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1.
Artigo em Inglês | MEDLINE | ID: mdl-38716221

RESUMO

Background: Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics. Methods: A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student t-test. Results: Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8+ T cells in PBMCs (P=0.0005), and altered frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8+ stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients. Conclusions: The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.

2.
Eur J Nucl Med Mol Imaging ; 51(7): 1856-1868, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38355741

RESUMO

PURPOSE: Accurately and early detection of intestinal fibrosis in Crohn's disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [18F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[18F]F-FDG PET/CT and magnetization transfer MR imaging (MTI). METHODS: Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated on[18F]F-FAPI and [18F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol. RESULTS: In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUVmean: R = 0.69) with pathological fibrosis than FDG (SUVmean: R = 0.17) and MTI (R = 0.52). CONCLUSION: The diagnostic efficacy of [18F]F-FAPI PET/CT in detecting CD fibrosis is superior to [18F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis.


Assuntos
Doença de Crohn , Modelos Animais de Doenças , Fibrose , Fluordesoxiglucose F18 , Intestinos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/complicações , Animais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Ratos , Fibrose/diagnóstico por imagem , Humanos , Masculino , Feminino , Adulto , Intestinos/diagnóstico por imagem , Intestinos/patologia , Estudos Prospectivos , Pessoa de Meia-Idade
3.
Chem Biodivers ; 21(4): e202400188, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38372184

RESUMO

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.


Assuntos
Apocynaceae , Iridoides , Humanos , Iridoides/farmacologia , Iridoides/química , Células HeLa , Apocynaceae/química , Óxido Nítrico/metabolismo , Cristalografia por Raios X , Estrutura Molecular
4.
Cancer Res ; 84(8): 1352-1371, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38335276

RESUMO

Liver metastasis is the leading cause of mortality in patients with colorectal cancer. Given the significance of both epithelial-mesenchymal transition (EMT) of tumor cells and the immune microenvironment in colorectal cancer liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multiomics analysis of 130 samples from 18 patients with synchronous CRLM integrated with external datasets to comprehensively evaluate the interaction between immune cells and EMT of tumor cells in liver metastasis. Single-cell RNA sequencing analysis revealed distinct distributions of nonmalignant cells between primary tumors from patients with metastatic colorectal cancer (mCRC) and non-metastatic colorectal cancer, showing that Th17 cells were predominantly enriched in the primary lesion of mCRC. TWEAK, a cytokine secreted by Th17 cells, promoted EMT by binding to receptor Fn14 on tumor cells, and the TWEAK-Fn14 interaction enhanced tumor migration and invasion. In mouse models, targeting Fn14 using CRISPR-induced knockout or lipid nanoparticle-encapsulated siRNA alleviated metastasis and prolonged survival. Mice lacking Il17a or Tnfsf12 (encoding TWEAK) exhibited fewer metastases compared with wild-type mice, while cotransfer of Th17 with tumor cells promoted liver metastasis. Higher TWEAK expression was associated with a worse prognosis in patients with colorectal cancer. In addition, CD163L1+ macrophages interacted with Th17 cells, recruiting Th17 via the CCL4-CCR5 axis. Collectively, this study unveils the role of immune cells in the EMT process and identifies TWEAK secreted by Th17 as a driver of CRLM. SIGNIFICANCE: TWEAK secreted by Th17 cells promotes EMT by binding to Fn14 on colorectal cancer cells, suggesting that blocking the TWEAK-Fn14 interaction may be a promising therapeutic approach to inhibit liver metastasis.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Células Th17 , Citocina TWEAK , Transição Epitelial-Mesenquimal/genética , Prognóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Receptor de TWEAK/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Microambiente Tumoral
5.
Br J Cancer ; 130(6): 951-960, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38245662

RESUMO

BACKGROUND: Accurate estimation of the long-term risk of recurrence in patients with non-metastatic colorectal cancer (CRC) is crucial for clinical management. Histology-based deep learning is expected to provide more abundant information for risk stratification. METHODS: We developed and validated a weakly supervised deep-learning model for predicting 5-year relapse-free survival (RFS) to stratify patients with different risks based on histological images from three hospitals of 614 cases with non-metastatic CRC. A deep prognostic factor (DL-RRS) was established to stratify patients into high and low-risk group. The areas under the curve (AUCs) were calculated to evaluate the performances of models. RESULTS: Our proposed model achieves the AUCs of 0.833 (95% CI: 0.736-0.905) and 0.715 (95% CI: 0.647-0.776) on validation cohort and external test cohort, respectively. The 5-year RFS rate was 45.7% for high DL-RRS patients, and 82.5% for low DL-RRS patients respectively in the external test cohort (HR: 3.89, 95% CI: 2.51-6.03, P < 0.001). Adjuvant chemotherapy was associated with improved RFS in Stage II patients with high DL-RRS (HR: 0.15, 95% CI: 0.06-0.38, P < 0.001). CONCLUSIONS: DL-RRS has a good predictive performance of 5-year recurrence risk in CRC, and will better serve the clinical decision-making.


Assuntos
Neoplasias Colorretais , Aprendizado Profundo , Humanos , Prognóstico , Recidiva Local de Neoplasia/patologia , Fatores de Risco , Neoplasias Colorretais/patologia , Estudos Retrospectivos
6.
Clin Transl Oncol ; 26(2): 389-397, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37713046

RESUMO

PURPOSE: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. METHODS: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. RESULTS: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043-1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142-2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102-3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084-12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672-28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan-Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. CONCLUSION: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Estudos Retrospectivos , Receptor ErbB-2 , Intervalo Livre de Doença
7.
Artigo em Inglês | MEDLINE | ID: mdl-37101716

RESUMO

Introduction: Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein, which played important role in mediating autophagy, smooth muscle contraction, protein glycosylation, and immune response. In recent years, the interest had risen for exploring the function of the TMEM genes in the cancer fields. As a consequence, in our pan-cancer research of the TMEM65, we explored the function of the gene in kinds of database and tried to apply the finding in the clinical practice. Methods: In this research, we provide a comprehensive investigation of TMEM65 expression in a pan-cancer manner containing 33 cancer types. We evaluated the association of TMEM65 with the prognosis, immune infiltration, drug sensitivity analysis, GSVA enrichment analysis, TMB, MSI, NEO, and hotspot mechanisms. Results: TMEM65 was abnormally expressed in 24 types of cancers and showed correlation with the OS for 6 cancers and PFI for 9 cancers and kpI for 3 types. Moreover, the TME score, CD8 T effector, and immune checkpoint scoring systems showed a close correlation with the TMEM65. Moreover, TMEM65 was strongly correlated with some of the most common tumor-related genes and certain pathways (TGF beta signaling, TNFA signaling, hypoxia, pyroptosis, DNA repairing, autophagy, ferroptosis, and other related genes). Additionally, the TMEM65 showed correlations with the tumor mutational burden (TMB), microsatellite instability (MSI), NEO, and drug sensitivity. Finally, we confirmed several pathways by the GSEA and GSVA for the TMEM65 at the breast cancer aspects. Nomogram prediction model was also established for the breast tumors based on the TMEM65 level and other variables. Conclusion: Above all, the TMEM65 played important roles in predicting the prognosis of the cancers and correlated with the tumor immunity in the pan-cancer analysis.

8.
Nutrients ; 14(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36145050

RESUMO

Background: Maternal passive smoking and vitamin D deficiency might elevate risk of spontaneous abortion. The study aimed to investigate the association of co-exposure to passive smoking and vitamin D deficiency with the risk of spontaneous abortion. Methods: A population-based case-control study was performed among non-smoking women in Henan Province, China, with 293 spontaneous abortion cases and 496 liveborn controls with term, normal birthweight. Results: Compared to women without exposure to passive smoking nor vitamin D deficiency, women with deficient vitamin D alone and women with exposure to passive smoking alone had increased risk of spontaneous abortion (OR = 1.76, 95%CI: 1.08~2.89; OR = 1.73, 95%CI: 1.11~2.69, respectively). The risk of spontaneous abortion was even higher for those with co-exposure to passive smoking and vitamin D deficiency (OR = 2.50, 95%CI: 1.63~3.84). A dose-response relationship was found of an incremental risk of spontaneous abortion with rising numbers of exposures to passive smoking and vitamin D deficiency (p < 0.001). Conclusion: Co-exposure to passive smoking and vitamin D deficiency was associated with an elevated risk of spontaneous abortion, and the risk of spontaneous abortion rose with rising numbers of exposures. Intervention programs need to specifically target the vulnerable groups of pregnant women with both malnutrition and unfavorable environmental exposure.


Assuntos
Aborto Espontâneo , Poluição por Fumaça de Tabaco , Deficiência de Vitamina D , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Poluição por Fumaça de Tabaco/efeitos adversos , Vitamina D , Deficiência de Vitamina D/complicações
9.
Cell Death Dis ; 13(5): 505, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35643812

RESUMO

The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Loss of XRCC2 compromises DNA damage repairs, and induced DNA damage burdens may increase the reliance on PARP-dependent DNA repairs of cancer cells to render cell susceptibility to PARP inhibitor therapy. Here we tested the hypothesis that XRCC2 loss sensitizes colorectal cancer (CRC) to PARP inhibitor in combination with radiotherapy (RT). We show that high levels of XRCC2 or PARP1 in LARC patients were significantly associated with poor overall survival (OS). Co-expression analyses found that low levels of PARP1 and XRCC2 were associated with better OS. Our in vitro experiments indicated that olaparib+IR led to reduced clonogenic survival, more DNA damage, and longer durations of cell cycle arrest and senescence in XRCC2-deficient cells relative to wild-type cells. Furthermore, our mouse xenograft experiments indicated that RT + olaparib had greater anti-tumor effects and led to long-term remission in mice with XRCC2-deficient tumors. These findings suggest that XRCC2-deficient CRC acquires high sensitivity to PARP inhibition after IR treatment and supports the clinical development for the use of olaparib as a radiosensitizer for treatment of XRCC2-deficient CRC.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/uso terapêutico , Humanos , Camundongos , Ftalazinas/farmacologia , Ftalazinas/uso terapêutico , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
10.
Am J Transl Res ; 14(4): 2301-2316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559406

RESUMO

BACKGROUND: Galectins (LGALS) are a family of carbohydrate-binding proteins, and LGALS family members have shown prognostic roles in various types of cancers. However, the prognostic significance of some LGALS family members has not been studied in breast malignancy. METHODS: The prognostic value of LGALS family mRNA expression in breast cancer patients was investigated according to distinct clinicopathological features (including lymph node, intrinsic subtype, pathological grade, HER2, and TP53 status) using the Kaplan-Meier plotter database. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression of LGALS in breast cancer and normal breast cells. The aberrant expression of specific LGALS and its correlation with breast cancer outcomes remains elusive. In the present analysis, we comprehensively explored an immunohistochemistry-based map of protein expression profiles in normal tissues, cancer, and cell lines from the widely available Human Protein Atlas (HPA) database. Immunohistochemistry was applied to evaluate the expression of LGALS between cancer and normal tissues. RESULTS: Our results showed that overexpression of LGALS2 mRNA were correlated with satisfactory overall survival among all breast cancer patients. Furthermore, LGALS2 and LGALS4 expression correlated with a better overall survival (OS) in grade III breast cancer patients; LGALS2 also predicted a better OS in basal-like subtype patients, luminal B patients, HER2-overexpressing patients, TP53 mutated and wild breast cancer patients. Notably, the mRNA and protein expression levels of LGALS2 were decreased in cancer cells compared with normal cells (P<0.05). Furthermore, LGALS2 expression in immunostaining score was lower in cancer tissues than in normal tissues (P<0.005). CONCLUSION: In conclusion, LGALS2 has potential as a valuable biomarker for envisaging a satisfactory prognosis in patients with breast tumours, particularly those with luminal and basal B types, all stages and grade III tumours.

11.
Liver Int ; 42(6): 1423-1431, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35319151

RESUMO

BACKGROUND AND AIMS: Radiological prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is essential but few models were clinically implemented because of limited interpretability and generalizability. METHODS: Based on 2096 patients in three independent HCC cohorts, we established and validated an MVI predicting model. First, we used data from the primary cohort to train a 3D-ResNet network for MVI prediction and then optimised the model with "expert-inspired training" for model construction. Second, we implemented the model to the other two cohorts using three implementation strategies, the original model implementation, data sharing model implementation and skeleton sharing model implementation, the latter two of which used part of the cohorts' data for fine-tuning. The areas under the receiver operating characteristic curve (AUCs) were calculated to compare the performances of different models. RESULTS: For the MVI predicting model, the AUC of the expert-inspired model was 0.83 (95% CI: 0.77-0.88) compared to 0.54 (95% CI: 0.46-0.62) of model before expert-inspiring. Taking this model as an original model, AUC on the second cohort was 0.76 (95% CI: 0.67-0.84). The AUC was improved to 0.83 (95% CI: 0.77-0.90) with the data-sharing model, and further improved to 0.85 (95% CI: 0.79-0.92) with the skeleton sharing model. The trend that the skeleton sharing model had an advantage in performance was similar in the third cohort. CONCLUSIONS: We established an expert-inspired model with better predictive performance and interpretability than the traditional constructed model. Skeleton sharing process is superior to data sharing and direct model implementation in model implementation.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Invasividade Neoplásica/patologia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Esqueleto/patologia
12.
Nat Prod Res ; 36(14): 3598-3602, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33430643

RESUMO

Two new flavanoids fissistiganoids A and B (1 and 2), together with two known pterocarpans derivatives (3 and 4), were isolated from the stems of Fissistigma tungfangense. The structures of these compounds were elucidated using comprehensive spectroscopic methods. The absolute configurations of fissistiganoids A and B (1 and 2) were determined by comparing their ECD spectra with quantum-mechanics ECD calculations. The inhibitory activities of all compounds against three cancer cell lines HeLa, MCF-7 and A549 were evaluated. Compounds 1-4 showed moderate inhibitory effects on HeLa, MCF-7 and A549 cells with IC50 values ranging from 12.5 to 42.3 µM.


Assuntos
Annonaceae , Pterocarpanos , Células A549 , Flavonoides/química , Flavonoides/farmacologia , Humanos , Estrutura Molecular
13.
Nutrients ; 15(1)2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36615784

RESUMO

Objective: Maternal dietary undernutrition is known to be associated with the risk of vitamin D (VD) deficiency. However, whether the risk of VD deficiency in women of reproductive age is influenced by the interaction between passive smoking and inadequate nutrition remains unknown. The aim of this study is to explore the interaction between passive smoking and dietary undernutrition on the risk of VD deficiency. Methods: A population-based case−control study including 1151 non-pregnant women of reproductive age between 18 and 40 years old was conducted in Henan Province, China from 2009 to 2010. Blood samples and information on exposure factors were collected. The prevalence of VD deficiency was estimated based on a result of serum 25-hydroxyvitamin D [25(OH)D] < 26.0 ng/mL. A multivariate logistic regression analysis was performed to explore the risk of VD deficiency. Results: The prevalence of VD deficiency was 61.5%. After adjusting for potential confounding factors, the interactions between passive smoking and no nutritional supplementation, passive smoking and insufficient egg intake, and passive smoking and insufficient milk dairy products intake were associated with the risk of VD deficiency, and the adjusted ORs were 3.40 (95% CI 2.26−5.13), 2.87 (95% CI 2.20−4.10), and 2.18 (95% CI 1.33−3.58), respectively. The interaction coefficients were calculated to be 2.35, 2.79, and 1.70, respectively, indicating there were significant interaction effects, as all of the coefficients were higher than 1. Conclusions: Our findings present that the risk of VD deficiency was potentially influenced by interactions between passive smoking and inadequate nutrition. Passive smoking might strengthen the effect of inadequate nutrition on the risk of VD deficiency among rural women of reproductive age. More attention should be paid to the health education and nutritional status improvement of women of reproductive age, especially in rural areas of developing countries.


Assuntos
Desnutrição , Poluição por Fumaça de Tabaco , Deficiência de Vitamina D , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Poluição por Fumaça de Tabaco/efeitos adversos , Estudos de Casos e Controles , Deficiência de Vitamina D/epidemiologia , Vitamina D , Comportamento Alimentar
14.
Fitoterapia ; 155: 105036, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34536535

RESUMO

Two novel aporphine-derived alkaloids, aporaloids A and B (1 and 2), together with eight known biogenetically related alkaloids (3-10), two known isoquinoline alkaloids (3 and 4), and six known aporphinoid alkaloids (5-10) were isolated from the stems of Fissistigma glaucescens. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 1 and 2 represent the rare example of a six-membered lactone ring aporphine-derived alkaloids from natural products. The inhibitory activities of all compounds against four cancer cell lines were evaluated. Aporaloids A and B (1 and 2) showed broad spectrum cytotoxic activities.


Assuntos
Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Aporfinas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Aporfinas/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química
15.
Chem Biodivers ; 18(5): e2100027, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33738965

RESUMO

Five undescribed triene derivatives, pinophols B-F (2-6), together with one known compound, pinophol A (1), were obtained from the mangrove endophytic fungus Penicillium herquei JX4. The structures of compounds 1-6 were elucidated using IR, HR-ESI-MS, and NMR methods. The absolute configurations of compounds 1-6 were confirmed by comparing their experimental or calculated ECD spectra. Pinophols C and D (3 and 4) showed inhibitory activities against LPS-induced NO production.


Assuntos
Óxido Nítrico/antagonistas & inibidores , Penicillium/química , Animais , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Estereoisomerismo
16.
Gland Surg ; 9(5): 1450-1468, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224820

RESUMO

BACKGROUND: The ability to predict high risk factors for recurrence after neoadjuvant chemotherapy (NAC) is controversial. The purpose of the present study was to investigate the prognostic significance of tumor location, tumor-infiltrating lymphocyte (TIL) level, and pretreatment lymphocyte-to-monocyte ratio (LMR) in determining the survival of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer after treatment with NAC. METHODS: The clinical data of 285 ER-positive, HER2-negative patients with clinical stage II-III breast cancer were analyzed from January 2009 to January 2015. To explore the prognostic factors for ER-positive, HER2-negative patients, we combined the conventional clinicopathological prognostic factors with tumor location, pretreatment LMR, and TIL. In addition, samples from 79 patients, who did not achieve pathological complete response (pCR) testing after NAC, were selected for hematoxylin-eosin (HE) staining to analyze the effect of TIL on prognosis. RESULTS: An LMR >5.2 was correlated with better 5-year disease-free survival (DFS) and overall survival (OS; P<0.001 and P<0.001, respectively). Patients with lower-inner/central quadrant tumors had lower 5-year DFS and OS than patients with tumors in the other quadrants (P=0.012 and P=0.048). Patients with a lower TIL level (≤10%) had better 5-year DFS than patients with a higher TIL level (P=0.010). According to the results of the multivariate analyses, tumor location was an independent prognostic factor for 5-year DFS (P=0.021). Pretreatment LMR was associated with both 5-year DFS and OS (P<0.001 and P<0.001, respectively). In the subgroup analysis stratified by TIL level, the TIL level and the initial clinical stage were associated with 5-year DFS (P=0.027 and P<0.001, respectively). CONCLUSIONS: We explored the prognostic significance of the tumor site, TIL level, and pretreatment LMR level for ER-positive, HER2-negative patients. We concluded that the lower-inner/central quadrant tumors, TIL >10%, and pretreatment LMR level ≤5.2 were correlated with a poor prognosis. More aggressive NAC and/or endocrine therapy with internal mammary node radiotherapy (IMN-RT) should be administered to address the relatively poor prognosis of patients with breast carcinoma presenting the aforementioned adverse factors.

18.
Sex Med ; 7(4): 396-402, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31451396

RESUMO

INTRODUCTION: Early pregnancies and their poor reproductive outcomes remain increasing concerns. AIM: This study aims to investigate the pregnancy rate and outcomes and to identify social factors associated with pregnancy among Chinese unmarried youths aged 15-24 years. METHODS: Data were obtained from the Survey of Youth Access to Reproductive Health in China, and 11,076 unmarried female youths were analyzed. Prevalence of pregnancy by various demographic and socioeconomic characteristics was calculated. Univariate and multivariable logistic regression models were used to identify factors associated with pregnancy. MAIN OUTCOME MEASURE: The main outcome is pregnancy among unmarried female youths during their lifetime. RESULTS: Among 11,076 female youths, 501 individuals reported 697 premarital pregnancies during their lifetime until the survey was conducted, approximately 62.9 (95% CI: 58.5-67.6) pregnancies per 1,000 female youths. Older age group (odds ratio [OR] = 4.49; 95% CI = 3.60-5.59), low education levels (primary school and below: OR = 1.78, 95% CI = 1.33-2.37; junior and senior high school: OR 1.44, 95% CI = 1.15-1.80), living in non-eastern regions (central: OR 1.34, 95% CI = 1.06-1.68; west: OR 1.62, 95% CI = 1.28-2.04), cigarette smoking (OR 3.60, 95% CI = 2.76-4.70), alcohol drinking (OR 1.59, 95% CI = 1.28-1.97), from family with mother's education of primary school and below (OR 1.65, 95% CI = 1.11-2.46), and the bottom economic status (OR 1.48, 95% CI = 1.14-1.91) were associated with higher risk of premarital pregnancy among female youths. CONCLUSION: The findings justify the national concern for pregnancy among unmarried youth in China. Strategies to improve sexual education in school and family, to enhance the reproductive services for youth, and to increase public awareness of the reproductive health of young people were warranted. Guo C, Pang L, Ding R, et al. Unmarried Youth Pregnancy, Outcomes, and Social Factors in China: Findings From a Nationwide Population-Based Survey. Sex Med 2019;7:396-402.

19.
Cancer Manag Res ; 11: 4691-4697, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191026

RESUMO

Aims: To examine the expression of CXCL16 in colorectal cancer (CRC) tissue and to clarify the relationships between CXCL16 and clinicopathological features and survival in CRC. Methods: A total of 142 consecutive CRC patients undergoing colorectal surgery at the Department of Gastrointestinal Center, First Affiliated Hospital, Sun Yat-sen University, between January 2010 and December 2010 were enrolled in this study. CXCL16 was measured by immunohistochemical staining in CRC tissue. Association between CXCL16 expression and clinicopathologic parameters was analyzed with a chi-square test. Survival curves were calculated by the Kaplan-Meier method, and the differences between CXCL16 high- and low-expression groups were analyzed using the log-rank test. Cox univariate and multivariate analyses were used to determine risk factors for overall survival (OS). Results: CXCL16 expression was elevated in CRC. CXCL16-positive expression was significantly related to tumor size (P=0.043), tumor differentiation (P=0.046) and distant metastasis (P=0.038), and there was a trend toward lymph node metastasis (P=0.070). CXCL16 expression, together with differentiation, depth of invasion, lymph node metastasis, and distant metastasis, was a significant independent prognostic factor for OS of patients with CRC (HR 2.026, 95% CI 1.128-3.640, P=0.018). Conclusion: CXCL16 expression was enhanced in CRC tissue and was negatively correlated with survival in CRC patients. Furthermore, CXCL16-positive expression was an independent prognostic factor for CRC patients, whilst the underlying mechanisms remain unclear; thus, further studies are needed.

20.
Hum Pathol ; 84: 62-70, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30236596

RESUMO

Solute carrier family 17 member 9 (SLC17A9) is a member of the family of transmembrane proteins that are involved in the transport of small molecules. The role of SLC17A9 in colorectal cancer (CRC) remains poorly understood. The present study aimed to demonstrate the clinicopathological significance and prognostic role of SLC17A9 in CRC. Here, we firstly analyzed the data from The Cancer Genome Atlas on SLC17A9 expression in CRC data sets and detected SLC17A9 expression level in 8 pairs of fresh CRC tissues and adjacent nontumorous tissues by quantitative real-time reverse-transcription polymerase chain reaction and Western blotting assays. Immunohistochemical staining was used to detect SLC17A9 protein expression in 144 CRC patients in our center. The bioinformatic analysis, Western blotting, and immunohistochemical analyses revealed that SLC17A9 was significantly up-regulated in CRC specimens compared with adjacent nontumorous tissues. SLC17A9 overexpression was significantly correlated with several clinicopathological features, such as advanced T stage (P < .001), N stage (P < .001), M stage (P < .001), TNM stage (P < .001), and tumor location (P = .01). A Kaplan-Meier survival curve suggested that higher SLC17A9 expression was statistically correlated with poor overall survival and disease-free survival in patients with CRC. Univariate and multivariate Cox regression analyses demonstrated that SLC17A9 was an independent prognostic predictor for survival of CRC patients. Therefore, our data suggested that SLC17A9 may play an important role in the progression of CRC and may potentially be used as an independent biomarker for prognostic evaluation of CRC.


Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Proteínas de Transporte de Nucleotídeos/biossíntese , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Regulação para Cima
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