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1.
Phys Rev Lett ; 124(9): 090601, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32202879

RESUMO

How do we search for the entire family tree of possible intermediate states, without unwanted random guesses, starting from a stationary state on the energy landscape all the way down to energy minima? Here we introduce a general numerical method that constructs the pathway map, which guides our understanding of how a physical system moves on the energy landscape. The method identifies the transition state between energy minima and the energy barrier associated with such a state. As an example, we solve the Landau-de Gennes energy incorporating the Dirichlet boundary conditions to model a liquid crystal confined in a square box; we illustrate the basic concepts by examining the multiple stationary solutions and the connected pathway maps of the model.

2.
Sci Rep ; 10(1): 4459, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157170

RESUMO

In a myriad of engineering situations, we often hope to establish a model which can acquire load conditions around structures through flow features detection. A data-driven method is developed to predict the pressure on a cylinder from velocity distributions in its wake flow. The proposed deep learning neural network is constituted with convolutional layers and fully-connected layers: The convolutional layers can process the velocity information by features extraction, which are gathered by the fully-connected layers to obtain the pressure coefficients. By comparing the output data of the typical network with Computational Fluid Dynamics (CFD) results as reference values, it suggests that the present convolutional neural network (CNN) is able to predict the pressure coefficient in the vicinity of the trained Reynolds numbers with various inlet flow profiles and achieves a high overall precision. Moreover, a transfer learning approach is adopted to preserve the feature detection ability by keeping the parameters in the convolutional layers unchanged while shifting parameters in the fully-connected layers. Further results show that this transfer learning network has nearly the same precision while significantly lower cost. The active prospects of convolutional neural network in fluid mechanics have also been demonstrated, which can inspire more kinds of loads prediction in the future.

3.
Phys Rev E ; 101(2-1): 022706, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32168669

RESUMO

We focus on a dilute uniform suspension of magnetic nanoparticles in a nematic-filled micron-sized shallow well with tangent boundary conditions as a paradigm system with two coupled order parameters. This system exhibits spontaneous magnetization without magnetic fields. We numerically obtain the stable nematic and associated magnetization morphologies, induced purely by the geometry, the boundary conditions, and the coupling between the magnetic nanoparticles and the host nematic medium. Our most striking observations pertain to domain walls in the magnetization profile, whose location can be manipulated by the coupling and material properties, and stable interior and boundary nematic defects, whose location and multiplicity can be tailored by the coupling too. These tailored morphologies are not accessible in uncoupled systems and can be used for multistable systems with singularities and stable interfaces.

4.
Mediators Inflamm ; 2020: 8098439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184702

RESUMO

Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, ß-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and ß-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events.

5.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32047612

RESUMO

The brain undergoes two aging programs: chronological and endocrinological. This is particularly evident in the female brain, which undergoes programs of aging associated with reproductive competency. Comprehensive understanding of the dynamic metabolic and neuroinflammatory aging process in the female brain can illuminate windows of opportunities to promote healthy brain aging. Bioenergetic crisis and chronic low-grade inflammation are hallmarks of brain aging and menopause and have been implicated as a unifying factor causally connecting genetic risk factors for Alzheimer's disease and other neurodegenerative diseases. In this review, we discuss metabolic phenotypes of pre-menopausal, peri-menopausal, and post-menopausal aging and their consequent impact on the neuroinflammatory profile during each transition state. A critical aspect of the aging process is the dynamic metabolic neuro-inflammatory profiles that emerge during chronological and endocrinological aging. These dynamic systems of biology are relevant to multiple age-associated neurodegenerative diseases and provide a therapeutic framework for prevention and delay of neurodegenerative diseases of aging. While these findings are based on investigations of the female brain, they have a broader fundamental systems of biology strategy for investigating the aging male brain. Molecular characterization of alterations in fuel utilization and neuroinflammatory mechanisms during these neuro-endocrine transition states can inform therapeutic strategies to mitigate the risk of Alzheimer's disease in women. We further discuss a precision hormone replacement therapy approach to target symptom profiles during endocrine and chronological aging to reduce risk for age-related neurodegenerative diseases.

6.
J Soc Psychol ; : 1-13, 2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32089107

RESUMO

Prior research has shown that greater willingness to apologize for an offense is prompted by greater guilt but lesser shame. Yet little work examined whether apologies indeed resolve moral emotions. This study investigated how the absence of apology psychologically affects harm-doers when they recall a past offense. Undergraduates (N = 284) were randomly assigned to one of the four experimental conditions wherein they recalled a past incident in which they hurt, offended, angered, or had some other negative effect on another person. Harm-doers who intended but failed to apologize reported greater PFQ-2 state guilt and shame, compared to others who refused to apologize or whose apologies were rejected. However, similar results were not found for ESS state shame. Results suggest that failing to apologize may impede transgressors from relieving moral emotional burdens, but only for those who intended to apologize.

7.
Sci Rep ; 10(1): 1724, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015423

RESUMO

S100A12 belongs to the S100 family and acts as a vital regulator in different types of tumors. However, the function of S100A12 in thyroid carcinoma has not yet been investigated. In this study, we analyzed the expression of S100A12 in human papillary thyroid cancer (PTC) samples and two PTC cell lines. In addition, we explored the effects of S100A12 on PTC cell progression in vitro and in vivo. Our results showed that S100A12 was significantly upregulated in PTC specimens. Moreover, silencing S100A12 markedly inhibited PTC cell proliferation, migration, invasion and cell cycle progression. In addition, knockdown of S100A12 significantly reduced the expression of CyclinD1, CDK4 and p-ERK in PTC cells. An in vivo study also showed that silencing S100A12 dramatically suppressed tumor cell growth and decreased Ki67 expression in a xenograft mouse model. This study provides novel evidence that S100A12 serves as an oncogene in PTC. Knockdown of S100A12 suppressed PTC cell proliferation, migration, and invasion and induced G0/G1 phase arrest via the inhibition of the ERK signaling pathway. Therefore, S100A12 may be a potent therapeutic target for PTC.

8.
Cancer Res ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060149

RESUMO

Tumor-associated macrophages (TAMs) play an indispensable role in the modulation of the cancer immune microenvironment. Despite the fact that TAMs may exert both anti-tumor and pro-tumor activities, the molecular mechanisms involved remain poorly understood. Here, we characterized a subpopulation of TAMs expressing DC-specific C-type lectin (DC-SIGN) and investigated its relevance to the prognosis and immune microenvironment of muscle-invasive bladder cancer (MIBC). DC-SIGN+ TAMs were abundant in a significant proportion of human MIBC specimens. High levels of DC-SIGN+ TAMs were associated with dismal prognosis and unresponsiveness to adjuvant chemotherapy in MIBC. Notably, multiple anti-inflammatory cytokines were enriched in DC-SIGN+ TAMs. RNA-seq analysis revealed that multiple M2-like signaling pathways were significantly upregulated in DC-SIGN+ TAMs. High infiltration of DC-SIGN+ TAMs was associated with CD8+ T cell tolerance in MIBC. Moreover, abrogating DC-SIGN function using a neutralizing antibody led to impaired expression of anti-inflammatory cytokines and augmented PD-1 inhibitor pembrolizumab-mediated cytotoxic effects of CD8+T cells towards MIBC cells. In summary, these results suggest that DC-SIGN+ TAM infiltration is closely linked to a pro-tumor immune microenvironment, and may serve as a promising therapeutic target in the immunotherapy of MIBC.

9.
Br J Nutr ; : 1-24, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31983360

RESUMO

Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. This study aimed to identify the optimal macronutrient intake for burn wound healing. The Geometric Framework (GF) was used to analyse wound healing after a 10% TBSA contact burn in mice ad libitum fed one of 11 high-energy diets, varying in macronutrient composition with protein (P5%-60%), carbohydrate (C20%-75%) and fat (F20%-75%). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High-carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of ~7 kJ/day (~15% of energy intake) was identified, above which no further benefit was gained. High-protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high-protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high-protein intake for mortality, and subsequent moderate-protein, high-carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.

10.
BMC Ophthalmol ; 20(1): 17, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914956

RESUMO

BACKGROUND: To evaluate the macular vessel density (VD) and ganglion cell complex (GCC) thickness in pre-perimetric (PPG) and early perimetric primary open-angle glaucoma (PG) eyes, and to compare the diagnostic ability of the two measurements to discriminate PPG and early PG eyes from healthy eyes. METHODS: Seventy-nine eyes in 72 subjects (31 normal, 26 PPG, and 22 early PG eyes) were included in the consecutive case series. Macular VD and GCC thickness were acquired simultaneously using the 6 × 6 mm2 high-density AngioRetina scanning mode. Diagnostic abilities were assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: Compared to healthy eyes, whole image VD (wiVD) and GCC thickness were significantly lower in PPG and early PG eyes (all P < 0.025). The percent reduction of wiVD was lower than that of GCC thickness in early PG eyes (P < 0.05), while they were similar in PPG eyes (P > 0.05). Regionally, greater VD attenuation and GCC thinning were identified in the perifovea than in the parafovea in both groups (all P < 0.05). Moreover, the percent reduction of VD was less than that of GCC thickness in the perifoveal region in PPG eyes (P < 0.05). The AUROCs for wiVD and GCC thickness were 0.824 and 0.881, respectively, in PPG eyes (P > 0.05), and 0.918 and 0.977, respectively, in early PG eyes (P > 0.05). CONCLUSIONS: Macular VD and GCC thickness significantly decreased in PPG and early PG eyes. The perifoveal region appeared to be more vulnerable to macular VD attenuation and GCC thinning in early glaucoma. Our results showed that macular VD measurements may be helpful for detecting and understanding early glaucomatous damage.

11.
PLoS One ; 15(1): e0225392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917799

RESUMO

Late onset Alzheimer's disease (LOAD) is a progressive neurodegenerative disease with four well-established risk factors: age, APOE4 genotype, female chromosomal sex, and maternal history of AD. Each risk factor impacts multiple systems, making LOAD a complex systems biology challenge. To investigate interactions between LOAD risk factors, we performed multiple scale analyses, including metabolomics, transcriptomics, brain magnetic resonance imaging (MRI), and beta-amyloid assessment, in 16 months old male and female mice with humanized human APOE3 (hAPOE3) or APOE4 (hAPOE4) genes. Metabolomic analyses indicated a sex difference in plasma profile whereas APOE genotype determined brain metabolic profile. Consistent with the brain metabolome, gene and pathway-based RNA-Seq analyses of the hippocampus indicated increased expression of fatty acid/lipid metabolism related genes and pathways in both hAPOE4 males and females. Further, female transcription of fatty acid and amino acids pathways were significantly different from males. MRI based imaging analyses indicated that in multiple white matter tracts, hAPOE4 males and females exhibited lower fractional anisotropy than their hAPOE3 counterparts, suggesting a lower level of white matter integrity in hAPOE4 mice. Consistent with the brain metabolomic and transcriptomic profile of hAPOE4 carriers, beta-amyloid generation was detectable in 16-month-old male and female brains. These data provide therapeutic targets based on chromosomal sex and APOE genotype. Collectively, these data provide a framework for developing precision medicine interventions during the prodromal phase of LOAD, when the potential to reverse, prevent and delay LOAD progression is greatest.

12.
Sensors (Basel) ; 20(2)2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31947525

RESUMO

In this paper, a flexible and stretchable energy harvester based on liquid-metal and fluorinated ethylene propylene (FEP) electret films is proposed and implemented for the application of wearable devices. A gallium liquid-metal alloy with a melting point of 25.0 °C is used to form the stretchable electrode; therefore, the inducted energy harvester will have excellent flexibility and stretchability. The solid-state electrode is wrapped in a dragon-skin silicone rubber shell and then bonded with FEP electret film and conductive film to form a flexible and stretchable energy harvester. Then, the open-circuit voltage of the designed energy harvester is tested and analyzed. Finally, the fabricated energy harvester is mounted on the elbow of a human body to harvest the energy produced by the bending of the elbow. The experimental results show that the flexible and stretchable energy harvester can adapt well to elbow bending and convert elbow motion into electric energy to light the LED in a wearable watch.

13.
Hematology ; 25(1): 63-70, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31984870

RESUMO

Background: Venous thromboembolism (VTE) is a common complication in cancer patients. We aim to evaluate the effect and safety of direct oral anticoagulants (DOACs) as primary prophylaxis in ambulatory cancer patients.Methods: We conducted a literature search in PubMed, EMBASE and ClinicalTrials for studies that evaluated DOACs for thromboprophylaxis in cancer patients. RevMan 5.3 software was used for this meta-analysis.Results: Three randomized controlled trials (RCTs) with a total of 1465 patients were pooled in the meta-analysis. DOACs significantly reduced the symptomatic VTE incidence during intervention period (RR 0.23, CI 0.11-0.47, P<0.0001, I2=9%). Significantly lower total VTE incidence (RR 0.53, CI 0.36-0.78, P = 0.001, I2 =30%) and PE incidence (RR 0.50, CI 0.28-0.89, P = 0.02, I2 =5%) were found during the observation period, and a trend for less symptomatic DVT events was found in the DOACs group (RR 0.62, CI 0.37-1.04, P = 0.07, I2 =5%). No differences for all-cause mortality were found between groups (RR 0.92, CI 0.74-1.15, P = 0.47, I2 =14%). DOACs did not significantly increase major bleeding risks (RR 1.66, CI 0.72-3.83, P = 0.24, I2 =0%) during the intervention period or clinically relevant non-major bleeding events (RR 1.50, CI 0.90-2.49, P = 0.12, I2 =0%) and total bleeding events during the observation period (RR 1.50, CI 0.98-2.29, P = 0.06, I2 =0%).Conclusion: DOACs are effective for thromboprophylaxis in ambulatory cancer patients, but there is a potential risk of bleeding. DOACs may be recommended in selected patients at high risk of VTE. More high-quality studies are needed to further validate our results.Abbreviations: CAT: cancer-associated thrombosis; CI: confidence interval; DOAC: direct oral anticoagulant; DVT: deep vein thrombosis; LMWH: low molecular weight heparin; NNH: number needed to harm; NNT: number needed to treat; PE: pulmonary embolism; RCT: randomized controlled trials; RR: risk ratio; RD: rate difference; VTE: venous thromboembolism.

14.
Food Chem Toxicol ; 135: 110921, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669597

RESUMO

Determining chemical carcinogenicity in the early stages of drug discovery is fundamentally important to prevent the adverse effect of carcinogens on human health. There has been a recent surge of interest in developing computational approaches to predict chemical carcinogenicity. However, the predictive power of many existing approaches is limited, and there is plenty of room for improvement. Here, we develop a new deep learning architecture, termed CapsCarcino, to distinguish between carcinogens and noncarcinogens. CapsCarcino is constructed based on a dynamic routing algorithm that requires less data, extracts more comprehensive information, and does not require feature selection. We find that CapsCarcino provides a significantly improved predictive and generalization ability over, and outperforms five other machine learning models. Specifically, the best model of CapsCarcino achieves an accuracy of 85.0% on an external validation dataset. In addition, we discover that the enhanced predictive capability of CapsCarcino over that of the other methods is robust and can be achieved using sparse datasets. Training on merely 20% of the dataset, CapsCarcino performs comparably to the other methods based on the full training dataset. Further mechanism analysis indicates that CapsCarcino could efficiently learn the characteristics of carcinogens even if structural alerts are insufficiently represented. The results indicate that CapsCarcino should be helpful for carcinogen risk assessment.


Assuntos
Carcinógenos/química , Aprendizado Profundo , Animais , Bases de Dados de Compostos Químicos/estatística & dados numéricos , Ratos
15.
Menopause ; 27(1): 57-65, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31567873

RESUMO

OBJECTIVE: PhytoSERM is a selective estrogen receptor beta (ERß) modulator comprised of three phytoestrogens: genistein, daidzein, and S-equol. The PhytoSERM formulation promotes estrogenic action in the brain while largely inactive or inhibitory in reproductive tissue. A phase Ib/IIa clinical trial (ClinicalTrial.gov ID: NCT01723917) of PhytoSERM demonstrated safety and pharmacokinetics profile of PhytoSERM. While this study was not powered for efficacy analysis, we conducted a pilot, retrospective analysis to identify potential responders to PhytoSERM treatment, and to determine the optimal populations to pursue in a phase II clinical trial of efficacy of the PhytoSERM formulation. METHODS: In this retrospective analysis involving 46 participants (n = 16, placebo; n = 18, 50 mg/d PhytoSERM; and n = 12, 100 mg/d PhytoSERM), the therapeutic effect of PhytoSERM was stratified by 2 genetic risk modulators for Alzheimer's disease: mitochondrial haplogroup and APOE genotype. RESULTS: Our retrospective responder analysis indicated that participants on 50 mg of daily PhytoSERM (PS50) for 12 weeks significantly reduced hot flash frequency compared with their baseline (mean [95% CI])-1.61, [-2.79, -0.42], P = 0.007). Participants on 50 mg of PhytoSERM also had significantly greater reduction in hot flash frequency at 12 weeks compared with the placebo group (-1.38, -0.17 [median PS50, median placebo], P = 0.04). Fifty milligrams of daily PhytoSERM also preserved cognitive function in certain aspects of verbal learning and executive function. Our analysis further suggests that mitochondrial haplogroup and APOE genotype can modify PhytoSERM response. CONCLUSION: Our data support a precision medicine approach for further development of PhytoSERM as a safe and effective alternative to hormone therapy for menopause-associated hot flash and cognitive decline. While definitive determination of PhytoSERM efficacy is limited by the small sample size, these data provide a reasonable rationale to extend analyses to a larger study set powered to address statistical significance.

16.
Urolithiasis ; 48(1): 79-84, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30877315

RESUMO

Forgotten ureteral stents (FUS) is a great threat to both patients and doctors. Applications on smartphones can significantly reduce the incidence of FUS. But existing applications do not have instant notification and consultation functions. To implement those function, we developed a ureteral stent tracking system embedded in a social networking service application, WeChat. "Ureteral Stent Tracking System" was developed on WeChat, a social media application using by 1.4 million active users. The study consecutively enrolled patients who underwent ureteral stent installation from April 2018 to July 2018. Each patient's information was recorded on the smartphone by the urologists to create a document immediately after the surgery. The system sends notifications twice a week to both patients and clinicians via the message function of WeChat. A total of 183 patients were enrolled. The most senior patient enrolled was 73 years old. 156 (85.2%) patients underwent stent extraction before the scheduled time. 22 did not undergo stent extraction before the scheduled time because of urinary tract infection or stone residue. They underwent stent extraction within 1 month after the scheduled time. Two patients did not come to the hospital until we had made a phone call to them, though they had received notification from the online system. During the study, no patient was lost-to-follow up. In bilateral stents cases, no stent was forgotten after extraction surgery. A total of 85 (46.4%) patients consulted 132 issues in the system. 52 (39.4%) patients complained about hematuria. 36 (27.3%) patients reported lower urinary tract symptoms. All the consultations were answered within 24 h. "Ureteral Stent Tracking System" implement instant notification and consultation functions via WeChat. It helps urologists to manage indwelling ureteral stents and to reduce the incidence of FUS efficiently.

17.
Int J Cancer ; 146(2): 542-552, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31584197

RESUMO

Our previous researches have identified immunoevasive subtype muscle-invasive bladder cancer (MIBC) characterized with immune cells infiltration patterns. Our study explored the clinical significance, immunoregulatory role and therapeutic value of intratumoral IL22-producing cells in MIBC. Two hundred and fifty-nine formalin-fixed paraffin-embedded MIBC samples and 83 freshly resected MIBC tissues and 391 TCGA MIBC samples were retrospectively evaluated. Immunohistochemistry and flow cytometry were applied to identify immune cell infiltration and functional status. In vitro intervention studies were to test the therapeutic and predictive potential of IL22+ cells. Our data revealed patients with high IL22+ cells infiltration suffered poor overall survival and recurrence-free survival in both training and validation cohorts. Only pT2 patients of combined cohort with low IL22+ cells infiltration gained survival benefits from adjuvant chemotherapy (ACT) significantly. Besides, immune contexture featured with increased pro-tumor cells and immunosuppressive cytokines was identified in patients with high IL22+ cells density. The expression pattern of exhausted and effector markers in CD8+ T cells from high IL22+ cells subgroup indicated their dysfunctional status. Importantly, nivolumab showed tumor-killing efficacy in tumors with high IL22+ cells infiltration, and immunosuppressive contexture with CD8+ T cells exhaustion was abrogated in tumors treated with anti-IL22 antibody. In summary, IL22+ cells infiltration determined immunosuppressive contexture with CD8+ T cell dysfunction. Tumor-infiltrating IL22+ cells could be used as an independent marker to predict prognosis and ACT responses. IL22+ cells infiltration possessed the potential to be a favorable predictor for nivolumab application and IL22 blockade could be a novel therapeutic strategy in MIBC.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Interleucinas/metabolismo , Nivolumabe/farmacologia , Evasão Tumoral/efeitos dos fármacos , Neoplasias da Bexiga Urinária/terapia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Quimioterapia Adjuvante/métodos , Cistectomia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Interleucinas/imunologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Nivolumabe/uso terapêutico , Prognóstico , Estudos Retrospectivos , Evasão Tumoral/imunologia , Bexiga Urinária/citologia , Bexiga Urinária/imunologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
18.
Onco Targets Ther ; 12: 10361-10374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819519

RESUMO

Purpose: Perineural invasion (PNI) is the neoplastic invasion of nerves by cancer cells, a process that may prove to be another metastatic route besides direct invasion, lymphatic spread, and vascular dissemination. Given the increasing incidence and association with poor prognosis, revealing the pathogenesis of perineural invasion is of great importance. Materials and methods: Four datasets related to PNI were downloaded from the Gene Expression Omnibus database and used to construct weighted gene co-expression network analysis (WGCNA). The intersection of potential pathways obtained from further correlation and enrichment analyses of different datasets was validated by the coculture model of Schwann cells (SCs), flow cytometry and immunohistochemistry (IHC). Results: GSE7055 and GSE86544 datasets were brought into the analysis for there were some significant modules related to PNI, while GSE103479 and GSE102238 datasets were excluded for insignificant differences. In total, 13,841 genes from GSE86544 and 10,809 genes from GSE7055 were used for WGCNA. As a consequence, 19 and 26 modules were generated, respectively. The purple module of GSE86544 and the dark gray module of GSE7055 were positively correlated with perineural invasion. Further correlation and enrichment analyses of genes from the two modules suggested that these genes were mainly enriched in cell cycle processes; especially, the terms S/G2/M phase were enriched. Three kinds of cells grew vigorously after coculture with SCs ex vivo. The Ki67 staining of the cervical cancer samples revealed that the Ki67 index of cancer cells surrounding nerves was higher than of those distant ones. Conclusion: Our work has identified cancer cell proliferation as a common response to neural cancerous microenvironments, proving a foundation for cancer cell colonization and metastasis.

19.
Anal Cell Pathol (Amst) ; 2019: 1907698, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871879

RESUMO

Kaempferol is a well-known natural flavonol reported to be a potential treatment for multiple cancers. In this study, we demonstrated that cell growth of androgen-sensitive LNCaP cells could be inhibited 33% by 5 µM kaempferol, around 60% by 10 µM kaempferol, and almost 100% by 15 µM kaempferol. Also, kaempferol showed relatively limited effect on PC-3 cells and nonmalignant RWPE-1 cells. In the presence of DHT, the IC50 for kaempferol was 28.8 ± 1.5 µM in LNCaP cells, 58.3 ± 3.5 µM in PC-3 cells, and 69.1 ± 1.2 µM in RWPE-1 cells, respectively. Kaempferol promotes apoptosis of LNCaP cells in a dose-dependent manner in the presence of dihydrotestosterone (DHT). Then, luciferase assay data showed that kaempferol could inhibit the activation of androgen receptors induced by DHT significantly. The downstream targets of androgen receptors, such as PSA, TMPRSS2, and TMEPA1, were found decreased in the presence of kaempferol in qPCR data. It was then confirmed that the protein level of PSA was decreased. Kaempferol inhibits AR protein expression and nuclear accumulation. Kaempferol suppressed vasculogenic mimicry of PC-3 cells in an in vitro study. In conclusion, kaempferol is a promising therapeutic candidate for treatment of prostate cancer, where the androgen signaling pathway as well as vasculogenic mimicry are involved.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31863349

RESUMO

Repairing osteochondral defects to restore joint function is a major challenge in regenerative medicine. However, with recent advances in tissue engineering, the development of potential treatments is promising. In recent years, in addition to single-layer scaffolds, double-layer or multilayer scaffolds have been prepared to mimic the structure of articular cartilage and subchondral bone for osteochondral repair. Although there are a range of different cells such as umbilical cord stem cells, bone marrow mesenchyml stem cell, and others that can be used, the availability, ease of preparation, and the osteogenic and chondrogenic capacity of these cells are important factors that will influence its selection for tissue engineering. Furthermore, appropriate cell proliferation and differentiation of these cells is also key for the optimal repair of osteochondral defects. The development of bioreactors has enhanced methods to stimulate the proliferation and differentiation of cells. In this review, we summarize the recent advances in tissue engineering, including the development of layered scaffolds, cells, and bioreactors that have changed the approach towards the development of novel treatments for osteochondral repair.

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