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1.
Food Res Int ; 195: 114947, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39277225

RESUMO

Mung beans were pretreated with a combination of ultrasonic and calcium ion to enhance the polyphenol content and antioxidant capacity during germination. Changes in polyphenol content and antioxidant capacity during germination, along with underlying mechanisms, were investigated. Both single ultrasound and combined ultrasound-Ca2+ pretreatments significantly increased the polyphenol content and enhanced the antioxidant capacity (p < 0.05) of mung beans depending on germination period. Among 74 polyphenolic metabolites identified in germinated mung beans, 50 were differential. Notably, 23 of these metabolites showed a significant positive correlation with antioxidant activity. Ultrasound pretreatment promoted flavonoid biosynthesis, whereas ultrasound-Ca2+ pretreatment favored the tyrosine synthesis pathway. Polyphenol composition and accumulation changes were mainly influenced by metabolic pathways like flavonoid, isoflavonoid, anthocyanin, and flavone/flavonol biosynthesis. The results suggest that ultrasound alone or combined with calcium ion pretreatments effectively enhance mung bean polyphenol content and antioxidant capacity during germination.


Assuntos
Antioxidantes , Cálcio , Germinação , Polifenóis , Sementes , Vigna , Germinação/efeitos dos fármacos , Polifenóis/metabolismo , Vigna/crescimento & desenvolvimento , Vigna/metabolismo , Cálcio/metabolismo , Antioxidantes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Flavonoides/metabolismo , Flavonoides/análise , Antocianinas/metabolismo
2.
Histopathology ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39104219

RESUMO

AIM: Manual detection and scoring of Ki67 hotspots is difficult and prone to variability, limiting its clinical utility. Automated hotspot detection and scoring by digital image analysis (DIA) could improve the assessment of the Ki67 hotspot proliferation index (PI). This study compared the clinical performance of Ki67 hotspot detection and scoring DIA algorithms based on virtual dual staining (VDS) and deep learning (DL) with manual Ki67 hotspot PI assessment. METHODS: Tissue sections of 135 consecutive invasive breast carcinomas were immunohistochemically stained for Ki67. Two DIA algorithms, based on VDS and DL, automatically determined the Ki67 hotspot PI. For manual assessment; two independent observers detected hotspots and calculated scores using a validated scoring protocol. RESULTS: Automated hotspot detection and assessment by VDS and DL could be performed in 73% and 100% of the cases, respectively. Automated hotspot detection by VDS and DL led to higher Ki67 hotspot PIs (mean 39.6% and 38.3%, respectively) compared to manual consensus Ki67 PIs (mean 28.8%). Comparing manual consensus Ki67 PIs with VDS Ki67 PIs revealed substantial correlation (r = 0.90), while manual consensus versus DL Ki67 PIs demonstrated high correlation (r = 0.95). CONCLUSION: Automated Ki67 hotspot detection and analysis correlated strongly with manual Ki67 assessment and provided higher PIs compared to manual assessment. The DL-based algorithm outperformed the VDS-based algorithm in clinical applicability, because it did not depend on virtual alignment of slides and correlated stronger with manual scores. Use of a DL-based algorithm may allow clearer Ki67 PI cutoff values, thereby improving the clinical usability of Ki67.

3.
J Pathol ; 264(1): 90-100, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39022850

RESUMO

Replication stress (RS) is a key trait of cancer cells, and a potential actionable target in cancer treatment. Accurate methods to measure RS in tumour samples are currently lacking. DNA fibre analysis has been used as a common technique to measure RS in cell lines. Here, we investigated DNA fibre analysis on fresh breast cancer specimens and correlated DNA replication kinetics to known RS markers and genomic alterations. Fresh, treatment-naïve primary breast cancer samples (n = 74) were subjected to ex vivo DNA fibre analysis to measure DNA replication kinetics. Tumour cell proliferation was confirmed by EdU incorporation and cytokeratin AE1/AE3 (CK) staining. The RS markers phospho-S33-RPA and γH2AX and the RS-inducing proto-oncogenes Cyclin E1 and c-Myc were analysed by immunohistochemistry. Copy number variations (CNVs) were assessed from genome-wide single nucleotide polymorphism (SNP) arrays. We found that the majority of proliferating (EdU-positive) cells in each sample were CK-positive and therefore considered to be tumour cells. DNA fibre lengths varied largely in most tumour samples. The median DNA fibre length showed a significant inverse correlation with pRPA expression (r = -0.29, p = 0.033) but was not correlated with Cyclin E1 or c-Myc expression and global CNVs in this study. Nuclear Cyclin E1 expression showed a positive correlation with pRPA levels (r = 0.481, p < 0.0001), while cytoplasmic Cyclin E1 expression exhibited an inverse association with pRPA expression (r = -0.353, p = 0.002) and a positive association with global CNVs (r = 0.318, p = 0.016). In conclusion, DNA fibre analysis performed with fresh primary breast cancer samples is feasible. Fibre lengths were associated with pRPA expression. Cyclin E1 expression was associated with pRPA and the percentage of CNVs. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias da Mama , Ciclina E , Replicação do DNA , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Ciclina E/genética , Ciclina E/metabolismo , Replicação do DNA/genética , Polimorfismo de Nucleotídeo Único , Proliferação de Células , Variações do Número de Cópias de DNA , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Idoso , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Adulto
4.
Int J Mol Sci ; 25(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38732268

RESUMO

Rice (Oryza sativa) is one of the most important staple foods worldwide. However, rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, seriously affects the yield and quality of rice. Calmodulin-binding transcriptional activators (CAMTAs) play vital roles in the response to biotic stresses. In this study, we showed that OsCAMTA3 and CAMTA PROTEIN LIKE (OsCAMTAPL), an OsCAMTA3 homolog that lacks the DNA-binding domain, functioned together in negatively regulating disease resistance in rice. OsCAMTA3 associated with OsCAMTAPL. The oscamta3 and oscamtapl mutants showed enhanced resistance compared to wild-type plants, and oscamta3/pl double mutants showed more robust resistance to M. oryzae than oscamta3 or oscamtapl. An RNA-Seq analysis revealed that 59 and 73 genes, respectively, were differentially expressed in wild-type plants and oscamta3 before and after inoculation with M. oryzae, including OsALDH2B1, an acetaldehyde dehydrogenase that negatively regulates plant immunity. OsCAMTA3 could directly bind to the promoter of OsALDH2B1, and OsALDH2B1 expression was decreased in oscamta3, oscamtapl, and oscamta3/pl mutants. In conclusion, OsCAMTA3 associates with OsCAMTAPL to regulate disease resistance by binding and activating the expression of OsALDH2B1 in rice, which reveals a strategy by which rice controls rice blast disease and provides important genes for resistance breeding holding a certain positive impact on ensuring food security.


Assuntos
Resistência à Doença , Regulação da Expressão Gênica de Plantas , Oryza , Doenças das Plantas , Proteínas de Plantas , Oryza/microbiologia , Oryza/genética , Oryza/imunologia , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Ascomicetos/patogenicidade , Regiões Promotoras Genéticas , Magnaporthe/patogenicidade , Transativadores/genética , Transativadores/metabolismo , Mutação
5.
Cell Rep ; 43(4): 114116, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38625790

RESUMO

Overexpression of Cyclin E1 perturbs DNA replication, resulting in DNA lesions and genomic instability. Consequently, Cyclin E1-overexpressing cancer cells increasingly rely on DNA repair, including RAD52-mediated break-induced replication during interphase. We show that not all DNA lesions induced by Cyclin E1 overexpression are resolved during interphase. While DNA lesions upon Cyclin E1 overexpression are induced in S phase, a significant fraction of these lesions is transmitted into mitosis. Cyclin E1 overexpression triggers mitotic DNA synthesis (MiDAS) in a RAD52-dependent fashion. Chemical or genetic inactivation of MiDAS enhances mitotic aberrations and persistent DNA damage. Mitosis-specific degradation of RAD52 prevents Cyclin E1-induced MiDAS and reduces the viability of Cyclin E1-overexpressing cells, underscoring the relevance of RAD52 during mitosis to maintain genomic integrity. Finally, analysis of breast cancer samples reveals a positive correlation between Cyclin E1 amplification and RAD52 expression. These findings demonstrate the importance of suppressing mitotic defects in Cyclin E1-overexpressing cells through RAD52.


Assuntos
Ciclina E , Instabilidade Genômica , Mitose , Proteínas Oncogênicas , Proteína Rad52 de Recombinação e Reparo de DNA , Humanos , Ciclina E/metabolismo , Ciclina E/genética , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Proteínas Oncogênicas/metabolismo , Proteínas Oncogênicas/genética , Replicação do DNA , Linhagem Celular Tumoral , Dano ao DNA , DNA/metabolismo , DNA/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia
6.
Chemistry ; 30(27): e202304118, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38433408

RESUMO

New chiral ligands could be obtained by introducing proline moieties and imidazoline moieties to binaphthyl skeletons. The chiral ligands exhibited balanced rigidity and flexibility which could allow the change of the conformations during the reactions on one hand, and could provide sufficient asymmetric induction on the other. The proline moiety could act as a linker connecting the binaphthyl skeletons and the imidazoline moieties as well as a coordinating group for the central metal, and the electronic and steric properties of the imidazoline groups could be carefully fine-tuned by the use of different substituents. In the presence of Cu(II) catalyst bearing such chiral ligands, aza-Friedel-Crafts reaction of 1-naphthols and electron-rich phenols with isatin-derived ketimines provided the desired products with good to excellent yields and up to 99 % ee. The reactions showed good scalability, and excellent ee could still be obtained when the reaction was carried out in gram-scale.

7.
Sportverletz Sportschaden ; 38(2): 64-72, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38471537

RESUMO

AIM: To evaluate the effect of a 12-week physical training regime comprising five components - speed, power, agility, reaction, quickness - on young football players' performance in terms of their capacity to move quickly in different phases. METHODS: The football players were randomly divided into an experimental group (n = 12) and a control group (n = 12). The rapid change of direction mobility was systematically investigated by using outdoor tests, the Illinois 505 Agility Test, the Square Pace Test, the Nebraska Agility Test, and the T-Shape Agility Test. RESULTS: With the intervention of training, considerable improvements were detected in all indicators, with the SPARQ training approach outperforming. CONCLUSION: The combined results indicate that SPARQ training can deliver favourable efficiency in terms of enhancing the agility of young football players.


Assuntos
Desempenho Atlético , Futebol , Humanos , Desempenho Atlético/fisiologia , Adolescente , Masculino , Futebol/fisiologia , Condicionamento Físico Humano , Criança , Teste de Esforço
8.
NPJ Breast Cancer ; 10(1): 1, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167507

RESUMO

Genomic instability, as caused by oncogene-induced replication stress, can lead to the activation of inflammatory signaling, involving the cGAS-STING and JAK-STAT pathways. Inflammatory signaling has been associated with pro-tumorigenic features, but also with favorable response to treatment, including to immune checkpoint inhibition. In this study, we aim to explore relations between inflammatory signaling, markers of replication stress, and immune cell infiltration in breast cancer. Expression levels of cGAS-STING signaling components (STING, phospho-TBK1, and phospho-STAT1), replication stress markers (γH2AX and pRPA), replication stress-related proto-oncogenes (Cyclin E1 and c-Myc) and immune cell markers (CD20, CD4, and CD57) are determined immunohistochemically on primary breast cancer samples (n = 380). RNA-sequencing data from TCGA (n = 1082) and METABRIC (n = 1904) are used to calculate cGAS-STING scores. pTBK1, pSTAT1 expression and cGAS-STING pathway scores are all increased in triple-negative breast cancers compared to other subtypes. Expression of γH2AX, pRPA, Cyclin E1, c-Myc, and immune cell infiltration positively correlate with p-STAT1 expression (P < 0.001). Additionally, we observe significant positive associations between expression of pTBK1 and γH2AX, pRPA, c-Myc, and number of CD4+ cells and CD20+ cells. Also, cGAS-STING scores are correlated with genomic instability metrics, such as homologous recombination deficiency (P < 0.001) and tumor mutational burden (P < 0.01). Moreover, data from the I-SPY2 clinical trial (n = 71) confirms that higher cGAS-STING scores are observed in breast cancer patients who responded to immunotherapy combined with chemotherapy. In conclusion, the cGAS-STING pathway is highly expressed in TNBCs and is correlated with genomic instability and immune cell infiltration.

9.
Mol Oncol ; 18(1): 6-20, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37067201

RESUMO

Oncogene-induced replication stress has been recognized as a major cause of genome instability in cancer cells. Increased expression of cyclin E1 caused by amplification of the CCNE1 gene is a common cause of replication stress in various cancers. Protein phosphatase magnesium-dependent 1 delta (PPM1D) is a negative regulator of p53 and has been implicated in termination of the cell cycle checkpoint. Amplification of the PPM1D gene or frameshift mutations in its final exon promote tumorigenesis. Here, we show that PPM1D activity further increases the replication stress caused by overexpression of cyclin E1. In particular, we demonstrate that cells expressing a truncated mutant of PPM1D progress faster from G1 to S phase and fail to complete licensing of the replication origins. In addition, we show that transcription-replication collisions and replication fork slowing caused by CCNE1 overexpression are exaggerated in cells expressing the truncated PPM1D. Finally, replication speed and accumulation of focal DNA copy number alterations caused by induction of CCNE1 expression was rescued by pharmacological inhibition of PPM1D. We propose that increased activity of PPM1D suppresses the checkpoint function of p53 and thus promotes genome instability in cells expressing the CCNE1 oncogene.


Assuntos
Neoplasias , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ciclina E/genética , Ciclina E/metabolismo , Instabilidade Genômica , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo
10.
J Org Chem ; 88(20): 14345-14350, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37791977

RESUMO

The copper(II)-catalyzed enantioselective aza-Friedel-Crafts reaction of indoles with isatin-derived N-Boc-ketimines was developed by using tunable chiral O-N-N tridentate ligands derived from BINOL and proline. In general, the reaction afforded chiral 3-indolyl-3-aminooxindoles under mild conditions in high yields (83-97%) with excellent ee (69-99%).

11.
J Org Chem ; 88(21): 14928-14944, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37874252

RESUMO

This paper describes the design and application of new binaphthyl-proline-based chiral ligands bearing imidazoline functional groups. These chiral ligands incorporate the advantages of both the binaphthyl and proline skeletons, they are featured with regulatable electronic and steric properties for the imidazoline functional groups, and form chiral complexes with different metal salts such as cuprous acetate. In the presence of an appropriate amount of a chiral catalyst, enantioselective conjugate addition of 4-hydroxycoumarin or related nucleophiles to different ß,γ-unsaturated α-ketoesters proceeded readily, giving the desired products in high yield (up to 99%) and excellent enantiomeric excess (up to 99%).

12.
J Agric Food Chem ; 71(40): 14575-14592, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37748081

RESUMO

Dipeptidyl peptidase IV (DPP-IV) inhibitory peptides can regulate type 2 diabetes by inhibiting the cleavage of glucagon-like peptide-1 and prolonging its half-life. The development of DPP-IV inhibitory peptides is still a hot topic. The primary structure of coix seed prolamins contains peptide sequence fragments that potentially inhibit DPP-IV; however, limited information is available regarding the extraction of peptides from coix seeds and the analysis of their conformational relationships. In this study, novel coix seed prolamin-derived peptides were obtained through single hydrolysis and double-enzyme stepwise hydrolysis. The inhibitory activity of these peptides against DPP-IV was evaluated to explore new functional properties of coix seeds. The results evidenced that the step-by-step enzymolysis (papain and alcalase) compared to single enzymolysis promoted the secondary structure disruption of the hydrolysates, enhanced the ß-turn structure, significantly increased the content of peptides below 1 kDa, and exhibited a substantial increase in DPP-IV inhibitory activity (97% inhibition). Three nontoxic DPP-IV inhibitory peptides, namely, LPFYPN, TFFPQ, and ATFFPQ (IC50 = 70.24, 176.87, 268.31 µM), were isolated and identified. All three peptides exhibited strong interactions with DPP-IV (all KA values >103). LPFYPN exhibited competitive inhibition, while TFFPQ and ATFFPQ demonstrated mixed competitive-noncompetitive inhibition. Hydrogen bonding and hydrophobic interactions were the main contributors to the coix seed prolamin peptides binding to DPP-IV. The central residue was a key amino acid in the parent peptide sequence, forming a more stable π-π stacking with residues in the active pocket, which may facilitate peptide activity. This study provides theoretical support for the development of coix seed-derived hypoglycemic peptides.

13.
Chem Commun (Camb) ; 59(46): 7096-7099, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37218456

RESUMO

Using binaphthyl-proline-based chiral ligands, Zn(II)-catalysed addition of alcohols and tert-butyl hydroperoxide to isatin-derived N-Boc ketimines provided the isatin-derived C3 N,O-aminals in up to 99% yield and up to 99% ee. The reactions could be carried out under mild conditions and a gram-scale reaction could be realized without the loss of the yield and enantioselectivity.

14.
Front Immunol ; 14: 1166377, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063864

RESUMO

Background: Glioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity. However, the role of QPCTL in glioma and the relationship between its expression and clinical outcomes remains unclear. Deciphering the role of QPCTL in glioma will provide a promising therapy for glioma cancer immunotherapy. Methods: QPCTL expression in glioma tissues and normal adjacent tissues was primarily analyzed in The Cancer Genome Atlas (TCGA) database, and further validated in another independent cohort from the Gene Expression Omnibus (GEO) database, Chinese Glioma Genome Atlas (CGGA), and Human Protein Atlas (HPA). The relationships between QPCTL expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which QPCTL interacted was built using the online STRING website. Meanwhile, we use Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to investigate the relationships between QPCTL expression and infiltrated immune cells and their corresponding gene marker sets. We analyzed the Differentially Expressed Genes (DEGs) including GO/KEGG and Gene Set Enrichment Analysis (GSEA) based on QPCTL-high and -low expression tumors. Results: In contrast to normal tissue, QPCTL expression was higher in glioma tumor tissue (p < 0.05). Higher QPCTL expression was closely associated with high-grade malignancy and advanced tumor stage. Univariate and multivariate analysis indicated the overall survival of glioma patients with higher QPCTL expression is shorter than those with lower QPCTL expression (p < 0.05). Glioma with QPCTL deficiency presented the paucity of infiltrated immune cells and their matching marker sets. Moreover, QPCTL is essential for glioma cell proliferation and tumor growth and is a positive correlation with glioma cell stemness. Conclusion: High QPCTL expression predicts high grades of gliomas and poor prognosis with impaired infiltration of adaptive immune cells in the tumor microenvironment as well as higher cancer stemness. Moreover, targeting QPCTL will be a promising immunotherapy in glioma cancer treatment.


Assuntos
Neoplasias Encefálicas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Glioma , Humanos , Antígeno CD47 , Glioma/genética , Glioma/terapia , Imunoterapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Microambiente Tumoral
15.
Front Nutr ; 10: 1117385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908915

RESUMO

There needs to be more information concerning the effect of different milling methods on the physicochemical properties of whole-grain mung bean flour. Therefore, the physicochemical properties of whole grain mung bean flour were analyzed using universal grinders (UGMB), ball mills (BMMB), and vibration mills (VMMB). The results showed that the particle size of the sample after ultrafine grinding treatment was significantly reduced to 21.34 µm (BMMB) and 26.55 µm (VMMB), and the specific surface area was increased. The particle distribution was uniform to a greater extent, and the color was white after treatment. Moreover, the water holding capacity (WHC), oil holding capacity (OHC), and swelling power (SP) increased, and the bulk density and solubility (S) decreased. The Rapid Viscosity Analyzer (RVA) indicated that the final viscosity of the sample after ultrafine grinding was high. Furthermore, rheological tests demonstrated that the consistency coefficient K, shear resistance, and viscosity were decreased. The results of functional experiments showed that the treated samples (BMMB and VMMB) increased their capacity for cation exchange by 0.59 and 8.28%, respectively, bile acid salt adsorption capacity increased from 25.56 to 27.27 mg/g and 26.38 mg/g, and nitrite adsorption capacity increased from 0.58 to 1.17 mg/g and 1.12 mg/g.

16.
Org Biomol Chem ; 21(8): 1764-1770, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36723244

RESUMO

High yields (up to 96%) and high ee (up to 92%) were achieved for chiral copper(II) complex-catalysed enantioselective Michael addition of malonates to ß,γ-unsaturated-α-ketoesters. The chiral ligands took advantage of both the binaphthyl and the proline moieties, and substituents with different electronic and steric features could be tolerated. The reactions could be carried out under mild conditions, and a gram scale reaction could be realised without the loss of yield and enantioselectivity.

17.
Int J Biol Sci ; 19(3): 897-915, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778129

RESUMO

Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD+/NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers.


Assuntos
Neoplasias , Humanos , Neoplasias/metabolismo , Mitocôndrias/metabolismo , Metabolismo Energético/genética , Ciclo do Ácido Cítrico/genética , Fosforilação Oxidativa , Microambiente Tumoral
18.
J Org Chem ; 88(5): 3046-3053, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36791262

RESUMO

New Cu(I) catalysts are effective in enantioselective Friedel-Crafts alkylation of a variety of indoles with different ß,γ-unsaturated α-ketoesters. A control study shows that such a catalyst system is less sensitive to air, and the reactions can be carried out without special cares such as glovebox operation or moisture/oxygen-free conditions. Preliminary computation results suggest that there exists π-π stacking between the substrate and the catalyst, and such an interaction seems to play a role in stabilizing the reaction intermediate and enhancing the stereoselectivity of the reactions. The desired products can be obtained in up to 98% yield at 99% enantiomeric excess. The same high enantioselectivity can be observed when the reaction is carried in a gram scale, indicating a good scalability of the catalyst system in enantioselective Friedel-Crafts alkylation of different indoles with ß,γ-unsaturated α-ketoesters.

19.
Rev. bras. med. esporte ; 29: e2022_0629, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1423410

RESUMO

ABSTRACT Introduction: The constant maintenance of muscular strength is a highly relevant care in training for tennis practice. The unstable platform is developed with the improvement of modern and technological resources, and the need to verify its effects on the athletes' physical fitness is requested. Objective: Study the effect of unstable platform training on tennis players' balance ability and assertiveness. Methods: 12 male tennis-practicing students of the Beijing Sports University School of Education 2020 class were randomly selected as research volunteers. Through a literature search, data statistics, and other methods, they were randomly divided into an experimental group and a control group. After 6 weeks of traditional training in the control group and the addition of unstable platform balance training in the experimental group, the results were compared. Results: The ability to stand with eyes open on the dominant leg was significantly improved in the experimental group. After routine training and balance training, the athletes in the experimental group had a great improvement in the assertiveness of passes (P<0.05), and the stability of the service was also improved (P<0.05). Conclusion: After training, all physical abilities were improved. The unstable platform training is a valid resource to improve athletes' balance and assertiveness ability. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução: A constante manutenção da força muscular é um cuidado altamente relevante no treinamento para a prática do tênis. A plataforma instável é desenvolvida com o aperfeiçoamento de recursos modernos e tecnológicos e a necessidade de verificar os seus efeitos sobre a aptidão física dos atletas é requisitada. Objetivo: Estudar o efeito do treinamento em plataforma instável sobre a capacidade de equilíbrio e assertividade dos tenistas. Métodos: Um total de 12 estudantes masculinos praticantes de tênis da classe 2020 da Escola de Educação da Universidade Esportiva de Beijing foram selecionados aleatoriamente como voluntários de pesquisa. Através de pesquisas bibliográficas, estatísticas de dados e outros métodos, eles foram divididos aleatoriamente em grupo experimental e grupo controle. Após 6 semanas de treinamento tradicional ao grupo controle e a adição de um treinamento de equilíbrio em plataforma instável no grupo experimental, comparou-se os resultados. Resultados: A capacidade de ficar em pé com os olhos abertos sobre a perna dominante foram significativamente aprimorados no grupo experimental. Após o treinamento de rotina e o treinamento de equilíbrio, os atletas do grupo experimental tiveram uma grande melhora na assertividade dos passes (P<0,05), e a estabilidade do saque também foi aprimorada(P<0,05). Conclusão: Após o treinamento, todas as habilidades físicas foram melhoradas. O treinamento em plataforma instável é um recurso válido para aprimorar a capacidade de equilíbrio e assertividade dos atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción: El mantenimiento constante de la fuerza muscular es un cuidado muy relevante en el entrenamiento para la práctica del tenis. La plataforma inestable se desarrolla con la mejora de los recursos modernos y tecnológicos y se solicita la comprobación de sus efectos sobre la aptitud física de los deportistas. Objetivo: Estudiar el efecto del entrenamiento en plataforma inestable sobre la capacidad de equilibrio y asertividad de los tenistas. Métodos: Un total de 12 estudiantes varones practicantes de tenis de la clase 2020 de la Escuela de Educación de la Universidad de Deportes de Pekín fueron seleccionados al azar como voluntarios para la investigación. Mediante la búsqueda de literatura, la estadística de datos y otros métodos, se dividieron aleatoriamente en grupo experimental y grupo de control. Tras 6 semanas de entrenamiento tradicional en el grupo de control y la adición del entrenamiento de equilibrio en plataforma inestable en el grupo experimental, se compararon los resultados. Resultados: La capacidad de mantenerse en pie con los ojos abiertos sobre la pierna dominante mejoró significativamente en el grupo experimental. Después del entrenamiento de rutina y del entrenamiento de equilibrio, los atletas del grupo experimental tuvieron una gran mejora en el asertividad de los pases (P<0,05), y también mejoró la estabilidad del saque (P<0,05). Conclusión: Tras el entrenamiento, todas las capacidades físicas mejoraron. El entrenamiento en plataforma inestable es un recurso válido para mejorar la capacidad de equilibrio y asertividad de los deportistas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

20.
Gland Surg ; 11(4): 720-741, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35531108

RESUMO

Background: Growing evidence proved that signal transducer and activators of transcription (STAT) proteins are cytoplasmic transcription factors known to play key roles in many cellular biological processes and may be prognostic predictors of some cancers. However, the role of each STAT family members in breast cancer (BRCA) is diverse and controversial. This study aimed to systematic mine the prognostic significance and immune infiltration of STAT family member in human BRCA. Methods: Based on The Cancer Genome Atlas (TCGA) database, we used the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas to analyze the expression of STAT family members in normal human breast and tumor tissues. The Kaplan-Meier Plotter, GEPIA and PrognoScan were utilized to assess the prognostic value of different STATs in BRCA. Then we used the cBioPortal, STRING, GeneMANIA and Metascape to make further mutation analysis, protein-protein interaction (PPI) analysis and subsequent functional enrichment analysis. Finally, the "ESTIMATE" and "ggcorrplot" package of R 17 software were used for immune infiltration analysis. Results: STAT2 [P<0.01, hazard ratio (HR) =1.23, 95% confidence interval (CI): 1.07-1.42] and STAT3 (P=0.018, HR =0.69, 95% CI: 0.51-0.94) could be an independent risk factor for predicting overall survival (OS). STAT4 could be used as an independent predictor of distant metastasis-free survival in BRCA based on both GSE19615 (P=0.021, HR =0.21, 95% CI: 0.06-0.79) and GSE2034 (P=0.015, HR =0.57, 95% CI: 0.37-0.90) datasets. Meanwhile, STAT5A, STAT5B and STAT6 also have been shown to independently predict the prognosis of BRCA. Additionally, the functional mechanisms of STAT4 co-expressed genes were mainly focused on immune-related pathways and its expression was associated with immune checkpoint-associated genes and immunomodulators in BRCA. Conclusions: Our study mined the prognostic significance of STAT family members in BRCA and their correlation with immune infiltration. The results suggest that individual STATs, except STAT1, may act as a prognostic biomarker for BRCA and provide a reference for further potential immunotherapies.

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