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1.
Mol Cell ; 76(1): 148-162.e7, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31447391

RESUMO

The rapid proliferation of cancer cells and dysregulated vasculature within the tumor leads to limited nutrient accessibility. Cancer cells often rewire their metabolic pathways for adaption to nutrient stress, and the underlying mechanism remains largely unknown. Glutamate dehydrogenase 1 (GDH1) is a key enzyme in glutaminolysis that converts glutamate to α-ketoglutarate (α-KG). Here, we show that, under low glucose, GDH1 is phosphorylated at serine (S) 384 and interacts with RelA and IKKß. GDH1-produced α-KG directly binds to and activates IKKß and nuclear factor κB (NF-κB) signaling, which promotes glucose uptake and tumor cell survival by upregulating GLUT1, thereby accelerating gliomagenesis. In addition, GDH1 S384 phosphorylation correlates with the malignancy and prognosis of human glioblastoma. Our finding reveals a unique role of α-KG to directly regulate signal pathway, uncovers a distinct mechanism of metabolite-mediated NF-κB activation, and also establishes the critical role of α-KG-activated NF-κB in brain tumor development.


Assuntos
Neoplasias Encefálicas/metabolismo , Proliferação de Células , Metabolismo Energético , Glioblastoma/metabolismo , Glucose/metabolismo , Glutamato Desidrogenase/metabolismo , Ácidos Cetoglutáricos/metabolismo , NF-kappa B/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular , Criança , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Glucose/deficiência , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glutamato Desidrogenase/genética , Células HEK293 , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , NF-kappa B/genética , Gradação de Tumores , Fosforilação , Transdução de Sinais , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Adulto Jovem
2.
Mol Cell ; 71(2): 201-215.e7, 2018 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-30029001

RESUMO

Macrophages are a dominant leukocyte population in the tumor microenvironment and actively promote cancer progression. However, the molecular mechanism underlying the role of macrophages remains poorly understood. Here we show that polarized M2 macrophages enhance 3-phosphoinositide-dependent protein kinase 1 (PDPK1)-mediated phosphoglycerate kinase 1 (PGK1) threonine (T) 243 phosphorylation in tumor cells by secreting interleukin-6 (IL-6). This phosphorylation facilitates a PGK1-catalyzed reaction toward glycolysis by altering substrate affinity. Inhibition of PGK1 T243 phosphorylation or PDPK1 in tumor cells or neutralization of macrophage-derived IL-6 abrogates macrophage-promoted glycolysis, proliferation, and tumorigenesis. In addition, PGK1 T243 phosphorylation correlates with PDPK1 activation, IL-6 expression, and macrophage infiltration in human glioblastoma multiforme (GBM). Moreover, PGK1 T243 phosphorylation also correlates with malignance and prognosis of human GBM. Our findings demonstrate a novel mechanism of macrophage-promoted tumor growth by regulating tumor cell metabolism, implicating the therapeutic potential to disrupt the connection between macrophages and tumor cells by inhibiting PGK1 phosphorylation.


Assuntos
Macrófagos/metabolismo , Fosfoglicerato Quinase/genética , Fosfoglicerato Quinase/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Glicólise , Humanos , Macrófagos/patologia , Camundongos , Camundongos Nus , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Fosforilação , Prognóstico , Microambiente Tumoral
3.
J Cell Mol Med ; 28(8): e18275, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568058

RESUMO

Breast cancer (BC) remains a significant health concern worldwide, with metastasis being a primary contributor to patient mortality. While advances in understanding the disease's progression continue, the underlying mechanisms, particularly the roles of long non-coding RNAs (lncRNAs), are not fully deciphered. In this study, we examined the influence of the lncRNA LINC00524 on BC invasion and metastasis. Through meticulous analyses of TCGA and GEO data sets, we observed a conspicuous elevation of LINC00524 expression in BC tissues. This increased expression correlated strongly with a poorer prognosis for BC patients. A detailed Gene Ontology analysis suggested that LINC00524 likely exerts its effects through RNA-binding proteins (RBPs) mechanisms. Experimentally, LINC00524 was demonstrated to amplify BC cell migration, invasion and proliferation in vitro. Additionally, in vivo tests showed its potent role in promoting BC cell growth and metastasis. A pivotal discovery was LINC00524's interaction with TDP43, which leads to the stabilization of TDP43 protein expression, an element associated with unfavourable BC outcomes. In essence, our comprehensive study illuminates how LINC00524 accelerates BC invasion and metastasis by binding to TDP43, presenting potential avenues for therapeutic interventions.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Feminino , Humanos , Bioensaio , Neoplasias da Mama/genética , Transformação Celular Neoplásica , Ontologia Genética , RNA Longo não Codificante/genética
4.
Mol Med ; 30(1): 183, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39438838

RESUMO

BACKGROUND: Overconsumption of retinoic acid (RA) or its analogues/derivatives has been linked to severe craniomaxillofacial malformations, such as cleft palate and midface hypoplasia. It has been noted that RA disturbed the proliferation and migration of embryonic palatal mesenchymal (EPM) cells in these malformations, yet the exact mechanisms underlying these disruptions remained unclear. METHODS: A model of retinoic acid (RA)-induced cleft palate in fetal mice was successfully established. Histological alterations in the palate were evaluated using Hematoxylin and Eosin (H&E) staining and RNA in situ hybridization (RNAscope). Cellular proliferation levels were quantified via the Cell Counting Kit-8 (CCK-8) assay and EdU incorporation assay, while cell migration capabilities were investigated using wound healing and Transwell assays. Mitochondrial functions were assessed through Mito-Tracker fluorescence, mitochondrial reactive oxygen species (ROS) measurement, ATP level quantification, and mitochondrial DNA (mtDNA) copy number analysis. Differential gene expression and associated signaling pathways were identified through bioinformatics analysis. Alterations in the transcriptional and translational levels of Lhx6 and genes associated with mitophagy were quantified using quantitative PCR (qPCR) and Western blot analysis, respectively. Mitochondrial morphology and the mitochondrial autophagosomes within cells were examined through transmission electron microscopy (TEM). RESULTS: Abnormal palatal development in mice, along with impaired proliferation and migration of human embryonic palatal mesenchymal (HEPM) cells, was associated with RA affecting mitochondrial function and concomitant downregulation of Lhx6. Knockdown of Lhx6 in HEPM cells resulted in altered cell proliferation, migration, and mitochondrial function. Conversely, the aberrant mitochondrial function, proliferation, and migration observed in RA-induced HEPM cells were ameliorated by overexpression of Lhx6. Subsequent research demonstrated that Lhx6 ameliorated RA-induced dysfunction in HEPM cells by modulating PINK1/Parkin-mediated mitophagy, thereby activating the MAPK signaling pathways. CONCLUSION: Lhx6 is essential for mitochondrial homeostasis via tuning PINK1/Parkin-mediated mitophagy and MAPK signaling pathways. Downregulation of Lhx6 by RA transcriptionally disturbs the mitochondrial homeostasis, which in turn leads to the proliferation and migration defect in HEPM cells, ultimately causing the cleft palate.


Assuntos
Fissura Palatina , Mitofagia , Fatores de Transcrição , Animais , Feminino , Humanos , Masculino , Camundongos , Movimento Celular , Proliferação de Células , Fissura Palatina/genética , Fissura Palatina/patologia , Fissura Palatina/metabolismo , Modelos Animais de Doenças , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Palato/embriologia , Palato/metabolismo , Palato/patologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tretinoína/farmacologia
5.
Anal Chem ; 96(29): 11673-11681, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-38994836

RESUMO

Drug resistance in multiple myeloma (MM) poses a significant challenge to treatment efficacy, primarily attributed to P-glycoprotein (P-gp) dysfunction. This study delves into the elusive spatial organization of P-gp, aiming to enhance our understanding of its role in MM drug resistance by exploring the intricate relationship between molecular function and spatial arrangement. Employing super-resolution imaging of P-gp with the inhibitor probe Tariquidar-TAMR labeling on MM cell membranes, the research uncovered a more pronounced clustering distribution of P-gp in drug-resistant cells (MM1R) compared to drug-sensitive counterparts (MM1S). Further exploration revealed the clustering distribution of P-gp was heightened as cellular drug resistance increased in hypoxic condition, directly emphasizing the strong correlation between P-gp cluster morphology and drug resistance. Additionally, stable P-gp cluster formation was influenced by cross-linking of membrane carbohydrates, and disrupting these glycoprotein clusters could reduce cellular drug resistance, suggesting that altering distribution patterns of P-gp can modulate drug responsiveness. Finally, dexamethasone (Dex) treatment was revealed to enhance P-gp clustering distribution, particularly in MM1S cells, indicating that change degree in P-gp distribution correlate with the modifiable space of cellular drug responsiveness. This study provides insights into the correlation between P-gp assembly and cellular drug responsiveness, deepening our understanding of functional changes in MM drug resistance and offering valuable perspectives for overcoming this challenge.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Mieloma Múltiplo/metabolismo , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Imagem Óptica , Membrana Celular/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Quinolinas
6.
Ann Surg Oncol ; 31(4): 2679-2688, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38142258

RESUMO

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Gástricas , Humanos , Idoso , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Pontuação de Propensão , Perda Sanguínea Cirúrgica , Resultado do Tratamento , Gastrectomia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
7.
Clin Genet ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39380244

RESUMO

Empty follicle syndrome (EFS) is a disorder characterised by the unsuccessful retrieval of oocytes from matured follicles following ovarian stimulation for in vitro fertilisation (IVF). Genetic factors significantly contribute to this pathology. To date, an increasing number of genetic mutations associated with GEFS have been documented, however, some cases still remain unexplained by these previously reported mutations. Here, we identified a novel homozygous missense ZP1 variant (c.1096 C > T, p.Arg366Trp) in a female patient with GEFS from a consanguineous family who failed to retrieve any oocytes during two cycles of IVF treatment. We conducted a molecular dynamics simulation analysis on the mutant ZP1 model, revealing that the mutant ZP1 protein has an altered 3D structure, lower fluctuation, higher compactness and higher instability than wild-type ZP1. Immunostaining, immunoblotting and co-immunoprecipitation results showed that the homozygous missense mutation in ZP1 impaired protein secretion and weakened interactions between ZP1 and other ZP proteins, which may affect the ZP assembly. This study contributes to a more comprehensive understanding of the genetic aetiopathogenesis of GEFS.

8.
Opt Lett ; 49(3): 594-597, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300067

RESUMO

High-purity structural colors with low fabrication cost are in demand for their commercial applications. Here, we demonstrate an all-dielectric Fabry-Pérot cavity structure consisting of four-layer lossy and lossless dielectric films alternately stacked for producing high-purity and angle-invariant reflective colors. Multiple cavity resonances function together to significantly suppress the undesired reflection with the enhanced optical absorption, leading to a distinct and saturated color with a high efficiency of ∼70%. Besides, due to the high refractive indices of constituent materials, the color appearance of the designed structure can be maintained well at ±50° incident angle for two polarization states. The excellent color performance of the proposed device together with cost-effective manufacturing convenience opens up new avenues for their large-area applications in various areas.

9.
Anal Biochem ; 696: 115696, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39442603

RESUMO

Due to the current increase in the number of people suffering from diabetes worldwide, how to monitor the blood glucose level in the human body has become an urgent problem to be solved nowadays. The electrochemical sensor method can be used for real-time glucose monitoring due to its advantages of real-time monitoring capability and high sensitivity. Reduced graphene oxide (rGO) has great potential for application in the field of sensors due to its advantages of large specific surface area, high stability, and good electrical and thermal conductivity. Meanwhile, the synergistic effect between two-dimensional transition metal sulfides and graphene can improve the electrochemical performance of materials due to their similar mechanical flexibility and strength. This article uses flake graphite, copper sulfate, and glucose oxidase (GOx) as raw materials to prepare CuS/rGO/GOx/GCE electrodes, and explores the performance of electrode electrocatalysis for glucose. The results showed that the prepared sensor was characterized by a low detection limit (1.75 nM) and a wide linear range (0.1-100 mM) for glucose detection, displaying a good overall detection performance, and its sensing mechanism and dynamic process were also investigated. In addition, the sensor has outstanding selectivity, anti-interference, repeatability, reproducibility and practicality.

10.
J Org Chem ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323758

RESUMO

Herein, we report a single-step, multicomponent approach to versatile γ-lactams through dual photoredox/nickel-catalyzed dicarbofunctionalization of α,ß-unsaturated γ-butyrolactam. This reaction utilized alkyl trimethylgermanium as a radical precursor and acyl chloride as the electrophile, demonstrating remarkable functional group compatibility.

11.
Eur J Nutr ; 63(7): 2753-2766, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39030442

RESUMO

BACKGROUND: With the implementation of the universal salt iodization, the iodine nutrition for children and adults has been appropriate, but pregnant women are still at risk of iodine deficiency. It is of great public health significance to explore the iodine status and knowledge, and influence factors and the appropriate health education methods among pregnant and lactating women. METHODS: From January 2022 to December 2023, at least 50 pregnant women and 50 lactating women were randomly selected from the resident population annually in 16 districts of Tianjin, North China. A total of 1671 pregnant women and 1658 lactating women were recruited. All participants' households salt and random urine samples were collected. A questionnaire was conducted to collect data on iodine related knowledge and behaviors as well as needs of health education from all participants. Logistic regression models were constructed to analyze the factors affecting the iodine related knowledge level. We used the Rasch model and the quadrantal graph to analyze the participants' knowledge level on different iodine-related questions and their needs for health education. RESULTS: The median urine iodine concentration (UIC) of pregnant and lactating women in Tianjin were 152.40 µg/L and 124.60 µg/L. In some districts, the median UIC of pregnant and lactating women below the appropriate range. The iodized salt coverage rate of pregnant and lactating women in Tianjin was 76.12% and 77.40%, respectively. In pregnant and lactating women who did not actively supplement with iodine, the median UIC in those who consumed non-iodized salt were significantly lower than that in those who consumed iodized salt (139.26 µg/L and 154.40 µg/L, P = 0.044; 94.60 µg/L and 123.80 µg/L, P < 0.001). Compared with the low knowledge score group, pregnant women in the high knowledge score group had a higher proportion of iodized salt consumption (71.25% and 78.05%, P = 0.003), and pregnant and lactating women in the high knowledge score group had a higher proportion of actively supplement iodine (44.61% and 55.34%, P < 0.001; 39.26% and 49.78%, P < 0.001). Health education may be the main factor affecting the iodine related knowledge scores for pregnant and lactating women, with adjusted odds ratios (OR) and 95% confidence intervals (CI) of 2.89 (2.30, 3.62) and 2.46 (1.97, 3.07), respectively. Pregnant and lactating women are most expected to acquire knowledge through healthcare professionals (72.11%) and wechat/website (74.91%), respectively. CONCLUSIONS: Pregnant and lactating women in some areas of Tianjin are at risk of iodine deficiency. Iodized salt consumption is an important way to ensure iodine nutrition of the population, and the lack of iodine related knowledge is an important factor affecting the consumption of iodized salt. Health education in different ways can be carried out for different people to improve the acceptance and efficiency of health education.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Iodo , Lactação , Estado Nutricional , Cloreto de Sódio na Dieta , Humanos , Feminino , Iodo/urina , Iodo/administração & dosagem , Iodo/deficiência , Cloreto de Sódio na Dieta/administração & dosagem , China , Gravidez , Adulto , Inquéritos e Questionários , Adulto Jovem
12.
BMC Psychiatry ; 24(1): 262, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594695

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a profound mental disorder with a multifactorial etiology, including genetics, environmental factors, and demographic influences such as ethnicity and geography. Among these, the studies of SCZ also shows racial and regional differences. METHODS: We first established a database of biological samples for SCZ in China's ethnic minorities, followed by a serum metabolomic analysis of SCZ patients from various ethnic groups within the same region using the LC-HRMS platform. RESULTS: Analysis identified 47 metabolites associated with SCZ, with 46 showing significant differences between Miao and Han SCZ patients. These metabolites, primarily fatty acids, amino acids, benzene, and derivatives, are involved in fatty acid metabolism pathways. Notably, L-Carnitine, L-Cystine, Aspartylphenylalanine, and Methionine sulfoxide demonstrated greater diagnostic efficacy in Miao SCZ patients compared to Han SCZ patients. CONCLUSION: Preliminary findings suggest that there are differences in metabolic levels among SCZ patients of different ethnicities in the same region, offering insights for developing objective diagnostic or therapeutic monitoring strategies that incorporate ethnic considerations of SCZ.


Assuntos
Esquizofrenia , Humanos , Povo Asiático/etnologia , China , Minorias Étnicas e Raciais , Etnicidade , Predisposição Genética para Doença , Esquizofrenia/diagnóstico , Esquizofrenia/etnologia , Esquizofrenia/metabolismo
13.
BMC Urol ; 24(1): 183, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198764

RESUMO

OBJECTIVE: To assess the rate at which sutureless partial nephrectomy (SLPN) transitions to standard partial nephrectomy (SPN), focusing on preoperative factors that might prompt such conversions. PATIENTS AND METHODS: In this retrospective study, we analyzed the efficacy of SLPN performed on adults at our institution from 2016 to 2023. The subjects were patients diagnosed with localized solid renal tumors. The primary technique employed was resection with scissors and argon beam coagulation for hemostasis, with suturing techniques used only when necessary. Predictive factors necessitating conversion to SPN were identified, and the associations among multiple variables were explored using various statistical analysis methods, including logistic regression, to identify key preoperative predictive factors. RESULTS: Our institution performed 353 SLPN, with 21 cases (5.9%) necessitating conversion to SPN. The conversion rates for the Laparoscopic Partial Nephrectomy (LPN) subgroup and the Robotic-assist Partial Nephrectomy (RPN) subgroup were 7.9% (17/215) and 2.9% (4/138), respectively, nearing statistical significance (P = .066). Significant differences were observed between the conversion group and the no conversion group in terms of preoperative estimated Glomerular Filtration Rate (eGFR), age at surgery, tumor size, and exophytic/endophytic characteristics. Multivariate analysis identified age at surgery, preoperative eGFR, radiological tumor size, and tumor exophytic/endophytic nature as significant predictors for conversion to SPN. CONCLUSION: This investigation highlights the efficacy and feasibility of SLPN while identifying critical factors influencing the necessity for conversion to SPN. The identified predictors, including younger surgical age, superior preoperative eGFR, and specific tumor characteristics, provide valuable insights for refining surgical strategies.


Assuntos
Neoplasias Renais , Laparoscopia , Nefrectomia , Humanos , Nefrectomia/métodos , Laparoscopia/métodos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Renais/cirurgia , Estudos Retrospectivos , Idoso , Técnicas de Sutura , Conversão para Cirurgia Aberta/estatística & dados numéricos , Adulto , Procedimentos Cirúrgicos Robóticos
14.
Ecotoxicol Environ Saf ; 269: 115795, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38091668

RESUMO

Drinking water is the main cause of iodine excess among Chinese residents and we have found that water iodine concentration (WIC) reduction was the effective intervening measure. In this study, to eliminate the hazards of water-borne excessive iodine, we firstly investigated the WIC of villages in Tianjin in 2017 to determine the distribution range. Secondly, the risk characterization of excessive iodine on residents in 6∼< 9 years old, 9∼< 12 years old, 12∼< 15 years old, 15∼< 18 years old and adults were evaluated, and the safe upper limit of WIC was determined. Finally, WIC was investigated again after the completion of WIC reduction in water-borne excessive-iodine villages in 2020, and the differences in urinary iodine concentration (UIC) and thyroid volume (Tvol) of children aged 8-10 years before and after WIC reduction were analyzed. The WIC of 2459 villages surveyed was 22.30 (8.60-58.80) µg/L and the maximum was 514 µg/L. There were 422 villages with WIC > 100 µg/L. Under the conditions of non-iodized salt intake, recommended amount of iodized salt intake and actual amount intake, the maximum of excessive iodine exposure hazard quotient (HQ) were the highest in the age group of 6∼< 9 years, which were 2.300, 2.663 and 2.771, the safe upper WIC limits were 223 µg/L, 142 µg/L and 118 µg/L and villages with HQ> 1 accounted for 4.14%, 6.09% and 6.88% of all villages, respectively. After the WIC reduction, the WIC of the former water-borne iodine-excess villages decreased to < 100 µg/L, and the UIC and Tvol of children decreased (both P < 0.001) and was within normal range. Determining the distribution range of water-borne iodine-excess areas, exploring appropriate intervening measure, carrying out risk assessment, determining the WIC safe upper limit, intervening and evaluating the intervention effect can be the process to eliminate the hazards of water-borne excessive iodine.


Assuntos
Água Potável , Iodo , Adulto , Criança , Humanos , Adolescente , Iodo/análise , Glândula Tireoide/química , Água Potável/análise , China , Valores de Referência
15.
Molecules ; 29(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38731534

RESUMO

Two unreported heteropolysaccharides, denoted as YCJP-1 and YCJP-2, were isolated from the herbs of Chloranthus japonicus. YCJP-1 was a heteropolysaccharide composed of glucose, galactose, arabinose, mannose, rhamnose, and a minor proportion of uronic acids, with the molecular weight mainly distributed in the 74,475-228,443 Da range. YCJP-2 was mainly composed of glucose, mannose, and galactose, with the molecular weights ranging from 848 to 5810 Da. To further evaluate the anti-gastric cancer effects of C. japonicus, the inhibitory effects of the crude polysaccharide (YCJP) and the purified polysaccharides (YCJP-1 and YCJP-2) were determined using a CCK-8 assay and colon-forming assay on MGC-803 and AGS gastric cancer cell lines. Our results showed that YCJP, YCJP-1, and YCJP-2 possess prominent inhibitory effects on the proliferation of MGC-803 and AGS cells, and the AGS cell was more sensitive to YCJP, YCJP-1, and YCJP-2. Moreover, YCJP-2 demonstrated superior anti-gastric cancer effects compared to YCJP-1. This could potentially be attributed to YCJP-2's higher glucose content and narrower molecular weight distribution.


Assuntos
Proliferação de Células , Polissacarídeos , Neoplasias Gástricas , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Peso Molecular , Caryophyllaceae/química
16.
Prostate ; 83(15): 1430-1445, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37517867

RESUMO

BACKGROUND: Melittin is a small molecule polypeptide extracted from the abdominal cavity of bees, which is used to treat inflammatory diseases and relieve pain. However, the antitumor effect of melittin and its mechanisms remain unclear, especially in castration-resistant prostate cancer (CRPC). METHODS: Through CCK-8 assay, colony formation assay, wound healing assay and Transwell migration assay, we explored the effect of melittin on CRPC cell lines. In addition, with microarray analysis, gene ontology analysis and kyoto encyclopedia of genes and genomes analysis, this study identified key genes and signaling pathways that influence the growth of PC-3 cells. Meanwhile, the effect of melittin on CRPC was also verified through subcutaneous tumor formation experiments. Finally, we also tested the relevant indicators of human prostate cancer (PCa) specimens through immunohistochemistry and H&E stating. RESULTS: Here, melittin was verified to inhibit the cell proliferation and migration of CPRC. Moreover, RNA-sequence analysis demonstrated that Interleukin-17 (IL-17) signaling pathway gene Lipocalin-2 (LCN2) was downregulated by melittin treatment in CRPC. Further investigation revealed that overexpression of LCN2 was able to rescue tumor suppression and cisplatin sensitivity which melittin mediated. Interestingly, the expression of LCN2 is highly related to metastasis in PCa. CONCLUSIONS: In brief, our study indicates that LCN2 plays an oncogenic role in CRPC and melittin may be selected as an attractive candidate for CRPC therapy.


Assuntos
Cisplatino , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Animais , Lipocalina-2/genética , Lipocalina-2/metabolismo , Lipocalina-2/farmacologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Interleucina-17/metabolismo , Interleucina-17/farmacologia , Meliteno/farmacologia , Meliteno/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Proliferação de Células , Movimento Celular
17.
Plant Cell Environ ; 46(1): 215-238, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36174546

RESUMO

In Arabidopsis, phosphate starvation (-Pi)-induced responses of primary root and lateral root growth are documented to be correlated with ambient iron (Fe) status. However, whether and how Fe participates in -Pi-induced root hair growth (RHG) remains unclear. Here, responses of RHG to different Fe concentrations under Pi sufficiency/deficiency were verified. Generally, distinct dosage effects of Fe on RHG appeared at both Pi levels, due to the generation of reactive oxygen species. Following analyses using auxin mutants and the phr1 mutant revealed that auxin and the central regulator PHR1 are required for Fe-triggered RHG under -Pi. A further proteomic study indicated that processes of vesicle trafficking and auxin synthesis and transport were affected by Fe under -Pi, which were subsequently validated by using a vesicle trafficking inhibitor, brefeldin A, and an auxin reporter, R2D2. Moreover, vesicle trafficking-mediated recycling of PIN2, an auxin efflux transporter, was notably affected by Fe under -Pi. Correspondingly, root hairs of pin2 mutant displayed attenuated responses to Fe under -Pi. Together, we propose that Fe affects auxin signalling probably by modulating vesicle trafficking, chiefly the PIN2 recycling, which might work jointly with PHR1 on modulating -Pi-induced RHG.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fosfatos/farmacologia , Ferro , Proteômica , Fatores de Transcrição , Proteínas de Arabidopsis/genética
18.
Neuroimmunomodulation ; 30(1): 226-236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37729881

RESUMO

Interleukin (IL)-33 was initially recognized as a constituent of the IL-1 cytokine family in 2005. It exerts pleiotropic effects by regulating immune responses via its binding to the receptor ST2 (IL-33R). The IL-33/ST2 pathway has been linked to several inflammatory disorders. In human and rodents, the broad expression of IL-33 in spinal cord tissues and brain indicates its central nervous system-specific functions. Growing evidence supports the protective effects of the IL-33/ST2 pathway in ischemic stroke, along with a better understanding of the underlying mechanisms. IL-33 plays a crucial role in the regulation of the release of inflammatory molecules from glial cells in response to neuropathological lesions. Moreover, IL-33/ST2-mediated neuroprotection following cerebral ischemia may be linked to T-cell function, specifically regulatory T cells. Soluble ST2 (sST2) acts as a decoy receptor in the IL-33/ST2 axis, blocking IL-33 signaling through the membrane ST2 receptor. sST2 has also been identified as a potential inflammatory biomarker of ischemic stroke. Targeting sST2 specifically to eliminate its inhibition of the protective IL-33/ST2 pathway in ischemic brain tissues is a promising approach for the treatment of ischemic stroke.


Assuntos
Isquemia Encefálica , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , AVC Isquêmico , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Doenças Neuroinflamatórias
19.
Arch Virol ; 168(9): 227, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566243

RESUMO

Feline coronavirus (FCoV) is the causative agent of feline infectious peritonitis and diarrhoea in kittens worldwide. In this study, a total of 73 feline diarrhoeal faecal samples were collected from animal hospitals and pet markets in ShanDong province from 2017 to 2019. FCoV was detected in 58.23% (46/73) of the samples, using the RT-PCR method. The results showed that the detection rate of FCoV in healthy cats and sick cats was 41.7% (10/24) and 81.6% (40/49), respectively. Full gene amplification and sequencing of the N, M, and S2 genes of FCoV isolates were performed. An amino acid mutation (M1058L) in the S2 gene was found that can be used as a marker for distinguishing feline enteric coronavirus (FECV) from feline infectious peritonitis virus (FIPV). This study provides new epidemiological information about FCoV that will aid in the prevention of FCoV in China.


Assuntos
Infecções por Coronavirus , Coronavirus Felino , Coronavirus Felino/genética , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Doenças do Gato/virologia , Animais , Gatos , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas M de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/genética , Masculino , Feminino
20.
Nanotechnology ; 34(32)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37137295

RESUMO

Molybdenum disulfide (MoS2) is an emerging class of new materials with a wide range of potential practical applications. However, the uncontrollability of monolayer MoS2synthesized by traditional chemical vapor deposition method and the low responsivity of MoS2photodetectors limit its further development in the field of photoelectric detection. To achieve controlled growth of monolayer MoS2and construct MoS2photodetectors with a high responsivity, we propose a novel single crystal growth strategy of high-quality MoS2by controlling the Mo to S vapor ratio near the substrate, and deposit a layer of hafnium oxide (HfO2) on the surface of MoS2to enhance the performance of the pristine metal-semiconductor-metal structure photodetector. At a reverse bias of 8 V, the HfO2passivated MoS2photodetector features an extremely high responsivity of1201AW-1,a response time of around 0.5 s, and a detectivity of7.7×1011Jones.Meanwhile, we deeply investigate the effect of the HfO2layer on the performance of the fabricated MoS2photodetector and propose a physical mechanism to interpret the obtained experiment results. These results might facilitate a better understanding on the performance modulation of the MoS2photodetectors and accelerate the development of MoS2-based optoelectronic devices.

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