Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 423
Filtrar
1.
Cancer Med ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636145

RESUMO

BACKGROUND: The prognostic value of lactate dehydrogenase (LDH) in colorectal cancer patients has remained inconsistent between nonmetastatic and metastatic settings. So far, very few studies have included LDH in the prognostic analysis of curative-intent surgery for colorectal liver metastases (CRLM). PATIENTS AND METHODS: Five hundred and eighty consecutive metastatic colorectal cancer patients who underwent curative-intent CRLM resection from Sun Yat-sen University Cancer Center (434 patients) and Sun Yat-sen University Sixth Affiliated Hospital (146 patients) in 2000-2019 were retrospectively collected. Overall survival (OS) was the primary end point. Cox regression model was performed to identify the prognostic values of preoperative serum LDH levels and other clinicopathology variables. A modification of the established Fong CRS scoring system comprising LDH was developed within this Chinese population. RESULTS: At the median follow-up time of 60.5 months, median OS was 59.5 months in the pooled cohort. In the multivariate analysis, preoperative LDH >upper limit of normal (250 U/L) was the strongest independent prognostic factor for OS (HR 1.73, 95% confidence interval [CI], 1.22-2.44; p < 0.001). Patients with elevated LDH levels showed impaired OS than patients with normal LDH levels (27.6 months vs. 68.8 months). Five-year survival rates were 53.7% and 22.5% in the LDH-normal group and LDH-high group, respectively. Similar results were also confirmed in each cohort. In the subgroup analysis, LDH could distinguish the survival regardless of most established prognostic factors (number and size of CRLM, surgical margin, extrahepatic metastases, CEA, and CA19-9 levels, etc.). Integrating LDH into the Fong score contributed to an improvement in the predictive value. CONCLUSION: Our study implicates serum LDH as a reliable and independent laboratory biomarker to predict the clinical outcome of curative-intent surgery for CRLM. Composite of LDH and Fong score is a potential stratification tool for CRLM resection. Prospective, international studies are needed to validate these results across diverse populations.

2.
PLoS One ; 16(9): e0257000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34516553

RESUMO

PURPOSE: To investigate the dynamics of the healing process after therapeutic subthreshold micropulse laser (SMPL) for diabetic macular edema (DME) using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: Patients with treatment-native or previously-treated DME were prospectively imaged using PS-OCT at baseline, 1, 2, 3, and 6 months. The following outcomes were evaluated: changes in the entropy value per unit area (pixel2) in the retinal pigment epithelium (RPE) on the B-scan image; changes in the entropy value in each stratified layer (retina, RPE, choroid) based on the ETDRS grid circle overlaid with en face entropy mapping, not only the whole ETDRS grid area but also a sector irradiated by the SMPL; and the relationship between edema reduction and entropy changes. RESULTS: A total of 11 eyes of 11 consecutive DME patients were enrolled. No visible signs of SMPL treatment were detected on PS-OCT images. The entropy value per unit area (pixel2) in the RPE tended to decrease at 3 and 6 months from baseline (35.8 ± 17.0 vs 26.1 ± 9.8, P = 0.14; vs 28.2 ± 18.3, P = 0.14). Based on the en face entropy mapping, the overall entropy value did not change in each layer in the whole ETDRS grid; however, decrease of entropy in the RPE was observed at 2, 3, and 6 months post-treatment within the SMPL-irradiated sectors (P < 0.01, each). There was a positive correlation between the change rate of retinal thickness and that of entropy in the RPE within the SMPL-irradiated sector at 6 months (r2 = 0.19, P = 0.039). CONCLUSION: Entropy measured using PS-OCT may be a new parameter that facilitates objective monitoring of SMPL-induced functional changes in the RPE that could not previously be assessed directly. This may contribute to a more promising therapeutic evaluation of DME. CLINICAL TRIAL: This clinical study was registered in UMIN-CTR (ID: UMIN000042420).

3.
Aging (Albany NY) ; 13(18): 22120-22133, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546972

RESUMO

This study aimed to expand our understanding of metformin (Met) in inhibiting hepatocellular carcinoma (HCC) progression and to investigate its underlying mechanism. Met was administrated to HCC cells at 5, 10, and 20 µM, after which the cell phenotype was evaluated. RNA-seq cluster analysis was used to screen for target genes modulated by Met. Luciferase activity and ChIP assays were performed to detect the effect of FOXO3 on the transcriptional activation of NLRP3. We evaluated the effect of Met and FOXO3 and on the growth of HCC cells in vivo. Met inhibited HCC cell proliferation and promoted apoptosis. Met also induced pyroptosis of HCC cells. FOXO3 was significantly upregulated by Met treatment, and FOXO3 activated transcription of NLRP3. Cells after Met treatment together with FOXO3 knockdown have a stronger colony formation and migration ability but a lower apoptosis rate compared to the Met treatment alone group. In vivo, Met inhibited HCC tumor growth. The tumors in Met treatment and FOXO3 knockdown group grew faster than in Met treatment group. Thus, Met attenuates HCC cell development by inducing apoptosis and pyroptosis. This effect of metformin is partially dependent on FOXO3 which can activate the transcription of NLRP3.

4.
ACS Appl Mater Interfaces ; 13(33): 39100-39111, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34382406

RESUMO

In this work, a nanoplatform (FeCORM NPs) loaded with an iron-carbonyl complex was constructed. By exploiting chemodynamic therapy (CDT) and immunogenic cell death (ICD)-induced immunotherapy (IMT), the nanoparticles exhibited excellent efficacy against lung metastasis of melanoma in vivo. The iron-carbonyl compound of the nanomaterials could be initiated by both glutathione (GSH) and hydrogen peroxide (H2O2) to release CO and generate ferrous iron through ligand exchange and oxidative destruction pathways. The released CO caused mitochondria damage, whereas the generated ferrous iron led to oxidative stress via the Fenton reaction. On the other hand, the nanomaterials induced ICD-based IMT, which worked jointly with CDT to exhibit excellent effects against lung metastasis of melanoma through a mouse model. This work demonstrated how a nanoplatform, simple and stable but showing excellent efficacy against tumors, could be built using simple building blocks via a self-assembling approach. Importantly, the system took advantage of relatively high levels of GSH and H2O2 in tumors to initiate the therapeutic effects, which rendered the nanoplatform with a capability to differentiate normal cells from tumor cells. In principle, the system has great potential for future clinical applications, not only in the treatment of lung metastasis of melanoma but also in suppressing other types of tumors.


Assuntos
Antineoplásicos/química , Monóxido de Carbono/química , Compostos de Ferro/química , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/metabolismo , Nanopartículas Metálicas/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Monóxido de Carbono/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenvolvimento de Medicamentos , Feminino , Glutationa/química , Humanos , Peróxido de Hidrogênio/química , Imunoterapia/métodos , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Neoplasias Experimentais , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
5.
Viruses ; 13(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34372508

RESUMO

Porcine circovirus type 2 (PCV2) causes many diseases in weaned piglets, leading to serious economic losses to the pig industry. This study investigated the immune response following oral administration of Lactobacillus casei ATCC393 (L. casei 393) expressing PCV2 capsid protein (Cap) fusion with the Escherichia coli heat-labile toxin B subunit (LTB) in mice. Recombinant L. casei strains were constructed using plasmids pPG611.1 and pPG612.1. The expression and localization of proteins from recombinant pPG611.1-Cap-LTB (pPG-1-Cap-LTB)/L. casei 393 and pPG612.1-Cap-LTB (pPG-2-Cap-LTB)/L. casei 393 were detected. All recombinant strains were found to be immunogenic by oral administration in mice and developed mucosal and systemic immune responses against PCV2. The titers of specific antibodies in mice administered pPG-2-Cap-LTB/L. casei 393 were higher than those in mice administered pPG-1-Cap-LTB/L. casei 393 in serum and the mucosal samples. The mucosal immune response was not only limited to the gastrointestinal tract but was also generated in other mucosal parts. Thus, the application of recombinant L. casei could aid in vaccine development for PCV2.

6.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360949

RESUMO

In recent years, the increasing incidence and mortality of cancer have inspired the development of accurate and rapid early diagnosis methods in order to successfully cure cancer; however, conventional methods used for detecting tumor cells, including histopathological and immunological methods, often involve complex operation processes, high analytical costs, and high false positive rates, in addition to requiring experienced personnel. With the rapid emergence of sensing techniques, electrochemical cytosensors have attracted wide attention in the field of tumor cell detection because of their advantages, such as their high sensitivity, simple equipment, and low cost. These cytosensors are not only able to differentiate tumor cells from normal cells, but can also allow targeted protein detection of tumor cells. In this review, the research achievements of various electrochemical cytosensors for tumor cell detection reported in the past five years are reviewed, including the structures, detection ranges, and detection limits of the cytosensors. Certain trends and prospects related to the electrochemical cytosensors are also discussed.


Assuntos
Biomarcadores Tumorais/análise , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Animais , Humanos
7.
Gut Microbes ; 13(1): 1956281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34369287

RESUMO

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in human and animal. To determine the mechanism of a bovine lactoferricin-lactoferrampin (LFCA)-encoding Lactobacillus reuteri CO21 (LR-LFCA) to enhance the intestinal mucosal immunity, we used a newborn piglet intestine model to study the intestinal response to ETEC. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine.4-day-old piglets were orally administered with LR-LFCA, LR-con (L. reuteri CO21 transformed with pPG612 plasmid) or phosphate buffered saline (PBS) for three consecutive days, within 21 days after these treatments, we found that LR-LFCA can colonize the intestines of piglets, improve the growth performance, enhance immune response and is beneficial for intestinal health of piglets by improving intestinal barrier function and modulating the composition of gut microbiota. Twenty-one days after, piglets were infected with ETEC K88 for 5 days, we found that oral administration of LR-LFCA to neonatal piglets attenuated ETEC-induced the weight loss of piglets and diarrhea incidence. LR-LFCA decreased the production of inflammatory factors and oxidative stress in intestinal mucosa of ETEC-infected piglets. Additionally, LR-LFCA increased the expression of tight junction proteins in the ileum of ETEC-infected piglets. Using LPS-induced porcine intestinal epithelial cells (IPEC-J2) in vitro, we demonstrated that LR-LFCA-mediated increases in the tight junction proteins might depend on the MLCK pathway; LR-LFCA might increase the anti-inflammatory ability by inhibiting the NF-κB pathway. We also found that LR-LFCA may enhance the antioxidant capacity of piglets by activating the Nrf2/HO-1 pathway. This study demonstrates that LR-LFCA is effective at maintaining intestinal epithelial integrity and host homeostasis as well as at repairing intestinal damage after ETEC infection and is thus a promising alternative therapeutic method for intestinal inflammation.

8.
J Am Heart Assoc ; 10(16): e020554, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34350769

RESUMO

Background Adventitial remodeling is a pathological hallmark of hypertension that results in target organ damage. Activated adventitial fibroblasts have emerged as critical regulators in this process, but the precise mechanism remains unclear. Methods and Results Interleukin 11 (IL-11) knockout and wild-type mice were subjected to angiotensin II (Ang II) infusion to establish models of hypertension-associated vascular remodeling. IL-11 mRNA and protein were increased especially in the adventitia in response to Ang II. Compared with wild-type mice, Ang II-treated IL-11 knockout mice showed amelioration of vascular hypertrophy, adventitial fibrosis, macrophage infiltration, and inflammatory factor expression. Recombination mouse IL-11 exacerbated adventitial fibrosis in Ang II-infused wild-type mice. Interestingly, IL-11 neutralizing antibody attenuated adventitial fibrosis, macrophage infiltration, and inflammatory factor expression after Ang II infusion for 7 days. Mechanistically, in primary cultured adventitial fibroblasts, Krüppel-like factor 15 negatively regulated Ang II-induced IL-11 expression. Ang II increased extracellular signal-regulated kinases 1 and 2 activation, especially in adventitia, and caused biphasic extracellular signal-regulated kinases 1 and 2 activation in adventitial fibroblasts. A rapid and early activation increased IL-11 production through decreasing Krüppel-like factor 15 expression, which, in turn, induced the second extracellular signal-regulated kinases 1 and 2 activation, resulting in posttranscriptional profibrotic gene expression. Conclusions These results demonstrate that extracellular signal-regulated kinases 1 and 2 activation is important for Krüppel-like factor 15-mediated IL-11 expression in adventitial fibroblasts to promote adventitial remodeling in Ang II-induced hypertension. Therefore, targeting the Krüppel-like factor 15/IL-11 axis might serve as a new therapeutic strategy for vascular diseases.

9.
Psychiatry Res Neuroimaging ; 316: 111344, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34358964

RESUMO

Schizophrenia is characterized by both disrupted neurodevelopmental processes and abnormal brain connectivity. However, few studies have examined the atypical features of brain network topography associated with schizophrenia during childhood and adolescence. We used graph theory to compare the grey matter structural networks of individuals (aged 10-15 years) with early-onset schizophrenia (EOS) (n = 25) and a typically-developing (TD) comparison group (n = 31). Compared with the TD group, EOS patients showed significantly increased clustering and local efficiency across a range of network densities (0.3 - 0.4). The network of EOS patients also had more modules (6 modules in EOS vs. 3 modules in controls), indicating a more segregated network at the cost of functional integration. Although our results were preliminary and failed to survive corrections for multiple comparisons, EOS patients might be characterized by altered nodal centrality in several higher-order associative regions including the prefrontal cortex, the hippocampus and the cerebellum. The EOS structural network also lacked the typical left-hemispheric-dominant hub distribution compared with the TD group. These findings suggest that brain structural network was not only globally but also regionally altered in EOS patients.


Assuntos
Substância Cinzenta , Esquizofrenia , Adolescente , Encéfalo/diagnóstico por imagem , Córtex Cerebral , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Esquizofrenia/diagnóstico por imagem
10.
Transl Vis Sci Technol ; 10(9): 35, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34448820

RESUMO

Purpose: This study investigated the relationship between retinal artery angle and visual function in eyes with idiopathic epiretinal membrane (ERM). Methods: Ultra-wide field fundus imaging was conducted to analyze ERM and normal contralateral eyes. In addition to the logMAR visual acuity (VA) measurement, the average of the vertical and horizontal metamorphopsia scores (Mave) was measured using m-Charts for each eye. We calculated the retinal artery angle (Yugami correlated angle [YCA]) in all the examined eyes using ImageJ software. The YCAs were then compared between the ERM and normal contralateral eyes. Additionally, the relationship between YCA and visual function was investigated in the ERM eyes. Results: Data from 40 patients with ERM were analyzed. The mean age of the participants was 67.1 ± 8.1 years. The YCA was significantly smaller in the ERM eyes, compared with the contralateral eyes (P < 0.001, respectively; Wilcoxon signed rank test). Among age, axial length, YCAs, central retinal thickness (CRT), and central choroidal thickness (CCT), the optimal model for logMAR VA included age, YCA, and CRT. On the other hand, the optimal model for Mave included YCA and CCT. Conclusions: The retinal artery angle may be useful for predicting visual function in eyes with ERM. Translational Relevance: Our established quantitative measurements in fundus photography have potential clinical use in predicting visual function in ERM.


Assuntos
Membrana Epirretiniana , Artéria Retiniana , Idoso , Membrana Epirretiniana/diagnóstico , Humanos , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico , Acuidade Visual
11.
J Autism Dev Disord ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264487

RESUMO

Interoception is believed to underlie socio-cognitive functions which are often impaired in individuals with autism spectrum disorders (ASD). In this study, Experiment 1 examined in a sample of 114 neurotypical college students the associations among autistic traits, alexithymia, and interoceptive accuracy (IA), which was assessed by a novel paradigm "Eye-tracking Interoceptive Accuracy Task (EIAT). In Experiment 2, EIAT and the Autism Spectrum Quotient were administered to 52 preschool children, 50 adolescents, and 50 adults. Experiment 1 supported the association between autistic traits and alexithymia, but failed to support their association with multidimensional interoception. Experiment 2 strongly supported the association between age and IA. We conclude that cardiac IA differs between neurotypical age groups, but shows limited relationship with autistic traits.

12.
J Sep Sci ; 44(18): 3441-3449, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34291571

RESUMO

Plant-derived alkaloids are bioactive natural ingredients, but their contents are relatively low in plants. Therefore, the efficient enrichment of alkaloids is a prerequisite for purification and further pharmacological research. In this study, an efficient and simple strategy for enrichment of steroidal alkaloids in Fritillaria was developed for the first time based on the fluorinated reverse-phase stationary phase (FC8HL). Superior selectivity between alkaloids and non-alkaloids was achieved in a non-aqueous system, and a simple solvent system containing low-content additives was applied to elute alkaloids. Key parameters that affected the elution were investigated, including different types of buffer salts and optimized concentrations. The optimized elution system was then applied to selectively enrich alkaloids from five species of Fritillaria. Its practicability was further demonstrated by enrichment of alkaloids from Fritillaria cirrhosa D.Don at a preparative level. This developed method has great potential for other types of hydrophobic alkaloids.

13.
J Autism Dev Disord ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34286394

RESUMO

Interoceptive accuracy has been widely measured using the Heartbeat Tracking Test (HTT). We devised the novel paradigm of Interoception-Exteroception Synchronicity Judgement (IESJ) task to assess participants' interoceptive accuracy, exteroceptive accuracy, and the balancing score which reflected the ability to allocate attentions between interoceptive and exteroceptive signals. This study administered the behavioural paradigms of the HTT and the IESJ as well as other self-report scales to 119 typically-developing youths. Individuals with lower autistic traits (n = 30) showed comparable interoceptive accuracy, exteroceptive accuracy, and balancing scores as their higher autistic traits counterparts (n = 33). Taken together, the high autistic traits subgroup exhibited higher levels of alexithymia but not empathy or interoception than the low autistic traits subgroup.

14.
J Am Heart Assoc ; 10(15): e019437, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34308664

RESUMO

Background Proteinuria and glomerular segmental fibrosis are inevitable complications of diabetic nephropathy though their mechanisms are poorly understood. Understanding the clinical characteristics and pathogenesis of proteinuria and glomerular segmental fibrosis in diabetic nephropathy is, therefore, urgently needed for patient management of this severe disease. Methods and Results Diabetes mellitus was induced in podocyte-specific glucocorticoid receptor knockout (GRPKO) mice and control littermates by administration of streptozotocin. Primary podocytes were isolated and subjected to analysis of Wnt signaling and fatty acid metabolism. Conditioned media from primary podocytes was transferred to glomerular endothelial cells. Histologic analysis of kidneys from diabetic GRPKO mice showed worsened fibrosis, increased collagen deposition, and glomerulomegaly indicating severe glomerular fibrosis. Higher expression of transforming growth factor-ßR1 and ß-catenin and suppressed expression of carnitine palmitoyltransferase 1A in nephrin-positive cells were found in the kidneys of diabetic GRPKO mice. Podocytes isolated from diabetic GRPKO mice demonstrated significantly higher profibrotic gene expression and suppressed fatty acid oxidation compared with controls. Administration of a Wnt inhibitor significantly improved the fibrotic features in GRPKO mice. The glomerular endothelium of diabetic GRPKO mice demonstrated the features of endothelial-to-mesenchymal transition. Moreover, endothelial cells treated with conditioned media from podocytes lacking GR showed increased expression of α-smooth muscle actin, transforming growth factor-ßR1 and ß-catenin levels. Conclusions These data demonstrate that loss of podocyte GR leads to upregulation of Wnt signaling and disruption in fatty acid metabolism. Podocyte-endothelial cell crosstalk, mediated through GR, is important for glomerular homeostasis, and its disruption likely contributes to diabetic nephropathy.

15.
Nano Lett ; 21(14): 6304-6313, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34264088

RESUMO

Adoptively transferred natural killer T (NKT) cells confer distinct cancer surveillance without causing obvious side effects, making them a promising candidate for cancer immunotherapy. However, their therapeutic efficacy is limited by inefficient tumor infiltration and inadequate activation in an immunosuppressive tumor microenvironment. To overcome these obstacles, we develop a strategy of using photothermal therapy (PTT) to promote the antitumor ability of adoptively transferred NKT cells. The transferred NKT cells are efficiently recruited to PTT-treated tumors in response to PTT-created inflammation. Moreover, PTT treatment promotes the activation of NKT cells and enhances the NKT cell-initiated immune cascade. As a consequence, the combined therapy of PTT plus NKT cell transfer exhibits excellent growth inhibition of local tumors. Moreover, it efficiently rejects distant tumors and elicits long-term immunological memory to prevent tumor recurrence. Overall, the current study opens new paths to the clinical translation of NKT cells for cancer immunotherapy.


Assuntos
Células T Matadoras Naturais , Neoplasias , Linhagem Celular Tumoral , Humanos , Imunoterapia , Neoplasias/terapia , Fototerapia , Microambiente Tumoral
16.
Physiol Genomics ; 53(8): 349-357, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34121455

RESUMO

Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure, and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD). We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of five patients with CAD and five controls. Bioinformatics analyses were adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the microRNA (miRNA)-targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA. In total, 13,160 downregulated and 12,905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle, and cellular metabolic process. Parental genes of the 10 dysregulated circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges. As potential competing endogenous RNAs (ceRNAs), dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into the diagnosis and prognosis of coronary artery disease.

17.
Asia Pac J Clin Nutr ; 30(2): 253-262, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34191428

RESUMO

BACKGROUND AND OBJECTIVES: Research has produced inconsistent findings on the association between dietary patterns and cognitive function. In the present study, we examined the association between dietary patterns and cognitive function among rural China's older adults and aimed to identify major dietary patterns. METHODS AND STUDY DESIGN: This cross-sectional study included 1176 individuals aged 65-85 years. Dietary intake was assessed using a food frequency questionnaire. Factor analysis and the Chinese Dietary Balance Index were respectively employed to determine dietary patterns and assess dietary quality. Cognitive function was evaluated using the Mini-Mental State Examination, and logistic regression analysis was performed to examine the relationship between dietary patterns and cognitive decline. RESULTS: Three main dietary patterns were identified and named on the basis of foods with high content: a "healthy dietary pattern," a "multigrain dietary pattern," and a "snack dietary pattern." With the increase in the score of the healthy dietary pattern, the Mini-Mental State Examination total score exhibited a significant downward trend (p<0.001). Moreover, we observed a prominent negative association between the healthy dietary pattern and mild cognitive impairment (4th to 1st quartile, OR=0.36; 95%CI, 0.24-0.54; p<0.001). After we adjusted for potential covariates, the negative correlation remained (4th to 1st quartile, OR=0.48; 95%CI, 0.28-0.81; p=0.006). However, no relation was observed between mild cognitive impairment and either the multigrain or snack dietary patterns. CONCLUSIONS: The healthy dietary pattern, which is based on the consumption of rice and flour, red meat, chicken, vegetables, seafood, and fruits, protects against cognitive dysfunction.

18.
J Ethnopharmacol ; 278: 114335, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34139281

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dopamine receptors are long-standing primary targets in the treatment of mental diseases and there is growing evidence that suggests relationships between obesity and the dopamine system, especially dopamine D1 and D2 receptors. Leaves of Nelumbo nucifera Gaertn. (lotus leaves) have been medically used for helping long-term maintenance of weight loss. Whether and how components of lotus leaves function through the dopamine receptors remains unclear. AIM OF THE STUDY: This work aimed to discover dopamine receptor-active alkaloids isolated from the lotus leaves, to evaluate their potencies and to analyze their structure activity relationship. MATERIALS AND METHODS: Dried lotus leaves were prepared and total extract was divided into alkaloids and flavones. Eight alkaloids were separated and characterized by a combination of high-performance liquid chromatography, quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance, and assayed by a fluorometric imaging plate reader platform. Human embryonic kidney 239 cell lines expressing dopamine D1, D2 and serotonin 2A (5-HT2A) receptors, respectively, were cultured and used in the assay. RESULTS: Alkaloids in the lotus leaves were the bioactive phytochemicals and inhibited dopamine from accessing the D1 and D2 receptors. All eight compounds functioned as D1-receptor antagonists and except N-nornuciferine, seven alkaloids functioned as D2-receptor antagonists. (S)-coclaurine and (R)-coclaurine are optical isomers and antagonized both D1 and D2 with equivalent potencies, suggesting that the optical rotation of the methylene linker in the monobenzyl isoquinoline backbone did not influence their activity. Among the eight alkaloids, O-nornuciferine was the potent antagonist to both receptors (the lowest IC50 values, D1: 2.09 ± 0.65 µM and D2: 1.14 ± 0.10 µM) while N-nornuciferine was found to be the least potent as it moderately antagonized D1 and was inactive on D2. O-nornuciferine was also a 5-HT2A antagonist (IC50~20 µM) while N-nornuciferine had no activity. These hinted the importance of a methyl group attached to the nitrogen atom in the aporphine backbone. Armepavine showed a nearly 10-fold selectivity to D2. CONCLUSIONS: In this work, eight alkaloids were isolated from the leaves of Nelumbo nucifera Gaertn. and assayed on the D1 and D2 receptors. They were D1/D2 antagonists with IC50 values in the mid- to low-micromolar range and O-nornuciferine was the most potent alkaloid among the eight. This family of alkaloids was biochemically evaluated on the dopamine receptors by the same platform for the first time.

19.
Cell Oncol (Dordr) ; 44(5): 1035-1049, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34176092

RESUMO

PURPOSE: In this study we aimed to assess the anti-tumor effect of co-inhibition of Aurora kinase A (AURKA) and heat shock transcription factor 1 (HSF1) on hepatocellular carcinoma (HCC), as well as to explore the mechanism involved. METHODS: Expression of AURKA and HSF1 in primary HCC tissues and cell lines was detected by immunohistochemistry (IHC), qRT-PCR and Western blotting. AURKA was knocked down in HepG2 and BEL-7402 HCC cells using lentivirus-mediated RNA interference. Next, CCK-8, clone formation, transwell and flow cytometry assays were used to assess their viability, migration, invasion and apoptosis, respectively. The expression of proteins related to cell cycle progression, apoptosis and endoplasmic reticulum stress (ERS) was analyzed using Western blotting. In addition, in vivo tumor growth of HCC cells was assessed using a nude mouse xenograft model, and the resulting tumors were evaluated using HE staining and IHC. RESULTS: Both AURKA and HSF1 were highly expressed in HCC tissues and cells, while being negatively related to HCC prognosis. Knockdown of AURKA significantly inhibited the colony forming and migrating capacities of HCC cells. In addition, we found that treatment with an AURKA inhibitor (Danusertib) led to marked reductions in the proliferation and migration capacities of the HCC cells, and promoted their apoptosis. Notably, combined inhibition of AURKA and HSF1 induced HCC cell apoptosis, while increasing the expression of ERS-associated proteins, including p-eIF2α, ATF4 and CHOP. Finally, we found that co-inhibition of AURKA and HSF1 elicited an excellent in vivo antitumor effect in a HCC mouse model with a relatively low cytotoxicity. CONCLUSIONS: Combined inhibition of AURKA and HSF1 shows an excellent anti-tumor effect on HCC cells in vitro and in vivo, which may be mediated by ERS. These findings suggest that both AURKA and HSF1 may serve as targets for HCC treatment.

20.
Nanotechnology ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34157697

RESUMO

A simple, effective and interesting method for gold nanoparticles (AuNPs) synthesis with nonthermal microplasma is developed in this study. The device of dielectric barrier discharge (DBD) microplasma generator with a spray portion is designed and fabricated for uniform AuNPs synthesis. The AuNPs can be synthesized effectively in situ by the DBD microplasma generated on the nozzle of the pneumatic micro-nebulizer. The mechanism of the AuNPs formation under microplasma, the effect of nebulization for uniform AuNPs synthesis and other significant parameters are investigated in the experiment. The morphology and optical properties of the synthesized gold nanoparticles are also characterized. The minimum particle size in average obtained by the proposed method is 4.9±1.1 nm. The particle size of AuNPs can be controlled by the various aqueous solution conditions in the range of 4.9 to 16.8 nm.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...