuttlefish ( spp.) ink (CI) were introduced, respectively, into the packing medium employed during golden seabream...
Four different concentrations of an aqueous extract of cuttlefish ( spp.) ink (CI) were introduced, respectively, into the packing medium employed during golden seabream () canning. The quality parameters of the resulting canned fish were determined and compared to the initial fish and the control canned muscle. An important effect of the CI concentration introduced in the packing medium was proved. The presence in the packing medium of a relatively low CI concentration (CI-2 batch) led to a lower ( < 0.05) lipid oxidation development (fluorescent compound formation), lower ( < 0.05) changes of colour parameters ( and values), and lower ( < 0.05) trimethylamine values in canned fish when compared to control canned samples. Additionally, the two lowest CI concentrations tested led to higher average values of C22:6ω3, ω3/ω6 ratios, and polyene index. On the contrary, the use of the most concentrated CI extract (CI-4 condition) led to a prooxidant effect (higher fluorescence ratio value). In agreement with environmental sustainability and circular economy requirements, the study can be considered the first approach to a novel and valuable use of the current marine byproduct for the quality enhancement of canned fish. On-coming research focused on the optimisation of the CI-extract concentration is envisaged.
PubMed: 38890914
DOI: 10.3390/foods13111685 -
Nature Communications Jun 2024Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a... (Randomized Controlled Trial)
Randomized Controlled Trial
Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: a double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice.
Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419)).
Topics: Humans; Oryza; Feces; Female; Male; Double-Blind Method; Child; Micronutrients; Nutritional Status; Food, Fortified; Inflammation; Gastrointestinal Microbiome; Biomarkers; Adolescent; Vitamin A; Zinc
PubMed: 38890302
DOI: 10.1038/s41467-024-49093-4 -
Scientific Reports Jun 2024Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and...
Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and stability, which can be overcome through nanocarrier delivery systems. This study used surface-modified Nano-crystalline cellulose (NCC) to deliver crocin to cancer cells. NCC modified with CTAB were loaded with crocin and then conjugated with folic acid (NCF-CR-NPs). The synthesized nanoparticles (NPs) were characterized using FTIR, XRD, DLS, and FESEM. The crystallinity index of NCC was 66.64%, higher than microcrystalline cellulose (61.4%). The crocin loading and encapsulation efficiency in NCF-CR-NPs were evaluated. Toxicity testing by MTT assay showed that NCF-CR-NPs had higher toxicity against various cancer cell lines, including colon cancer HT-29 cells (IC50 ~ 11.6 μg/ml), compared to free crocin. Fluorescent staining, flow cytometry, and molecular analysis confirmed that NCF-CR-NPs induced apoptosis in HT-29 cells by increasing p53 and caspase 8 expression. The antioxidant capacity of NCF-CR-NPs was also evaluated using ABTS and DPPH radical scavenging assays. NCF-CR-NPs exhibited high free radical scavenging ability, with an IC50 of ~ 46.5 μg/ml for ABTS. In conclusion, this study demonstrates the potential of NCF-CR-NPs to deliver crocin to cancer cells effectively. The NPs exhibited enhanced anti-cancer and antioxidant activities compared to free crocin, making them a promising nanocarrier system for crocin-based cancer therapy.
Topics: Carotenoids; Folic Acid; Humans; Cellulose; Nanoparticles; Apoptosis; Antineoplastic Agents; HT29 Cells; Drug Carriers; Antioxidants; Cell Line, Tumor; Drug Delivery Systems; Cell Survival
PubMed: 38886450
DOI: 10.1038/s41598-024-64758-2