Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.165
Filtrar
1.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614216

RESUMO

N6-metyladenosine (m6A), one of the most common RNA methylation modifications in mammals, has attracted extensive attentions owing to its regulatory roles in a variety of physiological and pathological processes. As a reversible epigenetic modification on RNAs, m6A is dynamically mediated by the functional interplay among the regulatory proteins of methyltransferases, demethylases and methyl-binding proteins. In recent years, it has become increasingly clear that m6A modification is associated with the production and function of microRNAs (miRNAs). In this review, we summarize the specific kinds of m6A modification methyltransferases, demethylases and methyl-binding proteins. In particular, we focus on describing the roles of m6A modification and its regulatory proteins in the production and function of miRNAs in a variety of pathological and physiological processes. More importantly, we further discuss the mediating mechanisms of miRNAs in m6A modification and its regulatory proteins during the occurrence and development of various diseases.


Assuntos
MicroRNAs , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Adenosina/metabolismo , Metilação , Metiltransferases/metabolismo , Epigênese Genética , Proteínas de Transporte/metabolismo , Fatores de Transcrição/metabolismo , Mamíferos/metabolismo
2.
Nat Commun ; 14(1): 391, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693873

RESUMO

The trait-based strategies of microorganisms appear to be phylogenetically conserved, but acclimation to climate change may complicate the scenario. To study the roles of phylogeny and environment on bacterial responses to sudden moisture increases, we determine bacterial population-specific growth rates by 18O-DNA quantitative stable isotope probing (18O-qSIP) in soils subjected to a free-air CO2 enrichment (FACE) combined with warming. We find that three growth strategies of bacterial taxa - rapid, intermediate and slow responders, defined by the timing of the peak growth rates - are phylogenetically conserved, even at the sub-phylum level. For example, members of class Bacilli and Sphingobacteriia are mainly rapid responders. Climate regimes, however, modify the growth strategies of over 90% of species, partly confounding the initial phylogenetic pattern. The growth of rapid bacterial responders is more influenced by phylogeny, whereas the variance for slow responders is primarily explained by environmental conditions. Overall, these results highlight the role of phylogenetic and environmental constraints in understanding and predicting the growth strategies of soil microorganisms under global change scenarios.

3.
Int J Colorectal Dis ; 38(1): 22, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36690760

RESUMO

PURPOSE: The purpose of this study was to compare the short-term outcomes between laparoscopic Hartmann reversal (LHR) and open Hartmann reversal (OHR) in patients who had undergone Hartmann surgery for colorectal cancer (CRC). METHODS: The patients who underwent Hartmann reversal (HR) at the First Affiliated Hospital of Chongqing Medical University from Jun 2013 to Jun 2022 were retrospectively enrolled. The LHR group and the OHR group were compared using propensity score matching (PSM) analysis. RESULTS: A total of 89 patients who underwent Hartmann reversal (HR) were enrolled in this study. There were 48 (53.9%) patients in the LHR group and 41 (46.1%) patients in the OHR group. After 1:1 ratio PSM, no difference in baseline information remained (p > 0.05). There was no significant difference in operation time, blood loss, postoperative hospital stay, and postoperative complications (p > 0.05) before and after PSM. In the multivariable logistic regression analysis, pre-operative albumin < 42.0 g/L was an independent risk factor (p = 0.013 < 0.05, OR = 0.248, 95% CI = 0.083-0.741) for the HR-related complications; however, LHR/OHR was not a predictive risk factor (p = 0.663, OR = 1.250, 95% CI = 0.500-3.122). CONCLUSION: Based on the current evidence, although there was no difference in short-term prognosis, LHR still had some advantages considering that it was less invasive to the patient.


Assuntos
Laparoscopia , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Complicações Pós-Operatórias , Prognóstico , Resultado do Tratamento
4.
Plant Physiol Biochem ; 195: 101-113, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36621304

RESUMO

The color and fragrance of rose flowers affect their commercial value. However, several rose varieties with new floral colors developed by the bud mutation method lost their fragrance during the breeding process, raising the question: Is there a relationship between floral color and aroma traits? Rose cultivar 'Yellow Island' (YI) with intensely aroma and yellow petals, while its bud mutant 'Past Feeling' (PF) with light aroma and pink petals mixing some yellow, two cultivars were used to explore this question using multiomics approaches. We investigated the genomic polymorphisms between PF and YI by whole-genome resequencing. 71 differentially abundant metabolites and 155 related differentially expressed genes identified in petals between PF and YI. From this, we constructed a model of metabolic changes affecting floral color and fragrance integrating shikimate, terpenoid, carotenoid, and green leaf volatile metabolites and predicted the associated key genes and transcription factors. This study provides a reference for understanding the molecular mechanism of variation in rose floral color and aroma traits.

5.
Int J Phytoremediation ; : 1-8, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36597829

RESUMO

Cadmium (Cd) is the main heavy metal pollutant in soil. The combination of genetic engineering technology and Rizobium rhizogenes mediated technology can effectively improve the enrichment efficiency of heavy metals in super accumulators and reduce soil heavy metal pollution. In this study, the transgenic hairy root system containing the IRT1 gene of Cd hyperaccumulator-Brassica campestris L. was successfully constructed by the R. rhizogenes mediated method (IRT1 gene come from Arabidopsis thaliana). The hairy roots of each subculture can grow stably within 6 weeks, and IRT1 gene will not be lost within 50 subcultures., which is detected using PCR method. The results of Cd enrichment experiments showed that after treatment with 100 µmol/L Cd for 14 days, the growth state of transgenic IRT1 hairy roots only showed slight browning. Also, the accumulation value of Cd reached 331.61 µg/g and the enrichment efficiency of transgenic IRT1 hairy roots was 13.8% higher than that of wild-type hairy roots. Western blotting results showed that the expression of IRT1 protein in transgenic hairy roots was significantly higher than that of wild-type hairy roots under Cd stress. The above results indicated that the overexpression of IRT1 gene can help B. campestris L. hairy roots to effectively cope with Cd stress and improve its ability to enrich Cd.


In this study, the transgenic hairy root system containing the IRT1 gene of Cd hyperaccumulator-Brassica campestris L. was successfully constructed by the Rizobium rhizogenes mediated method. At the same time, the growth state and cadmium enrichment efficiency of transgenic hairy roots under different concentrations of Cd stress were studied. Overexpression of IRT1 gene can effectively improve the tolerance of hairy root to Cd. The enrichment efficiency of transgenic IRT1 hairy roots was 13.8% higher than that of wild-type hairy roots. The transgenic IRT1 hairy root system established in this study can be used as a reliable experimental model for the study of Cd adsorption mechanism, and can be further regenerated to obtain transgenic IRT1 B. campestris L. plants for the study of heavy metal Cd pollution remediation.

6.
Mol Neurobiol ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36593434

RESUMO

Schwann cell (SC) myelination is a pivotal event in the normal physiological functioning of the peripheral nervous system (PNS), where myelination is finely controlled by a series of factors within SCs to ensure timely onset and correct myelin thickness for saltatory conduction. Among these, cyclic AMP (cAMP) is a promising factor for driving myelin gene expression in SCs. It has been shown that TGR5 activation is often associated with increased production of cAMP. Therefore, we speculated that the G-protein-coupled receptor (TGR5) might be involved in the PNS myelination. To test this hypothesis, sciatic nerve crush-injured mice were treated with INT-777, a specific agonist of TGR5, which significantly improved remyelination and functional recovery. Furthermore, rats that underwent sciatic nerve transection were treated with INT-777, which also promoted nerve regeneration and functional recovery. In primary SCs, the stimulatory effect of INT-777 on myelin gene expression was largely counteracted by H89, a potent inhibitor of cAMP-dependent protein kinase A (PKA). Additionally, INT-777 stimulated cell migration was blunted in the presence of H89. Overall, these data indicate that INT-777 is capable of promoting peripheral nerve regeneration and functional recovery after injury, and these benefits are likely due to the activation of the TGR5/cAMP/PKA axis. As such, INT-777, together with other TGR5 agonists, may hold great therapeutic potential for treating peripheral nerve injury.

7.
J Asian Nat Prod Res ; : 1-15, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36632044

RESUMO

This paper describes a rare phenomenon of multi-conformers caused by conformational change of A-ring in the C18- and C19- N-dealkyl diterpenoid alkaloids. The possible reasons for the generation of multiple conformational isomers are complex, which could be affected by the substituents at C-1, C-3, C-13, C-14, and C-15, pH, solvents, the intramolecular hydrogen bond between 1α-OCH3/1α-OH and N-H groups, acid-base treatment, preparation methods, and work-up procedures.

8.
Anal Sci ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607557

RESUMO

Herein, we developed a novel fluorescent assay using spherical identification probes and toehold-mediated strand displacement reaction-initiated silver nanoclusters (AgNCs) "on-off" signal switch. In this strategy, the target was captured by the spherical probes to induce the activity of exonuclease III (Exo III), catalyzing the cyclic cleavage of substrates to produce a mass of trigger strands. After magnetic bead separation, the intermediates in the supernatant activated downstream toehold-mediated strand displacement reaction to change the structure of silver nanocluster templates, leading to fluorescence intensity reduction. Furthermore, it is demonstrated that the application of spherical identification probes could reduce the signal leakage and the limit of detection. In addition, AgNCs with perfect optical property were ingeniously combined to realize signal output, which reduced the cost and time of synthesis. Under the optimal conditions, the sensing method displayed a good linear range from 250 pM to 25 nM with a detectable minimum concentration of 250 pM. And the practical application potential in complex biological matrices was also evaluated. Considering these advantages, this constructed strategy opens a new path for nucleic acid detection with better performance. A simple, label- and hairpin-free fluorescent system based on spherical identification probe and toehold-mediated strand displacement reaction-initiated silver nanoclusters (AgNCs) "on-off" signal switch was successfully constructed to detect target DNA.

9.
Regen Biomater ; 10: rbac100, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36683745

RESUMO

Mechanical stiffness is recognized as a key physical factor and directs cell function via a mechanotransduction process, from extracellular physical cues to intracellular signaling cascades that affect transcriptional activity. Cells continually receive mechanical signals from both the surrounding matrix and adjacent cells. However, how mechanical stiffness cue at cell-substrate interfaces coordinates cell-cell junctions in guiding mesenchymal stem cell behaviors is poorly understood. Here, polydimethylsiloxane substrates with different stiffnesses were used to study mechanosensation/transduction mechanisms in controlling odontogenic differentiation of dental papilla cells (DPCs). DPC phenotypes (morphology and differentiation) changed in response to the applied force derived from stiff substrates. Significantly, higher expression of paxillin on stiffer substrates promoted DPC dentinogenesis. Upon treatment with siRNA to knockdown paxillin, N-cadherin increased mainly in the cytomembrane at the area of cell-cell contacts, whereas ß-catenin decreased in the nuclei. The result of a double luciferase reporter assay showed that stiffness promoted ß-catenin binding to TCF, which could coactivate the target genes associated with odontogenic differentiation, as evidenced by bioinformatics analysis. Finally, we determined that the addition of a ß-catenin inhibitor suppressed DPC mineralization in all the stiffness groups. Thus, our results indicated that a mechanotransduction process from cell-substrate interactions to cell-cell adhesions was required for DPC odontogenic differentiation under the stimulation of substrate stiffness. This finding suggests that stem cell fate specification under the stimulus of stiffness at the substrates is based on crosstalk between substrate interactions and adherens junctions, which provides an essential mechanism for cell-based tissue engineering.

10.
Exp Eye Res ; : 109387, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36646298

RESUMO

The purpose of this study was to investigate the efficacy and safety of microbial transglutaminases (mTGases) during scleral collagen cross-linking (CXL) in vivo. Sixteen New Zealand white albino rabbits were treated with sub-Tenon's injections of 2 ml of 1 U/ml mTGases in the right eye and 2 ml of phosphate buffer saline (PBS) in the left eye. The rabbits were killed 2 weeks after the injection, and all eyeballs, including some scleral strips, were processed. The elastic modulus was measured with a biomaterials tester. Histopathological analysis and transmission electron microscopy (TEM) were used for the morphological observations. The elastic modulus of the mTGase-treated sclera was 15.79 ±â€¯2.93 MPa, and that of the control was 6.91 ±â€¯2.23 MPa, indicating an increase of 129% after the mTGases treatment (P < 0.05). The density of the scleral collagen bundles and diameter of the collagen fibrils increased compared with those in the control group. No apoptosis was detected in the retina or posterior sclera by TUNEL staining, and no histological damage was observed on the TEM scan. This study is based on a short-term study on animal models. These results indicate that mTGase-mediated scleral CXL is a promising approach to effectively stiffen the sclera and safe enough for retina, and may be a useful treatment modality for strengthening scleral tissue.

11.
Hematology ; 28(1): 1-9, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36652402

RESUMO

OBJECTIVES: Chromosome segregation 1-like (CSE1L) is abundant and strongly expressed in solid tumors. However, the expression and role of CSE1L in chronic myeloid leukemia(CML) remain largely unknown. MATERIALS AND METHODS: The relative expression levels of CSE1L in bone marrow granulocytes from patients with primary CML and non-hematologic controls were measured by flow cytometry. Cell counting kit-8 analysis, DNA Content Quantitation Assay, and Annexin V-PE/7-AAD staining were applied to assess the effects of CSE1L knockdown on cell proliferation, cell cycle progression, and apoptosis. RESULTS: Elevated expression of CSE1L was detected in bone marrow granulocytes of patients with primary CML. In the CML cell line K562 cells, CSE1L knockdown impaired cell proliferation blocked the cell cycle shift from G0/G1 phase to the S phase, and promoted apoptosis. Knockdown of CSE1L reduced Bcl-2 protein expression and increased Bax protein expression. Meanwhile, knockdown of CSE1L enhanced the expression of phospho-AMPK protein and decreased the expression of phospho-mTOR protein. The expression of total AMPK and mTOR proteins was not affected. In addition, CSE1L expression levels were decreased in imatinib-treated K562 cells. CONCLUSIONS: CSE1L plays a pivotal role in K562 cell survival and growth. These functions may be partially dependent on the AMPK/mTOR signaling pathway to achieve. In addition, CSE1L may have had a future impact on the treatment of CML patients.


Assuntos
Proteínas Quinases Ativadas por AMP , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Apoptose , Proliferação de Células , Células K562
12.
Trends Biotechnol ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36658007

RESUMO

The sense of touch events, achieved by artificial tactile sensory systems (ATSSs), is a milestone in the progress of human-machine interactions. However, it has been a challenge for ATSSs to serve functions comparable with the human tactile perception system (HTPS). The biomimetic strategies and technologies inspired by HTPS are considered an optimal solution to this challenge. Recent studies have reported bioinspired strategies for improving specific aspects of ATSS performance, such as feature collection, signal conversion, and information computation. Here, we present a systematic interpretation of biomechanisms for HTPSs, and correspondingly, address biomimetic strategies and technologies contributing to ATSSs as an integral system. This review will benefit the development and application of ATSSs in the future.

14.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36674732

RESUMO

MiRNAs are critical regulators of numerous physiological and pathological processes. Ascosphaera apis exclusively infects bee larvae and causes chalkbrood disease. However, the function and mechanism of miRNAs in the bee larval response to A. apis infection is poorly understood. Here, ame-miR-34, a previously predicted miRNA involved in the response of Apis mellifera larvae to A. apis invasion, was subjected to molecular validation, and overexpression and knockdown were then conducted to explore the regulatory functions of ame-miR-34 in larval body weight and immune response. Stem-loop RT-PCR and Sanger sequencing confirmed the authenticity of ame-miR-34 in the larval gut of A. mellifera. RT-qPCR results demonstrated that compared with that in the uninfected larval guts, the expression level of ame-miR-34 was significantly downregulated (p < 0.001) in the guts of A. apis-infected 4-, 5-, and 6-day-old larvae, indicative of the remarkable suppression of host ame-miR-34 due to A. apis infection. In comparison with the corresponding negative control (NC) groups, the expression level of ame-miR-34 in the larval guts in the mimic-miR-34 group was significantly upregulated (p < 0.001), while that in the inhibitor-miR-34 group was significantly downregulated (p < 0.01). Similarly, effective overexpression and knockdown of ame-miR-34 were achieved. In addition, the body weights of 5- and 6-day-old larvae were significantly increased compared with those in the mimic-NC group; the weights of 5-day-old larvae in the inhibitor-miR-34 group were significantly decreased in comparison with those in the inhibitor-NC group, while the weights of 4- and 6-day-old larvae in the inhibitor-miR-34 group were significantly increased, indicating the involvement of ame-miR-34 in modulating larval body weight. Furthermore, the expression levels of both hsp and abct in the guts of A. apis-infected 4-, 5-, and 6-day-old larvae were significantly upregulated after ame-miR-34 overexpression. In contrast, after ame-miR-34 knockdown, the expression levels of the aforementioned two key genes in the A. apis-infected 4-, 5-, and 6-day-old larval guts were significantly downregulated. Together, the results demonstrated that effective overexpression and knockdown of ame-miR-34 in both noninfected and A. apis-infected A. mellifera larval guts could be achieved by the feeding method, and ame-miR-34 exerted a regulatory function in the host immune response to A. apis invasion through positive regulation of the expression of hsp and abct. Our findings not only provide a valuable reference for the functional investigation of bee larval miRNAs but also reveal the regulatory role of ame-miR-34 in A. mellifera larval weight and immune response. Additionally, the results of this study may provide a promising molecular target for the treatment of chalkbrood disease.


Assuntos
Imunidade , MicroRNAs , Abelhas/genética , Animais , Larva/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Peso Corporal
15.
Sci Total Environ ; 863: 160810, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36496028

RESUMO

The rapid development of the use of agricultural plastic greenhouses in China in recent years has played an important role in the generation of economic benefits from agriculture. However, it has also led to severe negative environmental impacts. Thus, it is necessary to explore the spatial and temporal evolution of agricultural plastic greenhouses in China as well as their environmental impacts so as to obtain a deeper understanding of agricultural intensification and the sustainable development of the facility agriculture industry. To this end, this study analyzed the spatial and temporal evolution characteristics of agricultural plastic greenhouses and their greenhouse gas emissions within the 2000-2020 period based on the extraction of the spatial distribution of greenhouses in China in 2000, 2010, and 2020. Landsat imagery and statistical data combined with the random forest classification method as well as life cycle analysis, were used in this study. The results obtained showed that: (1) Within the 2000-2020 period, the area covered by agricultural plastic greenhouses in China expanded from 1594.66 to 11,838.77 km2, with most of the greenhouses predominantly distributed in the North China Plain. (2) The increase in total greenhouse gas emissions between 2000 and 2010 was mainly due to the expansion of agricultural plastic greenhouse and an increase in agricultural material inputs, whereas the increase between 2010 and 2020 was mainly due to the expansion of agricultural plastic greenhouse. (3) Greenhouse gas emissions from nitrogenous fertilizers and greenhouse construction materials accounted for 45 % and 36 % of the total greenhouse gas emissions, respectively. These findings are of great significance as they enhance understanding regarding land intensification development and its accompanying environmental impacts in China.

16.
Neuropsychologia ; 179: 108464, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36565993

RESUMO

In the field of bilingualism, researchers have proposed an assimilation hypothesis that posits that bilinguals apply the neural network of their native language to process their second language. In Chinese-English bilinguals, the bilateral fusiform gyrus has been identified as the key brain region showing the assimilation process. Specifically, in contrast to left-lateralized activation in the fusiform gyrus in native English speakers, Chinese-English bilinguals recruit the bilateral fusiform cortex to process English words as they do in the processing of Chinese characters. Nevertheless, it is unclear which type of information processing is assimilated in the fusiform gyrus. Using representational similarity analysis (RSA) and psychophysiological interaction (PPI) analysis, this study examined the differences in information representation and functional connectivity between both languages in the fusiform subregions in Chinese-English bilinguals. Univariate analysis revealed that both Chinese and English naming elicited strong activations in the bilateral fusiform gyrus, which confirmed the assimilation process at the activation intensity level. RSA indicated that the neural pattern of English phonological information was assimilated by Chinese in the anterior and middle right fusiform gyrus, while those of orthographic and visual form information were not. Further PPI analysis demonstrated that the neural representation of English phonological information in the right anterior fusiform subregion was related to its interaction with the frontotemporal areas for high-level linguistic processing, while the neural representation of English orthographic information in the right middle fusiform subregion was linked to its interaction with the left inferior occipital cortex for visual processing. These results suggest that, despite the recruitment of similar neural resources in one's native and second languages, the assimilation of information representation is limited in the bilateral fusiform cortex. Our results shed light on the neural mechanisms of second language processing.


Assuntos
Imageamento por Ressonância Magnética , Multilinguismo , Humanos , Leitura , Idioma , Encéfalo/fisiologia , Mapeamento Encefálico
17.
Brain Res Bull ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36470555

RESUMO

The mechanism of electroacupuncture (EA) pretreatment-induced neuroprotection remains unclear. In this study, we found that neuronal Triggering receptor expressed on myeloid cells 2 (TREM2) expression was increased and peaked at 48h and 72h after ischemia/reperfusion. After specific knockdown of TREM2 in excitatory neurons, neurological function was damaged, and the infarct volume was enlarged. Furthermore, the expression of LC3II/LC3I and Beclin1 was decreased, while the expression of p62 was increased. EA pretreatment enhanced TREM2, LC3II/LC3I and Beclin1 expression while reducing p62 in the ischemic penumbra area. The EA-induced neuroprotective effects and improvements in autophagic flux were abolished by specific knockdown of TREM2 in excitatory neurons. Taken together, our findings provide novel mechanistic insight into EA-induced ischemic tolerance and suggest a promising therapeutic strategy of targeting neuronal TREM2 to treat brain ischemia.

18.
Fish Shellfish Immunol ; : 108468, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464079

RESUMO

Trained immunity has been widely observed in mammals. Its identification in red swamp crayfish (Procambarus clarkii) is important for disease resistance in the crayfish farming industry. In this study, the mortality, expression of immune genes, production of reactive oxygen species (ROS), and phagocytosis ability of haemocytes in crayfish infected by pathogens (Vibrio parahaemolyticus or white spot syndrome virus) and crayfish trained with ß-glucan or PBS (the control) were assessed when they were re-challenged by the pathogens. The results showed that the mortality of the trained and re-challenged crayfish were significantly lower than those of the untrained and challenged crayfish. Furthermore, the expression of immune genes, including Resistance (R), ALF, crustin2, and proPO, ROS levels, and phagocytosis ability of haemocytes, was significantly improved in the trained crayfish compared to that in the untrained crayfish. Interestingly, we found that the immune memory of trained crayfish lasted for at least 18 days. Together, these results indicate that crayfish develops trained immunity that can play an important role in the disease resistance. This suggests that trained immunity may be applied to improve disease resistance and crayfish production.

19.
Theranostics ; 12(18): 7717-7728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451862

RESUMO

Background: The therapeutic efficacy of allergen specific immunotherapy (SIT) is recognized, but needs improved. Psychological stress influences the immune system's function. The objective of this study is to elucidate the effects of psychological stress on compromising the effectiveness of SIT. Methods: A murine model with the airway allergic disorder (AAD) was established. Mice were treated with SIT with or without restraint stress (Rs). Results: Rs was found to significantly hamper the efficacy of SIT in mice with AAD. Induction of IL-10+ dendritic cells and type 1 regulatory T cells were reduced by Rs in the airway tissues. Rs-induced cortisol release subverted immune tolerance generation. Expression of MARCH1 was elevated in dendritic cells of the allergic lesion sites. The Rs-induced MARCH1 mediated the immune impairment in AAD mice. Genetic ablation of MARCH1 in dendritic cells efficiently blocked the Rs-compromised the therapeutic efficacy of SIT. Conclusion: Rs can increase the expression of MARCH1 in DCs of the allergic lesion sites. MARCH1 interferes with the immune regulatory properties in DCs, and impairs the immune regulatory capacity. Blocking MARCH1 can counteract the Rs-affected SIT efficacy.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade , Camundongos , Animais , Esteroides , Estresse Psicológico/terapia , Hipersensibilidade/terapia , Transdução de Sinais , Ubiquitina-Proteína Ligases
20.
Theranostics ; 12(18): 7903-7919, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451866

RESUMO

Background & Aims: Abnormal activation of mTOR through loss of tuberous sclerosis complex (Tsc) frequently occurs in hepatocellular carcinoma (HCC). Mutant Kras could induce aggressive HCCs. Here, we aim to identify the predictive or prognostic biomarkers for HCC patients with Kras mutant and mTOR hyperactivation, and to provide potential therapeutic approaches for this subtype of HCCs. Methods: We generated transgenic mice in which hepatocytic mTOR was hyperactivated through Tsc1 insufficiency with or without oncogenic KrasG12D. Bioinformatics and gain- or loss-of-function studies were used to illustrate the mechanisms underlying oncogenic pathway alterations. Transcriptional profiling was used to identify biomarker for the subtype of HCC. The therapeutic efficacy of targeting mTOR was tested in a liver orthotropic homogeneous murine model. Results: Oncogenic KrasG12D facilitated mTOR activation via the Mek/Erk/ROS axis, leading to HCC tumorigenesis and metastasis. Inhibition of Mek/Erk enhanced the anticancer effect of mTOR inhibitor via reduction of mTOR activity. Paternally expressed 3 (PEG3) was responsible for Kras/Erk- and mTOR-driven HCC. Elevated PEG3 protein interacted with STAT3 and promoted its transcriptional activity, resulting in the upregulation of proliferation- and metastasis-related proteins. Targeting mTOR significantly inhibited these actions in vitro and in vivo. Moreover, in clinical samples, PEG3 was identified as a new poor prognostic marker for HCC patients with Kras/Erk and mTOR hyperactivation. Conclusion: These findings reveal the underlying mechanism of hepatocytic Kras/Erk-driven mTOR activation and its downstream targets (PEG3 and STAT3) in HCC, identify PEG3 as a new prognostic biomarker for HCC with Kras/Erk and mTOR hyperactivation, and provide a potential therapeutic strategy for this subset of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Genes ras , Serina-Treonina Quinases TOR , Carcinogênese/genética , Quinases de Proteína Quinase Ativadas por Mitógeno , Fatores de Transcrição Kruppel-Like
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...