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1.
Plant Signal Behav ; 19(1): 2358270, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38796845

RESUMEN

Trans-acting small interfering RNAs (tasiRNAs) are 21-nt phased (phased siRNAs) resulting from successive DCL-catalyzed processing from the end of a double-stranded RNA substrate originating from the RDR of an AGO-catalyzed cleaved RNA at a micro RNA target site. Plant tasiRNAs have been synthesized to produce synthetic tasiRNAs (syn-tasiRNAs) targeting viral RNAs that confer viral resistance. In this study, we engineered syn-tasiRNAs to target potato virus Y (PVY) infection by replacing five native siRNAs of TAS1c with 210-bp fragments from the coat protein (CP) region of the PVY genome. The results showed that the transient expression of syn-tasiR-CPpvy2 in Nicotiana benthamiana (N. benthamiana) plants conferred antiviral resistance, supported by the absence of PVY infection symptoms and viral accumulation. This indicated that syn-tasiR-CPpvy2 successfully targeted and silenced the PVY CP gene, effectively inhibiting viral infection. syn-tasiR-CPpvy1 displayed attenuated symptoms and decreased viral accumulation in these plants However, severe symptoms of PVY infection and a similar amount of viral accumulation as the control were observed in plants expressing syn-tasiR-CPpvy3. syn-tasiR-CPpvy/pvx, which targets both PVY and potato virus X (PVX), was engineered using a single precursor. After the transient expression of syn-tasiR-CPpvy/pvx3 and syn-tasiR-CPpvy/pvx5 in N. benthamiana, the plants were resistant to both PVY and PVX. These results suggested that engineered syn-tasiRNAs could not only specifically induce antiviral resistance against one target virus but could also be designed for multi-targeted silencing of different viruses, thereby preventing complex virus infection in plants.


Asunto(s)
Proteínas de la Cápside , Resistencia a la Enfermedad , Nicotiana , Enfermedades de las Plantas , Potyvirus , ARN Interferente Pequeño , Nicotiana/virología , Nicotiana/genética , Nicotiana/inmunología , Proteínas de la Cápside/metabolismo , Proteínas de la Cápside/genética , Potyvirus/fisiología , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/genética , Plantas Modificadas Genéticamente/virología
2.
Cell Mol Life Sci ; 80(11): 312, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37796333

RESUMEN

Increasing evidence indicate that the expression of defense genes at the right place and the right time are regulated by host-defense transcription factors. However, the precise mechanisms of this regulation are not well understood. Homeodomain transcription factors, encoded by homeobox genes, play crucial role for the development of multicellular eukaryotes. In this study, we demonstrated that homeodomain transcription factor CEH-37 (known as OTX2 in mammals) was a key transcription factor for host defense in Caenorhabditis elegans. Meanwhile, CEH-37 acted in the intestine to protect C. elegans against pathogen infection. We further showed that the homeodomain transcription factor CEH-37 positively regulated PMK-1/ p38 MAPK activity to promote the intestinal immunity via suppression phosphatase VHP-1. Furthermore, we demonstrated that this function was conserved, because the human homeodomain transcription factor OTX2 also exhibited protective function in lung epithelial cells during Pseudomonas aeruginosa infection. Thus, our work reveal that CEH-37/OTX2 is a evolutionarily conserved transcription factor for defense against pathogen infection. The finding provides a model in which CEH-37 decreases VHP-1 phosphatase activity, allowing increased stimulation of PMK-1/p38 MAPK phosphorylation cascade in the intestine for pathogen resistance.


Asunto(s)
Proteínas de Caenorhabditis elegans , Factores de Transcripción , Animales , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Inmunidad Innata , Proteínas de Unión al ADN/metabolismo , Mamíferos/metabolismo , Fosfatasas de Especificidad Dual
3.
Plants (Basel) ; 12(9)2023 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-37176794

RESUMEN

Potato (Solanum tuberosum L.) is an important vegetable crop that plays a pivotal role in the world, especially given its potential to feed the world population and to act as the major staple food in many developing countries. Every year, significant crop loss is caused by viral diseases due to a lack of effective agrochemical treatments, since only transmission by insect vectors can be combated with the use of insecticides, and this has been an important factor hindering potato production. With the rapid development of molecular biology and plant genetic engineering technology, transgenic approaches and non-transgenic techniques (RNA interference and CRISPR-cas9) have been effectively employed to improve potato protection against devastating viruses. Moreover, the availability of viral sequences, potato genome sequences, and host immune mechanisms has remarkably facilitated potato genetic engineering. In this study, we summarize the progress of antiviral strategies applied in potato through engineering either virus-derived or plant-derived genes. These recent molecular insights into engineering approaches provide the necessary framework to develop viral resistance in potato in order to provide durable and broad-spectrum protection against important viral diseases of solanaceous crops.

4.
iScience ; 26(3): 106265, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36936783

RESUMEN

Delay aging, especially in healthy life extension, brought the most interest to the medical field. Searching for anti-aging drugs with relative safety profiles bring natural products in hotspot. In this study, we find that dioscin promotes the health span extension in wild-type Caenorhabditis elegans. Through the genetic screening in C. elegans, we further reveal that dioscin activates the transcription factor SBP-1/SREBP by the UPRER transcription factor XBP-1 to upregulate transcription of the Δ9 desaturase FAT-5 and FAT-7, resulting in increased monounsaturated fatty acid content which requires for healthy life span extension. Intriguingly, through tissue-specific knockdown, we find that dioscin modulates the health span by activating SBP-1 in the intestine. Unexpectedly, dietary supplementation of POA and OA rescues XBP-1, SBP-1 mutants-induced shortened life span phenotype. Considering the conservation of MUFAs metabolism, dioscin may promote health span in other species, including mammals. Our work suggests that dioscin might be a promising candidate for developing anti-aging agent.

5.
Aging (Albany NY) ; 15(6): 2046-2065, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36988497

RESUMEN

The identity of the mechanism by which the Baixiangdan capsule (BXD) and the Shuyu capsule (SY) control anger-out (AO) and anger-in (AI) in rodents is unclear. The current study clarified the intervention role of BXD and SY on AO and AI male rats. We further explored the differences between BXD and SY in the treatment of AO and AI rats. Social isolation combined with the resident-intruder paradigm was used to establish the anger-out and AI rats models. On this basis, GABA content in the dorsal raphe nucleus (DRN) and serotonin (5-HT) contents in these brain regions were detected using ELISA after various time courses (0, 1, 3, 5, and 7 days) treated with BXD and SY. Co-expression of 5-HT and GB1 in the DRN was detected. GB1-specific agonist baclofen and GB1-specific inhibitor CGP35348 were injected into the DRN. Changes in 5-HT levels in these brain regions were then detected. After treatment, rats in the BXD group exhibited lower aggressive behavior scores, longer latencies of aggression, lower total distances in the open field test, and a higher sucrose preference coefficient. Meanwhile, rats in the SY group exhibited higher aggressive behavior scores, shorter latencies of aggression, higher total distances in the open field test, and higher sucrose preference coefficients. With increasing medication duration, 5-HT levels in these brain regions were increased gradually, whereas GABA levels in the DRN were decreased gradually, and all recovered to normal levels by the 7th day. A large number of 5-HT-positive cells could be found in the immunofluorescence section in the DRN containing GABABR1 (GB1)-positive cells, indicating that 5-HT neurons in the DRN co-expressed with GB1. Furthermore, after the drug intervention, the 5-HT level in the DRN was elevated to a normal level, and the GB1 level in the DRN was decreased to a normal level. After the microinjection of baclofen into the DRN, the 5-HT contents in these brain regions were decreased. By contrast, the 5-HT contents were increased after injection with CGP35348. BXD and SY could effectively improve the abnormal behavior changes of AO and AI rats, and the optimal duration of action was 7 days. The improvement way is as follows: Decreased abnormal increase of GABA and GB1 in the DRN further mediated synaptic inhibition and increased 5-HT level in the DRN, leading to increased 5-HT levels in the PFC, hypothalamus, and hippocampus. Therefore, GB1-mediated GABA in the DRN could regulate 5-HT levels in these brain regions, which may be one of the ways by which BXD and SY treat AO and AI, respectively.


Asunto(s)
Baclofeno , Serotonina , Ratas , Masculino , Animales , Núcleo Dorsal del Rafe , Neuronas , Ira
6.
Environ Sci Pollut Res Int ; 30(6): 14959-14974, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36161572

RESUMEN

Contamination of leafy vegetables grown in heavy metal(loid)-polluted mining areas pose serious health risks. This study aimed to explore the heavy metal(loid) contamination of leafy vegetables near two mining areas, by collecting samples from 14 different leafy vegetable species in Yunnan Province, China. The lead (Pb), cadmium (Cd), arsenic (As), and copper (Cu) contents of the samples were determined, and risks to human health were calculated using the hazard quotient and hazard index (HI). Moreover, Malabar spinach was identified as a leafy vegetable that exhibits low accumulation of heavy metal(loid)s. The accumulation capacity of different Malabar spinach varieties was verified, and a Cd soil safety threshold was determined using a pot experiment. Overall, Pb and Cd were the main soil and vegetable contaminants found in both study sites. The HI values for all leafy vegetables, apart from Malabar spinach, were greater than 1, indicating the presence of risks to human health; moreover, the health risks were greater for children than adults. The Malabar spinach pot experiment results showed that only some Cd forms exceeded China's maximum permissible standards. Furthermore, Malabar spinach varieties A (instant Malabar spinach), C (extra-large leaf green vine Malabar spinach), and F (large leaf Malabar spinach) displayed the lowest Cd accumulation. We calculated Cd total and bioavailable soil safety thresholds of 4.75 and 0.77 mg kg-1, respectively. However, further research is required to validate soil heavy metal safety thresholds for different vegetables. Ultimately, the heavy metal(loid) contamination of leafy vegetables described here was more serious than anticipated. Finally, the results of this study can inform residents living near these mining areas of a low-risk leafy vegetable, which will reduce the harm caused by heavy metal(loid) contamination in the area.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Niño , Adulto , Humanos , Cadmio/análisis , Verduras , Spinacia oleracea , Bioacumulación , Plomo , Contaminación de Alimentos/análisis , Contaminantes del Suelo/análisis , China , Metales Pesados/análisis , Suelo , Hojas de la Planta/química , Medición de Riesgo , Monitoreo del Ambiente/métodos
7.
J Ethnopharmacol ; 305: 116061, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-36577489

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: As a typical prescription for soothing the liver, Xiangshao granule has a good effect on the symptoms of irritability and anxiety. Clinical evidence suggests that it has significant efficacy in the treatment of Premenstrual dysphoria disorder (PMDD). However, the underlying mechanism remains unclear. AIM OF THE STUDY: PMDD is a common disease in women of childbearing age, seriously affecting their family, society, and daily work life. The registered herbal medicine, Xiangshao granules, is used for relieving PMDD dysphoria and irritability symptoms with excellent efficacy in China. This study was focused on the deep intervention mechanism of Xiangshao granules in treating PMDD. MATERIALS AND METHODS: The vaginal smear and open field test were used to screen rats in nonreception phase of estrus cycle with similar macroscopic behaviors and regular estrus cycle. The rat model of PMDD irritability was established through social isolation and residential invasion, with which, the irritability symptoms of PMDD patients with menstrual cycle dependence was also well simulated. Elevated plus Maze Test and Social interaction activities were used to measure the anxiety-like behavior of rats. TUNEL Staining and Hematoxylin-Eosin staining were used to measure apoptosis of hippocampal neurons. RT-PCR, Western blot and immunofluorescence were used to measure the expression of GR, JIK, p-JIK, p38, P-P38, JNK, caspase 3, and caspase 12. RESULTS: In this study, Xiangshao granules showed consistent therapeutic effects similar with those in clinic, significantly reducing aggressive and anxiety-like behaviors with improved social skills in PMDD rats. In mechanism, Xiangshao granules lowered the apoptosis of hippocampal neurons and weakened the morphological damage of the hippocampal brain evidenced by the decreased mRNA and protein expression of glucocorticoid receptor, caspase-3, and caspase-12. In addition, administration of Xiangshao granules led to the decreased expression of JIK in the PMDD irritability rat model which agreed well with the previous studies. The JNK/p38 mitogen-activated protein kinases (MAPKs) signaling pathway is abnormally activated in the hippocampal brain region of PMDD rats, while treated with Xiangshao granules could increase JIK expression and inhibit the abnormal activation of the JNK/p38 MAPK signaling pathway, effectively reducing the stress damage in the hippocampus. CONCLUSIONS: Xiangshao Granules Reduce the Aggressive Behavior and Hippocampal Injury of Premenstrual Irritability in Rats by Regulating JIK/JNK/p38 Signal Pathway.


Asunto(s)
Sistema de Señalización de MAP Quinasas , Transducción de Señal , Animales , Femenino , Ratas , Apoptosis , Encéfalo/metabolismo , Hipocampo/metabolismo , Quinasas Janus , Ciclo Menstrual , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
8.
Lab Med ; 54(3): 324-326, 2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-36221950

RESUMEN

Hemolytic transfusion reaction (HTR) is an important type of transfusion-associated reaction and usually occurs after alloimmunization to red blood cell antigens. The HTRs caused by passively transferred Kidd blood group antibodies are not well documented. Here, we report about a premature infant who developed HTR owing to a passive anti-Jka antibody transfer following fresh frozen plasma transfusion. Anti-Jka antibody was detected in the infant's plasma and was also found in the donor plasma with a titer of 1:128. We reported this case to the local blood center, and they subsequently began testing for irregular antibodies of donor plasma, which is recommended but not mandated in China. This case reveals an unusual cause of HTR and emphasizes a possible need to screen donor plasma for antibodies to minimize risks to recipients.


Asunto(s)
Transfusión de Componentes Sanguíneos , Reacción a la Transfusión , Humanos , Recién Nacido , Plasma , Anticuerpos , Recien Nacido Prematuro , Isoanticuerpos
9.
J Environ Manage ; 326(Pt A): 116677, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36356537

RESUMEN

A field survey and pot experiment were carried out to screen tolerant plants growing in cadmium (Cd)-polluted mining areas which were co-polluted with acid in soil, and the related physiological and biochemical mechanisms were also analyzed. Thirty-seven species of wild plants and their corresponding soil were collected from a farmland around the mining areas. Ageratum (Ageratum conyzoides L.) with strong Cd-accumulative ability was selected, and its tolerance experiment for acid and Cd with different levels were carried out separately or orthogonally, respectively. Furthermore, the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and the contents of malondialdehyde (MDA), photosynthetic pigments, soluble sugar and proline in its leaves were determined. The results showed that the Cd accumulation in ageratum and sticktight (Bidens pilosa L.) was relatively high, but the latter has been well documented, so we focused on ageratum in the present work. In pot experiment, ageratum grew normally at 100 mg kg-1 Cd in soil, and the Cd concentrations in its roots, stems and leaves were 75.37 ± 7.37, 31.01 ± 3.76 and 53.92 ± 10.05 mg kg-1, respectively. In the case of acid tolerance experiment, all plant individuals of ageratum grew normally when soil pH was over 3.5. In the orthogonal experiment, the Cd accumulation in this plant increased with the decrease of soil pH under the same Cd treatment. Under strong acid conditions, the activity of SOD in leaves of ageratum was increased significantly. When the Cd concentration was 10 mg kg-1 and the soil pH was 5.5 or 3.5, the activities of POD and CAT were significantly increased. In addition, based on stepwise regression analysis, the leaf Cd concentration was significantly positive correlated with the activities of SOD and POD in leaves of ageratum. Therefore, ageratum not only had a strong tolerance for Cd and acid pollution in soil, but also had a strong ability to accumulate Cd. As a common plant in the mining area, it has a great potential for the phytoremediation of Cd and acid co-contaminated soil.


Asunto(s)
Ageratum , Contaminantes del Suelo , Cadmio/análisis , Contaminantes del Suelo/análisis , Biodegradación Ambiental , Suelo/química , Raíces de Plantas/química , Superóxido Dismutasa , Antioxidantes/análisis
10.
Nat Prod Res ; : 1-7, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36111662

RESUMEN

Three new coumarin derivatives named maytenucoums A-C (1-3), along with six known analogs (4-9), were isolated from the branches of Maytenus hookeri. Their structures were determined by comprehensive spectroscopic data analysis, including NMR and HR-ESIMS. In the preliminary assays, compound 4 showed cytotoxic activity against the A549, SK-Hep1 and HCT116 cells with IC50 values of 29.0, 28.6 and 54.4 µM, respectively.

11.
Mol Plant Pathol ; 23(10): 1555-1564, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35700092

RESUMEN

Proteins of the alkylation B (AlkB) superfamily show RNA demethylase activity removing methyl adducts from N6 -methyladenosine (m6 A). m6 A is a reversible epigenetic mark of RNA that regulates human virus replication but has unclear roles in plant virus infection. We focused on Potyvirus-the largest genus of plant RNA viruses-and report here the identification of AlkB domains within P1 of endive necrotic mosaic virus (ENMV) and an additional virus of a putative novel species within Potyvirus. We show that Nicotiana benthamiana m6 A levels are reduced by infection of plum pox virus (PPV) and potato virus Y (PVY). The two potyviruses lack AlkB and the results suggest a general involvement of RNA methylation in potyvirus infection and evolution. Methylated RNA immunoprecipitation sequencing of virus-infected samples showed that m6 A peaks are enriched in plant transcript 3' untranslated regions and in discrete internal and 3' terminal regions of PPV and PVY genomes. Down-regulation of N. benthamiana AlkB homologues of the plant-specific ALKBH9 clade caused a significant decrease in PPV and PVY accumulation. In summary, our study provides evolutionary and experimental evidence that supports the m6 A implication and the proviral roles of AlkB homologues in Potyvirus infection.


Asunto(s)
Virus de Plantas , Virus Eruptivo de la Ciruela , Potyvirus , Alquilación , Humanos , Enfermedades de las Plantas , Virus de Plantas/genética , Virus Eruptivo de la Ciruela/genética , Potyvirus/genética , ARN de Planta , Nicotiana
12.
Environ Sci Pollut Res Int ; 29(40): 60616-60630, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35426553

RESUMEN

Bacteria play a vital role in ecological processes of soil contaminated by heavy metals. Here, soil sampling was carried out around a tailings pile contaminated to different degrees by cadmium (Cd), lead (Pb) and arsenic (As). The bacteria in the soil were cultured, separated and purified on Luria-Bertani medium, and the changes in bacterial communities in soils with different pollution levels were analysed with 16S rRNA sequencing. Bacillus pacificus strain MZ520364 was found to be highly tolerant to Cd, Pb and As, and single-metal and multimetal tolerance experiments were further conducted with this strain. The results obtained from alpha diversity and operational taxonomic unit (OTU) statistical analyses showed a significant difference in bacterial composition among soils with different metal pollution levels, and the highest bacterial diversity was found at the most severely polluted site. Evidence from variance partitioning analysis (VPA) and the Spearman correlation heatmap analysis showed that the leading factors affecting bacterial community composition were cation exchange content (CEC), pH, total Zn, total As, and available As concentrations in soil. Additionally, in the single-metal treatments, B. pacificus MZ520364 could tolerate 600 mg/L Cd2+, 1000 mg/L Pb2+ or 700 mg/L As3+. When Cd, Pb and As coexisted, the best growth of B. pacificus MZ520364 was present at 120 mg/L Cd2+, 200 mg/L Pb2+ and 150 mg/L As3+. The effect of Cd, Pb and As on the growth of the strain followed the order of Cd > As > Pb, and the heavy metal combination showed more toxicity than single metals. In summary, our results revealed the ecological impact of soil physicochemical properties on the diversity and richness of soil bacterial communities and suggested that B. pacificus MZ520364 may be used for the remediation of Cd-Pb-As co-contaminated soil.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Bacterias , Cadmio/análisis , Plomo/análisis , Metales Pesados/análisis , ARN Ribosómico 16S , Suelo , Contaminantes del Suelo/análisis
13.
iScience ; 25(3): 103874, 2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35243236

RESUMEN

The longevity of an organism is influenced by both genetic and environmental factors. With respect to genetic factors, a significant effort is being made to identify pharmacological agents that extend lifespan by targeting pathways with a defined role in the aging process. Sanguinarine (San) is a benzophenanthridine alkaloid that exerts a broad spectrum of properties. In this study, we utilized Caenorhabditis elegans to examine the mechanisms by which sanguinarine influences aging and innate immunity. We find that 0.2 µM sanguinarine extends healthspan in C. elegans. We further show that sanguinarine generates reactive oxygen species (ROS), which is followed by the activation of PMK-1/SKN-1pathway to extend healthspan. Intriguingly, sanguinarine increases resistance to pathogens by reducing the bacterial burden in the intestine. In addition, we also find that sanguinarine enhances innate immunity through PMK-1/SKN-1 pathway. Our data suggest that sanguinarine may be a viable candidate for the treatment of age-related disorders.

14.
Front Oncol ; 12: 825783, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35350571

RESUMEN

Background: The MTA1 protein encoded by metastasis-associated protein 1 (MTA1) is a key component of the ATP-dependent nucleosome remodeling and deacetylase (NuRD) complex, which is widely upregulated in cancers. MTA1 extensively affects downstream gene expression by participating in chromatin remodeling. Although it was defined as a metastasis-associated gene in first reports and metastasis is a process prominently affected by the tumor microenvironment, whether it affects the microenvironment has not been investigated. In our study, we elucidated the regulatory effect of MTA1 on tumor-associated macrophages (TAMs) and how this regulation affects the antitumor effect of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment of colorectal cancer. Methods: We detected the cytokines affected by MTA1 expression via a cytokine antibody array in control HCT116 cells and HCT116 cells overexpressing MTA1. Multiplex IHC staining was conducted on a colorectal cancer tissue array from our cancer cohort. Flow cytometry (FCM) was performed to explore the polarization of macrophages in the coculture system and the antitumor killing effect of CTLs in the coculture system. Bioinformatics analysis was conducted to analyze the Cancer Genome Atlas (TCGA) colorectal cancer cohort and single-cell RNA-seq data to assess the immune infiltration status of the TCGA colorectal cancer cohort and the functions of myeloid cells. Results: MTA1 upregulation in colorectal cancer was found to drive an immunosuppressive tumor microenvironment. In the tumor microenvironment of MTA1-upregulated colorectal cancer, although CD8+ T cells were significantly enriched, macrophages were significantly decreased, which impaired the CTL effect of the CD8+ T cells on tumor cells. Moreover, upregulated MTA1 in tumor cells significantly induced infiltrated macrophages into tumor-associated macrophage phenotypes and further weakened the cytotoxic effect of CD8+ T cells. Conclusion: Upregulation of MTA1 in colorectal cancer drives an immunosuppressive tumor microenvironment by decreasing the microphages from the tumor and inducing the residual macrophages into tumor-associated microphage phenotypes to block the activation of the killing CTL, which contributes to cancer progression.

15.
Materials (Basel) ; 15(4)2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35207839

RESUMEN

The mechanical properties and deformation microstructure of cast 304 Cu-containing austenitic stainless steel at 10-3/s strain rate in the range of 700~1200 °C were studied by Gleeble thermal simulator, metallographic microscope and scanning electron microscope. The results showed that the thermoplasticity of 304 Cu-containing austenitic stainless steel was higher than 60% when the temperature was higher than 1000 °C, and the tensile strength as a whole decreased with the increase in temperature. During the tensile process, the morphology and content of ferrite in the test steel were the main factors affecting the high-temperature thermoplastic of the billet. The inclusions near the fracture and the existence of ferrite at the grain boundary greatly affected the formation of microcracks and holes and the fracture.

16.
Aging Cell ; 21(3): e13567, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35146893

RESUMEN

Metformin, a widely prescribed first-line drug for the treatment of type II diabetes mellitus, has been shown to extend lifespan and delay the onset of age-related diseases. The precisely mechanisms by which these effects are realized remain elusive. We find that metformin exposure is restricted to adults, which is sufficient to extend lifespan. However, limiting metformin exposure to the larvae has no significant effect on Caenorhabditis elegans longevity. Here, we show that after metformin treatment, the level of S-adenosylmethionine (SAM) is reduced in adults but not in the larvae. Potential mechanisms by which reduced SAM might increase lifespan include altering the histone methylation. However, the molecular connections between metformin, SAM limitation, methyltransferases, and healthspan-associated phenotypes are unclear. Through genetic screening of C. elegans, we find that metformin promotes the healthspan through an H3K4 methyltransferase/demethylase complex to downregulate the targets, including mTOR and S6 kinase. Thus, our studies provide molecular links between meformin, SAM limitation, histone methylation, and healthspan and elucidate the mode action of metformin-regulated healthspan extension will boost its therapeutic application in the treatment of human aging and age-related diseases.


Asunto(s)
Proteínas de Caenorhabditis elegans , Diabetes Mellitus Tipo 2 , Metformina , Animales , Caenorhabditis elegans/fisiología , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Histonas , Longevidad/genética , Metformina/farmacología , Metformina/uso terapéutico , S-Adenosilmetionina/farmacología , S-Adenosilmetionina/uso terapéutico
17.
Neurochem Int ; 150: 105180, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34509561

RESUMEN

The identity of the mechanism that controls aggressive behavior in rodents is unclear. Serotonin (5-HT) and GABA are associated with aggressive behavior in rodents. However, the regulatory relationship between these chemicals in the different brain regions of rats has not been fully defined. This study aimed to clarify the role of GABABR1 in DRN-mediated GABA to regulate 5-HT expression in multiple brain regions in male rats with high and low aggressive behavior. Rat models of highly and less aggressive behavior were established through social isolation plus resident intruder. On this basis, GABA content in the DRN and 5-HT contents in the PFC, hypothalamus, hippocampus and DRN were detected using ELISA. Co-expression of 5-HT and GB1 in the DRN was detected by immunofluorescence and immunoelectron microscopy at the tissue and subcellular levels, respectively. GB1-specific agonist baclofen and GB1-specific inhibitor CGP35348 were injected into the DRN by stereotaxic injection. Changes in 5-HT levels in the PFC, hypothalamus and hippocampus were detected afterward. After modeling, rats with highly aggressive behavior exhibited higher aggressive behavior scores, shorter latencies of aggression, and higher total distances in the open field test than rats with less aggressive behavior. The contents of 5-HT in the PFC, hypothalamus and hippocampus of rats with high and low aggressive behavior (no difference between the two groups) were significantly decreased, but the change in GABA content in the DRN was the opposite. GB1 granules could be found on synaptic membranes containing 5-HT granules, which indicated that 5-HT neurons in the DRN co-expressed with GB1, which also occurred in double immunofluorescence results. At the same time, we found that the expression of GB1 in the DRN of rats with high and low aggressive behavior was significantly increased, and the expression of GB1 in the DRN of rats with low aggressive behavior was significantly higher than that in rats with high aggressive behavior. Nevertheless, the expression of 5-HT in DRN was opposite in these two groups. After microinjection of baclofen into the DRN, the 5-HT contents in the PFC, hypothalamus and hippocampus of rats in each group decreased significantly. In contrast, the 5-HT contents in the PFC, hypothalamus and hippocampus of rats in each group increased significantly after injection with CGP35348. The significant increase in GABA in the DRN combined with the significant increase in GB1 in the DRN further mediated the synaptic inhibition effect, which reduced the 5-HT level of 5-HT neurons in the DRN, resulting in a significant decrease in 5-HT levels in the PFC, hypothalamus and hippocampus. Therefore, GB1-mediated GABA regulation of 5-HT levels in the PFC, hypothalamus and hippocampus is one of the mechanisms of highly and less aggressive behavior originating in the DRN. The increased GB1 level in the DRN of LA-behavior rats exhibited a greater degree of change than in the HA-group rats, which indicated that differently decreased 5-HT levels in the DRN may be the internal mechanisms of high and low aggression behaviors.


Asunto(s)
Agresión/fisiología , Encéfalo/metabolismo , Núcleo Dorsal del Rafe/metabolismo , Receptores de GABA-B/biosíntesis , Serotonina/biosíntesis , Ácido gamma-Aminobutírico/biosíntesis , Agresión/psicología , Animales , Agonistas de Receptores GABA-B/administración & dosificación , Expresión Génica , Masculino , Microinyecciones/métodos , Ratas , Receptores de GABA-B/genética , Serotonina/genética , Aislamiento Social/psicología , Ácido gamma-Aminobutírico/genética
18.
Ecotoxicol Environ Saf ; 221: 112415, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34171691

RESUMEN

In order to understand the mechanisms of arsenic (As) accumulation and detoxification in aquatic plants exposed to different As species, a hydroponic experiment was conducted and the three aquatic plants (Hydrilla verticillata, Pistia stratiotes and Eichhornia crassipes) were exposed to different concentrations of As(III), As(V) and dimethylarsinate (DMA) for 10 days. The biomass, the surface As adsorption and total As adsorption of three plants were determined. Furthermore, As speciation in the culture solution and plant body, as well as the arsenate reductase (AR) activities of roots and shoots, were also analyzed. The results showed that the surface As adsorption of plants was far less than total As absorption. Compared to As(V), the plants showed a lower DMA accumulation. P. stratiotes showed the highest accumulation of inorganic arsenic but E. crassipes showed the lowest at the same As treatment. E. crassipes showed a strong ability to accumulate DMA. Results from As speciation analysis in culture solution showed that As(III) was transformed to As(V) in all As(III) treatments, and the oxidation rates followed as the sequence of H. verticillata>P. stratiotes>E. crassipes>no plant. As(III) was the predominant species in both roots (39.4-88.3%) and shoots (39-86%) of As(III)-exposed plants. As(V) and As(III) were the predominant species in roots (37-94%) and shoots (31.1-85.6%) in As(V)-exposed plants, respectively. DMA was the predominant species in both roots (23.46-100%) and shoots (72.6-100%) in DMA-exposed plants. The As(III) contents and AR activities in the roots of P. stratiotes and in the shoots of H. verticillata were significantly increased when exposed to 1 mg·L-1 or 3 mg·L-1 As(V). Therefore, As accumulation mainly occurred via biological uptake rather than physicochemical adsorption, and AR played an important role in As detoxification in aquatic plants. In the case of As(V)-exposed plants, their As tolerance was attributed to the increase of AR activities.


Asunto(s)
Araceae , Arseniato Reductasas/metabolismo , Arsénico , Ácido Cacodílico , Eichhornia , Hydrocharitaceae , Proteínas de Plantas/metabolismo , Contaminantes Químicos del Agua , Adsorción , Araceae/química , Araceae/metabolismo , Arsénico/química , Arsénico/metabolismo , Ácido Cacodílico/química , Ácido Cacodílico/metabolismo , Eichhornia/química , Eichhornia/metabolismo , Hydrocharitaceae/química , Hydrocharitaceae/metabolismo , Hidroponía , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Brotes de la Planta/química , Brotes de la Planta/metabolismo , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/metabolismo
19.
Chin Med J (Engl) ; 134(13): 1561-1568, 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34133350

RESUMEN

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION: Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.


Asunto(s)
Displasia Broncopulmonar , Recien Nacido con Peso al Nacer Extremadamente Bajo , Peso al Nacer , China/epidemiología , Salas de Parto , Femenino , Edad Gestacional , Humanos , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Masculino , Embarazo
20.
Artículo en Inglés | MEDLINE | ID: mdl-33641104

RESUMEN

To find maize varieties with both safe production and soil remediation, 11 maize varieties were planted in field soil which was combinedly polluted by cadmium (Cd), arsenic (As), and lead (Pb). The plant growth, accumulation, phytochemical forms, and translocation of Cd, As, and Pb in different tissues were examined. Furthermore, maize varieties with low metal accumulation in their edible parts but high accumulation in other parts were selected as remediation candidates and pollution-safe varieties. The results showed that the growth of varieties Yayu69, Longhuang2502, and Shennongyu10 were the least affected by heavy metals. The concentrations of Cd, As, and Pb in all of the tested maize grains met the national feed hygiene standards, and the grain concentrations of the three metals in Yayu69, Shengnongyu10, and Yunrui62 all met the national food safety standards. According to the extraction efficiency of Cd, As, and Pb and heavy metal concentrations in grains, four types of maize were classified as follows: (1) the first category was suitable for both soil remediation and safe production, including the varieties Yayu69 (Cd, Pb), Jinyi418 (As, Cd), and Shengnongyu10 (Pb); (2) the second category had a high concentration of metals in edible part but did not exceed the limiting value in national feed hygiene standards, and the metal extraction efficiency was also high, including Beiyu1521 (Cd) and Longhuang2502 (Cd, As, Pb); (3) the third category included heavy metal exclusion varieties with low metals accumulation, such as Yayu749 (Cd), Yunrui62 (As, Pb), and Yunrui8 (As); and (4) the fourth type covered risk maize varieties with food safety risks and unsuitable cultivation at sites polluted with toxic metals, including Chuangui1586 (Pb) and Enyu69 (As). The variety Yayu69 (a Cd/Pb low accumulator in grain) contained a low percentage of inorganic (FE) and water-soluble (FW) Cd (4%) and Pb (6%) in roots, respectively, but the percentage of FE and FW Cd and Pb in the variety Beiyu1521 (a Cd/Pb high accumulator in grain) was up to 29% and 13%. Our results provided a new perspective in applying maize varieties with different metal-accumulating ability in their different parts to achieve the remediation of metal-polluted soil and the sustainable development of agricultural production.

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