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1.
Acta Pharmacol Sin ; 45(2): 378-390, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37798352

RESUMO

Reinforced cellular responses to endoplasmic reticulum (ER) stress are caused by a variety of pathological conditions including cancers. Human rhomboid family-1 protein (RHBDF1), a multiple transmembrane protein located mainly on the ER, has been shown to promote cancer development, while the binding immunoglobulin protein (BiP) is a key regulator of cellular unfolded protein response (UPR) for the maintenance of ER protein homeostasis. In this study, we investigated the role of RHBDF1 in maintaining ER protein homeostasis in breast cancer cells. We showed that deleting or silencing RHBDF1 in breast cancer cell lines MCF-7 and MDA-MB-231 caused marked aggregation of unfolded proteins in proximity to the ER. We demonstrated that RHBDF1 directly interacted with BiP, and this interaction had a stabilizing effect on the BiP protein. Based on the primary structural motifs of RHBDF1 involved in BiP binding, we found a pentapeptide (PE5) targeted BiP and inhibited BiP ATPase activity. SPR assay revealed a binding affinity of PE5 toward BiP (Kd = 57.7 µM). PE5 (50, 100, 200 µM) dose-dependently promoted ER protein aggregation and ER stress-mediated cell apoptosis in MCF-7 and MDA-MB-231 cells. In mouse 4T1 breast cancer xenograft model, injection of PE5 (10 mg/kg, s.c., every 2 days for 2 weeks) significantly inhibited the tumor growth with markedly increased ER stress and apoptosis-related proteins in tumor tissues. Our results suggest that the ability of RHBDF1 to maintain BiP protein stability is critical to ER protein homeostasis in breast cancer cells, and that the pentapeptide PE5 may serve as a scaffold for the development of a new class of anti-BiP inhibitors.


Assuntos
Neoplasias da Mama , Proteínas de Transporte , Humanos , Animais , Camundongos , Feminino , Proteínas de Transporte/metabolismo , Neoplasias da Mama/tratamento farmacológico , Estresse do Retículo Endoplasmático , Apoptose , Resposta a Proteínas não Dobradas , Proteínas Reguladoras de Apoptose/metabolismo , Imunoglobulinas/metabolismo , Proteínas de Membrana/metabolismo
2.
Pharmacol Res ; 198: 106995, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37979663

RESUMO

Melanoma is a dangerous form of skin cancer, making it important to investigate new mechanisms and approaches to enhance the effectiveness of treatment. Here, we establish a positive correlation between the human rhomboid family-1 (RHBDF1) protein and melanoma malignancy. We demonstrate that the melanoma RHBDF1 decrease dramatically inhibits tumor growth and the development of lung metastases, which may be related to the impaired glycolysis. We show that RHBDF1 function is essential to the maintenance of high levels of glycolytic enzymes, especially glucose-6-phosphate isomerase (GPI). Additionally, we discover that the E3 ubiquitin ligase tripartite motif-containing 32 (TRIM32) mediates the K27/K63-linked ubiquitination of GPI and the ensuing lysosomal degradation process. We prove that the multi-transmembrane domain of RHBDF1 is in competition with GPI, preventing the latter from interacting with NCL1-HT2A-LIN41 (NHL) domain of TRIM32. We also note that the mouse RHBDF1's R747 and Y799 are crucial for competitive binding and GPI protection. Artificially silencing the Rhbdf1 gene in a mouse melanoma model results in declined lactic acid levels, elevated cytotoxic lymphocyte infiltration, and improved tumor responsiveness to immunotherapy. These results provide credence to the hypothesis that RHBDF1 plays a significant role in melanoma regulation and suggest that blocking RHBDF1 may be an efficient technique for reestablishing the tumor immune microenvironment (TIME) in melanoma and halting its progression.


Assuntos
Glucose-6-Fosfato Isomerase , Melanoma , Humanos , Animais , Camundongos , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/metabolismo , Proteínas de Membrana/metabolismo , Ubiquitinação , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Melanoma/genética , Melanoma/terapia , Imunoterapia , Microambiente Tumoral , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Fatores de Transcrição/metabolismo
3.
J Clin Nurs ; 32(21-22): 7677-7690, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37727891

RESUMO

BACKGROUND: Current guidelines stress the importance of exercise, especially multicomponent exercise to older adults with chronic conditions. AIM: To critically synthesise evidence that evaluates the effects of multicomponent exercise on quality of life, depression and anxiety after stroke. DESIGN: Systematic review and meta-analysis followed the PRISMA 2020 statement. METHODS: A systematic search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL and PsycINFO from inception to 12 June 2023 was performed. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). Meta-analyses were conducted using Review Manager 5.4 and narrative syntheses were adopted whenever meta-analysis was inappropriate. The overall certainty of the evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 15,351 records identified, nine were eligible and data were available for seven randomised controlled trials, three of which were identified as having a high risk of bias, one as low risk, and five as having some concerns. Subgroup pooled analyses indicated that multicomponent exercise engaged in longer exercise sessions (>60 min) was effective in improving quality of life immediately post-intervention and through 3-6 months post-intervention. However, multicomponent exercise did not significantly affect depression and anxiety. CONCLUSIONS: Multicomponent exercise with longer duration of exercise sessions has promising effects on both short- to medium-term quality of life among stroke survivors. PATIENT OR PUBLIC CONTRIBUTION: This does not apply to our work as it is a review paper. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers could consider encouraging the patients to participate in multicomponent exercise sessions for more than 60 min. It is important to note that stroke survivors should be supervised by trained personnel at the beginning of the training. REGISTRATION: The protocol was registered on PROSPERO.


Assuntos
Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Idoso , Depressão , Ansiedade , Sobreviventes
4.
Support Care Cancer ; 30(6): 5167-5174, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35246728

RESUMO

OBJECTIVE: To examine the dyadic effects of rumination and self-disclosure on posttraumatic growth among newly diagnosed gynecological cancer couples. METHODS: This cross-sectional study recruited 400 newly diagnosed gynecological cancer couples from a tertiary general hospital from July to December 2020. Questionnaires were administered to collect information on demographic and cancer-related characteristics, rumination, self-disclosure, and posttraumatic growth. The actor-partner interdependence model was used to explore the dyadic effects of rumination and self-disclosure on posttraumatic growth. RESULTS: Gynecological cancer survivors reported more posttraumatic growth than their spouses. The patients' deliberate rumination and self-disclosure and spouses' self-disclosure had actor and partner effects on their own and their spouses' posttraumatic growth. Besides, the patients' intrusive rumination and spouses' deliberate rumination had actor effects on their own posttraumatic growth. CONCLUSIONS: Spouses' posttraumatic growth was influenced by their own and their wives' deliberate rumination and self-disclosure, while survivors' posttraumatic growth was affected by their own deliberate rumination, intrusive rumination, self-disclosure, and their spouses' self-disclosure. Promoting deliberate rumination and self-disclosure could facilitate the couples' posttraumatic growth. Besides, reducing intrusive rumination may be useful for the survivors and indirectly contribute to spouses' posttraumatic growth. This study indicates that couple-centered interventions may be crucial and more effective in facilitating posttraumatic growth among newly diagnosed gynecological cancer couples.


Assuntos
Sobreviventes de Câncer , Neoplasias , Crescimento Psicológico Pós-Traumático , Estudos Transversais , Revelação , Humanos , Cônjuges
5.
Cancer Cell Int ; 21(1): 590, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736454

RESUMO

BACKGROUND: The rhomboids are a family of multi-transmembrane proteins, many of which have been implicated in facilitating tumor progression. Little is yet known, however, about rhomboid-associated biomarkers in cancers. An analysis of such biomarkers could yield important insights into the role of the rhomboids in cancer pathology. METHODS: In this study, we carried out the univariate Cox regression analysis and compared gene expression patterns of several rhomboid genes in 30 types of cancers by using The Cancer Genome Atlas (TCGA) database and the methods delineated in Gene Expression Profiling Interactive Analysis (GEPIA). We then used datasets GSE47032, GSE126964, GSE68417 and 75 paired pathological specimens to verify the influences of the rhomboid genes in cancer progression. Moreover, we carried out Weighted Gene Correlation Network Analysis (WGCNA) to investigate gene-related functions and we exploited potential correlations between rhomboid genes expression and immune cell infiltration in cancer tissues. Furthermore, we constructed gene-knockdown cancer cell lines to investigate rhomboid gene functions. RESULTS: We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels. Silencing of the RHBDF2 gene in KIRC cell lines leads to significantly diminished cell proliferation and migration; this is in good agreement with the identification of an enhanced presence of a number of cell growth and migration promoting signaling molecules in KIRC tumors. We found that, although high level of RHBDF2 correlated with increased infiltration of lymphocytes in cancer tissues, artificially overexpressed RHBDF2 led to an inhibition of the activity of the infiltrated immune cells through sustaining PD-L1 protein level. Furthermore, we show that RHBDF2 related cell migration and PD-L1 regulation were potentially mediated by EGFR signaling pathway. CONCLUSIONS: RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression and may serve as a critical prognostic biomarker for the disease.

6.
J Org Chem ; 84(4): 2200-2208, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30688072

RESUMO

A Pd-catalyzed ring-opening reaction of 2 H-azirines with carboxylic acids was developed. This reaction undergoes nucleophilic addition between 2,3-diaryl-2 H-azirines and carboxylic acids followed by C-N single-bond cleavage and a subsequent thermal rearrangement. This method enables the rapid construction of valuable α-amido ketone derivatives with high atomic efficiency and superb functional group tolerance.

7.
Pestic Biochem Physiol ; 154: 32-38, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30765054

RESUMO

Cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), is a polyphagous lepidopteran pest distributed worldwide with a broad spectrum of host plants. However, the mechanism of H. armigera adaptation to various insecticides and defensive allelochemicals in its host plants is not fully understood. Therefore, this study examined the influence of consumption of plant allelochemicals on larval tolerance to methomyl and chlorpyrifos insecticides in H. armigera and its possible mechanism. Twelve plant allelochemicals were screened to evaluate their effects on larval sensitivity to methomyl. Of which flavone, coumarin, DIMBOA (2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one) and visnagin significantly reduced larval sensitivity to methomyl. Application of cytochrome P450 inhibitor piperonyl butoxide (PBO) significantly increased the mortality of methomyl-treated larvae. In contrast, PBO addition significantly decreased the mortality of chlorpyrifos-treated larvae. Moreover, allelochemical consumption enhanced the activities of glutathione S-transferase, carboxylesterase, cytochrome P450 and acetylcholinesterase in the midgut and fat body. The qRT-PCR analysis confirms that P450 genes, CYP6B2, CYP6B6 and CYP6B7 were induced by the four allelochemicals in the midguts and the fat bodies. In conclusion, the generalist H. armigera can take benefit of plant allelochemicals from its host plants to elaborate its defense against insecticides.


Assuntos
Resistência a Inseticidas/efeitos dos fármacos , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Mariposas/efeitos dos fármacos , Feromônios/farmacologia , Compostos Fitoquímicos/farmacologia , Animais , Carboxilesterase/genética , Clorpirifos/toxicidade , Sistema Enzimático do Citocromo P-450/genética , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/genética , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Larva/genética , Masculino , Metomil/toxicidade , Mariposas/genética
8.
Pestic Biochem Physiol ; 157: 211-218, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153471

RESUMO

Herbivore attack leads to enhanced production of defensive compounds to mount anti-herbivore defense in plants via activation of the jasmonate signaling pathway. On the other hand, some herbivores can eavesdrop on plants defense signaling and up-regulate their cytochrome P450 genes to increase detoxification of defensive compounds. However, the ecological risk of eavesdropping on plant defense signaling is largely unknown. In this study, we examined the induction of cytochrome P450s by methyl jasmonate (MeJA) and its consequence on the toxicity of aflatoxin B1 (AFB1) to Helicoverpa armigra larvae. The results show that MeJA applications either in a diet or volatile exposure enhanced the toxicity of AFB1 to the larvae. RNA sequences analysis revealed that cytochrome P450 CYP6AE19 was highly induced when MeJA was applied with AFB1. In addition, HaGST encoding glutathione-S-transferase that mainly transforms aflatoxin B1 exo-8,9-epoxide to aflatoxin B1 exo-8,9-glutathione was also induced. RNA interference of CYP6AE19 via injecting a double-stranded RNA decreased mortality of larvae exposed to AFB1; while injecting a double-stranded RNA of HaGST increased larval mortality. Furthermore, a protein model was generated and a subsequent docking simulation for AFB1 suggests the bioactivation as a major mechanism of AFB1. This study provides evidence that MeJA increased larval mortality of H. armigera via induction of CYP6AE19 that can bioactivate AFB1.


Assuntos
Acetatos/farmacologia , Aflatoxina B1/metabolismo , Ciclopentanos/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Mariposas/efeitos dos fármacos , Mariposas/metabolismo , Oxilipinas/farmacologia , Animais , Larva/efeitos dos fármacos , Larva/metabolismo , Oxirredução/efeitos dos fármacos
9.
Chem Biodivers ; 16(1): e1800344, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30358064

RESUMO

The actinomycete genus Streptomyces is characterized by producing bioactive secondary metabolites, including antibiotics. In this study, chemical and biological investigations were carried out on Streptomyces strain 4205 isolated from the paddy soil, leading to the identification and characterization of 10 albocycline-type macrolides, among which 4 compounds were new, namely albocyclines A-D (1-4). The structures of 1-10 were identified according to the 1D- and 2D-NMR spectroscopic data. Furthermore, compounds 1-10 were evaluated for antimicrobial activity. Compounds 5-7 displayed antimicrobial activities against Candidaalbicans ATCC 90028 with the same MIC value of 10.0 mg/mL and the IC50 values of 1.5, 1.0, and 1.0 mg/mL, respectively. Thus, the research on Streptomyces sp. is of vital significance for developing new antibiotic agents.


Assuntos
Antibacterianos/farmacologia , Streptomyces/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Bactérias/classificação , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cryptococcus neoformans/efeitos dos fármacos , Meios de Cultura , Fermentação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Concentração Inibidora 50 , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Testes de Sensibilidade Microbiana , Microbiologia do Solo , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
10.
Plant Cell Environ ; 40(5): 779-787, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28042888

RESUMO

Rice ratooning is practiced in many rice-growing countries for achieving increased rice production with limited labour input. Here, we report that attack by insect herbivores, or treatment with a defense signaling compound in parent plants, can prime anti-herbivore defense responses in subsequent ratoon plants. We compared the defense responses of rice ratoons generated from parent plants that had been either infested by Cnaphalocrocis medinalis (rice leaffolder, LF) caterpillars or treated with methyl jasmonate (MeJA) during vegetative growth, with ratoons generated from control parent plants. Ratoon plants generated from parents receiving prior LF infestation or MeJA treatment exhibited higher jasmonic acid (JA) levels, as well as elevated levels of transcripts of defense-related genes associated with JA signaling. In addition, elevated activities of peroxidase, polyphenol oxidase and trypsin protease inhibitor were observed, as well as enhanced resistance towards subsequent LF infestation. Pre-priming of ratoon defense responses was significantly reduced in plants where expression of OsAOS (allene oxide synthase, involved in JA biosynthesis) or OsCOI1 (CORONATINE INSENSITIVE1, involved in JA perception) was inhibited by RNA interference. Our results indicate that herbivore exposure or MeJA treatment in rice parent plants enhances anti-herbivore resistance in subsequently generated ratoons through priming of JA-mediated defenses.


Assuntos
Resistência à Doença , Herbivoria/fisiologia , Oryza/fisiologia , Oryza/parasitologia , Doenças das Plantas/parasitologia , Acetatos/farmacologia , Animais , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Larva/efeitos dos fármacos , Larva/fisiologia , Lepidópteros/fisiologia , Oryza/efeitos dos fármacos , Oryza/genética , Oxilipinas/metabolismo , Oxilipinas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Inibidores de Proteases/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/efeitos dos fármacos
11.
Biomed Environ Sci ; 30(7): 517-525, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28756811

RESUMO

OBJECTIVE: Mycobacterium avium (M. avium) and Mycobacterium intracellulare (M. intracellulare) are the major causative agents of nontuberculous mycobacteria (NTM)-related pulmonary infections. However, little is known about the differences in drug susceptibility profiles between these two species. METHODS: A total of 393 NTM isolates were collected from Shanghai Pulmonary Disease Hospital. Sequencing of partial genes was performed to identify the strains at species level. The minimum inhibitory concentration (MIC) was used to evaluate the drug susceptibility against 20 antimicrobial agents. Variable number of tandem repeat (VNTR) typing was conducted to genotype these two species. RESULTS: A total of 173 (44.0%) M. avium complex (MAC) isolates were identified, including 41 (10.4%) M. avium isolates and 132 (33.6%) M. intracellulare isolates. Clarithromycin and amikacin were the two most effective agents against MAC isolates. The Hunter-Gaston Discriminatory Index (HGDI) values for VNTR typing of M. avium and M. intracellulare isolates were 0.993 and 0.995, respectively. Levofloxacin resistance was more common among the unclustered strains than among the clustered strains of M. intracellulare. CONCLUSION: M. intracellulare was the most common NTM species in China. Clarithromycin and amikacin had high antimicrobial activities against MAC. VNTR typing of MAC isolates revealed a high discriminatory power. Levofloxacin resistance was associated with unclustered strains of M. intracellulare.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Genótipo , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/genética , Infecção por Mycobacterium avium-intracellulare/microbiologia , Humanos , Infecção por Mycobacterium avium-intracellulare/epidemiologia
12.
Biomed Environ Sci ; 30(5): 376-379, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28549494

RESUMO

We performed molecular identification of clinical isolates of Mycobacterium fortuitum (M. fortuitum) and conducted drug susceptibility testing to analyze the in vitro susceptibility of clinical M. fortuitum isolates and potential molecular mechanism conferring resistance to fluoroquinolone and macrolide drugs. The results showed that moxifloxacin had the highest in vitro activity against M. fortuitum, and most M. fortuitum isolates were resistant to clarithromycin and linezolid in China. The loss of genetic mutation in clarithromycin- and amikacin-resistant isolates indicates that some other intrinsic mechanism conferring clarithromycin and amikacin resistance plays an essential role in M. fortuitum infection.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana , Mycobacterium fortuitum/efeitos dos fármacos , China , Testes de Sensibilidade Microbiana
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(1): 178-83, 2015 Jan.
Artigo em Zh | MEDLINE | ID: mdl-25993844

RESUMO

In order to rapidly acquire maize growing information in the field, a non-destructive method of maize chlorophyll content index measurement was conducted based on multi-spectral imaging technique and imaging processing technology. The experiment was conducted at Yangling in Shaanxi province of China and the crop was Zheng-dan 958 planted in about 1 000 m X 600 m experiment field. Firstly, a 2-CCD multi-spectral image monitoring system was available to acquire the canopy images. The system was based on a dichroic prism, allowing precise separation of the visible (Blue (B), Green (G), Red (R): 400-700 nm) and near-infrared (NIR, 760-1 000 nm) band. The multispectral images were output as RGB and NIR images via the system vertically fixed to the ground with vertical distance of 2 m and angular field of 50°. SPAD index of each sample was'measured synchronously to show the chlorophyll content index. Secondly, after the image smoothing using adaptive smooth filtering algorithm, the NIR maize image was selected to segment the maize leaves from background, because there was a big difference showed in gray histogram between plant and soil background. The NIR image segmentation algorithm was conducted following steps of preliminary and accuracy segmentation: (1) The results of OTSU image segmentation method and the variable threshold algorithm were discussed. It was revealed that the latter was better one in corn plant and weed segmentation. As a result, the variable threshold algorithm based on local statistics was selected for the preliminary image segmentation. The expansion and corrosion were used to optimize the segmented image. (2) The region labeling algorithm was used to segment corn plants from soil and weed background with an accuracy of 95. 59 %. And then, the multi-spectral image of maize canopy was accurately segmented in R, G and B band separately. Thirdly, the image parameters were abstracted based on the segmented visible and NIR images. The average gray value of each channel was calculated including red (ARed), green (AGreen), blue (ABlue), and near-infrared (ANIR). Meanwhile, the vegetation indices (NDVI (normalized difference vegetation index), RVI (ratio vegetation index); and NDGI(normalized difference green index)) which are widely used in remote sensing were applied. The chlorophyll index detecting model based on partial least squares regression method (PLSR) was built with detecting R2=0. 5960 and predicting R2= 0. 568 5. It was feasible to diagnose chlorophyll index of maize based on multi-spectral images.


Assuntos
Clorofila/análise , Folhas de Planta/química , Zea mays/química , Algoritmos , Análise dos Mínimos Quadrados , Modelos Teóricos , Análise de Regressão , Solo , Análise Espectral
14.
Se Pu ; 42(2): 120-130, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38374592

RESUMO

Environmental factors, such as environmental pollutants, behaviors, and lifestyles, are the leading causes of chronic noncommunicable diseases. Estimates indicate that approximately 50% of all deaths worldwide can be attributed to environmental factors. The exposome is defined as the totality of human environmental (i.e., all nongenetic) exposures from conception, including general external exposure (e.g., climate, education, and urban environment), specific external exposure (e.g., pollution, physical activity, and diet), and internal exposure (e.g., metabolic factors, oxidative stress, inflammation, and protein modification). As a new paradigm, this concept aims to comprehensively understand the link between human health and environmental factors. Therefore, a comprehensive measurement of the exposome, including accurate and reliable measurements of exposure to the external environment and a wide range of biological responses to the internal environment, is of great significance. The measurement of the general external exposome depends on advances in environmental sensors, personal-sensing technologies, and geographical information systems. The determination of exogenous chemicals to which individuals are exposed and endogenous chemicals that are produced or modified by external stressors relies on improvements in methodology and the development of instrumental approaches, including colorimetric, chromatographic, spectral, and mass-spectrometric methods. This article reviews the research strategies for chemical exposomes and summarizes existing exposome-measurement methods, focusing on mass spectrometry (MS)-based methods. The top-down and bottom-up approaches are commonly used in exposome studies. The bottom-up approach focuses on the identification of chemicals in the external environment (e.g., soil, water, diet, and air), whereas the top-down approach focuses on the evaluation of endogenous chemicals and biological processes in biological samples (e.g., blood, urine, and serum). Low- and high-resolution MS (LRMS and HRMS, respectively) have become the most popular methods for the direct measurement of exogenous and endogenous chemicals owing to their superior sensitivity, specificity, and dynamic range. LRMS has been widely applied in the targeted analysis of expected chemicals, whereas HRMS is a promising technique for the suspect and unknown screening of unexpected chemicals. The development of MS-based multiomics, including proteomics, metabolomics, epigenomics, and spatial omics, provides new opportunities to understand the effects of environmental exposure on human health. Metabolomics involves the sum of all low-molecular-weight metabolites in a living system. Nontargeted metabolomics can measure both endogenous and exogenous chemicals, which would directly link exposure to biological effects, internal dose, and disease pathobiology, whereas proteomics could play an important role in predicting potential adverse health outcomes and uncovering molecular mechanisms. MS imaging (MSI) is an emerging technique that provides unlabeled in-depth measurements of endogenous and exogenous molecules directly from tissue and cell sections without changing their spatial information. MSI-based spatial omics, which has been widely applied in biomarker discovery for clinical diagnosis, as well as drug and pollutant monitoring, is expected to become an effective method for exposome measurement. Integrating these response measurements from metabolomics, proteomics, spatial omics, and epigenomics will enable the generation of new hypotheses to discover the etiology of diseases caused by chemical exposure. Finally, we highlight the major challenges in achieving chemical exposome measurements.


Assuntos
Poluentes Ambientais , Expossoma , Humanos , Multiômica , Exposição Ambiental/efeitos adversos , Espectrometria de Massas , Poluentes Ambientais/toxicidade
15.
Int J Gen Med ; 17: 2299-2309, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799198

RESUMO

Objective: This study aimed to explore specific biochemical indicators and construct a risk prediction model for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: This study included 234 T2D patients, of whom 166 had DKD, at the First Hospital of Jilin University from January 2021 to July 2022. Clinical characteristics, such as age, gender, and typical hematological parameters, were collected and used for modeling. Five machine learning algorithms [Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF)] were used to identify critical clinical and pathological features and to build a risk prediction model for DKD. Additionally, clinical data from 70 patients (nT2D = 20, nDKD = 50) were collected for external validation from the Third Hospital of Jilin University. Results: The RF algorithm demonstrated the best performance in predicting progression to DKD, identifying five major indicators: estimated glomerular filtration rate (eGFR), glycated albumin (GA), Uric acid, HbA1c, and Zinc (Zn). The prediction model showed sufficient predictive accuracy with area under the curve (AUC) values of 0.960 (95% CI: 0.936-0.984) and 0.9326 (95% CI: 0.8747-0.9885) in the internal validation set and external validation set, respectively. The diagnostic efficacy of the RF model (AUC = 0.960) was significantly higher than each of the five features screened with the highest feature importance in the RF model. Conclusion: The online DKD risk prediction model constructed using the RF algorithm was selected based on its strong performance in the internal validation.

16.
J Chem Ecol ; 39(7): 1036-44, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23797931

RESUMO

Mycorrhizas play a vital role in soil fertility, plant nutrition, and resistance to environmental stresses. However, mycorrhizal effects on plant resistance to herbivorous insects and the related mechanisms are poorly understood. This study evaluated effects of root colonization of tomato (Solanum lycopersicum Mill.) by arbuscular mycorrhizal fungi (AMF) Glomus mosseae on plant defense responses against a chewing caterpillar Helicoverpa arimigera. Mycorrhizal inoculation negatively affected larval performance. Real time RT-PCR analyses showed that mycorrhizal inoculation itself did not induce transcripts of most genes tested. However, insect feeding on AMF pre-inoculated plants resulted in much stronger defense response induction of four defense-related genes LOXD, AOC, PI-I, and PI-II in the leaves of tomato plants relative to non-inoculated plants. Four tomato genotypes: a wild-type (WT) plant, a jasmonic acid (JA) biosynthesis mutant (spr2), a JA-signaling perception mutant (jai1), and a JA-overexpressing 35S::PS plant were used to determine the role of the JA pathway in AMF-primed defense. Insect feeding on mycorrhizal 35S::PS plants led to higher induction of defense-related genes relative to WT plants. However, insect feeding on mycorrhizal spr2 and jai1 mutant plants did not induce transcripts of these genes. Bioassays showed that mycorrhizal inoculation on spr2 and jai1 mutants did not change plant resistance against H. arimigera. These results indicates that mycorrhizal colonization could prime systemic defense responses in tomato upon herbivore attack, and that the JA pathway is involved in defense priming by AMF.


Assuntos
Herbivoria , Mariposas , Micorrizas/fisiologia , Imunidade Vegetal , Transdução de Sinais/fisiologia , Solanum lycopersicum/microbiologia , Animais , Ciclopentanos/metabolismo , Genes de Plantas , Larva , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Oxilipinas/metabolismo , Folhas de Planta/metabolismo , Simbiose
17.
Int J Gen Med ; 16: 5921-5934, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106974

RESUMO

Purpose: China lifted its strict zero-Covid approach on December 7, 2022. This study aimed to investigate depression and anxiety symptoms and their associations among Chinese residents after the change in public policy. Methods: A cross-sectional sample of 925 Chinese residents (726 females and 199 males) was recruited using convenience and snowball sampling approach between 16 and 25 December 2022. Participants completed online questionnaires on basic information, depression, anxiety, COVID-19 related perceptions, and protective behaviors change. Results: Mild and moderate-to-severe depression symptoms were reported by 35.6% and 19.1% of participants, respectively. Nearly 40% of participants reported mild anxiety and 18.7% reported moderate-to-severe anxiety. Results from multinomial logistic regression analysis indicated that male gender, younger age, the presence of chronic disease, poorer self-rated mental health status, perceived impact, and worry were risk factors for both depression and anxiety, while higher education and protective behaviors change were protective factors. Besides, living with or caring for children (4-6 years), family members or other housemates currently with influenza-like symptoms, and perceived severity were also risk factors for depression. Conclusion: Our findings provided initial evidence that Chinese residents may face heightened depression and anxiety during the early stage after the policy was released. Furthermore, we identified some vulnerable populations in need of prioritizing mental health assistance and some potentially modifiable factors associated with depression and anxiety, which provides an important guide for developing timely and effective psychological interventions and preparing for future pandemics.

18.
West J Nurs Res ; 44(4): 367-374, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33666119

RESUMO

Self-management is essential for patients who require regular hemodialysis treatment. This study aimed to explore the relationships between social support, sense of coherence (SOC), and self-management in hemodialysis patients and to examine whether SOC plays a mediating role. In a cross-sectional study, 402 hemodialysis patients from four tertiary hospitals were recruited. Data were analyzed using structural equation modeling. Social support, SOC, and self-management were significantly correlated with each other. The proposed model provided a good fit to the data. Social support had a direct effect on self-management and SOC, partially mediated the effect of social support on self-management (ß = 0.248, p = 0.001). Social support and SOC explained 69% of the variance in self-management. Our findings indicate that health care providers can enhance social support with an emphasis on strengthening SOC strategies to better improve self-management in hemodialysis patients.


Assuntos
Autogestão , Senso de Coerência , Estudos Transversais , Humanos , Diálise Renal , Apoio Social , Inquéritos e Questionários
19.
Ying Yong Sheng Tai Xue Bao ; 33(3): 844-854, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35524540

RESUMO

Plants, grown in the immobile soils, have evolved various strategies in response to environmental stresses, including the "stress memory" and "defense priming" mechanisms. The environmental stresses cannot immediately change the DNA base sequence in plants in the short-term. Therefore, epigenetic inheritance is a key mechanism for stress memory and defense priming. In particular, histone modification is considered to be the most important mechanism, which offers the possibility of stress memory. We summarized research advances in plant histone modifications involved in stress memory and defense priming under biotic and abiotic stresses, and proposed pro-blems in the field and the focus and directions in the future research. In-depth understanding of the relationship between histone modification and environmental stresses would facilitate the quick adaptation of plants to harsh environments, and provide theoretical and technical guidance for plant phenotype shaping, organ regeneration, and crop genetic improvement.


Assuntos
Regulação da Expressão Gênica de Plantas , Código das Histonas , Epigênese Genética , Histonas/genética , Plantas/genética , Estresse Fisiológico
20.
Mycorrhiza ; 21(8): 721-731, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21484338

RESUMO

Arbuscular mycorrhizas are the most important symbioses in terrestrial ecosystems and they enhance the plant defense against numerous soil-borne pathogenic fungi and nematodes. Two corn (Zea mays) varieties, Gaoyou-115 that is susceptible to sheath blight disease caused by Rhizoctonia solani and Yuenong-9 that is resistant, were used for mycorrhizal inoculation in this study. Pre-inoculation of susceptible Gaoyou-115 with arbuscular mycorrhizal fungus (AMF) Glomus mosseae significantly reduced the disease incidence and disease severity of sheath blight of corn. HPLC analysis showed that AMF inoculation led to significant increase in 2,4-dihydroxy-7-methoxy-2 H-1,4-benzoxazin-3(4 H)-one (DIMBOA) accumulation in the roots of both corn varieties and in leaves of resistant Yuenong-9. R. solani inoculation alone did not result in accumulation of DIMBOA in both roots and leaves of the two corn varieties. Our previous study showed that DIMBOA strongly inhibited mycelial growth of R. solani in vitro. Real-time PCR analysis showed that mycorrhizal inoculation itself did not affect the transcripts of most genes tested. However, pre-inoculation with G. mosseae induced strong responses of three defense-related genes PR2a, PAL, and AOS, as well as BX9, one of the key genes in DIMBOA biosynthesis pathway, in the leaves of corn plants of both Yuenong-9 and Gaoyou-115 after the pathogen attack. Induction of defense responses in pre-inoculated plants was much higher and quicker than that in non-inoculated plants upon R. solani infection. These results indicate that induction of accumulation of DIMBOA, an important phytoalexin in corn, and systemic defense responses by AMF, plays a vital role in enhanced disease resistance of mycorrhizal plants of corn against sheath blight. This study also suggests that priming is an important mechanism in mycorrhiza-induced resistance.


Assuntos
Benzoxazinas/imunologia , Glomeromycota/crescimento & desenvolvimento , Micorrizas/crescimento & desenvolvimento , Doenças das Plantas/imunologia , Zea mays/imunologia , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Glomeromycota/genética , Glomeromycota/isolamento & purificação , Micorrizas/genética , Micorrizas/isolamento & purificação , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Rhizoctonia/fisiologia , Zea mays/genética , Zea mays/microbiologia
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