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1.
Cancer Manag Res ; 16: 269-279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585434

RESUMO

Purpose: To compare the oncologic outcomes of prophylactic extended-field radiation therapy (EFRT) and whole pelvic radiation therapy (WPRT) in cervical patients at high risk of para-aortic lymph node (PALN) recurrence. Patients and Methods: From July 1999 to May 2022, a total of 115 patients with cervical cancer and high-risk features of PALN recurrence based on tumor markers, positive LNs and extensive parametrial invasion were retrospectively analyzed. All patients had received EFRT or WPRT at a dose of 39.6-45 Gy and concurrent chemotherapy. In EFRT, coverage was extended to include the para-aortic region below the level of the left renal vein or T12. Results: Twenty-eight and 87 patients underwent EFRT and WPRT, respectively. For patients who survived, the median follow-up time was 60.8 months (range 9.2-131.6 months) in the EFRT group and 115.9 months (range 16.9-212.1 months) in the WPRT group. The 5-year overall survival (OS) and pelvic, extrapelvic and PALN recurrence rates were 87.7% vs 60.8% (p=0.019), 10.9% vs 25.3% (p=0.119), 18.1% vs 45.8% (p=0.011), and 0% vs 30.4% (p=0.005), respectively, between the EFRT and WPRT groups. Multivariate analysis revealed that EFRT and 2018 FIGO stage IV disease status were significant predictors of OS and extrapelvic recurrence. Conclusion: Compared to WPRT, EFRT significantly improved OS and reduced extrapelvic and PALN recurrence in patients with cervical cancer with high-risk recurrence features.

2.
Mol Nutr Food Res ; 68(6): e2300443, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456781

RESUMO

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Masculino , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos , Glucose/farmacologia , Metilaminas , Colina/farmacologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38501382

RESUMO

OBJECTIVE: Nutritional and inflammatory statuses have been associated with complications in microvascular-free flaps during head and neck surgeries. This study aimed to evaluate the potential of nutritional indicators in predicting postoperative free flap complications. STUDY DESIGN: We conducted a 20-year retrospective, case-control study within a defined cohort. SETTING: The study involved head and neck cancer patients from the Chang Gung Research Database who underwent simultaneous tumor ablation and free flap wound reconstruction between January 1, 2001, and December 31, 2019. METHODS: We employed logistic regression and stratified analysis to assess the risk of free flap complications and the subsequent need for flap revision or redo in relation to nutritional indicators and other clinical variables. RESULTS: Of the 8066 patients analyzed, 687 (8.5%) experienced free flap complications. Among these, 197 (2.4%) had free flap failures necessitating a redo of either a free flap or a pedicled flap. Beyond comorbidities such as chronic obstructive pulmonary disease, end-stage renal disease, and a history of prior radiotherapy, every 10-unit decrease in the preoperative prognostic nutritional index (PNI) was consistently associated with an increased risk of both free flap complications and failure. The covariate-adjusted odds ratios were 1.90 (95% confidence interval [CI]: 1.42-2.54) and 1.89 (95% CI: 1.13-3.17), respectively. CONCLUSION: A lower preoperative PNI suggests a higher likelihood of microvascular free flap complications in head and neck surgeries. Further randomized controlled trial designs are required to establish causality.

4.
Cancers (Basel) ; 16(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38473396

RESUMO

BACKGROUND: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. METHODS: In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. RESULTS: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. CONCLUSIONS: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

5.
Support Care Cancer ; 32(3): 203, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430411

RESUMO

PURPOSE: Nasopharyngeal carcinoma (NPC) patients may experience symptom distress and depression during and after radiation therapy, which negatively impacts quality of life (QOL). We sought to identify trajectories of symptom distress, depression, social support, and QOL in patients with NPC receiving intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton therapy (IMPT). METHODS: A multicenter prospective longitudinal study recruited NPC patients from two leading medical centers in Taiwan. The 121 NPC patients were followed from before RT (T0), at 4 weeks after beginning RT (T1), at 6 weeks of RT or the end of treatment (T2), and at 4 weeks post-RT (T3). Generalized estimating equation analysis was used to identify the factors related to QOL. RESULTS: Patients' symptom distress and depression increased from T0, peaked at T2, and decreased at T3. Physical-QOL and psychosocial-QOL decreased from T0 to T2, then increased by T3. Patients who had early-stage cancer, received a lower RT dose, had less symptom distress, and had less depression were more likely to have better QOL. Greater physical-QOL was associated with IMPT receipt, higher education level, early cancer stage, lower radiation dose, less symptom distress, and less depression. Patients who had good physical performance, received a lower radiation dose, had less symptom distress, and had less depression were more likely to have better psychosocial-QOL. CONCLUSION: Radiation dose, symptom distress, and depression were the most important factors affecting QOL in patients with NPC. Understanding the factors associated with the trajectory of QOL can guide care during radiation treatment.


Assuntos
Neoplasias Nasofaríngeas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Qualidade de Vida , Estudos Longitudinais , Estudos Prospectivos , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 313-317, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387941

RESUMO

Long non-coding RNA (lncRNA) can affect the occurrence and development of diseases by directly or indirectly regulating target genes and their signal pathways. With the deepening of research, more and more lncRNA have been found to be involved in regulating the occurrence, development and drug resistance of multiple myeloma (MM). Therefore, it is necessary to study the role and molecular mechanism of abnormal expression of lncRNA in MM, which can provide theoretical basis for clinical diagnosis and targeted therapy.


Assuntos
Mieloma Múltiplo , RNA Longo não Codificante , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais
7.
Int J Surg ; 110(4): 1913-1918, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38265436

RESUMO

BACKGROUND: Contraction-type lymphatic vessels (LV) are considered suboptimal for lymphaticovenous anastomosis (LVA). However, despite these pathological changes, their functionality and link to outcomes have not been fully elucidated. The aim of this study was to determine the impact on outcomes when contraction-type LVs were used for LVA compared to the noncontraction-type (normal + ectatic) counterpart for treating lower limb lymphedema. STUDY DESIGN: Eighty-three patients with gynecologic cancer-related unilateral lower-limb lymphedema who underwent LVA as their primary treatment were enrolled in this study. The study group included 20 patients who used only contraction-type LVs. An additional 63 patients (control group) received noncontraction-type LVs only. Patients with a history of LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, functional parameters, and pre-LVA and post-LVA volume changes were recorded and matched using propensity scores. The primary endpoint was the volume change at 6/12 months after LVA. RESULTS: After matching, 20 patients were included in each group. All parameters were matched, except that the study group still had a significantly inferior indocyanine green (ICG)-positive ratio, lymph flow-positive ratio, and washout-positive ratios ( P <0.001, P =0.003, and P <0.001, respectively) when compared to the control group after matching. However, at 1-year follow-up, the postoperative percentage volume reduction was comparable between the groups ( P= 0.619). CONCLUSION: The use of contraction-type LVs for LVA is encouraged when no other LVs are available.


Assuntos
Anastomose Cirúrgica , Extremidade Inferior , Vasos Linfáticos , Linfedema , Pontuação de Propensão , Humanos , Feminino , Pessoa de Meia-Idade , Linfedema/cirurgia , Linfedema/etiologia , Vasos Linfáticos/cirurgia , Estudos Retrospectivos , Extremidade Inferior/cirurgia , Idoso , Adulto , Resultado do Tratamento , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/complicações
8.
Otolaryngol Head Neck Surg ; 170(1): 141-150, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37727942

RESUMO

OBJECTIVE: To investigate the clinical benefit of routine esophageal screening in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. METHODS: This retrospective study selected newly diagnosed HNSCC patients from the Chang Gung Research Database between January 2007 and December 2019. Patients who underwent endoscopic esophageal examinations within 2 months of the initial diagnosis of HNSCC were included in the screening group. The clinical outcomes of the screening and nonscreening groups were analyzed. RESULTS: In total, 13,627 HNSCC patients were included, comprising 1032 females and 12,640 males (mean age 55.0 years), and the esophageal screening group included 7033 (51.4%) patients. The prevalence rate of esophageal tumors was 4.5%. Hypopharyngeal cancer patients were the most likely to have (13.4%) second primary esophageal tumors. The American Joint Committee on Cancer stage of the esophageal tumor was lower in the esophageal screening group than in the nonesophageal screening group. The oral, oropharyngeal, and hypopharyngeal cancer patients in the esophageal screening group had better survival outcomes than their counterparts in the nonesophageal screening group. CONCLUSION: Endoscopic esophageal screening of newly diagnosed HNSCC patients can detect esophageal tumors at an early stage and improve overall survival. Esophageal screening could be a routine survey in HNSCC patients, particularly those with lifestyle risk factors and in countries with a high prevalence of esophageal cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Neoplasias de Cabeça e Pescoço , Neoplasias Hipofaríngeas , Segunda Neoplasia Primária , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Neoplasias Hipofaríngeas/diagnóstico , Esofagoscopia/efeitos adversos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Segunda Neoplasia Primária/epidemiologia
9.
Biomedicines ; 11(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38001947

RESUMO

This study evaluated the clinical characteristics of head and neck cancer (HNC) patients with hepatitis B (HBV) or hepatitis C (HCV) who underwent concurrent chemoradiotherapy (CCRT) and examined the prognostic impact of antiviral therapies. In a 19-year retrospective analysis of 8224 HNC patients treated with CCRT, 29.8% (2452) were diagnosed with HBV or HCV, of whom 714 received antiviral therapy. For non-metastatic HNC patients on CCRT, factors such as gender, Charlson Comorbidity Index (CCI), liver cirrhosis markers (Fibrosis-4, APRI), and initial tumor stage were significant determinants of their overall survival. However, the presence of HBV or HCV and the administration of antiviral treatments did not yield distinct survival outcomes. In summary, antiviral therapy for HBV or HCV did not affect the 5-year survival rates of non-metastatic HNC patients undergoing CCRT, while gender, tumor stage, CCI, and liver cirrhosis were notable prognostic indicators.

10.
Diagnostics (Basel) ; 13(19)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37835827

RESUMO

This study aimed to compare the diagnostic performances of endoscopic ultrasound (EUS) and FDG PET/CT in the preoperative T-staging of esophageal squamous cell carcinoma (ESCC) and determine whether their innovative coordination achieves better prediction. In total, 100 patients diagnosed with ESCC, 57 without (CRT[-]sub) and 43 with (CRT[+]sub) neoadjuvant chemoradiotherapy, undergoing EUS and FDG PET/CT, followed by surgical resection of the tumor, were included in this analysis. EUS classified T-stages based on the depth of primary tumor invasion, and FDG PET/CT used thresholded maximal standardized uptake value (SUVmax) classifications. By employing pathology results as the reference standard, we assessed the accuracy of EUS and FDG PET/CT, evaluated their concordance using the κ statistic, and conducted a comparative analysis between the two modalities through McNemar's chi-square test. FDG PET/CT had higher overall accuracy than EUS (for CRT[-]sub: 71.9%, κ = 0.56 vs. 56.1%, κ = 0.31, p = 0.06; for CRT[+]sub: 65.1%, κ = 0.50 vs. 18.6%, κ = 0.05, p < 0.01) in predicting pT- and ypT-stage. Our proposed method of incorporating both FDG PET/CT and EUS information could achieve higher accuracies in differentiating between early and locally advanced disease in the CRT[-]sub group (82.5%) and determining residual viable tumor in the CRT[+]sub group (83.7%) than FDG PET/CT or EUS alone. FDG PET/CT had a better diagnostic ability than EUS to predict the (y)pT-stage of ESCC. Our complementary method, which combines the advantages of both imaging modalities, can deliver higher accuracy for clinical applications of ESCC.

11.
J Pers Med ; 13(9)2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37763136

RESUMO

BACKGROUND: Incidence of fungal rhinosinusitis has increased in recent few years. We investigated the differences in microbiological findings between patients with fungal and non-fungal rhinosinusitis by growing microbiological cultures from samples obtained from sinus surgery. METHODS: Using the Chang Gung Research Database, we enrolled all chronic rhinosinusitis (CRS) patients who had ever undergone sinus surgery from 2001 to 2019 and had microbiological culture during sinus surgery. Enrolled patients were divided into fungal and non-fungal groups, based on fungal culture and surgical pathology. RESULTS: A total of 898 patients were diagnosed with fungal rhinosinusitis and 2884 with non-fungal rhinosinusitis. The fungal group had a higher age distribution (56.9 ± 13.1 vs. 47.0 ± 14.9), a larger proportion of females (62.4% vs. 37.0%), more unilateral lesions (80.4% vs. 41.6%), a lower incidence of the need for revision surgery (3.6% vs. 6.0%, p = 0.004), and a higher proportion of Pseudomonas aeruginosa in the culture (14.3% vs. 4.6%, p < 0.001). CONCLUSIONS: This large-scale study showed that Pseudomonas aeruginosa are more commonly found in patients with fungal rhinosinusitis and in patients who needed revision surgery, suggesting that efforts aimed at eliminating Pseudomonas are needed in order to improve the disease outcomes of patients with fungal rhinosinusitis.

12.
Phys Rev Lett ; 131(9): 091902, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37721827

RESUMO

We compute for the first time the long-distance penguin contribution to the double radiative B-meson decays by applying the perturbative factorization theorem. The numerically dominant penguin amplitude arises from the soft-gluon radiation off the light up-quark loop rather than the counterpart charm-loop effect. Importantly, the long-distance up-quark penguin contribution brings about the substantial cancellation of the known factorizable power correction, thus enabling B_{d,s}→γγ to become new benchmark probes of physics beyond the standard model.

13.
Cancer Manag Res ; 15: 719-728, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37485039

RESUMO

Background: Few instruments are available for assessing the otorhinologic-related quality of life (QOL) in nasopharyngeal carcinoma (NPC) patients. Therefore, we evaluated whether the 22-item Sinonasal Outcome Test (SNOT-22) could be applied to these patients. Methods: Patients diagnosed with NPC, who had been treated with standard protocol and followed up in our institute between 2019 and 2022, were invited to join the cross-sectional study during their clinic visits. All participants completed the SNOT-22 and Eustachian Tube Dysfunction Questionnaire-7 once they were recruited. Confirmatory factor analysis (CFA) was performed to decide the most suitable model for the underlying SNOT-22 subdomains, along with various validity and reliability tests. Results: We identified a total of 275 patients, with 84 (30.5%) women and 191 (69.5%) men. The mean age was 54.1 years (standard deviation: 11.2). Among these patients, 171 (62.1%) were in late stages, and 260 (94.5%) received chemoradiotherapy as treatment. The median interval between primary RT treatment and questionnaire completion was 50 months (interquartile range: 29-93). CFA supported a five-factor model for the SNOT-22 for NPC patients, including nasal, ear/facial, sleep, function, and emotion domains. The internal consistency and test-retest reliability of the SNOT-22 domain score were good. In addition, known-group validity was good for the SNOT-22 total score and domain scores according to the disease recurrence status. Conclusion: Psychometric analyses supported the reliability and validity of a five-domain SNOT-22 for assessing otorhinologic-related QOL in NPC patients.

14.
Mar Drugs ; 21(7)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37504941

RESUMO

Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer's disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against H2O2/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3ß and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Humanos , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/metabolismo , Fosfatidilserinas/farmacologia , Fosfatidilserinas/química , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Neurônios , Hipocampo
15.
Mar Drugs ; 21(6)2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37367679

RESUMO

The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.


Assuntos
Epilepsia , Ácidos Graxos Ômega-3 , Feminino , Gravidez , Camundongos , Animais , Pentilenotetrazol/toxicidade , Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-3/farmacologia , Dieta , Fosfolipídeos , Suplementos Nutricionais , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle
16.
Mol Carcinog ; 62(7): 951-962, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37014154

RESUMO

Sprouty2 (SPRY2) is known to inhibit the RAS/MAPK/ERK pathway, and is a potential study target for cancer. The effect of SPRY2 in colorectal cancer (CRC) and whether it is influenced by KRAS mutation are not known. We manipulated SPRY2 gene expression and used an activating KRAS-mutant plasmid to determine its effect on CRC cell function in vitro and/or in vivo. We performed SPRY2 immunohistochemical staining in 143 CRC specimens and analyzed the staining results with various clinicopathological characteristics in relation to KRAS mutation status. SPRY2 knockdown in Caco-2 cells carrying the wild-type (WT) KRAS gene upregulated phosphorylated ERK (p-ERK) levels and increased cell proliferation in vitro, but inhibited cell invasion. However, SPRY2 knockdown in SW480 cells (activating KRAS mutant) or Caco-2 cells transfected with KRAS-mutant plasmid did not significantly alter p-ERK levels, cell proliferation, or invasion. The xenografts of SPRY2-knockdown Caco-2 cells were larger with less deep muscle invasion than those of control cells. The clinical cohort study revealed a positive association of SPRY2 protein expression with pT status, lymphovascular invasion, and perineural invasion in KRAS-WT CRCs. However, the associations were not observed in KRAS-mutant CRCs. Interestingly, high SPRY2 expression was related to shorter cancer-specific survival in both KRAS-WT and KRAS-mutant CRC patients. Our study demonstrated the dual role of SPRY2 as an inhibitor of RAS/ERK-driven proliferation and as a promoter of cancer invasion in KRAS-WT CRC. SPRY2 may promote the invasion and progression of KRAS-WT CRC, and might also enhance KRAS-mutant CRC progression through pathways other than invasion.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Células CACO-2 , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Linhagem Celular Tumoral , Estudos de Coortes , Neoplasias Colorretais/patologia , Proliferação de Células , Mutação , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
17.
J Sci Food Agric ; 103(11): 5529-5538, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37069483

RESUMO

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.


Assuntos
Aterosclerose , Ácidos e Sais Biliares , Camundongos , Animais , Ácidos e Sais Biliares/metabolismo , Camundongos Knockout , Colesterol , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL
18.
J Agric Food Chem ; 71(18): 6908-6919, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37098125

RESUMO

Homeostasis of reactive oxygen species is required to maintain sperm maturation and capacitation. Docosahexaenoic acid (DHA) is accumulated in testicles and spermatozoa and has the ability to manipulate the redox status. The effects of dietary n-3 polyunsaturated fatty acid (n-3 PUFA) deficiency from early life to adulthood on the physiological and functional properties of males under the redox imbalance of testicular tissue deserve attention. The consecutive injection of hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) for 15 days to induce oxidative stress in testicular tissue was used to elucidate the consequences of testicular n-3 PUFA deficiency. The results indicated that reactive oxygen species treatment in adult male mice with DHA deficiency in the testis could reduce spermatogenesis and disrupt sex hormone production, as well as trigger testicular lipid peroxidation and tissue damage. N-3 PUFA deficiency from early life to adulthood resulted in higher susceptibility to testicular dysfunction in the germinal function of supplying germ cells and the endocrine role of secreting hormones through the mechanism of aggravating mitochondria-mediated apoptosis and destruction of blood testicular barrier under oxidative stress, which might provide a basis for humans to reduce susceptibility to chronic disease and maintain reproductive health in adulthood through dietary interventions of n-3 PUFAs.


Assuntos
Ácidos Graxos Ômega-3 , Humanos , Camundongos , Masculino , Animais , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio/farmacologia , Sêmen , Testículo , Ácidos Docosa-Hexaenoicos/farmacologia
19.
Biomater Sci ; 11(6): 2177-2185, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36740962

RESUMO

Biosafety is a critical issue for the successful translocation of nanomaterial-based therapeutic/diagnostic agents from bench to bedside. For instance, after the withdrawal of clinically approved magnetic resonance (MR) imaging contrast agents (CAs) due to their biosafety issues, there is a massive demand for alternative, efficient, and biocompatible MR contrast agents for future MRI clinical applications. To this end, here we successfully demonstrate the in vivo MR contrast abilities and biocompatibilities of ligand-free FeSn2 alloy NPs for tracking in vivo lung tumors. In vitro and in vivo results reveal the FeSn2 alloy NPs acting as appreciable T2 weighted MR contrast agents to locate tumors. The construction of iron (Fe) on biocompatible tin (Sn) greatly facilitates the reduction of the intrinsic toxicities of Fe in vivo resulting in no significant abnormalities in liver and kidney functions. Therefore, we envision that constructing ligand-free alloy NPs will be a promising candidate for tracking in vivo tumors in future clinical applications.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Humanos , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Ferro , Neoplasias Pulmonares/diagnóstico por imagem
20.
Food Funct ; 14(5): 2349-2361, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36843452

RESUMO

Previous studies have found that eicosapentaenoic acid-enriched phospholipids (EPA-PLs) alleviated glucose and lipid metabolism, which was accompanied by an increase of cluster of differentiation 36 (CD36). However, the effects of EPA-PLs on glucose and lipid metabolism in the case of CD36 mutation are unclear. Thus, spontaneously hypertensive rats/NCrl (SHR) were used as a CD36 mutation model to determine the effects of dietary 2% EPA-PLs for 4 weeks on glucose and lipid metabolism. The results showed that the intervention of EPA-PLs significantly alleviated the abnormal increase of serum free fatty acid levels and glycerol levels in SHRs. Moreover, the administration of EPA-PLs decreased the triglyceride levels and cholesterol levels by 31.1% and 37.9%, respectively, in the liver. Dietary EPA-PLs had no effect on epididymal fat weight, but EPA-PLs inhibited adipocyte hypertrophy in SHRs. Further mechanistic research found that EPA-PL pretreatment significantly reduced triacylglycerol catabolism and increased fatty acid ß-oxidation. Additionally, the administration of EPA-PLs decreased the area under the curve of the intraperitoneal glucose tolerance test and fasting serum insulin levels by activating the IRS/PI3K/AKT signaling pathway. Furthermore, EPA-PL pretreatment significantly increased the CD36 gene expression in the liver tissues, adipose tissues and muscle tissues even in the case of CD36 mutation. These results indicated that EPA-PLs alleviate glucose and lipid metabolism in the case of CD36 mutation, which provides a precise nutrition strategy for people with CD36 mutation.


Assuntos
Glucose , Metabolismo dos Lipídeos , Ratos , Animais , Glucose/metabolismo , Ratos Endogâmicos SHR , Fosfolipídeos/metabolismo , Ácido Eicosapentaenoico/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo
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