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1.
Tissue Cell ; 89: 102471, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39029315

RESUMO

Lectin galactoside-binding soluble 3-binding protein (LGALS3BP) is associated with cancer metastasis and is a promising prognostic marker in neoplasms. In hepatocellular carcinoma (HCC), the prognostic impact and pro-metastatic function of LGALS3BP remain unclear. This study evaluated the endogenous LGALS3BP expression in HCC tissue and its association with prognosis. LGALS3BP protein levels were significantly elevated in clinical HCC tissues and cell lines. Increased LGALS3BP expression was closely associated with disease progression in HCC patients, and they also exhibited an unfavorable prognosis. Furthermore, the knockdown of LGALS3BP inhibited the growth, migration, and invasion of HCC cells in vitro. In mice xenografts, silencing LGALS3BP significantly inhibited tumor cell growth in vivo. Mechanically, upon LGALS3BP depletion, the tumor-suppressive function was dependent on inactivating Phosphatidylinositol 3-kinase (PI3K)/V-akt murine thymoma viral oncogene homolog (AKT) signaling pathway. Collectively, these findings suggest that LGALS3BP employs a pro-tumorigenic function in HCC and may be a promising HCC prognostic marker.


Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Prognóstico , Animais , Linhagem Celular Tumoral , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Camundongos , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Pessoa de Meia-Idade , Proliferação de Células/genética , Movimento Celular/genética , Camundongos Nus , Invasividade Neoplásica , Antígenos de Neoplasias , Biomarcadores Tumorais
2.
Cell Rep Med ; 5(5): 101522, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38701781

RESUMO

Neuroinflammation plays a significant role in ischemic injury, which can be promoted by oxidized mitochondrial DNA (Ox-mtDNA). Cytidine/uridine monophosphate kinase 2 (CMPK2) regulates mtDNA replication, but its role in neuroinflammation and ischemic injury remains unknown. Here, we report that CMPK2 expression is upregulated in monocytes/macrophages and microglia post-stroke in humans and mice, respectively. Microglia/macrophage CMPK2 knockdown using the Cre recombination-dependent adeno-associated virus suppresses the inflammatory responses in the brain, reduces infarcts, and improves neurological outcomes in ischemic CX3CR1Cre/ERT2 mice. Mechanistically, CMPK2 knockdown limits newly synthesized mtDNA and Ox-mtDNA formation and subsequently blocks NLRP3 inflammasome activation in microglia/macrophages. Nordihydroguaiaretic acid (NDGA), as a CMPK2 inhibitor, is discovered to reduce neuroinflammation and ischemic injury in mice and prevent the inflammatory responses in primary human monocytes from ischemic patients. Thus, these findings identify CMPK2 as a promising therapeutic target for ischemic stroke and other brain disorders associated with neuroinflammation.


Assuntos
AVC Isquêmico , Microglia , Doenças Neuroinflamatórias , Animais , Humanos , Masculino , Camundongos , Lesões Encefálicas/patologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/genética , Isquemia Encefálica/patologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Inflamassomos/metabolismo , AVC Isquêmico/patologia , AVC Isquêmico/metabolismo , AVC Isquêmico/genética , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética
3.
Asian J Surg ; 47(6): 2613-2622, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565445

RESUMO

BACKGROUND: The optimal proximal margin (PM) length for Siewert II/III adenocarcinoma of the esophagogastric junction (AEJ) remains unclear. This study aimed to determine the optimal PM length using an abdominal approach to guide surgical decision-making. METHODS: A prospective study analyzed 304 consecutive patients diagnosed with Siewert II/III AEJ between January 2019 and December 2021. Total gastrectomy was performed via the abdominal approach, and PM length was measured on fixed gross specimens. X-Tile software determined the optimal PM cut-point based on progression-free survival (PFS). Univariate analyses compared baseline characteristics across PM groups, while survival analyses utilized Kaplan-Meier estimation and Cox proportional hazards regression for assessing the impact of margin length on survival. Multivariable analyses were conducted to adjust for confounding variables. RESULTS: The study included 264 AEJ cases classified as Siewert II (71.97%) or III (28.03%). The median gross PM length was 1.0 cm (IQR: 0.5 cm-1.5 cm, range: 0 cm-6 cm). PM length ≥1.2 cm was associated with a lower risk of disease progression compared to PM length 0.4 cm on PFS (HR = 0.41, 95% CI 0.20-0.84, P = 0.015). Moreover, PM ≥ 1.2 cm improved prognosis in subgroups of T4 or N3, tumor size <4 cm, Siewert II, and Lauren classification. CONCLUSIONS: For Siewert type II/III AEJ, a proximal margin length ≥1.2 cm (1.65 cm in situ) is associated with improved outcomes. These findings offer valuable insights into the association between PM length and outcomes in Siewert II/III AEJ, providing guidance for surgical approaches and aiding clinical decision-making to enhance patient outcomes.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Gastrectomia , Margens de Excisão , Neoplasias Gástricas , Humanos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Gastrectomia/métodos , Idoso , Prognóstico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Estudos Prospectivos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/mortalidade
4.
Methods Mol Biol ; 2782: 39-63, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38622391

RESUMO

T cells are a heterogeneous group of cells that can be classified into different subtypes according to different classification methods. The body's immune system has a highly complex and effective regulatory network that allows for the relative stability of immune system function. Maintaining proper T cell homeostasis is essential for promoting protective immunity and limiting autoimmunity and tumor formation. Among the T cell family members, more and more T cell subsets have gradually been characterized. In this chapter, we summarize the functions of some key T cell subsets and their impact on immune homeostasis.


Assuntos
Neoplasias , Linfócitos T Reguladores , Humanos , Subpopulações de Linfócitos T , Autoimunidade , Homeostase
5.
J Chromatogr A ; 1710: 464436, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37837724

RESUMO

A method for determining tobacco-specific nitrosamines (TSNAs) in tobacco and cigarette smoke using liquid chromatography-tandem mass spectrometry was established. The established method amended the deficiencies that exist in current mainstream methods. In this method, TSNAs in tobacco and cigarette smoke were extracted by water. The aqueous extract was then extracted by dichloromethane, and the extract could be analyzed by liquid chromatography-tandem mass spectrometry after a solvent replacement. This method was used to analyze flue-cured tobacco samples, and the response of the target compounds was about 10 times higher than that of the ammonium acetate extraction method. When analyzing cigarette smoke samples, the response strength and chromatographic peak purity of the target compounds were also significantly improved. The proposed method exhibited good linearities for both tobacco and cigarette smoke samples (r2 > 0.99). The limits of detection (LODs) for tobacco and cigarette smoke samples were 0.2-1.0 ng/g and 0.1-0.3 ng/cigarette, respectively. Additionally, this method exhibited desirable accuracy and precision. The TSNAs recovery values from tobacco and cigarette smoke samples ranged from 95.7 % to 107.7 % with inter- and intra-day relative standard deviations (RSDs) of less than 7.4 %. This method is simple, effective, and has wide adaptability. It is a useful upgrade to the existing methods for analyzing TSNAs in tobacco and cigarette smoke.


Assuntos
Fumar Cigarros , Nitrosaminas , Nitrosaminas/análise , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Cromatografia Líquida
6.
World J Surg Oncol ; 21(1): 316, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814242

RESUMO

Adenocarcinoma of the gastroesophageal junction (AEG) has become increasingly common in Western and Asian populations. Surgical resection is the mainstay of treatment for AEG; however, determining the distance from the upper edge of the tumor to the esophageal margin (PM) is essential for accurate prognosis. Despite the relevance of these studies, most have been retrospective and vary widely in their conclusions. The PM is now widely accepted to have an impact on patient outcomes but can be masked by TNM at later stages. Extended PM is associated with improved outcomes, but the optimal PM is uncertain. Academics continue to debate the surgical route, extent of lymphadenectomy, preoperative tumor size assessment, intraoperative cryosection, neoadjuvant therapy, and other aspects to further ensure a negative margin in patients with gastroesophageal adenocarcinoma. This review summarizes and evaluates the findings from these studies and suggests that the choice of approach for patients with adenocarcinoma of the esophagogastric junction should take into account the extent of esophagectomy and lymphadenectomy. Although several guidelines and reviews recommend the routine use of intraoperative cryosections to evaluate surgical margins, its generalizability is limited. Furthermore, neoadjuvant chemotherapy and radiotherapy are more likely to increase the R0 resection rate. In particular, intraoperative cryosections and neoadjuvant chemoradiotherapy were found to be more effective for achieving negative resection margins in signet ring cell carcinoma.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Prognóstico , Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Esofagectomia , Estadiamento de Neoplasias
7.
Thromb Res ; 229: 53-68, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37413892

RESUMO

BACKGROUND: HIV-infected individuals are known to be at higher risk for thrombotic cardiovascular disease (CVD), which may also be differentially affected by components of anti-HIV drugs. To identify the effects of a series of FDA-approved anti-HIV drugs on platelet aggregation in humans, focusing on the novel pharmacological effects of rilpivirine (RPV), a reverse transcriptase inhibitor, on platelet function both in vitro and in vivo and the mechanisms involved. METHODS AND RESULTS: In vitro studies showed that RPV was the only anti-HIV reagent that consistently and efficiently inhibited aggregation elicited by different agonists, exocytosis, morphological extension on fibrinogen, and clot retraction. Treatment of mice with RPV significantly prevented thrombus formation in FeCl3-injured mesenteric vessels, postcava with stenosis surgery, and ADP -induced pulmonary embolism models without defects in platelet viability, tail bleeding, and coagulation activities. RPV also improved cardiac performance in mice with post-ischemic reperfusion. A mechanistic study revealed that RPV preferentially attenuated fibrinogen-stimulated Tyr773 phosphorylation of ß3-integrin by inhibiting Tyr419 autophosphorylation of c-Src. Molecular docking and surface plasmon resonance analyses showed that RPV can bind directly to c-Src. Further mutational analysis showed that the Phe427 residue of c-Src is critical for RPV interaction, suggesting a novel interaction site for targeting c-Src to block ß3-integrin outside-in signaling. CONCLUSION: These results demonstrated that RPV was able to prevent the progression of thrombotic CVDs by interrupting ß3-integrin-mediated outside-in signaling via inhibiting c-Src activation without hemorrhagic side effects, highlighting RPV as a promising reagent for the prevention and therapy of thrombotic CVDs.


Assuntos
Fármacos Anti-HIV , Trombose , Humanos , Camundongos , Animais , Integrina beta3/metabolismo , Fosforilação , Rilpivirina/metabolismo , Rilpivirina/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Reposicionamento de Medicamentos , Simulação de Acoplamento Molecular , Plaquetas/metabolismo , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Trombose/metabolismo , Fármacos Anti-HIV/metabolismo , Fármacos Anti-HIV/farmacologia , Fibrinogênio/metabolismo
8.
Opt Express ; 31(10): 16770-16780, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37157749

RESUMO

For wide dynamic range gas concentration detection based on tunable diode laser absorption spectroscopy (TDLAS), direct absorption spectroscopy (DAS) and wavelength modulation spectroscopy (WMS) are usually used in combination. However, in some application scenarios such as high-speed flow field detection, natural gas leakage, or industrial production, the requirements of wide-range, fast response and calibration-free must be met. Taking applicability and cost of TDALS-based sensor into consideration, a method of optimized direct absorption spectroscopy (ODAS) based on signal correlation and spectral reconstruction is developed in this paper. This method can achieve adaptive selection of the optimal benchmark spectrum for spectral reconstruction. Moreover, methane (CH4) is taken as an example to carry out the experimental verification. Experimental results proved that the method satisfies wide dynamic range detection of more than 4 orders of magnitude. It is worth noting that when measuring large absorbance with concentration of 75 × 104 ppm with DAS and ODAS method, respectively, the maximum value of residual is reduced from 3.43 to 0.07. Furthermore, whether measuring gas of small or large absorbance with different concentrations, which vary from 100 ppm to 75 × 104 ppm, the correlation coefficient between standard concentrations and inverted concentrations is 0.997, showing the linear consistency of the method in wide dynamic range. In addition, the absolute error is 1.81 × 104 ppm when measuring large absorbance of 75 × 104 ppm. It greatly improves the accuracy and reliability with the new method. In summary, the ODAS method can not only fulfill the measurement of gas concentration in wide range, but also further expand the application prospects of TDLAS.

9.
Phytomedicine ; 114: 154740, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36965373

RESUMO

BACKGROUND: As a multifaceted metabolic disorder, insulin resistance is accompanied by the preceding onset of type 2 diabetes mellitus, hyperinsulinemia, metabolic dysfunction-associated fatty liver disease (MAFLD) and other metabolic syndromes. Currently, the number of existing drugs and mechanism-based strategies is limited to alleviate insulin resistance in clinics. As a natural polyphenol product derivative, 1,3,6,7-tetrapropylene acyloxy-ketone (TPX) showed a significant hypoglycemic effect in our previous studies. However, whether TPX could improve hepatic insulin sensitivity was unknown. PURPOSE: To explore whether insulin sensitivity can be improved by the treatment with TPX and further investigate its mechanism(s) of activity. METHODS: To mimic hyperglycemia and insulin resistance in vitro, human HepG2 and HL-7702 hepatocytes were exposed to high glucose. Cellular glucose uptake, glucose consumption, glycogen synthesis, and glucose production were quantified after TPX treatment. The effects of TPX on AMP-activated protein kinase (AMPK) phosphorylation, glucose metabolism, and insulin signal transduction were evaluated by western blotting and network pharmacology analysis. The eGFP-membrane of glucose transporter type 4 (GLUT4) lentivirus transfected cells were constructed to investigate the effects of TPX on GLUT4 mobilization. Reactive oxygen species activity in high glucose-induced insulin-resistant cells was measured by DCFH-DA to show oxidative stress. RESULTS: Treatment with TPX improved glycogen synthesis and inhibited gluconeogenesis by regulating GSK3ß, G6Pase, and PEPCK. Furthermore, high glucose-induced inhibition of glucose consumption, glucose uptake, and GLUT4-mediated membrane translocation were reverted by TPX. Accordingly, mechanistic investigations revealed that TPX interacted with AMPK protein and activated the phosphorylation of AKT, thereby improving energy homeostasis and further ameliorating hepatic insulin resistance. Network pharmacology analysis and molecular docking further confirmed AMPK as an active target of TPX. Concordantly, the pharmacological activity of TPX was reversed by the AMPK inhibitor compound C when hepatocytes were exposed to high glucose stimulation. CONCLUSION: In summary, our study confirmed TPX contributions to insulin resistance improvements by targeting AMPK and PI3K/AKT to restore the insulin signaling pathway, which may be an important potential treatment strategy for insulin-resistance-related diseases, including MAFLD and diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Simulação de Acoplamento Molecular , Hepatócitos , Transdução de Sinais , Glucose/metabolismo , Insulina/metabolismo , Glicogênio/metabolismo
10.
Cancer Cell ; 41(4): 693-710.e8, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-36963400

RESUMO

Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8+ T subsets, as well as cytotoxic CD4+ T subsets. Notably, a distinct subpopulation of CD4+ T cells exhibits innate-like features with preferential interleukin-8 (IL-8) expression. With IL-8-humanized mouse strain, we demonstrate that IL-8-producing CD4+ T, myeloid, and tumor cells orchestrate myeloid-derived suppressor cell infiltration and angiogenesis, which results in enhanced tumor growth but reduced ICB efficacy. Antibody-mediated IL-8 blockade or the inhibition of its receptor, CXCR1/2, unleashes anti-PD-1-mediated antitumor immunity. Our findings thus highlight IL-8 as a combinational immunotherapy target for glioma.


Assuntos
Glioma , Inibidores de Checkpoint Imunológico , Interleucina-8 , Animais , Camundongos , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/patologia , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia/métodos , Interleucina-8/metabolismo , Linfócitos T , Microambiente Tumoral
11.
J Chromatogr Sci ; 61(5): 403-409, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35567797

RESUMO

Eleven consecutive N'-n-acylnornicotines from cherry-red tobacco were structurally elucidated and quantitively analyzed using chromatography and mass spectrometry. All of these N'-n-acylnornicotines are first reported in cherry-red tobacco, whereas N'-propionylnornicotine, N'-n-valerylnornicotine, N'-n-nonanoylnornicotine and N'-n-undecanoylnornicotine are first reported in natural products. The concentration distribution of the identified N'-n-acylnornicotines was studied and it was found that N'-n-octanoylnornicotine and N'-n-hexanoylnornicotine showed the highest concentration, accounting for 94% of the detected N'-n-acylnornicotines. The cherry-red color density of the related tobacco leaves was found to be positively correlated with the concentration of the N'-n-acylnornicotines, whereas the ultraviolet-visible spectra of the N'-n-acylnornicotines showed no absorption larger than 300 nm, indicating the discovered compounds are not responsible for the cherry-red color appearance.


Assuntos
Nicotiana , Cromatografia , Espectrometria de Massas/métodos , Nicotina/análise , Nicotina/química , Nicotiana/química
12.
J Psychiatr Res ; 155: 511-517, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36191519

RESUMO

Major depressive disorder (MDD), insomnia (INS) and chronic pain (CP) often have high comorbidity and show high genetic correlation. Here we aimed to better characterize their novel, shared and disorder-specific genetic architecture. Based on genome-wide association study (GWAS) summary data, we applied the conditional false discovery rate (condFDR) and conjunctional FDR (conjFDR) approach to investigate the novel and overlapped genetic loci for MDD, INS and CP. In addition, putative disorder-specific SNP associations were analyzed by conditioning the other two traits. The functions of the identified genomic loci were explored by performing gene set enrichment analysis (GSEA) for the loci mapped genes. We identified 22, 43 and 91 novel risk loci for MDD, INS and CP. GSEA for the loci mapped genes highlighted olfactory signaling pathway for MDD novel loci, breast cancer related gene set for both INS and CP novel loci, and nervous system related development, structure and activity for CP. Furthermore, we identified three loci jointly associated with the three disorders, including 13q14.3 locus with nearby gene OLFM4, 14q21.1 locus with nearby gene LRFN5 and 5q21.2 locus located in intergenic region. In addition, we identified one specific loci for MDD, 7 for INS and 11 for CP respectively by conditioning the other two traits, which were mapped to 68 genes for MDD, 85 for INS and 100 for CP. The MDD specific genes are enriched in immune system related pathways. This study increases understanding of the genetic architectures underlying MDD, INS and CP. The shared underlying genetic risk may help to explain the high comorbidity rates of the disorders.


Assuntos
Dor Crônica , Transtorno Depressivo Maior , Distúrbios do Início e da Manutenção do Sono , Dor Crônica/genética , DNA Intergênico , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único/genética , Distúrbios do Início e da Manutenção do Sono/genética
13.
Front Pharmacol ; 13: 945949, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016555

RESUMO

Objective: The aim of the study was to explore the evidence of JWRJD in the treatment of cryptozoospermia. Methods: A total of 162 cryptozoospermia patients with varicocele who refused to undergo surgery were included from January 2021 to December 2021. They were divided into the Jiawei Runjing Decoction group (group A), tamoxifen group (group B), and no treatment group (group C), and after the follow-up for 3 months, therapeutic effectiveness was compared. Network pharmacology was used to analyze and validate the effects and mechanisms of JWRJD. Results: Fifty-eight patients were treated with JWRJD, 55 with tamoxifen, and 49 without any treatment. After treatment, five patients were lost: one in group A, one in group B, and three in group C. The sperm count and the decrease of FSH in group A were significantly higher, but the degree of decline in the testicular volume and the degree of vein expansion have decreased significantly, which were closely related to the testicular volume (TV) [especially changes in the left testicular volume (ΔL-TV)], citric acid (CC) and its changes (ΔCC), and the vein width (VW) [especially left spermatic vein width (L-VW) and mean vein width (M-VW) and their changes (ΔL-VW and ΔM-VW)], as well as the sperm count before the treatment (bSC), which were the significant indexes to predict the therapeutic effect, especially for patients >35 years old and with grade III varicoceles. Network pharmacological analysis verifies that it can be regulated by fluid shear stress and the atherosclerosis pathway to improve the testicular microenvironment for spermatogenesis. Conclusion: JWRJD may promote spermatogenesis in cryptozoospermia patients with varicocele, which may be closely related to improving the testicular microenvironment, especially for >35 year olds and grade III varicocele patients.

14.
Bioorg Med Chem ; 71: 116936, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35917766

RESUMO

Phidianidines A and B are novel marine indole alkaloids with various biological activities. Based on their potential anti-inflammatory properties, a series of phidianidine derivatives were designed, synthesized, and tested for their effects on IL-17A production in PMA/ionomycin-stimulated T-cell-lymphoma EL-4 cells. Compounds 9a and 22c exhibited excellent anti-inflammatory activity and low toxicity, with IC50 values of 7.7 µM and 5.3 µM for IL-17A production in PMA/ionomycin-stimulated EL-4 cells, respectively. Further mechanistic study showed that 9a could decrease the STAT3 phosphorylation at Y705 to inhibit IL-17A production in EL-4 cells, indicating its ability of preventing the differentiation of Th17 cells and their possible function. This research may give an insight for the discovery of marine indole alkaloid derived anti-inflammatory drug leads for the treatment of T cell-mediated diseases.


Assuntos
Alcaloides Indólicos , Interleucina-17 , Anti-Inflamatórios/farmacologia , Ionomicina , Relação Estrutura-Atividade
15.
Front Mol Neurosci ; 15: 845212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35283726

RESUMO

Background: Major depressive disorder (MDD) has become a leading cause of disability worldwide. However, the diagnosis of the disorder is dependent on clinical experience and inventory. At present, there are no reliable biomarkers to help with diagnosis and treatment. DNA methylation patterns may be a promising approach for elucidating the etiology of MDD and predicting patient susceptibility. Our overarching aim was to identify biomarkers based on DNA methylation, and then use it to propose a methylation prediction score for MDD, which we hope will help us evaluate the risk of breast cancer. Methods: Methylation data from 533 samples were extracted from the Gene Expression Omnibus (GEO) database, of which, 324 individuals were diagnosed with MDD. Statistical difference of DNA Methylation between Promoter and Other body region (SIMPO) score for each gene was calculated based on the DNA methylation data. Based on SIMPO scores, we selected the top genes that showed a correlation with MDD in random resampling, then proposed a methylation-derived Depression Index (mDI) by combining the SIMPO of the selected genes to predict MDD. A validation analysis was then performed using additional DNA methylation data from 194 samples extracted from the GEO database. Furthermore, we applied the mDI to construct a prediction model for the risk of breast cancer using stepwise regression and random forest methods. Results: The optimal mDI was derived from 426 genes, which included 245 positive and 181 negative correlations. It was constructed to predict MDD with high predictive power (AUC of 0.88) in the discovery dataset. In addition, we observed moderate power for mDI in the validation dataset with an OR of 1.79. Biological function assessment of the 426 genes showed that they were functionally enriched in Eph Ephrin signaling and beta-catenin Wnt signaling pathways. The mDI was then used to construct a predictive model for breast cancer that had an AUC ranging from 0.70 to 0.67. Conclusion: Our results indicated that DNA methylation could help to explain the pathogenesis of MDD and assist with its diagnosis.

16.
Leuk Res ; 108: 106605, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34090063

RESUMO

Some studies have elucidated that Minimal residual disease (MRD) in patient with Mantle Cell Lymphoma (MCL) was a significant prognostic factor, with potential value in assessing overall survival (OS) and progression-free survival (PFS). However, most studies were widely varied in included population, sample sources and MRD detection time points. Some studies even have conflicting results. In view of this, a meta-analysis was performed to evaluate association of MRD levels with clinical outcomes in patients with MCL. We identified 7 included articles, which were published in recent 20 years. Then, we extracted or calculated hazard ratios (HRs) and their 95 % confidence intervals (CIs). Our results reveal that patients with MRD negativity have improved OS (HR = 0.63; 95 % CI: 0.50-0.79) and PFS (HR = 0.40, 95 % CI: 0.21-0.76), comparing with patients with MRD positivity. There are also consistent results in subgroups based on sample sources and MRD detection time points. Our study also demonstrates that MRD level is a strong prognostic factor of clinical outcomes. Thus, MRD is expected to be an effective clinical indicator for assessing prognosis and guide treatment decisions in MCL patients.


Assuntos
Linfoma de Célula do Manto/mortalidade , Neoplasia Residual/mortalidade , Humanos , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Prognóstico , Resultado do Tratamento
17.
J Anal Methods Chem ; 2021: 8874827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33542846

RESUMO

The mining of weak correlation information between two data matrices with high complexity is a very challenging task. A new method named principal component analysis-based multiconfidence ellipse analysis (PCA/MCEA) was proposed in this study, which first applied a confidence ellipse to describe the difference and correlation of such information among different categories of objects/samples on the basis of PCA operation of a single targeted data. This helps to find the number of objects contained in the overlapping and nonoverlapping areas of ellipses obtained from PCA runs. Then, a quantitative evaluation index of correlation between data matrices was defined by comparing the PCA results of more than one data matrix. The similarity and difference between data matrices was further quantified through comprehensively analyzing the outcomes. Complicated data of tobacco agriculture were used as an example to illustrate the strategy of the proposed method, which includes rich features of climate, altitude, and chemical compositions of tobacco leaves. The number of objects of these data reached 171,516 with 14, 4, and 5 descriptors of climate, altitude, and chemicals, respectively. On the basis of the new method, the complex but weak relationship between these independent and dependent variables were interestingly studied. Three widely used but conventional methods were applied for comparison in this work. The results showed the power of the new method to discover the weak correlation between complicated data.

18.
Sci Rep ; 11(1): 1547, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452378

RESUMO

A fast, sensitive, and reliable analytical method was developed and validated for simultaneous identification and quantification of spirodiclofen, spiromesifen, and spirotetramat and their relevant metabolites in edible fungi by ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). First, sample extraction was done with acetonitrile containing 1% formic acid followed by phase separation with the addition of MgSO4:NaOAc. Then, the supernatant was purified by primary secondary amine (PSA), octadecylsilane (C18), and graphitized carbon black (GCB). The linearities of the calibrations for all analytes were excellent (R2 ≥ 0.9953). Acceptable recoveries (74.5-106.4%) for all analytes were obtained with good intra- and inter- relative standard deviations of less than 14.5%. The limit of quantification (LOQs) for all analytes was 10 µg kg-1. For accurate quantification, matrix-matched calibration curve was applied to normalize the matrix effect. The results indicated that the method was suitable for detecting the three acaricides and their relevant metabolites in edible fungi.


Assuntos
4-Butirolactona/análogos & derivados , Compostos Aza/análise , Compostos de Espiro/análise , 4-Butirolactona/análise , 4-Butirolactona/química , 4-Butirolactona/metabolismo , Acaricidas/toxicidade , Agaricales/química , Agaricales/efeitos dos fármacos , Compostos Aza/química , Compostos Aza/metabolismo , China , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Alimentos/análise , Fungos , Limite de Detecção , Compostos de Espiro/química , Compostos de Espiro/metabolismo , Espectrometria de Massas em Tandem/métodos
19.
World J Surg Oncol ; 18(1): 302, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213468

RESUMO

BACKGROUND: Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication. METHODS: Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression. RESULT: In multivariable analysis, age (OR 1.081, 95% CI, 1.047-1.117), BMI (OR 1.233, 95% CI, 1.116-1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829-8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325-6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632-7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963-5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086-1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003-1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068-0.785) was independent protective factor of FDGE. CONCLUSION: Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.


Assuntos
Gastroparesia , Neoplasias Gástricas , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgia
20.
Artigo em Inglês | MEDLINE | ID: mdl-32908558

RESUMO

PURPOSE: This study aimed to investigate the effects of different concentrations of Yiqi Xingnao (YQXN) oral liquid on cerebral ischemia/reperfusion (I/R) injury in rats and YQXN's related mechanisms. METHODS: Rats were pretreated with 3 mL/kg, 6 mL/kg, and 12 mL/kg YQXN and Naoxuekang capsule (NXK). Afterwards, cerebral I/R model rats were established by a middle cerebral artery occlusion surgery. Neurological deficits, histopathology, and cerebral infarction volume were used to evaluate the effects of YQXN. Evans blue and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were utilized to determine the blood-brain barrier permeability and cell apoptosis, respectively. The expression of VEGF and Bcl-2 was analyzed by real-time quantification PCR (RT-qPCR) and western blot. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured using corresponding assay kits. RESULTS: The rats pretreated with YQXN had improved neurological deficits, reduced infarct volume and blood-brain barrier permeability, and ameliorated ischemia-induced morphology change in injured brain tissues. TUNEL staining results showed that different concentrations of YQXN inhibited cell apoptosis of neurocytes in I/R rats. Besides, RT-qPCR and western blot analyses indicated that the expression levels of VEGF and Bcl-2 were significantly upregulated by YQXN compared with the I/R group (P < 0.05). Additionally, rats in the I/R group had lower SOD activity and higher MDA content than those in the sham-operated group, while their levels were recovered by YQXN (P < 0.05). CONCLUSION: YQXN could alleviate cerebral I/R injury by suppressing blood-brain barrier permeability, neuron apoptosis, and oxidative stress, promoting angiogenesis.

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