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Objective: This study extracts atherosclerosis indices from six channels of C u n k o u and discusses the data distribution, aims to explore the connection between cardiology of modern medicine (MM) and traditional Chinese medicine (TCM) pulse diagnosis. Methods: We use a device capable of simultaneously collecting the pulse signals of the Cun, G u a n and Chi to test the population participating in routine physical examinations. Firstly, we collected pressure pulse waves from six channels of C u n k o u of 1045 healthy subjects (578 men and 467 women, average age=37.99±16.02 years). Secondly, we extracted the two most common arteriosclerosis indices pulse transit time (PTT) and Augmentation index (AIx) from six-channel pulse waves. Lastly, T-test and correlation test were taken to analyze the differences and relevance of the atherosclerosis indices extracted from six channels of C u n k o u . Results: When analyzing AIx and PTT at different wrist, it was found that AIx of left wrist is significantly higher than that of right wrist (P<0.001), while the PTT of left wrist is significantly lower than that of right wrist (P<0.001), a phenomenon that is common in both men and women. Furthermore, regardless of whether it is left or right wrist, the AIx at Chi channel is higher than that at Cun (P<0.05) and G u a n (P<0.05). At the same time, the PTT at G u a n is bigger than that at Cun in two wrists (P<0.05). However, when the specific channel is not considered, there is no significant difference in AIx and PTT between each channel and the corresponding wrist (P>0.05). In addition, regardless of gender, when the specific channel is not considered, AIx and PTT of each wrist are significantly correlated with age (P<0.001). Conclusions: The differences of the atherosclerosis indices AIx and PTT in six channels support that the method of six-channel pulse diagnosis is indispensable in TCM. Additionally, the pulse waves obtained from each channel can be utilized as a dependable foundation for diagnosing atherosclerotic conditions. This study is beneficial for promoting the integration of TCM and MM in diagnosing disease.
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BACKGROUND: Knowledge feature (KF) with clear physiological significance of photoplethysmography are widely used in predicting blood pressure. However, KF primarily focus on local information of photoplethysmography, which may struggle to capture the overall characteristics. METHODS: Firstly, functional data analysis (FDA) was introduced to extract two types of data feature (DF). Furthermore, data-knowledge co-driven feature (DKCF) was proposed by combining FDA and constraints of KF. Finally, random forest, ada boost, gradient boosting, support vector machine and deep neural network were adopted, to compare the abilities of KF, DFs and DKCF in predicting blood pressure with two datasets (A published dataset and a self-collected dataset). RESULTS: Under the premise of extracting only 9 features, the average mean absolute errors (MAE) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) obtained by DKCF are both the smallest in dataset 1. In dataset 2, DKCF acquires the smallest MAE in predicting SBP and obtains the second smallest MAE in predicting DBP. CONCLUSIONS: The results demonstrate that low-dimensional DKCF of photoplethysmography is closely correlated with blood pressure, which may serve as an important indicator for health assessment.
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Pressão Sanguínea , Fotopletismografia , Humanos , Fotopletismografia/métodos , Pressão Sanguínea/fisiologia , Masculino , Feminino , Determinação da Pressão Arterial/métodos , Adulto , Máquina de Vetores de Suporte , Redes Neurais de Computação , Pessoa de Meia-IdadeRESUMO
The voltage-gated sodium channel ß2 subunit protein (SCN2B) plays a crucial role in neuropathic pain. However, the role and mechanisms of SCN2B in orofacial neuropathic pain are still unclear. This study aimed to investigate the upstream regulatory mechanisms of SCN2B in the trigeminal ganglion (TG) underlying orofacial neuropathic pain. Chronic constriction injury of the infraorbital nerve (CCI-ION) of mice was performed to establish the model of orofacial neuropathic pain. Von Frey filament test was performed to detect the head withdrawal threshold (HWT) of mice. Quantitative reverse transcription-polymerase chain, western blotting (WB), fluorescence in situ hybridization, and immunofluorescence (IF) staining were used to detect the expression and distribution of SCN2B and miR-6954-3p in the TG of mice. A luciferase activity assay was carried out to prove the binding between SCN2B messenger ribonucleic acid (mRNA) and miR-6954-3p. After the CCI-ION surgery, the levels of Scn2b mRNA and protein significantly increased and miR-6954-3p decreased in the TG of mice with decreasing HWT. IF staining revealed that SCN2B was expressed specifically in the TG neurons. Silencing SCN2B in the TG of CCI-ION mice significantly increased the HWT. Importantly, the 3'-untranslated region of Scn2b mRNA was proved to bind with miR-6954-3p. Fluorescence in situ hybridization and IF staining demonstrated that miR-6954-3p was expressed in TG neurons and co-expressed with SCN2B. Furthermore, intraganglionic injection of miR-6954-3p agomir into the TG of CCI-ION mice resulted in the downregulation of SCN2B and increased the HWT. These findings suggest that the downregulation of miR-6954-3p in the TG promotes orofacial neuropathic pain by promoting SCN2B expression following trigeminal nerve injury. PERSPECTIVE: This study points to the important role of SCN2B in orofacial neuropathic pain. Furthermore, miR-6954-3p is proven to regulate the expression of SCN2B by binding to the 3'-untranslated region of Scn2b mRNA. These findings indicate that SCN2B and miR-6954-3p are potential therapeutic targets for the treatment of orofacial neuropathic pain.
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Regulação para Baixo , Dor Facial , MicroRNAs , Neuralgia , Subunidade beta-2 do Canal de Sódio Disparado por Voltagem , Animais , Masculino , Camundongos , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Dor Facial/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genética , Neuralgia/metabolismo , Gânglio Trigeminal/metabolismo , Subunidade beta-2 do Canal de Sódio Disparado por Voltagem/metabolismo , FemininoRESUMO
Aquatic ecosystems are being increasingly polluted by microplastics (MPs), which calls for an understanding of how MPs affect microbially driven biogenic element cycling in water environments. A 28-day incubation experiment was conducted using freshwater lake water added with three polymer types of MPs (i.e., polyethylene, polypropylene, polystyrene) separately or in combination at a concentration of 1 items/L. The effects of various MPs on microbial communities and functional genes related to carbon, nitrogen, phosphorus, and sulfur cycling were analyzed using metagenomics. Results showed that Sphingomonas and Novosphingobium, which were indicator taxa (genus level) in the polyethylene treatment group, made the largest functional contribution to biogenic element cycling. Following the addition of MPs, the relative abundances of genes related to methane oxidation (e.g., hdrD, frhB, accAB) and denitrification (napABC, nirK, norB) increased. These changes were accompanied by increased relative abundances of genes involved in organic phosphorus mineralization (e.g., phoAD) and sulfate reduction (cysHIJ), as well as decreased relative abundances of genes involved in phosphate transport (phnCDE) and the SOX system. Findings of this study underscore that MPs, especially polyethylene, increase the potential of greenhouse gas emissions (CO2, N2O) and water pollution (PO43-, H2S) in freshwater lakes at the functional gene level.
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Gases de Efeito Estufa , Lagos , Metagenômica , Microplásticos , Poluentes Químicos da Água , Lagos/microbiologia , Lagos/química , Gases de Efeito Estufa/análise , Microplásticos/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Poluição da Água/análise , Microbiota/efeitos dos fármacos , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/metabolismoRESUMO
The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer. Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis (YTE-17), attributing these effects to the regulation of multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited. In this study, we conducted isobaric tags for relative and absolute quantification (iTRAQ) analysis on intestinal epithelial cells (IECs) exposed YTE-17, both in vitro and invivo, revealing a significant inhibition of the Wnt family member 5a (Wnt5a)/c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment (TME), specifically focusing on macrophage-mediated T helper 17 (Th17) cell induction in a colitis-associated cancer (CAC) model with Wnt5a deletion. Additionally, we performed the single-cell RNA sequencing (scRNA-seq) on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition, lineage, and functional status of immune mesenchymal cells during different stages of colorectal cancer (CRC) progression. Remarkably, our findings demonstrate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17, leading to the restoration of regulatory T (Treg)/Th17 cell balance in azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Furthermore, we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages. Notably, our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical ß-catenin oncogenic pathway in vivo. Specifically, we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with ß-catenin activity within the TME, involving macrophages and T cells. In summary, our study undergoes the potential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment, thereby mitigating the risk of malignancies.
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OBJECTIVE: The current models of estimating vascular age (VA) primarily rely on the regression label expressed with chronological age (CA), which does not account individual differences in vascular aging (IDVA) that are difficult to describe by CA. This may lead to inaccuracies in assessing the risk of cardiovascular disease based on VA. To address this limitation, this work aims to develop a new method for estimating VA by considering IDVA. This method will provide a more accurate assessment of cardiovascular disease risk. METHODS: Relative risk difference in vascular aging (RRDVA) is proposed to replace IDVA, which is represented as the numerical difference between individual predicted age (PA) and the corresponding mean PA of healthy population. RRDVA and CA are regard as the influence factors to acquire VA. In order to acquire PA of all samples, this work takes CA as the dependent variable, and mines the two most representative indicators from arteriosclerosis data as the independent variables, to establish a regression model for obtaining PA. RESULTS: The proposed VA based on RRDVA is significantly correlated with 27 indirect indicators for vascular aging evaluation. Moreover, VA is better than CA by comparing the correlation coefficients between VA, CA and 27 indirect indicators, and RRDVA greater than zero presents a higher risk of disease. CONCLUSION: The proposed VA overcomes the limitation of CA in characterizing IDVA, which may help young groups with high disease risk to promote healthy behaviors.
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Doenças Cardiovasculares , Humanos , Envelhecimento , Fatores de RiscoRESUMO
Orofacial neuropathic pain is a common symptom induced by orofacial nerve injury caused by a range of trauma or dental and maxillofacial procedures but lacks effective treatment. Circular RNAs (circRNAs) participate in the regulatory processes of neuropathic pain. Nevertheless, the biological roles of circRNAs in orofacial neuropathic pain remain unexplored. In this study, circRNA sequencing and Real-time quantitative polymerase chain reaction (RT-qPCR) were carried out. Notably, a novel circRNA named circ_lrrc49 was identified to be downregulated following chronic constriction injury of the infraorbital nerve (CCI-ION) in mice on day 14. Subsequent RNA Antisense Purification (RAP)-mass spectrometry and RNA immunoprecipitation found a direct interaction between circ_lrrc49 and increased sodium tolerance 1 homolog (Ist1). Western blot (WB) identified decreased expression of Ist1 on day 14 post-CCI-ION. Considering the known relationship between Ist1 and autophagy, LC3-II and p62 were detected to be upregulated, and an accumulation of autophagosomes were observed at the same time point. Besides, the knockdown of circ_lrrc49 by small interfering RNA (siRNA) reduced Ist1 expression, increased LC3-II, p62 levels and autophagosomes amount, and evoked orofacial mechanical hypersensitivity, which could be counteracted by the Ist1 overexpression. Similarly, the knockdown of Ist1 by siRNA also increased LC3-II and p62 levels and evoked orofacial mechanical hypersensitivity without influence on circ_lrrc49. Moreover, autophagy activation by rapamycin alleviated orofacial mechanical hypersensitivity evoked by CCI-ION or circ_lrrc49 knockdown. In conclusion, our data revealed the existence of a circ_lrrc49/Ist1/autophagy signaling axis contributing to the progression of orofacial neuropathic pain. These discoveries reveal the intricate molecular processes that drive orofacial neuropathic pain and identify circ_lrrc49 as a promising target for potential therapeutic interventions.
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Autofagia , Regulação para Baixo , Camundongos Endogâmicos C57BL , Neuralgia , RNA Circular , Gânglio Trigeminal , Animais , Masculino , Camundongos , Autofagia/fisiologia , Neuralgia/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Gânglio Trigeminal/metabolismo , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismoRESUMO
Theoretically pulse wave velocity (PWV) is obtained by calculating the distance between two waveform probes divided by the time difference, and PWV ratio is used to assess the arterial stiffness gradient (SG) from proximal to distal. The aim was to investigate segmental upper-limb PWV (ulPWV) differences and the effects of hypertension and or aging on each ulPWV and SG. The study collected multi-waveform signals and conduction distances from 167 healthy individuals and 92 hypertensive patients. The results showed significant differences between ulPWVs (P < 0.001), with increased and then decreased vascular stiffness along the proximal transmission to the distal peripheral artery and then to the finger. Adjusted for age and sex, ulPWVs in hypertension exceeded that of healthy individuals, with significant differences between groups aged ≥ 50 years (P < 0.05). The hrPWV/rfPWV (heart-radial/radial-finger) was reduced in hypertension and differed significantly between the aged ≥ 50 years (P = 0.015); the ratio of baPWV (brachial-ankle) to ulPWV differed significantly between groups (P < 0.05). Hypertension affected the consistency of rfPWV with hfPWV (heart-finger). The findings suggest that segmented ulPWV is instrumental in providing stiffness corresponding to the physiological structure of the vessel. The superimposition of hypertension and or aging exacerbates peripheral arterial stiffness, as well as alteration in stiffness gradient.
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Hipertensão , Rigidez Vascular , Humanos , Rigidez Vascular/fisiologia , Análise de Onda de Pulso/métodos , Artérias , Extremidade SuperiorRESUMO
Major challenges when ensiling sugarcane tops include fermentation that results in high quantities of alcohol and decrease in nutrient digestibility due to the accumulation of fiber components. Increased efforts to apply bacteria-enzyme inoculants in silage have the potential to improve nutrient digestibility. This study aimed to evaluate the effects of ensiling sugarcane tops with bacteria-enzyme inoculants or mixed bacterial inoculants on growth performance, nutrient digestibility, and rumen microbiome in beef cattle. Chopped sugarcane tops were ensiled in plastic bags for 60 d after application of 1) no inoculant (control check, CK); 2) bacteria-enzyme inoculants containing Pediococcus acidilactici, Saccharomyces cerevisiae, cellulase, and xylanase (T1, viable colony-forming units of each bacterial strain ≥108 CFU/g; enzyme activity of each enzyme ≥200 U/g); or 3) mixed bacterial inoculants containing Lactobacillus plantarum, Bacillus subtilis, and Aspergillus oryzae (T2, viable colony-forming units of each bacterial strain ≥107 CFU/g). Silages were fed to eighteen Holstein bull calves (nâ =â 6/treatment) weighing 163.83â ±â 7.13 kg to determine intake in a 49-d experimental period. The results showed that beef cattle-fed T1 silage or T2 silage had a significantly higher (Pâ <â 0.05) average daily gain than those fed CK silage, but the difference in dry matter intake was not significant (Pâ >â 0.05). The apparent digestibility of crude protein (CP) and acid detergent fiber (ADF) were higher (Pâ <â 0.05) for beef cattle-fed T1 silage or T2 silage than for those fed CK silage. The rumen bacterial community of beef cattle-fed T1 silage or T2 silage had a tendency to increase (Pâ >â 0.05) abundance of Firmicutes and Rikenellaceae_RC9_gut_group than those fed CK silage. Rumen fungal communities of beef cattle-fed T1 or T2 silage had a tendency to increase (Pâ >â 0.05) abundance of Mortierellomycota and of Mortierella than those fed CK silage. Spearman's rank correlation coefficient showed that the apparent digestibility of ADF for beef cattle was positively correlated with unclassified_p_Ascomycota of the fungal genera (Pâ <â 0.05). Neocalimastigomycota of the fungal phyla was strongly positively correlated with the apparent digestibility of neutral detergent fiber (NDF) (Pâ <â 0.05). Ruminococcus was positively correlated with the apparent digestibility of CP (Pâ <â 0.05). It was concluded that both T1 and T2 improved the growth performance of beef cattle by improving the ruminal apparent digestibility of CP and ADF, and had no significant impact on major rumen microbial communities in beef cattle.
Major challenges when ensiling sugarcane tops include fermentation that results in high quantities of alcohol and decrease in nutrient digestibility due to the accumulation of fiber components. Increased efforts to apply bacteria-enzyme inoculants in silage have the potential to improve nutrient digestibility. This study aimed to evaluate the effects of ensiling sugarcane tops with bacteria-enzyme inoculants or mixed bacterial inoculants on the growth performance, nutrient digestibility, and rumen microbiome in beef cattle. Chopped sugarcane tops were ensiled in plastic bags for 60 d after application of 1) no inoculant (control check, CK); 2) bacteria-enzyme inoculants (Pediococcus acidilactici, Saccharomyces cerevisiae, cellulase, and xylanase), termed treatment T1; or 3) mixed bacterial inoculants (Lactobacillus plantarum, Bacillus subtilis, and Aspergillus oryzae), termed treatment T2. Silages were fed to 18 Holstein bull calves (nâ =â 6/treatment) weighing 163.83â ±â 7.13 kg to determine intake in a 49-d experimental period. It was concluded that both T1 and T2 improved the growth performance of beef cattle by improving the ruminal apparent digestibility of crude protein and acid detergent fiber, and had no significant impact on major rumen microbial communities in beef cattle.
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Inoculantes Agrícolas , Microbiota , Saccharum , Bovinos , Animais , Masculino , Rúmen/metabolismo , Detergentes/metabolismo , Detergentes/farmacologia , Silagem/análise , Nutrientes , Bactérias/metabolismo , Saccharomyces cerevisiae , Fermentação , Digestão , Zea mays/metabolismoRESUMO
The diamondback moth (Plutella xylostella) is one of the most destructive lepidopteran pests of cruciferous vegetables. However, DBM has developed resistance to current chemical and biological insecticides used for its control, indicating the necessity for finding new insecticides against it. Bio-insecticides derived from plant extracts are eco-friendly alternatives to synthetic pesticides. The aims of this study were to evaluate the insecticidal activity of Consolida ajacis seed extracts against DBM, the underlying mechanism of the control effect of promising extracts, and the identification of the main insecticidal compounds of these extracts. The results showed that ethyl acetate extract of C. ajacis seed exhibited strong contact toxicity (LC50: 5.05 mg/mL), ingestion toxicity, antifeedant, and oviposition deterrent activities against DBM, among the extracts evaluated. At 72 h, glutathiase, acetylcholinesterase, carboxylesterase, peroxidase, and superoxide dismutase activities were inhibited, but catalase activity was activated. The main compound identified from the extract was ethyl linoleate, which had the most significant insecticidal activity on the diamondback moths. This study's findings provide a better understanding of the insecticidal activity of ethyl acetate extract obtained from C. ajacis and its main component (ethyl linoleate). This will help in the development of new insecticides to control DBM.
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Inseticidas , Mariposas , Ranunculaceae , Feminino , Animais , Inseticidas/farmacologia , AcetilcolinesteraseRESUMO
Exposure to ionizing radiation leads to oxidative damages in living cells. NADPH provides the indispensable reducing power to regenerate the reduced glutathione to maintain cellular redox equilibria. In mammalian cells, pentose phosphate pathway (PPP) is the major route to produce NADPH by using glycolytic intermediates, and the rate-limiting step of PPP is controlled by glucose-6-phosphate dehydrogenase (G6PD). Nevertheless, whether G6PD is timely co-opted under ionizing radiation to cope with oxidative stress remains elusive. Here we show that cellular G6PD activity is induced 30 min after ionizing radiation, while its protein expression is mostly unchanged. Mechanistically, casein kinase 2 (CK2) phosphorylates G6PD T145 under ionizing radiation, which consolidates the enzymatic activity of G6PD by facilitating G6PD binding with its substrate NADP+. Further, CK2-dependent G6PD T145 phosphorylation promotes NADPH production, decreases ROS level and supports cell proliferation under ionizing radiation. Our findings report a new anti-oxidative signaling route under ionizing radiation, by which CK2-mediated rapid activation of G6PD orchestrates NADPH synthesis to maintain redox homeostasis, thereby highlighting its potential value in the early treatment of ionizing radiation-induced injuries.
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Caseína Quinase II , Glucosefosfato Desidrogenase , Animais , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , NADP/metabolismo , Fosforilação , Oxirredução , Radiação Ionizante , Homeostase , Via de Pentose Fosfato , Mamíferos/metabolismoRESUMO
Microplastics originate from the physical, chemical, or biological degradation of plastics in the environment. Once ingested by organisms at the bottom of the food chain, microplastics are passed on to organisms at higher trophic levels, posing a threat to human health. The distribution of microplastics and the metabolic pathways involved in their microbial degradation in surface sediments of drinking water reservoirs are still poorly understood. This study analyzed the occurrence patterns of microplastics and microbial community structure associated with microplastic biodegradation in surface sediments from a deep reservoir at various hydrostatic pressures. Based on the results of Fourier-transform and laser direct infrared spectroscopy, elevating the pressure resulted in altered sizes and shapes of microplastics in sediment samples with the presence of microorganisms. The influence of hydrostatic pressure on small-sized microplastics (20-500 µm) was pronounced. For instance, high pressure accelerated the breakdown of fibers, pellets, and fragments into smaller-sized microplastics. In particular, the mean size of polyethylene terephthalate microplastics decreased from 425.78 µm at atmospheric pressure to 366.62 µm at 0.7 Mpa. Metagenomic analysis revealed an increase in the relative abundances of plastic-degrading genera, such as Rhodococcus, Flavobacterium, and Aspergillus, in response to elevated pressures. Eight functional genes for biodegradation of polystyrene, polyethylene, and polyethylene terephthalate microplastics were annotated, including paaK, ladA, tphA3. Of these, tphA3 gene abundance was negatively influenced by hydrostatic pressure, providing direct evidence for the pathway by which microbial metabolism of polyethylene terephthalate led to decreased microplastic size under high pressure conditions. This study presents novel insights into hydrostatic pressure-driven microbial community structure, functional gene abundance, and key metabolic pathways associated with biodegradation of microplastics in reservoir sediments.
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Microplásticos , Poluentes Químicos da Água , Humanos , Plásticos/análise , Pressão Hidrostática , Polietilenotereftalatos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Sedimentos Geológicos/químicaRESUMO
The anti-EGFR antibody cetuximab is used as a first-line targeted therapeutic drug in colorectal cancer. It has previously been reported that the efficacy of the EGFR antibody cetuximab is limited by the emergence of acquired drug resistance. In our previous study the transmissibility effect of exosomes from drug resistant tumor cells to sensitive tumor cells was identified. It can therefore be hypothesized that drug resistant cells might affect neighboring and distant cells via regulation of exosome composition and behavior. However, the mechanism of exosomes in KRAS-wild-type colorectal cancer (CRC) remains unknown. In the present study, functional analysis of overall survival post-diagnosis in patients with KRAS wild-type and those with mutant CRC was performed using human CRC specimens. Furthermore, it was demonstrated that multidrug resistance (MDR) cancer cell-derived exosomes were potentially a key factor, which promoted cetuximab-resistance in CRC cells and reduced the inhibitory effect of cetuximab in CRC xenograft models. The Cell Counting Kit-8 and colony formation assays were performed to assess the effects of exosomes derived from CRC/MDR cells on cetuximab resistance. Sphere formation assay results demonstrated that exosomes derived from CRC/MDR cells altered the self-renewal and multipotential ability of stem-cell-associated markers and facilitated resistance to cetuximab in cetuximab-sensitive cells. Furthermore, exosomes derived from CRC/MDR cells decreased sensitivity to cetuximab via the activation of PI3K/AKT signaling, which promoted Sox2 and programmed death-ligand 1 (PD-L1) mRNA and protein expression according to reverse transcription-quantitative PCR, western blotting and immunohistochemistry analyses, as well as apoptosis resistance both in vitro and in vivo according to a TUNEL assay. In conclusion, the results of the present study demonstrated that exosomes derived from CRC/MDR cells may promote cetuximab resistance in KRAS wild-type cells via activation of the PI3K/AKT signaling pathway-mediated expression of Sox2 and PD-L1, which will be useful for investigating a potential clinical target in predicting cetuximab resistance.
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The lepidopteran crop pest Plutella xylostella causes severe constraints on Brassica cultivation. Here, we report a novel role for RPX1 (resistance to P. xylostella) in resistance to this pest in Arabidopsis thaliana. The rpx1-1 mutant repels P. xylostella larvae, and feeding on the rpx1-1 mutant severely damages the peritrophic matrix structure in the midgut of the larvae, thereby negatively affecting larval growth and pupation. This resistance results from the accumulation of defence compounds, including the homoterpene (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), due to the upregulation of PENTACYCLIC TRITERPENE SYNTHASE 1 (PEN1), which encodes a key DMNT biosynthetic enzyme. P. xylostella infestation and wounding induce RPX1 protein degradation, which may confer a rapid response to insect infestation. RPX1 inactivation and PEN1 overexpression are not associated with negative trade-offs for plant growth but have much higher seed production than the wild-type in the presence of P. xylostella infestation. This study offers a new strategy for plant molecular breeding against P. xylostella.
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Arabidopsis , Brassica , Mariposas , Triterpenos , Animais , Arabidopsis/genética , Mariposas/fisiologia , Larva/fisiologia , Triterpenos/metabolismo , Brassica/metabolismoRESUMO
The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is one of the most highly polyphagous invasive pests causing serious damage to maize crops in China. However, little is known about the gut immune responses to the environment, particularly along the migration routes in Jianghuai, China, throughout the autumn and winter. In this study, high-throughput sequencing and real-time quantitative PCR (RT-qPCR) were employed to examine the variations in immune genes and gut microbiome communities between captive and wild fall armyworm populations. Results showed that the diversity and community of the gut's microbes were higher in wild populations, and the average weighted UniFrac distance between bacterial taxa varied. A wide variety of immune genes were more abundant in the wild populations than in others. Results indicated that diets and different survival conditions impacted the gut microbiota and immune system of S. frugiperda, which was crucial for environmental adaptation. These differences in gut microbiota and immune responses between wild and captive Fall armyworms are critical for comprehending the symbiotic relationship between microbes, immune genes, and hosts. They also highlight the need for increased focus on developing more effective and environmentally friendly pest control methods.
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Microbioma Gastrointestinal , Animais , China , Sistema Imunitário , Larva , Spodoptera/genética , Zea mays/genéticaRESUMO
BACKGROUND: Chronological age (CA) has been adopted as an important independent risk factor in cardiovascular risk assessment. However, different individuals with same CA may have distinct actual vascular aging due to various lifestyles. Therefore, it is difficult to fully describe the difference of actual vascular aging by CA. OBJECTIVE: This study proposes a new index vascular age (VA) to avoid the limitations of CA. METHOD: In this work, VA refers to the sum of CA and lifestyle impact (AgeLI). Firstly, we take the pulse signal features and CA as independent variables and dependent variable respectively, and adopt cross validation to train Support Vector Regression model. Then we acquire the predicted chronological age (PA) of all subjects with the model. Secondly, we obtain the function model between CA and PA, and calculate the expectation of PA (ePA) for each subject. Simultaneously, we take the difference between PA and ePA as the estimated value of AgeLI to further calculate VA. Finally, in order to evaluate the effectiveness of VA, we compare the correlations between CA, PA, VA and 8 objective indices such as augmentation index, pulse transit time, diastolic augmentation index, etc. RESULTS: In general, VA and PA are closer to these 8 objective indices than CA. Moreover, VA is also superior to PA in vascular aging evaluation. CONCLUSION: The VA suggested in this study emphasizes the difference of vascular aging in same CA group, which can better reflect the actual vascular aging than CA and PA.
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Envelhecimento , Análise de Onda de Pulso , Humanos , Fatores de Risco , Medição de RiscoRESUMO
The fall armyworm (FAW), Spodoptera frugiperda, is a highly polyphagous lepidopteran pest, with its growth and adaptation affected by different host plants. However, little is known about the effects of host plants on ovarian development in this species. Thus, we evaluated the effects of feeding on corn (Zea mays L.) and goosegrass (Eleusine indica), on the ovarian development of S. frugiperda. Using various stages of S. frugiperda, we also evaluated the larval and pupal weights, number of eggs, and differentiation of ovarioles over time. Results showed that females fed on goosegrass had shorter ovarioles and laid less eggs than those fed on corn. Transcriptome analysis identified 3,213 genes involved in ovarian development in the fall armyworm. Of these, 881 genes were differentially expressed when fed on corn and goosegrass. The analysis also indicated that the hormone biosynthetic pathways may be involved in the reproductive system. In relation to the reproductive function, nine juvenile hormone (JH) biosynthetic genes, four 20-hydroxyecdysone (20E) biosynthetic genes, and four ovary-relevant functional genes were identified. The time course of the expression profiles of these hormone- and ovary development-related genes was measured by quantitative real-time PCR (qRT-PCR). In total, six of them showed a decreasing trend in the ovary of the FAW fed on goosegrass, while two genes showed an increasing trend. Our results showed that significant changes in the reproductive activity/ovary development in the FAW occurred in response to different diets. These results serve as bases for evaluating how optimal host plants and feeding preference affect ovarian development in the FAW.
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Radiation-induced oral mucositis is the most common complication for patients who receive head/neck radiotherapy. Nicotinamide adenine dinucleotide (NAD+) is vital for DNA damage repair under ionizing radiation, through functioning as either the substrate for protein poly(ADP-ribosyl)ation at DNA break sites or the cofactor for multiple DNA repair-related enzymes, which therefore can result in a significant consumption of cellular NAD+ during DNA repair. Mammalian cells produce NAD+ mainly by recycling nicotinamide via the salvage pathway, in which the rate-limiting step is governed by nicotinamide phosphoribosyltransferase (NAMPT). However, whether NAMPT is co-opted under ionizing radiation to timely fine-tune NAD+ homeostasis remains elusive. Here we show that ionizing radiation evokes NAMPT activation within 30 min without apparent changes in its protein expression. AMPK rapidly phosphorylates NAMPT at S314 under ionizing radiation, which reinforces the enzymatic activity of NAMPT by increasing NAMPT binding with its substrate phosphoribosyl pyrophosphate (PRPP). AMPK-mediated NAMPT S314 phosphorylation substantially restores NAD+ level in the irradiated cells and facilitates DNA repair and cell viability. Our findings demonstrate a new post-translational modification-based signalling route, by which cells can rapidly orchestrate NAD+ metabolism to support DNA repair, thereby highlighting NAMPT as a potential target for the prevention of ionizing radiation-induced injuries.
Assuntos
Proteínas Quinases Ativadas por AMP , NAD , Nicotinamida Fosforribosiltransferase , Radiação Ionizante , Proteínas Quinases Ativadas por AMP/metabolismo , Citocinas/metabolismo , Homeostase , Humanos , NAD/metabolismo , Niacinamida , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Fosforribosil PirofosfatoRESUMO
Background: Recent studies have demonstrated the contribution of non-coding RNAs (ncRNAs) to neuropathic pain. However, the expression profile of ncRNAs in the trigeminal ganglion (TG) and their functional mechanism underlying trigeminal neuropathic pain are still unclear. Methods: In the present study, the trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve (CCI-ION) was used to study the expression profile and potential regulatory mechanism of miRNAs, lncRNAs, circRNAs, and mRNAs in the TG by RNA-sequencing (RNA-seq) and bioinformatics analysis. CCI-ION mice suffered from mechanical allodynia from 3 days to 28 days after surgery. Results: The RNA-seq results discovered 67 miRNAs, 216 lncRNAs, 14 circRNAs, 595 mRNAs, and 421 genes were differentially expressed (DE) in the TG of CCI-ION mice 7 days after surgery. And 39 DEGs were known pain genes. Besides, 5 and 35 pain-related DE mRNAs could be targeted by 6 DE miRNAs and 107 DE lncRNAs, respectively. And 23 pain-related DEGs had protein-protein interactions (PPI) with each other. GO analysis indicated membrane-related cell components and binding-related molecular functions were significantly enriched. KEGG analysis showed that nociception-related signaling pathways were significantly enriched for DE ncRNAs and DEGs. Finally, the competing endogenous RNA (ceRNA) regulatory network of DE lncRNA/DE circRNA-DE miRNA-DE mRNA existed in the TG of mice with trigeminal neuropathic pain. Conclusion: Our findings demonstrate ncRNAs are involved in the development of trigeminal neuropathic pain, possibly through the ceRNA mechanism, which brings a new bright into the study of trigeminal neuropathic pain and the development of novel treatments targeting ncRNAs.