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1.
Front Endocrinol (Lausanne) ; 15: 1354426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721144

RESUMO

Purpose: Postoperative thyroglobulin (Tg) generally serves as a biomarker to monitor the recurrence or persistence of differentiated thyroid cancer (DTC), whereas it constrains to interference from anti-thyroglobulin antibody (TgAb). This study aimed to determine the value of postoperative TgAb as a surrogate for monitoring tumor status in DTCs with positive TgAb after successful radioactive iodine (RAI) remnant ablation. Methods: We retrospectively enrolled DTC patients with positive (≥40 IU/mL, Roche) postoperative TgAb measurements. An index of TgAb change (ΔTgAb) was defined to describe the TgAb decrease rate. DTC status was defined as either no evidence of disease (NED) or persistent/recurrent disease (PRD). Univariate and multivariate binary logistic analyses were used to identify the independent risk factors of PRD. Receiver operating characteristic (ROC) curves were performed to determine the optimal cutoff values of each risk factor, and DeLong's test was conducted to compare their predictive powers. Kaplan-Meier curves were used to assess the impact of different TgAb trends in the first year on progression-free survival. Results: Of the 232 patients enrolled, the median diagnosis age was 34 years (range, 18-62 years), with a male-to-female ratio of 1:4.66 (41/191). Among them, after a median follow-up of 44 months (range, 4-128 months),183 (78.87%) patients were evaluated as NED, while the other 49 (21.12%) had either persistent (n = 25) or recurrent disease (n = 24). Multivariate regression showed that ΔTgAb (P < 0.001) and lymph node metastasis (LNM) rate (P = 0.009) were independently relevant to the presence of PRD, with optimal cutoff values of 47.0% and 35.1%, respectively. It is important to note that there is a high negative predictive value (96.93%) of ΔTgAb with the cutoff of 47.0%. DeLong's test showed that ΔTgAb alone and the combination of ΔTgAb and LNM rate were significantly greater than the isolated LNM rate (both P < 0.001) in predicting NED, while there was no statistical difference of the predictive power between ΔTgAb and the combination (P = 0.203). Additionally, patients with ΔTgAb >47.0% had longer progression-free survival than those with ΔTgAb ≤47.0% (not reached vs. 50 months, P < 0.001), and those with ΔTgAb >47.0% or negative conversion within the first year after RAI ablation had longer progression-free survival. Conclusion: Our study suggested that ΔTgAb could serve as a valuable indicator of disease status in DTC patients with positive TgAb. A ΔTgAb of >47.0% is conducive to identify those with NED and may help to obviate their overtreatment. The decrease rate and negative conversion of TgAb in the first year were good predictors of disease-free survival in patients.


Assuntos
Autoanticorpos , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Adulto , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Pessoa de Meia-Idade , Autoanticorpos/sangue , Estudos Retrospectivos , Prognóstico , Adulto Jovem , Adolescente , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Biomarcadores Tumorais/sangue , Tireoidectomia , Tireoglobulina/imunologia , Tireoglobulina/sangue , Radioisótopos do Iodo/uso terapêutico , Seguimentos
2.
Heliyon ; 10(8): e29620, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38699743

RESUMO

Increasing pressures on land resources requires increased land use efficiency. Over 900 million ha of sandy soils throughout the world are extensively used for agricultural crop production, most requiring nutrient inputs. Although use of humic substances together with inorganic fertilizer as soil amendments has been introduced, their synergistic effects on plant growth in sandy soils are not well addressed. We assessed the efficacy of a lignite waste derived humic substance on barley (Hordeum vulgare L.) growth, with and without inorganic fertilizer. Ten treatments were applied to sandy soils, comprising sole application of the humic product at four rates (NH1, NH2, NH3, NH4), sole application of fertilizer (F), and their combinations (F + NH1, F + NH2, F + NH3, F + NH4). Synergistic effects of nano humus and fertilizer were more notable than the corresponding sole application, particularly on plant biomass and seed production. Combined application with inorganic fertilizer increased root biomass by 92 % (0.1 g per plant), shoot biomass by 80 % (0.5 g per plant), root length by 24 % (3.6 cm), and seed production by 38 % (5 seeds per head) averagely relative to the untreated control, suggesting a strong synergistic effect. The increased seed production was particularly important from an agricultural perspective. Four application rates of nano humus all showed beneficial effects on barley growth with no significant differences. The most distinct positive effect of the humic product as a sole application was on root growth. Our study confirmed that a lignite waste derived humic product, nano humus, together with fertilizer may be an effective soil amendment to enhance agricultural plant growth in sandy soil regions.

3.
Cancer Commun (Lond) ; 44(4): 469-490, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38512764

RESUMO

BACKGROUND: Chemoresistance is a major cause of treatment failure in gastric cancer (GC). Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an N6-methyladenosine (m6A)-binding protein involved in a variety of cancers. However, whether m6A modification and hnRNPA2B1 play a role in GC chemoresistance is largely unknown. In this study, we aimed to investigate the role of hnRNPA2B1 and the downstream mechanism in GC chemoresistance. METHODS: The expression of hnRNPA2B1 among public datasets were analyzed and validated by quantitative PCR (qPCR), Western blotting, immunofluorescence, and immunohistochemical staining. The biological functions of hnRNPA2B1 in GC chemoresistance were investigated both in vitro and in vivo. RNA sequencing, methylated RNA immunoprecipitation, RNA immunoprecipitation, and RNA stability assay were performed to assess the association between hnRNPA2B1 and the binding RNA. The role of hnRNPA2B1 in maintenance of GC stemness was evaluated by bioinformatic analysis, qPCR, Western blotting, immunofluorescence, and sphere formation assays. The expression patterns of hnRNPA2B1 and downstream regulators in GC specimens from patients who received adjuvant chemotherapy were analyzed by RNAscope and multiplex immunohistochemistry. RESULTS: Elevated expression of hnRNPA2B1 was found in GC cells and tissues, especially in multidrug-resistant (MDR) GC cell lines. The expression of hnRNPA2B1 was associated with poor outcomes of GC patients, especially in those who received 5-fluorouracil treatment. Silencing hnRNPA2B1 effectively sensitized GC cells to chemotherapy by inhibiting cell proliferation and inducing apoptosis both in vitro and in vivo. Mechanically, hnRNPA2B1 interacted with and stabilized long noncoding RNA NEAT1 in an m6A-dependent manner. Furthermore, hnRNPA2B1 and NEAT1 worked together to enhance the stemness properties of GC cells via Wnt/ß-catenin signaling pathway. In clinical specimens from GC patients subjected to chemotherapy, the expression levels of hnRNPA2B1, NEAT1, CD133, and CD44 were markedly elevated in non-responders compared with responders. CONCLUSION: Our findings indicated that hnRNPA2B1 interacts with and stabilizes lncRNA NEAT1, which contribute to the maintenance of stemness property via Wnt/ß-catenin pathway and exacerbate chemoresistance in GC.


Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Ribonucleoproteínas Nucleares Heterogêneas , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , RNA Longo não Codificante/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
4.
Int J Biol Macromol ; 264(Pt 1): 130411, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437932

RESUMO

Bamboo has tremendous carbon sequestration potential, and bamboo green is underutilized. This work devised a green-keeping technique in bamboo flattening that preserved natural bamboo green in-situ. The impacts of flattening and green-keeping on bamboo morphology, chemical composition, physical qualities, and composite applications were examined. Bamboo cells were wrinkled after flattening, while bamboo green exhibited a more homogenous surface. Bamboo cellulose crystallinity increased after flattening, hemicellulose deteriorated little, and relative lignin content increased. The hydrophobicity and mildew resistance of the surface of G-FB (green-kept flattened bamboo board) were improved. Compared to untreated bamboo, FB and G-FB had 61.1 % and 49.5 % higher tensile strength and 8.0 % and 33.2 % higher MOR. G-FB-made flooring exhibited a MOR of 134.7 MPa and upgraded surface properties. Bamboo green preservation boosted utilization of materials and improved flattened bamboo's exterior surface without affecting lamination bonding. Simple bamboo green preservation multifunctionalizes flattened bamboo composites.


Assuntos
Celulose , Lignina , Lignina/química , Celulose/química , Propriedades de Superfície , Resistência à Tração
5.
Life Sci ; 338: 122385, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38184271

RESUMO

AIMS: This study aims to investigate the effects of berberine (BBR) on the intestinal microbiome (IM) and serum metabolome in ulcerative colitis (UC). Furthermore, the underlying molecular mechanisms of BBR in treating UC also will be explored systematically. MATERIALS AND METHODS: A multi-omics approach that integrates the 16s rDNA, serum metabolome, transcriptomics and bioinformatics was profiled to investigate the potential effects of BBR on the IM, serum metabolites and metabolic pathways, and gene expression. In addition, BBR-induced fecal microbiota transplantation (BBR_FMT) was conducted in pseudo germ-free mice combined with the UC model to explore the effects of the IM on metabolic pathways and gene expression. The results of the transcriptomics and metabolic pathway-related genes were further examined by real-time PCR and western blot. KEY FINDINGS: BBR ameliorated the community of IM and significantly promoted the abundance of f__Muribaculaceae, Bacteroides, Dubosiella, Allobaculum and Akkermansia. The metabolic profiles in UC mice were significantly modulated by BBR treatment. Furthermore, the inflammation-related metabolites and metabolic pathways in serum were negatively correlated with the abundance of Bacteroides and Akkermansia, which were induced by BBR treatment. BBR_FMT significantly inhibited the arachidonic acid (AA) metabolism pathway and its multiple markers with the mediation of the IM. SIGNIFICANCE: BBR ameliorated serum metabolic homeostasis by regulating the IM. The inhibition of the AA metabolism pathway and its multiple markers was one of the mechanisms of BBR in the treatment of UC.


Assuntos
Berberina , Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Camundongos , Animais , Colite Ulcerativa/tratamento farmacológico , Berberina/farmacologia , Berberina/uso terapêutico , Inflamação , Homeostase , Sulfato de Dextrana/farmacologia
6.
Patterns (N Y) ; 5(1): 100906, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38264714

RESUMO

Electronic health record (EHR) data are increasingly used to support real-world evidence studies but are limited by the lack of precise timings of clinical events. Here, we propose a label-efficient incident phenotyping (LATTE) algorithm to accurately annotate the timing of clinical events from longitudinal EHR data. By leveraging the pre-trained semantic embeddings, LATTE selects predictive features and compresses their information into longitudinal visit embeddings through visit attention learning. LATTE models the sequential dependency between the target event and visit embeddings to derive the timings. To improve label efficiency, LATTE constructs longitudinal silver-standard labels from unlabeled patients to perform semi-supervised training. LATTE is evaluated on the onset of type 2 diabetes, heart failure, and relapses of multiple sclerosis. LATTE consistently achieves substantial improvements over benchmark methods while providing high prediction interpretability. The event timings are shown to help discover risk factors of heart failure among patients with rheumatoid arthritis.

7.
Cytotherapy ; 25(12): 1285-1292, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37815776

RESUMO

BACKGROUND AIMS: Aging is accompanied by a decline in cellular proteome homeostasis, mitochondrial, and metabolic function. Mesenchymal stromal cell (MSC) therapies have been reported to extend lifespan and delay some age-related pathologies, yet the anti-aging rate and mechanisms remain unclear. Here, we investigated the effects and mechanism by transplantation of stem cells from human exfoliated deciduous teeth (SHED) into the naturally aged mice model. METHODS: SHED were cultured in vitro and injected into mice by caudal vein. The in vivo imaging uncovered that SHED labeled by DiR dye mainly migrated to the liver, spleen, and lung organs of wild-type mice. As the main metabolic organ and SHED homing place, the liver was selected for proteomics and aging clock algorithm (LiverClock) analysis, which was constructed to estimate the proteomic pattern related to liver age state. RESULTS: After 6 months of continuous SHED injections, the liver proteomic pattern was reversed from senescent (∼30 months) to a youthful state (∼3 months), accompanied with upregulation of hepatocytes marker genes, anti-aging protein Klotho, a global improvement of liver functional pathways proteins, and a dramatic regulation of ribosomal and mitochondrial proteins, including upregulation of translation elongation and ribosome-sparing proteins Rpsa and Rplp0; elongation factors Eif4a1, Eef1b2, Eif5a; protein-folding chaperones Hsp90aa and Hspe1; ATP synthesis proteins Atp5b, Atp5o, Atp5j; and downregulation of most ribosomal proteins, suggesting that the proteome homeostasis destruction and mitochondria dysfunction in the aged mice liver might be relieved after SHED treatment. CONCLUSIONS: SHED treatment could dramatically relieve the senescent state of the aged liver, affect ribosome component proteins and upregulate the ribosomal biogenesis proteins in the aged mice liver. These results may help understand the improvements and mechanisms of SHED treatment in anti-aging.


Assuntos
Proteínas Mitocondriais , Proteoma , Humanos , Animais , Camundongos , Idoso , Proteômica , Fígado , Ribossomos , Células-Tronco , Dente Decíduo
8.
Angew Chem Int Ed Engl ; 62(50): e202314025, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37881154

RESUMO

Enzyme-prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core-shell reactor partitioning enzyme and prodrug by ZIF-8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn-prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF-8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC50 value (26.3±2.6 µg/mL) are measured for B16-F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core-shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer.


Assuntos
Antineoplásicos , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , NADP , Antineoplásicos/farmacologia , Dacarbazina , Sistema Enzimático do Citocromo P-450 , Neoplasias/tratamento farmacológico
9.
J Cancer Res Clin Oncol ; 149(18): 16659-16668, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37721570

RESUMO

PURPOSE: Genome-wide association studies have identified SMAD7 as a colorectal cancer (CRC) susceptibility gene. However, its underlying mechanism has not yet been characterized. This study screened functional SNPs (fSNPs) related to colorectal cancer through Reel-seq and obtained regulatory proteins on functional SNPs. METHODS: The candidate fSNPs on the SMAD7 locus were screened by Reel-seq method. Eight SNPs such as rs8085824 were identified as functional SNPs by luciferase reporter assay and EMSA, SDCP-MS and AIDP-WB revealed that HNRNPK can specifically bind to the rs8085824-C allele. The knockdown of HNRNPK by RNAi proved that HNRNPK could affect cell function by regulating SMAD7. RESULTS: Eight functional SNPs was found on the SMAD7 locus in linkage disequilibrium (LD) with R2 > 0.8, i.e., rs12953717, rs7227023, rs34007497, rs58920878, rs8085824, rs4991143, rs4939826, and rs7227023. We also identified allele-imbalanced binding of HNRNPK to rs8085824, H1-3 to rs12953717, THOC6 to rs7227023, and DDX21 to rs58920878. Further functional analysis revealed that these proteins are the regulatory proteins that modulate the expression of SMAD7 in the human colorectal cancer cell line DLD1. In particular, we discovered that siRNA knockdown of HNRNPK inhibits cell proliferation and cell clonal formation by downregulating SMAD7, as the decreased cell proliferation and cell clonal formation in the siRNA HNRNPK knockdown cells was restored by SMAD7 overexpression. CONCLUSION: Our findings reveal a mechanism which underlies the contribution of the fSNP rs8085824 on the SMD7 locus to CRC susceptibility.


Assuntos
Neoplasias Colorretais , Predisposição Genética para Doença , Humanos , Estudo de Associação Genômica Ampla , Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , RNA Interferente Pequeno , Proteína Smad7/genética , RNA Helicases DEAD-box/genética , Proteínas de Ligação a RNA/genética
10.
Nat Struct Mol Biol ; 30(10): 1495-1504, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37679563

RESUMO

Anion exchanger 1 (AE1), a member of the solute carrier (SLC) family, is the primary bicarbonate transporter in erythrocytes, regulating pH levels and CO2 transport between lungs and tissues. Previous studies characterized its role in erythrocyte structure and provided insight into transport regulation. However, key questions remain regarding substrate binding and transport, mechanisms of drug inhibition and modulation by membrane components. Here we present seven cryo-EM structures in apo, bicarbonate-bound and inhibitor-bound states. These, combined with uptake and computational studies, reveal important molecular features of substrate recognition and transport, and illuminate sterol binding sites, to elucidate distinct inhibitory mechanisms of research chemicals and prescription drugs. We further probe the substrate binding site via structure-based ligand screening, identifying an AE1 inhibitor. Together, our findings provide insight into mechanisms of solute carrier transport and inhibition.


Assuntos
Proteína 1 de Troca de Ânion do Eritrócito , Bicarbonatos , Proteína 1 de Troca de Ânion do Eritrócito/química , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Bicarbonatos/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Sítios de Ligação , Domínios Proteicos
11.
Expert Rev Gastroenterol Hepatol ; 17(9): 921-935, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37589220

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic disease characterized by the presence of systemic inflammation, manifesting not only as gastrointestinal symptoms but also as extraintestinal bone complications, including osteopenia and osteoporosis. However, the association between IBD and osteoporosis is complex, and the presence of multifactorial participants in the development of osteoporosis is increasingly recognized. Unlike in adults, delayed puberty and growth hormone/insulin-like growth factor-1 axis abnormalities are essential risk factors for osteoporosis in pediatric patients with IBD. AREAS COVERED: This article reviews the potential pathophysiological mechanisms contributing to osteoporosis in adult and pediatric patients with IBD and provides evidence for effective prevention and treatment, focusing on pediatric patients with IBD. A search was performed from PubMed and Web of Science inception to February 2023 to identify articles on IBD, osteoporosis, pediatric, and fracture risk. EXPERT OPINION: A comprehensive treatment pattern based on individualized principles can be used to manage pediatric IBD-related osteoporosis.


Assuntos
Doenças Ósseas Metabólicas , Doenças Inflamatórias Intestinais , Osteoporose , Adulto , Humanos , Criança , Densidade Óssea , Osteoporose/epidemiologia , Osteoporose/etiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/diagnóstico
12.
Ecotoxicol Environ Saf ; 263: 115216, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37421894

RESUMO

Cadmium (Cd) and arsenic (As) in co-contaminated soil can enter the human body harming health via the food chain, such as vegetables. Biochar derived from waste has been used to reduce heavy metal uptake by plant, but long-term effects of biochar under Cd and As co-contaminated soil needs to be investigated. A following mustard (Brassica juncea) was grown on co-contaminated soil amended with different raw materials of biochar including biochars pyrolyzed by lignite coal (LCB), rice straw (RSB), silkworm excrement (SEB), and sugar refinery sludge (SSB). The results showed that compared to the control, Cd and As contents of mustard shoot in SSB treatment decreased by 45-49% and 19-37% in two growing seasons, respectively, which was the most effective among 4 biochars. This probably due to SSB owns more abundant Fe-O functional groups. Biochar also altered the microbial community composition, specifically SSB increased proteobacteria abundance by 50% and 80% in the first and second growing seasons, thereby promoted the simultaneous immobilization of Cd and As in soils which may reduce the potential risks to humans. In summary, considering the long-term effects and security of SSB application on mustard, not only is it an effective waste recycle option, but it should also be promoted as a promising approach for safe vegetable production in Cd and As co-contaminated soils.


Assuntos
Arsênio , Poluentes do Solo , Humanos , Cádmio/toxicidade , Cádmio/análise , Mostardeira , Arsênio/toxicidade , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Carvão Vegetal , Verduras , Solo
13.
J Dairy Sci ; 106(7): 5018-5028, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37268588

RESUMO

Ketosis is a common nutritional metabolic disease during the perinatal period in dairy cows. Although various risk factors have been identified, the molecular mechanism underlying ketosis remains elusive. In this study, subcutaneous white adipose tissue (sWAT) was biopsied for transcriptome sequencing on 10 Holstein cows with type II ketosis [blood ß-hydroxybutyric acid (BHB) >1.4 mmol/L; Ket group] and another 10 cows without type II ketosis (BHB ≤1.4 mmol/L; Nket group) at d 10 after calving. Serum concentrations of nonesterified fatty acids (NEFA) and BHB, as indicators of excessive fat mobilization and circulating ketone bodies, respectively, were significantly higher in the Ket group than in the Nket group. Aspartate transaminase (AST) and total bilirubin (TBIL), as indicators of liver damage, were higher in the Ket group than in the Nket group. Weighted gene co-expression network analysis (WGCNA) of the sWAT transcriptome revealed modules significantly correlated with serum BHB, NEFA, AST, TBIL, and total cholesterol. The genes in these modules were enriched in the regulation of the lipid biosynthesis process. Neurotrophic tyrosine kinase receptor type 2 (NTRK2) was identified as the key hub gene by intramodular connectivity, gene significance, and module membership. Quantitative reverse transcription PCR analyses for these samples, as well as a set of independent samples, validated the downregulation of NTRK2 expression in the sWAT of dairy cows with type II ketosis. NTRK2 encodes tyrosine protein kinase receptor B (TrkB), which is a high-affinity receptor for brain-derived neurotrophic factor, suggesting that abnormal lipid mobilization in cows with type II ketosis might be associated with impaired central nervous system regulation of adipose tissue metabolism, providing a novel insight into the pathogenesis underlying type II ketosis in dairy cows.


Assuntos
Doenças dos Bovinos , Cetose , Gravidez , Feminino , Bovinos , Animais , Lactação/metabolismo , Ácidos Graxos não Esterificados , Parto , Gordura Subcutânea/metabolismo , Cetose/veterinária , Bilirrubina , Ácido 3-Hidroxibutírico , Doenças dos Bovinos/metabolismo
14.
Int J Hematol ; 118(4): 483-488, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37269505

RESUMO

This article describes a potential treatment for early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), a relatively rare and highly aggressive hematologic malignancy. A 59-year-old woman admitted to our hospital with enlarged cervical lymph nodes, weight loss, abnormal count, and morphology of peripheral blood cells was diagnosed with ETP-ALL according to morphology, immunology, cytogenetics, and molecular biology. The patient initially received two cycles of the VICP regimen, including vincristine, idarubicin, cyclophosphamide, and prednisone, and had a response with positive minimal residual disease (MRD). The patient was then given venetoclax plus the CAG regimen, including aclarubicin, cytosine arabinoside, and granulocyte colony-stimulating factor. After one cycle, the patient achieved complete remission with negative MRD and was eligible for allogeneic hematopoietic stem cell transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Precursoras de Linfócitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Feminino , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Aclarubicina , Fator Estimulador de Colônias de Granulócitos , Citarabina , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico
15.
Epilepsy Res ; 193: 107161, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37163909

RESUMO

Epilepsy can seriously affect children's cognitive and behavioral development. The mechanistic target of rapamycin(mTOR) pathway plays an important role in neurodevelopment and epilepsy, but the mechanism of mechanistic target of rapamycin complex 2 (mTORC2) in epilepsy is still unclear. Here, we compared the similarities and differences of the mechanisms of action of mechanistic target of rapamycin complex 1 (mTORC1) and mTORC2 complex in the pathogenesis of epilepsy. Our research results show that the levels of apoptosis in cortical and hippocampal neurons were upregulated in epileptic rats (F = 32.15, 30.96; both P < 0.01), and epilepsy caused neuronal damage (F = 8.13, 9.43; both P < 0.01). The mTORC2-Akt pathway was activated in the cortex and hippocampus of epileptic rats. Inhibition of mTORC2 resulted in decreased levels of apoptosis and reduced neuronal damage in the cortex and hippocampus of epileptic rats. In the hippocampus, selective inhibition of mTORC2 increased lysosome-associated membrane protein 2 A (LAMP2A) protein expression compared with the control group, and the difference was statistically significant (F = 3.02, P < 0.05). Finally, we concluded that in the hippocampus, selective inhibition of mTORC2 can improve epileptic brain injury in rats by increasing chaperone-mediated autophagy (CMA) levels.


Assuntos
Lesões Encefálicas , Autofagia Mediada por Chaperonas , Epilepsia , Ratos , Animais , Sirolimo/farmacologia , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Epilepsia/tratamento farmacológico , Autofagia
16.
Curr Med Chem ; 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37226795

RESUMO

INTRODUCTION: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear. OBJECTIVE: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it. METHODS: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays. Results:The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme. CONCLUSION: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.

17.
Arch Biochem Biophys ; 743: 109642, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37211224

RESUMO

Renal cell carcinoma is one of the most common malignancies worldwide, and kidney renal clear cell carcinoma (KIRC) is the most common histopathological type of renal cell carcinoma. However, the mechanism of KIRC progression remains poorly understood. Apolipoprotein M (ApoM) is a plasma apolipoprotein and a member of the lipid transport protein superfamily. Lipid metabolism is essential for tumor progression, and its related proteins can be used as therapeutic targets for tumors. ApoM influences the development of several cancers, but its relationship with KIRC remains unclear. In this study, we aimed to investigate the biological function of ApoM in KIRC and to reveal its potential molecular mechanisms. We found that ApoM expression was significantly reduced in KIRC and was strongly correlated with patient prognosis. ApoM overexpression significantly inhibited KIRC cell proliferation in vitro, suppressed the epithelial mesenchymal transition (EMT) of KIRC cells, and decreased their metastatic capacity. Additionally, the growth of KIRC cells was inhibited by ApoM overexpression in vivo. In addition, we found that overexpression of ApoM in KIRC attenuated Hippo-YAP protein expression and YAP stability and thus inhibited KIRC growth and progression. Therefore, ApoM may be a potential target for the treatment of KIRC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Apolipoproteínas M/metabolismo , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Rim/patologia , Neoplasias Renais/metabolismo , Transdução de Sinais , Proteínas de Sinalização YAP
18.
Toxics ; 11(4)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37112591

RESUMO

Cadmium (Cd) is one of the heavy metals that contaminate rice cultivation, and reducing Cd contamination in rice through agronomic measures is a hot research topic. In this study, foliar sprays of gibberellins (GA) and brassinolide (BR) were applied to rice under Cd stress in hydroponic and pot experiments. After foliar spraying of GR and BR, the biomass of rice plants grown in either hydroponics or soil culture was significantly higher or even exceeded that in the absence of Cd stress. In addition, photosynthetic parameters (maximum fluorescence values), root length and root surface area, and CAT, SOD and POD activities were significantly improved. The MDA content decreased in the shoots, suggesting that the application of GR and BA may have enhanced photosynthesis and antioxidant function to alleviate Cd stress. Furthermore, the BR and GA treatments decreased the Cd content of rice roots, shoots and grains as well as the Cd transfer coefficient. Cd chemical morphology analysis of rice roots and shoots showed that the proportion of soluble Cd (Ethanol-Cd and Water-Cd) decreased, whereas the proportion of NaCl-Cd increased. Analysis of the subcellular distribution of Cd in rice roots and above ground showed that the proportion of Cd in the cell wall increased after foliar spraying of GA and BR. The results indicate that after foliar application of GA and BR, more of the Cd in rice was transformed into immobile forms and was fixed in the cell wall, thus reducing the amount in the seeds. In summary, foliar sprays of GA and BR can reduce the toxic effects of Cd on rice plants and reduce the Cd content in rice grains, with GA being more effective.

19.
Food Chem (Oxf) ; 6: 100170, 2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-36950347

RESUMO

This study aimed to identify the regulatory mechanisms of white, blue, red lights on carotenoid and tocochromanol biosynthesis in mung bean sprouts. Results showed that three lights stimulated the increase of the predominated lutein (3.2-8.1 folds) and violaxanthin (2.1-6.1 folds) in sprouts as compared with dark control, as well as ß-carotene (20-36 folds), with the best yield observed under white light. Light signals also promoted α- and γ-tocopherol accumulation (up to 1.8 folds) as compared with dark control. The CRTISO, LUT5 and DXS (1.24-6.34 folds) exhibited high expression levels under light quality conditions, resulting in an overaccumulation of carotenoids. The MPBQ-MT, TC and TMT were decisive genes in tocochromanol biosynthesis, and were expressed up to 4.19 folds as compared with control. Overall, the results could provide novel insights into light-mediated regulation and fortification of carotenoids and tocopherols, as well as guide future agricultural cultivation of mung bean sprouts.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36767054

RESUMO

This study established a comprehensive evaluation indicator model for the safety culture among residents during COVID-19 and an obstacle degree model for the identification of the major factors affecting the residents' safety culture. The results show that the overall level of the safety culture among residents was 0.6059. Safety education, channels for learning knowledge regarding safety, and implementation of safety management systems are currently the major obstacles affecting safety culture among residents, but there is still space for improvement in the future. Furthermore, the level of safety culture was strongly related to the distance from the infected, because this changes the risk of viral infection. There are also differences in obstacle factors in different regions. Therefore, it is necessary to implement measures targeting the improvement of safety culture in accordance with the risk of viral infection. Strategies for strengthening the safety culture are also given in this study for consideration in strategic decision making with the aim of promoting the improvement of safety culture among residents, which may help to reduce the risk of infection with COVID-19 for residents.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Gestão da Segurança
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