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1.
Biomolecules ; 11(4)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805919

RESUMO

The androgen receptor (AR) is one of the main components in the development and progression of prostate cancer (PCa), and treatment strategies are mostly directed toward manipulation of the AR pathway. In the metastatic setting, androgen deprivation therapy (ADT) is the foundation of treatment in patients with hormone-sensitive prostate cancer (HSPC). However, treatment response is short-lived, and the majority of patients ultimately progress to castration-resistant prostate cancer (CRPC). Surmountable data from clinical trials have shown that the maintenance of AR signaling in the castration environment is accountable for disease progression. Study results indicate multiple factors and survival pathways involved in PCa. Based on these findings, the alternative molecular pathways involved in PCa progression can be manipulated to improve current regimens and develop novel treatment modalities in the management of CRPC. In this review, the interaction between AR signaling and other molecular pathways involved in tumor pathogenesis and its clinical implications in metastasis and advanced disease will be discussed, along with a thorough overview of current and ongoing novel treatments for AR signaling inhibition.

2.
Nano Lett ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784095

RESUMO

Overlimiting current (OLC) through electrolytes interfaced with perm-selective membranes has been extensively researched for understanding fundamental nano-electrokinetics and developing efficient engineering applications. This work studies how a network of microchannels in a nonuniform array, which mimics a natural pore configuration, can contribute to OLC. Here, micro/nanofluidic devices are fabricated with arrays of parallel microchannels with nonuniform size distributions, which are faced with a perm-selective membrane. All cases maintain the same surface and bulk conduction to allow probing of the sensitivity only by the nonuniformity. Rigorous experimental and theoretical investigation demonstrates that overlimiting conductance has a maximum value depending on the nonuniformity. Furthermore, in operando visualization reveals that the nonuniform arrays induce flow loops across the microchannel network enhancing advective transport. This recirculating flow eliminates local salt accumulations so that it can effectively suppress undesirable salt crystallization. Therefore, these results can significantly advance not only the fundamental understanding of the driving mechanism of the OLC but also the design rule of electrochemical membrane applications.

3.
Biochem Biophys Res Commun ; 553: 30-36, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33756343

RESUMO

Recently, there is a rapid increase in the incidence of obesity, a condition for which there are no effective therapeutic agents. Capmatinib (CAP), a novel mesenchymal-to-epithelial transition inhibitor, is reported to attenuate pro-inflammatory mediators and oxidative stress. In this study, the effects of CAP on lipogenesis in the adipocytes were examined. Treatment with CAP dose-dependently suppressed lipid accumulation in, and differentiation of, and increased lipolysis in, 3T3-L1 adipocytes. Additionally, CAP treatment augmented adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and FNDC5 expression in the adipocytes. Transfection with si-AMPK or si-FNDC5 mitigated the CAP-induced suppression of lipogenesis and enhanced lipolysis. Furthermore, transfection with si-FNDC5 mitigated the CAP-induced phosphorylation of AMPK. These results suggest that the anti-obesity effect of CAP is mediated through the irisin/AMPK pathway and that CAP is a novel therapeutic agent for obesity.

4.
Anal Chem ; 93(10): 4425-4433, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33647202

RESUMO

Integrated bioassay systems that combine microfluidics and radiation detectors can deliver medical radiopharmaceuticals to live cells with precise timing, while minimizing radiation dose and sample volume. However, the spatial resolution of many radiation imaging systems is limited to bulk cell populations. Here, we demonstrate microfluidics-coupled radioluminescence microscopy (µF-RLM), a new integrated system that can image radiotracer uptake in live adherent cells growing inside microincubators with spatial resolution better than 30 µm. Our method enables on-chip radionuclide imaging by incorporating an inorganic scintillator plate (CdWO4) into a microfluidic chip. We apply this approach to investigate the factors that influence the dynamic uptake of [18F]fluorodeoxyglucose (FDG) by cancer cells. In the first experiment, we measured the effect of flow on FDG uptake of cells and found that a continuous flow of the radiotracer led to fourfold higher uptake than static incubation, suggesting that convective replenishment enhances molecular radiotracer transport into cells. In the second set of experiments, we applied pharmacokinetic modeling to show that lactic acidosis inhibits FDG uptake by cancer cells in vitro and that this decrease is primarily due to downregulation of FDG transport into the cells. The other two rate constants, which represent FDG export and FDG metabolism, were relatively unaffected by lactic acidosis. Lactic acidosis is common in solid tumors because of the dysregulated metabolism and inefficient vasculature. In conclusion, µF-RLM is a simple and practical approach for integrating high-resolution radionuclide imaging within standard microfluidics devices, thus potentially opening venues for investigating the efficacy of radiopharmaceuticals in in vitro cancer models.

5.
Pflugers Arch ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586023

RESUMO

Innate-like CD5+ B1a cells localized in serous cavities are activated by innate stimuli, such as lipopolysaccharide (LPS), leading to T cell-independent antibody responses. Although ion channels play crucial roles in the homeostasis and activation of immune cells, the electrophysiological properties of B1a cells have not been investigated to date. Previously, in the mouse B cell lymphoma cells, we found that the voltage-independent two-pore-domain potassium (K2P) channels generate a negative membrane potential and drive Ca2+ influx. Here, we newly compared the expression and activities of K2P channels in mouse splenic follicular B (FoB), marginal zone B (MZB), and peritoneal B1a cells. Next-generation sequencing analysis showed higher levels of transcripts for TREK-2 and TWIK-2 in B1a cells than those in FoB or MZB cells. Electrophysiological analysis, using patch clamp technique, revealed higher activity of TREK-2 with the characteristic large unitary conductance (~ 250 pS) in B1a than that in FoB or MZB cells. TREK-2 activity was further increased by LPS treatment (>2 h), which was more prominent in B1a than that in MZB or FoB cells. The cytosolic Ca2+ concentration of B cells was decreased by high-K+-induced depolarization (ΔRKCl (%)), suggesting the basal Ca2+ influx to be driven by negative membrane potential. The LPS treatment significantly increased the ΔRKCl (%) in B1a, though not in FoB and MZB cells. Our study was the first to compare the K2P channels in mouse primary B cell subsets, elucidating the functional upregulation of TREK-2 and augmentation of Ca2+ influx by the stimulation of Toll-like receptor 4 in B1a cells.

6.
Sens Actuators B Chem ; : 129663, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33612970

RESUMO

The global outbreak of coronavirus disease and rapid spread of the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent a significant threat to human health. A key mechanism of human SARS-CoV-2 infection is initiated by the combination of human angiotensin-converting enzyme 2 (hACE2) and the receptor-binding domain (RBD) of the SARS-CoV-2-derived spike glycoprotein. Despite the importance of these protein interactions, there is still insufficient detection methods to observe their activity at the cellular level. Herein, we developed a novel fluorescence resonance energy transfer (FRET)-based hACE2 biosensor to monitor the interaction between hACE2 and SARS-CoV-2 RBD. This biosensor facilitated the visualization of hACE2-RBD activity with high spatiotemporal resolutions at the single-cell level. Further studies revealed that the FRET-based hACE2 biosensors were sensitive to both exogenous and endogenous hACE2 expression, suggesting that they might be safely applied to the early stage of SARS-CoV-2 infection without direct virus use. Therefore, our novel biosensor could potentially help develop drugs that target SARS-CoV-2 by inhibiting hACE2-RBD interaction.

7.
Adv Med Sci ; 66(1): 155-161, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33592358

RESUMO

PURPOSE: Meteorin-like protein (METRNL) (also known as IL-41), recently identified as a myokine, is released in response to muscle contraction. It improves the skeletal muscle insulin sensitivity through exerting a beneficial anti-inflammatory effect. However, no independent studies have been published to verify the effects of METRNL on human umbilical vein endothelial cells (HUVECs) and THP-1 human monocytes. MATERIALS AND METHODS: The levels of NFκB and IκB phosphorylation as well as the expression of adhesion molecules were assessed by Western blotting analysis. Cell adhesion assay demonstrated the interactions between HUVEC and THP-1 â€‹cells. We used enzyme-linked immunosorbent assay (ELISA) to measure the levels of TNFα and MCP-1 in culture medium. RESULTS: Treatment with METRNL suppressed the secretion of TNFα and MCP-1 as well as NFκB and IκB phosphorylation and inflammatory markers in lipopolysaccharide (LPS)-treated HUVECs and THP-1 â€‹cells. Furthermore, treatment with METRNL ameliorated LPS-induced attachment of THP-1 monocytes to HUVECs via inhibition of adhesion molecule expression and apoptosis. Treatment of HUVEC and THP-1 â€‹cells with METRNL enhanced AMPK phosphorylation and PPARδ expression in a dose-dependent manner. Small interference (si) RNA-mediated suppression of AMPK or PPARδ restored all these changes. CONCLUSIONS: It has therefore been shown that METRNL ameliorates inflammatory responses through AMPK and PPARδ-dependent pathways in LPS-treated HUVEC. In sum, the current study may suggest the suppressive potential of METRNL against endothelial inflammation.

8.
Int J Mol Sci ; 22(3)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33503844

RESUMO

Advances in high-throughput screening of metabolic stability in liver and gut microbiota are able to identify and quantify small-molecule metabolites (metabolome) in different cellular microenvironments that are closest to their phenotypes. Metagenomics and metabolomics are largely recognized to be the "-omics" disciplines for clinical therapeutic screening. Here, metabolomics activity screening in liver disease (LD) and gut microbiomes has significantly delivered the integration of metabolomics data (i.e., a set of endogenous metabolites) with metabolic pathways in cellular environments that can be tested for biological functions (i.e., phenotypes). A growing literature in LD and gut microbiomes reports the use of metabolites as therapeutic targets or biomarkers. Although growing evidence connects liver fibrosis, cirrhosis, and hepatocellular carcinoma, the genetic and metabolic factors are still mainly unknown. Herein, we reviewed proof-of-concept mechanisms for metabolomics-based LD and gut microbiotas' role from several studies (nuclear magnetic resonance, gas/lipid chromatography, spectroscopy coupled with mass spectrometry, and capillary electrophoresis). A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to improve liver health.

9.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440664

RESUMO

Prostate cancer (PCa) has a vast clinical spectrum from the hormone-sensitive setting to castration-resistant metastatic disease. Thus, chemotherapy regimens and the administration of androgen receptor axis-targeted (ARAT) agents for advanced PCa have shown limited therapeutic efficacy. Scientific advances in the field of molecular medicine and technological developments over the last decade have paved the path for immunotherapy to become an essential clinical modality for the treatment of patients with metastatic PCa. However, several immunotherapeutic agents have shown poor outcomes in patients with advanced disease, possibly due to the low PCa mutational burden. Adoptive cellular approaches utilizing chimeric antigen receptor T cells (CAR-T) targeting cancer-specific antigens would be a solution for circumventing the immune tolerance mechanisms. The immunotherapeutic regimen of CAR-T cell therapy has shown potential in the eradication of hematologic malignancies, and current clinical objectives maintain the equivalent efficacy in the treatment of solid tumors, including PCa. This review will explore the current modalities of CAR-T therapy in the disease spectrum of PCa while describing key limitations of this immunotherapeutic approach and discuss future directions in the application of immunotherapy for the treatment of metastatic PCa and patients with advanced disease.


Assuntos
Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Neoplasias/imunologia , Terapia Combinada , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/metabolismo , Resultado do Tratamento
10.
J Endourol ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33478345

RESUMO

Purpose: Forgotten ureteral stents are associated with safety issues, increased cost, and medicolegal disputes. Tracking ureteral stents is cumbersome because of the variety in placement periods. We developed and validated an electronic medical record (EMR) system-based algorithm for monitoring patients with ureteral stent placements. Materials and Methods: The Stent Tracking Algorithm Registry (STAR) is automatically activated once the physician enters the stent placement or replacement billing code into the EMR billing system. At 120 days, an overdue notification is generated and sent to the attending physician through an EMR pop-up dashboard and e-mail. The model is automatically deactivated when the stent of the corresponding laterality is removed. To validate the feasibility of STAR, we performed a retrospective review of 2194 patients who received stent placements between November 2006 and September 2019. Results: Among 2194 patients, STAR retrospectively identified 354 (16.1%) patients suspected of harboring forgotten ureteral stents. A total of 12 (0.5%) patients actually had forgotten ureteral stents and were contacted for removal. A total of 124 (5.7%) patients were identified because of the omission of the stent removal billing code, whereas 209 (9.5%) patients were identified because of being lost to follow-up after referral to another health care facility or death. There were no cases in which STAR identified patients whose stents were removed or replaced at an appropriate time frame. Conclusions: STAR provides an efficient interface with which to prevent the occurrence of forgotten ureteral stents. This model can be integrated into any EMR system that utilizes coding algorithms.

11.
Infect Immun ; 89(4)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33468581

RESUMO

Thymosin beta-4 (Tß4) is an actin-sequestering peptide that plays important roles in regeneration and remodeling of injured tissues. However, its function in a naturally occurring pathogenic bacterial infection model has remained elusive. We adopted Tß4-overexpressing transgenic (Tg) mice to investigate the role of Tß4 in acute pulmonary infection and systemic sepsis caused by Legionella pneumophila Upon infection, Tß4-Tg mice demonstrated significantly lower bacterial loads in the lung, less hyaline membranes and necrotic abscess, with lower interstitial infiltration of neutrophils, CD4+, and CD8+ T cells. Bronchoalveolar lavage fluid of Tß4-Tg mice possessed higher bactericidal activity against exogenously added L. pneumophila, suggesting that constitutive expression of Tß4 could efficiently control L. pneumophila Furthermore, qPCR analysis of lung homogenates demonstrated significant reduction of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), which primarily originate from lung macrophages, in Tß4-Tg mice after pulmonary infection. Upon L. pneumophila challenge of bone marrow-derived macrophages (BMDM) in vitro, secretion of IL-1ß and TNF-α proteins was also reduced in Tß4-Tg macrophages, without affecting their survival. The anti-inflammatory effects of BMDM in Tß4-Tg mice on each cytokine were affected when triggering with tlr2, tlr4, tlr5, or tlr9 ligands, suggesting that anti-inflammatory effects of Tß4 are likely mediated by the reduced activation of Toll-like receptors (TLR). Finally, Tß4-Tg mice in a systemic sepsis model were protected from L. pneumophila-induced lethality compared to wild-type controls. Therefore, Tß4 confers effective resistance against L. pneumophila via two pathways, a bactericidal and an anti-inflammatory pathway, which can be harnessed to treat acute pneumonia and septic conditions caused by L. pneumophila in humans.

12.
Mol Ther ; 29(4): 1471-1486, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33348053

RESUMO

Mesenchymal stromal cells (MSCs) are considered as a promising therapeutic tool for liver fibrosis, a main feature of chronic liver disease. Because small extracellular vesicles (sEVs) harboring a variety of proteins and RNAs are known to have similar functions with their derived cells, MSC-derived sEVs carry out the regenerative capacities of MSCs. Human tonsil-derived MSCs (T-MSCs) are reported as a novel source of MSCs, but their effects on liver fibrosis remain unclear. In the present study, we investigated the effects of T-MSC-derived sEVs on liver fibrosis. The expression of profibrotic genes decreased in human primary hepatic stellate cells (pHSCs) co-cultured with T-MSCs. Treatment of T-MSC-sEVs inactivated human and mouse pHSCs. Administration of T-MSC-sEVs ameliorated hepatic injuries and fibrosis in chronically damaged liver induced by carbon tetrachloride (CCl4). miR-486-5p highly enriched in T-MSC-sEVs targeting the hedgehog receptor, smoothened (Smo), was upregulated, whereas Smo and Gli2, the hedgehog target gene, were downregulated in pHSCs and liver tissues treated with T-MSC-sEVs or miR-486-5p mimic, indicating that sEV-miR-486 inactivates HSCs by suppressing hedgehog signaling. Our results showed that T-MSCs attenuate HSC activation and liver fibrosis by delivering sEVs, and miR-486 in the sEVs inactivates hedgehog signaling, suggesting that T-MSCs and their sEVs are novel anti-fibrotic therapeutics for treating chronic liver disease.

13.
J Cell Physiol ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33283879

RESUMO

Endoplasmic reticulum (ER) stress plays a causative role in the development of nonalcoholic fatty liver disease (NAFLD). Kynurenic acid (KA) is a tryptophan metabolite that has been shown to exert anti-inflammatory effects in macrophages and endothelial cells. However, the role of KA in ER stress-associated development of NAFLD has not been fully explored. In the current study, we observed decreased KA levels in the serum of obese subjects. Treated hepatocytes with KA attenuated palmitate-induced lipid accumulation and downregulated lipogenesis-associated genes as well as ER stress markers in a dose-dependent manner. Furthermore, KA augmented AMP-activated protein kinase (AMPK) phosphorylation, oxygen-regulated protein 150 (ORP150) expression, and autophagy markers. The small interfering RNA-mediated suppression of AMPK and ORP150, or 3-methyladenine also abrogated the effects of KA on ER stress and lipid accumulation in hepatocytes. In accordance with in vitro observations, KA administration to mice fed a high-fat diet ameliorated hepatic lipid accumulation and decreased the expression of lipogenic genes as well as ER stress. Moreover, KA treatment increased hepatic AMPK phosphorylation, ORP150 expression, and autophagy related markers in mouse livers. Knockdown of AMPK using in vivo transfection mitigated the effects of KA on hepatic steatosis and ER stress as well as autophagy and ORP150 expression. These results suggest that KA ameliorates hepatic steatosis via the AMPK/autophagy- and AMPK/ORP150-mediated suppression of ER stress. In sum, KA might be used as a promising therapeutic agent for treatment of NAFLD.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33189896

RESUMO

BACKGROUND: Non-gestational choriocarcinoma is a rare ovarian malignancy whose prognosis is worse than that of gestational choriocarcinoma. Debulking surgery is the primary treatment for ovarian carcinoma. However, fertility preservation is important in young women. CASE: A 15-year-old girl with no sexual experience was admitted for abnormal uterine bleeding. Ultrasonography showed a solid mass in the right ovary and serum ß-hCG levels were markedly elevated. We performed right oophorectomy, omentectomy, and peritoneal washing cytology. The uterus and left adnexa were preserved. She was diagnosed with non-gestational choriocarcinoma, stage IIA. She received adjuvant chemotherapy (EMA-CO regimen) and has been disease-free for more than 5 years. SUMMARY AND CONCLUSION: Fertility-sparing surgery combined with chemotherapy is an acceptable treatment option for young patients with locally advanced non-gestational choriocarcinoma.

15.
Phys Med Biol ; 65(22): 225005, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200751

RESUMO

The purpose of this study is to leverage radioluminescence imaging for the development of an automated high-dose-rate (HDR) brachytherapy quality assurance (QA) system that enables simultaneous measurements of dwell position, dwell time, wire velocity, and relative source strength in a single test. The system consists of a radioluminescence phosphor sheet (a mixture of Gd2O2S:Tb and PDMS) positioned atop a HDR needle applicator, a complementary metal-oxide-semiconductor digital camera used to capture the emitted radioluminescence signals from the scintillator sheet, and an in-house graphical user interface for signal processing. The signal processing was used to extract source intensity, location, and elapsed time, yielding the final measurements on dwell position, dwell time, and wire velocity. The source strength relative to the well chamber calibration (in unit of Air-Kerma strength, Sk ) is measured by establishing a calibration curve that correlates Sk with the detector response. Validation experiments are performed using three customized treatment plans. With these plans, the dwell position and dwell time are verified for a range of 110.0 cm-117.5 cm and 2 s-16 s, respectively, and the linear correlation with Sk is demonstrated for the source strength varying between 28 348 U (cGy cm2 h-1) and 41 906 U. The wire velocity, i.e. the speed of the radioactive source averaged over the distance in between dwell positions, is calculated for various distances ranging from 5 mm to 50 mm. Results show that the mean deviations of the measured dwell position and dwell time are 0.1 mm (range from 0 to 0.2 mm) and 32.5 ms (range from 0 to 60.0 ms) with respect to the planned values, respectively, and the system response is highly linear with Sk ( R2 = 0.998). Moreover, the measured wire velocities are comparable to previously reported values. Benefitting from the compact hardware design and image processing algorithms, the system provides a practical, reliable, and comprehensive solution for HDR QA.

16.
J Fungi (Basel) ; 6(4)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003327

RESUMO

The present investigation aimed to determine the fungal toxicity of Isaria tenuipes (My-It) against the dengue mosquito vector Aedes aegypti L. and its non-target impact against the aquatic predator Toxorhynchitessplendens. Lethal concentrations (LC50 and LC90) of My-It were observed in 2.27 and 2.93 log ppm dosages, respectively. The sub-lethal dosage (My-It-1 × 104 conidia/mL) displayed a significant oviposition deterrence index and also blocked the fecundity rate of dengue mosquitos in a dose-dependent manner. The level of major detoxifying enzymes, such as carboxylesterase (α-and ß-) and SOD, significantly declined in both third and fourth instar larvae at the maximum dosage of My-It 1 × 105 conidia/mL. However, the level of glutathione S-transferase (GST) and cytochrome P-450 (CYP450) declined steadily when the sub-lethal dosage was increased and attained maximum reduction in the enzyme level at the dosage of My-It (1 × 105 conidia/mL). Correspondingly, the gut-histology and photomicrography results made evident that My-It (1 × 105 conidia/mL) heavily damaged the internal gut cells and external physiology of the dengue larvae compared to the control. Moreover, the non-target toxicity against the beneficial predator revealed that My-It at the maximum dosage (1 × 1020 conidia/mL) was found to be less toxic with <45% larval toxicity against Tx.splendens. Thus, the present toxicological research on Isaria tenuipes showed that it is target-specific and a potential agent for managing medically threatening arthropods.

17.
Sci Rep ; 10(1): 18119, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093618

RESUMO

Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospyros kaki, leaves (EEDK) induces cancer cell death and inhibits cell proliferation. Using fluorescence resonance energy transfer (FRET) technology with genetically-encoded biosensors, we first found that EEDK stimulates a PDGFR-Rac signaling cascade in live cells. Moreover, we found that downstream of the PDGFR-Rac pathway, JNKs are activated by EEDK. In contrast, JNK-downstream inhibitors, such as CoCl2, T-5224, and pepstatin A, attenuated EEDK-induced cell death. Thus, we illustrate that the PDGFR-Rac-JNK signaling axis is triggered by EEDK, leading to cancer cell death, suggesting the extract of persimmon leaves may be a promising anti-cancer agent.

18.
PLoS One ; 15(9): e0238705, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941440

RESUMO

OBJECTIVE: To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection. MATERIALS AND METHODS: Vaginal microbiota was analyzed using next-generation sequencing in women with normal, cervical intraepithelial neoplasia (CIN), or cervical cancer. RESULTS: A marked decrease of Lactobacillus crispatus was found in the CIN/cancer groups compared with that in the normal group. The diversity of microorganisms increased in patients with CIN or cervical cancer with HPV infection. Atopobium vaginae (OR 4.33, 95% CI 1.15-16.32), Dialister invisus (OR 4.89, 95% CI 1.20-19.94), Finegoldia magna (OR 6.00, 95% CI 1.08-33.27), Gardnerella vaginalis (OR 7.43, 95% CI 1.78-31.04), Prevotella buccalis (OR 11.00, 95% CI 2.00-60.57), and Prevotella timonensis (OR 6.00, 95% CI 1.46-24.69) were significantly associated with the risk of CIN 2/3 or cervical cancer. CONCLUSION: Women with the CIN and cervical cancer showed a high diversity in vaginal microbiota. Depletion of Lactobacillus crispatus and increased abundance of anaerobic bacteria were detected in women with cervical disease.


Assuntos
Carcinogênese/patologia , Microbiota , Papillomaviridae/fisiologia , Infecções por Papillomavirus/microbiologia , Vagina/microbiologia , Bactérias/classificação , Biodiversidade , Feminino , Humanos , Análise de Componente Principal , Especificidade da Espécie
19.
Phys Med Biol ; 65(17): 175013, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32869751

RESUMO

Fiber-coupled scintillation dosimeters are a cost-effective alternative to the conventional ion chambers in radiation dosimetry. However, stem effects from optical fibers such as Cerenkov radiation incur significant errors in the readout signal. Here we introduce a second near-infrared window dosimeter, dubbed as NIR2D, that can potentially be used as real-time radiation detector for clinical megavoltage beams. Lanthanide-based rare-earth NaYF4 nano-phosphors doped with both erbium and cerium elements were synthesized, and a compact 3D printed reader device integrated with a photodetector and data acquisition system was designed. The performance of the NIR2D was tested using a pre-clinical orthovoltage radiation source and a clinical megavoltage radiation source. The system was tested for dose linearity (100, 200, 600 MU), dose rate dependency (100, 200, 400, 600 MU min-1), and energy dependency (6, 10, 15 MV). Test results with the clinical linear accelerator demonstrated excellent dose linearity and dose rate independency when exposed to 6 MV linac beams-both data follows a linear trendline with R2 > 0.99. On the other hand, the NIR2D was energy dependent, where the readout dropped by 9% between 6 and 15 MV. For stem effects, we observed a finite Cerenkov contribution of 1%-3% when exposed between 100-600 MU min-1 (6 MV) and 3%-6% when exposed between 5-15 MV (600 MU min-1). While the stem effects were still observable, we expect that enhancing the current optical setup will simultaneously improve the scintillation signal and reduce the stem effects.


Assuntos
Raios Infravermelhos , Aceleradores de Partículas , Radiometria/instrumentação , Fibras Ópticas
20.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751945

RESUMO

The clinical spectrum of prostate cancer (PCa) varies from castration-naive to metastatic castration-resistant disease. Despite the administration of androgen synthesis inhibitors and chemotherapy regimens for castration-resistant prostate cancer, the treatment options for this entity are limited. The utilization of the immune system against cancer cells shows potential as a therapeutic modality for various solid tumors and hematologic malignancies. With technological advances over the last decade, immunotherapy has become an integral treatment modality for advanced solid tumors. The feasibility of immunotherapy has shown promise for patients with PCa, and with advances in molecular diagnostic platforms and our understanding of immune mechanisms, immunotherapy is reemerging as a potential treatment modality for PCa. Various combinations of individualized immunotherapy and immune checkpoint blockers with androgen receptor-targeted therapies and conventional cytotoxic agents show promise. This article will review the current status of immunotherapy, including new discoveries and precision approaches to PCa, and discuss future directions in the continuously evolving landscape of immunotherapy.

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