RESUMO
BACKGROUND: The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) simultaneously profiles the RNA transcriptome and the surface protein expression. The surface protein markers in CITE-Seq can be used to identify cell populations similar to the iterative filtration process in flow cytometry, also called "gating", and is an essential step for downstream analyses and data interpretation. While several packages allow users to interactively gate cells, they often do not process multi-omic sequencing datasets and may require writing redundant code to specify gate boundaries. To streamline the gating process, we developed CITEViz which allows users to interactively gate cells in Seurat-processed CITE-Seq data. CITEViz can also visualize basic quality control (QC) metrics allowing for a rapid and holistic evaluation of CITE-Seq data. RESULTS: We applied CITEViz to a peripheral blood mononuclear cell CITE-Seq dataset and gated for several major blood cell populations (CD14 monocytes, CD4 T cells, CD8 T cells, NK cells, B cells, and platelets) using canonical surface protein markers. The visualization features of CITEViz were used to investigate cellular heterogeneity in CD14 and CD16-expressing monocytes and to detect differential numbers of detected antibodies per patient donor. These results highlight the utility of CITEViz to enable the robust classification of single cell populations. CONCLUSIONS: CITEViz is an R-Shiny app that standardizes the gating workflow in CITE-Seq data for efficient classification of cell populations. Its secondary function is to generate basic feature plots and QC figures specific to multi-omic data. The user interface and internal workflow of CITEViz uniquely work together to produce an organized workflow and sensible data structures for easy data retrieval. This package leverages the strengths of biologists and computational scientists to assess and analyze multi-omic single-cell datasets. In conclusion, CITEViz streamlines the flow cytometry gating workflow in CITE-Seq data to help facilitate novel hypothesis generation.
Assuntos
Leucócitos Mononucleares , Software , Humanos , Análise de Sequência de RNA/métodos , Fluxo de Trabalho , Citometria de Fluxo , Proteínas de Membrana , Análise de Célula Única/métodos , Perfilação da Expressão Gênica/métodosRESUMO
OBJECTIVE: Molnupiravir (MOV) is an oral antiviral drug that received use authorization in Vietnam for the treatment of mild COVID-19 (F0). There was a need to develop alternative approaches that allowed patients to access medication, decongest hospitals, clinics, and facilities, and protect people from infection. During the COVID-19 crisis, the Ninh Thuan Health Authorities implemented the home delivery of medication by community health workers. This study conducted in collaboration with two important Italian entities [the Aldo Moro University of Bari City and the 118 Department of Territorial Emergency System (118 SET) of Taranto City] aimed to evaluate the implementation of home delivery F0 treatment package assessing the rate of infection recovering during the coronavirus pandemic in Ninh Thuan province, Vietnam. PATIENTS AND METHODS: A convergent mixed methods research, based on a longitudinal study with quantitative research and qualitative assessments, evaluated four implementation outcomes: the feasibility, fidelity, coverage, sustainability, and effectiveness of the initiative. Data sources included routinely collected data, a telephonic survey of patients, an analysis of set-up and recurrent costs, as well as descriptive exploratory qualitative and quantitative analysis. RESULTS: After taking the MOV for 5 days, only 35 out of the initial 400 F0 patients remained positive, while 365 patients (91.2%) were negative (CT≥30). Whilst, the successful rate after using the drug during the course accounted for 99.85% and 100% after the entire treatment course, without any death. After 5 days of taking the drug, a positive test result (CT<30) was associated with age group ≥60 (OR=2.7) and comorbidities (OR=3.0) (p<0.05) compared to negative and positive results (CT≥30). Negative factors impacting F0 at home include a shortage of healthcare workers, inadequate supply of thermometers and SpO2 meters, and insufficient financial support for healthcare workers. CONCLUSIONS: MOV caused a reduction in the risk of hospitalization or death in mild COVID-19 patients, and molnupiravir was also found to be well tolerated and safe without any major adverse events during the administration period.
Assuntos
COVID-19 , Citidina/análogos & derivados , Hidroxilaminas , Humanos , Vietnã/epidemiologia , Estudos Longitudinais , PandemiasRESUMO
Introduction: Mesenchymal chondrosarcoma (MC) is a rapidly progressive sarcoma that predominantly impacts the bones. Making up only 3% of chondrosarcomas, about one-third of these tumours develop in extra-skeletal sites. Case presentation: The authors present a clinical case of a 42-year-old patient who was diagnosed with MC 8 years ago, now admitted to the hospital with a palpable epigastric mass. Clinical and laboratory examinations showed consistent results for MC tumours, with metastasis to the body and tail of the pancreas and invasion of the splenic vein. Surgical resection and systemic screening were performed to ensure that there were no lesions elsewhere. Regular follow-up has found no localized lesions or complications after 15 months. Clinical discussion: Metastatic extra-skeletal mesenchymal chondrosarcoma of the pancreas is exceptionally rare. To our current understanding, only 14 such cases have been documented in medical literature. The symptoms of pancreatic metastasis are diverse and the radiographic features of metastatic mesenchymal chondrosarcoma are not typically distinct. Conclusions: Although MC tumours do not frequently occur in sites other than the axial system, a tumour presenting later in a patient with a history of MC should be reviewed to confirm the diagnosis of metastatic MC. Treatment can vary between surgery, radiation therapy and systemic therapy.
RESUMO
Grid-based systematic search methods are used to investigate molecule-molecule, molecule-surface, and surface-surface contributions to interparticle interactions in order to identify the crystal faces that most strongly affect particle behavior during powder blend formulation and delivery processes. The model system comprises terbutaline sulfate (TBS) as an active pharmaceutical ingredient (API) and α-form lactose monohydrate (LMH). A combination of systematic molecular modeling and X-ray computed tomography (XCT) is used to determine not only the adhesive and cohesive interparticle energies but, also the agglomeration behavior during manufacturing and de-agglomeration behavior during delivery after inhalation. This is achieved through a detailed examination of the balance between the adhesive and cohesive energies with the XCT results confirming the blend segregation tendencies, through the particle-particle de-agglomeration process. The results reveal that the cohesive interaction energies of TBS-TBS are higher than the adhesive energies between TBS and LMH, but that the cohesive energies of LMH-LMH are the smallest between molecule and molecule, molecule and surface, and surface and surface. This shows how systematic grid-search molecular modeling along with XCT can guide the digital formulation design of inhalation powders in order to achieve optimum aerosolization and efficacy for inhaled medicines. This will lead to faster pharmaceutical design with less variability, higher quality, and enhanced performance.
RESUMO
Background The objective of this study was to assess the accessibility and content of the critical care fellowship websites provided on the Electronic Residency Application Services (ERAS) website. Methods Using the online information provided by ERAS, we compiled a list of Accreditation Council for Graduate Medical Education (ACGME)-accredited critical care fellowship programs. Each of the links provided by ERAS was evaluated by a standard search on Google as follows: the program name + "critical care fellowship". After assembling the working links, those websites were subsequently evaluated based on the program description, application process, and educational content. Results We reviewed 59 critical care fellowship programs that were obtained from ERAS. Of the 59 programs, one retracted its participation and was not included in the study, and six other programs were excluded due to repeated links on ERAS, nonworking links, and websites without any content. We analyzed the data collected from the remaining 52 programs. Our data shows a general lack of information being provided to prospective critical care candidates. Conclusions ERAS is a major source of information for prospective fellows looking for critical care fellowships in the current match. Unfortunately, the majority of the programs evaluated lack substantial information for prospective candidates. Despite many websites containing adequate information regarding program descriptions, there was a lack of information regarding the application process and educational activities.
RESUMO
BACKGROUND: Although recent decades have witnessed a growing interest in mindfulness with the development of many mindfulness scales and their adaptation to different cultures, there has been no attempt at developing or adapting a mindfulness scale for Vietnamese people. To fill this gap and encourage the study of mindfulness in Vietnam, we adapted a 20-item short-form of the Five Facet Mindfulness Questionnaire (FFMQ-20) into Vietnamese, which we called the FFMQ-V, and examined its psychometric properties in a series of three independent studies. METHODS: In Study 1, using a college sample (N = 412) we conducted several exploratory factor analyses to elucidate the factor structure of the FFMQ-V. In Study 2, using an independent college sample (N = 344) we performed a confirmatory factor analysis (CFA) to test the goodness-of-fit for all obtained factor models from Study 1. In this study, we also examined the discriminant validities of the FFMQ-V by correlating mindfulness and other related psychological constructs, including acceptance, nonattachment, depression, anxiety, and stress. In Study 3, we replicated all data analyses in Study 2 using a community sample of young adults (N = 574). RESULTS: Across all Studies, our results indicated that the hierarchical five-factor model with method factors best captured the latent structure of the FFMQ-V. Our results also showed that the mindfulness facets met our expectations as they correlated positively with the acceptance and nonattachment and negatively with the depression, anxiety, and stress. CONCLUSIONS: In aggregate, our EFA and CFA results provided strong evidence for the hierarchical five-factor model with method factors in both community and college samples, suggesting that the FFMQ-V can be used to measure trait mindfulness of the Vietnamese young adults.
Assuntos
Atenção Plena , População do Sudeste Asiático , Adulto Jovem , Humanos , Reprodutibilidade dos Testes , Psicometria/métodos , Atenção Plena/métodos , Inquéritos e QuestionáriosRESUMO
Giant cell arteritis (GCA), also known as temporal arteritis (TA), is a systemic autoimmune inflammation of medium and large arteries. It is the most common vasculitis affecting adults older than 50, with an incidence of 20/100,000 and an average age of onset of 70. Typically, patients initially present with new-onset headaches, visual changes and disturbances, jaw claudication, arthralgias, and tender or swollen temporal or occipital arteries. Our patient is a 73-year-old male who presented to the emergency room with 10 days of bilateral headache radiating to the occipital area associated with fevers, persistent chills, generalized weakness, and a headache described as constant, dull, 9 out of 10 pain, and minor pain with neck flexion. Lab work revealed an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The patient had tender palpation to his temples and due to a high suspicion of giant cell arteritis, he was started on high-dose steroids with rapid relief of his symptoms. Biopsy showed evidence of active non-granulomatous vasculitis and confirmed bilateral temporal arteritis within the context of the clinical setting. GCA patients are more likely to be women and typically present with unilateral headache (66% of GCA), jaw claudication (50%), fevers (50%), and transient visual loss (16-54%). Here, we describe a 73-year-old male with a past medical history of cerebral vascular accident (CVA), diabetes, and cancer that presented with 10 days of bilateral headaches and fevers. Unlike the usual presentation, our patient denied any vision and joint pain changes, and the temporal arteries were not stiff to palpation. This patient presentation is unique to previous reports in the limited display of symptoms and absence of the most commonly associated manifestations. Although his presentation supported GCA, the features of elevated ESR and CRP, headache, and fever were too general to diagnose GCA exclusively, and his additional symptoms of rhinorrhea and sinus pain more likely supported infection. Our case indicates the importance of maintaining a high index of clinical suspicion for GCA in the elderly population presenting with headaches and elevated ESR and CRP. GCA, also known as temporal arteritis (TA), is a systemic autoimmune inflammation of medium and large arteries. Typically, patients initially present with new-onset headaches, visual changes and disturbances, jaw claudication, arthralgias, and tender or swollen temporal or occipital arteries. Diagnosis requires high clinical suspicion, and treatment revolves around high doses of steroids.
RESUMO
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises lung function and necessitates oxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety of the allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the progression of lung development in four infants with established BPD. METHODS: UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno- and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and patient conditions were evaluated during hospitalization and at 7 days and 1, 6 and 12 months postdischarge. RESULTS: No intervention-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and were weaned off of oxygen support. Chest X-rays and CT scans confirmed the progressive reductions in fibrosis. CONCLUSIONS: Allo-UC-MSC administration is safe in preterm infants with established BPD. Trial registration This preliminary study was approved by the Vinmec International Hospital Ethics Board (approval number: 88/2019/QD-VMEC; retrospectively registered March 12, 2019).
Assuntos
Displasia Broncopulmonar , Transplante de Células-Tronco Hematopoéticas , Nascimento Prematuro , Assistência ao Convalescente , Povo Asiático , Displasia Broncopulmonar/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Alta do Paciente , Gravidez , Cordão UmbilicalRESUMO
To design safe and electrochemically stable electrolytes for lithium-ion batteries, this study describes the synthesis and the utilization of new deep eutectic solvents (DESs) based on the mixture of 2,2,2-trifluoroacetamide (TFA) with a lithium salt (LiTFSI, lithium bis[(trifluoromethane)sulfonyl]imide). These prepared DESs were characterized in terms of thermal properties, ionic conductivity, viscosity, and electrochemical properties. Based on the appearance of the product and DSC measurements, it appears that this system is liquid at room temperature for LiTFSI mole fraction ranging from 0.25 to 0.5. At χLiTFSI = 0.25, DESs exhibited favorable electrolyte properties, such as thermal stability (up to 148 °C), relatively low viscosity (42.2 mPa.s at 30 °C), high ionic conductivity (1.5 mS.cm-1 at 30 °C), and quite large electrochemical stability window up to 4.9-5.3 V. With these interesting properties, selected DES was diluted with slight amount of ethylene carbonate (EC). Different amounts of EC (x = 0-30 %wt) were used to form hybrid electrolytes for battery testing with high voltage LiMn2O4 cathode and Li anode. The addition of the EC solvent into DES expectedly aims at enhancing the battery cycling performance at room temperature due to reducing the viscosity. Preliminary results tests clearly show that LiTFSI-based DES can be successfully introduced as an electrolyte in the lithium-ion batteries cell with a LiMn2O4 cathode material. Among all of the studied electrolytes, DES (LiTFSI: TFA = 4:1 + 10 %wt EC) is the most promising. The EC-based system exhibited a good specific capacity of 102 mAh.g-1 at C/10 with the theoretical capacity of 148 mAh.g-1 and a good cycling behavior maintaining at 84% after 50 cycles.
RESUMO
Waters coproduced with hydrocarbons from unconventional oil and gas reservoirs such as the hydraulically fractured Middle Devonian Marcellus Shale in the Appalachian Basin, USA, contain high levels of total dissolved solids (TDS), including Ba, which has been variously ascribed to drilling mud dissolution, interaction with pore fluids or shale exchangeable sites, or fluid migration through fractures. Here, we show that Marcellus Shale produced waters contain some of the heaviest Ba (high 138Ba/134Ba) measured to date (δ138Ba = +0.36 to +1.49 ± 0.06) and are distinct from overlying Upper Devonian/Lower Mississippian reservoirs (δ138Ba = -0.83 to -0.52). Marcellus Shale produced water values do not overlap with drilling mud barite (δ138Ba ≈ 0.0) and are significantly offset from Ba reservoirs within the producing portion of the Marcellus Shale, including exchangeable sites and carbonate cement. Precipitation, desorption, and diffusion processes are insufficient or in the wrong direction to produce the observed enrichments in heavy Ba. We hypothesize that the produced water is derived primarily from brines adjacent to and most likely below the Marcellus Shale, although such deep brines have not yet been obtained for Ba isotope analysis. Barium isotopes show promise for tracking formation waters and for understanding water-rock interaction under downhole conditions.
Assuntos
Gás Natural , Poluentes Químicos da Água , Região dos Apalaches , Bário , Isótopos , Campos de Petróleo e Gás , Águas ResiduáriasRESUMO
Optimizing hydrocarbon production and waste management from unconventional oil and gas extraction requires an understanding of the fluid-rock chemical interactions. These reactions can affect flow pathways within fractured shale and produced water chemistry. Knowledge of these chemical reactions also provides valuable information for planning wastewater treatment strategies. This study focused on characterizing reservoir reactions through analysis of produced water chemistry from the Marcellus Shale Energy and Environmental Laboratory field site in Morgantown, WV, USA. Analysis of fracturing fluids, time-series produced waters (PW) over 16 months of operation of two hydraulically fractured gas wells, and shale rocks from the same well for metal concentrations and multiple isotope signatures (δ2H and δ18O of water, δ7Li, δ11B, 87Sr/86Sr) showed that the chemical and isotopic composition of early (<10 days) PW samples record water-rock interactions during the fracturing period. Acidic dissolution of carbonate minerals was evidenced by the increase in TOC, B/Na, Sr/Na, Ca/Na, and the decrease in 87Sr/86Sr in PW returning in the first few days toward the 87Sr/86Sr signature of carbonate cement. The enrichment of 6Li in these early (e.g., day 1) PW samples is most likely a result of desorption of Li from clays and organic matter due to the injection of fracturing fluid. Redox-active trace elements appear to be controlled by oxidation-reduction reactions and potentially reactions involving wellbore steel. Overall, PW chemistry is primarily controlled by mixing between early PW with local in-situ formation water however certain geochemical reactions (e.g., carbonate cement dissolution and desorption of 6Li from clays and organic matter) can be inferred from PW composition monitored immediately over the first ten days of water return.
RESUMO
OBJECTIVE: To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). METHODS: This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). RESULTS: Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7â¯kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPAâ¯≥â¯the 50th percentile compared to <50th percentile (pâ¯=â¯0.91, 0.45, 0.71, 0.74, 0.60, and 0.74 respectively) and (pâ¯=â¯0.99, 0.59, 0.14, 0.77, and 0.85 respectively). When adjusting for prognostic factors, elevated VFA trended towards shorter OS (25.1 vs 59.5â¯months, HRâ¯=â¯1.68 [0.92-3.05]).Patients receiving bevacizumab had similar OS compared to those who did not (37.6 vs 44.5â¯months, pâ¯=â¯0.409). When stratified by adiposity markers, no subset demonstrated benefit from bevacizumab. CONCLUSION: Obesity has been associated with increased levels of vascular endothelial growth factor (VEGF), the main target for bevacizumab therapy. Imaging measurements of VFA may provide prognostic information for patients with EC but no adiposity marker was predictive of improved response to bevacizumab.
RESUMO
OBJECTIVE: Adiposity has been hypothesized to interfere with the activity of bevacizumab (BEV), an anti-angiogenic agent. Measurements of adiposity, BMI, surface fat area (SFA), and visceral fat area (VFA) were investigated as prognostic of oncologic outcomes among patients treated with chemotherapy, with or without BEV, on GOG 218, a prospective phase III trial. METHOD: Pretreatment computed tomography (CT) for 1538 GOG 218 participants were analyzed. Proportional hazards models assessed association between adiposity and overall survival (OS) adjusted for other prognostic factors. The predictive value of adiposity as a function of BEV treatment was assessed in 1019 patients randomized to either chemotherapy (CT)â¯+â¯placebo (P)â¯ââ¯P or CTâ¯+â¯BEVâ¯ââ¯BEV. RESULTS: After adjusting for prognostic factors, SFA was not associated with the overall hazard of death (pâ¯=â¯0.981). There was a non-significant 0.1% (pâ¯=â¯0.062) increase in hazard of death associated with a unit increase in VFA. When comparing the treatment HRs for patients who did and did not receive BEV, there was no association with SFA (pâ¯=â¯0.890) or VFA (pâ¯=â¯0.106). A non-significant 0.8% increase in the hazard of death with unit increase in BMI (pâ¯=â¯0.086) was observed. BMI values were not predictive of a longer survival for patients with BEV vs placebo (pâ¯=â¯0.606). CONCLUSION: Measures of adiposity strongly correlated to one another but were not predictive of efficacy for BEV. VFA is a weak prognostic factor.
Assuntos
Tecido Adiposo/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adiposidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/patologia , Obesidade/fisiopatologia , Neoplasias Ovarianas/diagnóstico por imagem , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Tomografia Computadorizada por Raios XRESUMO
Ureteral injury is an uncommon but potentially morbid complication following any open or endoscopic pelvic procedure. Gynecologic surgeries alone make up 50 percent of nonurologic ureteral injuries leading to prolonged hospital stays, secondary interventions, and potential loss of renal function. The use of AmnioFix ® a processed dehydrated, immunologically privileged cellular amniotic membrane allograft has been well established in urologic and gynecologic procedures. These allografts contain human extracellular matrix components, growth factors, and cytokines that mediate inflammation and facilitate would healing. We report the first application of AmnioFix on a denuded ureter during a case of robotic-assisted excision of endometriosis. We include a literature review and discussion on the management outcomes of iatrogenic injury to the ureters.
RESUMO
BACKGROUND: Surgical resection remains the standard treatment for adrenocortical carcinoma. Higher rates of local and peritoneal recurrence have been reported with the laparoscopic approach compared to open resection, although the evidence is limited. A dilemma occurs when tumors appear benign in nature, measure >5 cm, or when patients request a minimally invasive surgical approach. We describe the first reported case to date of successful robot-assisted laparoscopic adrenalectomy for myxoid variant adrenocortical carcinoma. CASE PRESENTATION: A 38 year old female presented with a large 8.0 cm enhancing left adrenal mass concerning for pheochromocytoma, given refractory hypertension and symptoms of palpitations and headaches. Functional work up was negative. The patient underwent robot-assisted laparoscopic left adrenalectomy after appropriate alpha and beta blockade. Histological sections demonstrated a cortical neoplasm with prominent myxoid changes consistent with myxoid adrenocortical carcinoma. The patient's symptoms resolved and serial imaging demonstrated no recurrence three and nine months, post-operatively. CONCLUSION: Myxoid adrenocortical carcinoma is a rare and aggressive entity best managed with surgical resection. Though open resection for invasive adrenal cancer remains the gold standard, minimally invasive approaches are being increasingly used, whether deliberately or not. We describe the first reported robot-assisted laparoscopic adrenalectomy for invasive myxoid adrenocortical carcinoma.
RESUMO
After brain injury, neural stem cell-derived neuronal precursors (neuroblasts) in the ventricular-subventricular zone migrate toward the lesion. However, the ability of the mammalian brain to regenerate neuronal circuits for functional recovery is quite limited. Here, using a mouse model for ischemic stroke, we show that neuroblast migration is restricted by reactive astrocytes in and around the lesion. To migrate, the neuroblasts use Slit1-Robo2 signaling to disrupt the actin cytoskeleton in reactive astrocytes at the site of contact. Slit1-overexpressing neuroblasts transplanted into the poststroke brain migrated closer to the lesion than did control neuroblasts. These neuroblasts matured into striatal neurons and efficiently regenerated neuronal circuits, resulting in functional recovery in the poststroke mice. These results suggest that the positioning of new neurons will be critical for functional neuronal regeneration in stem/progenitor cell-based therapies for brain injury.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neurogênese , Neuroglia/metabolismo , Neurônios/metabolismo , Receptores Imunológicos/metabolismo , Regeneração , Transdução de Sinais , Citoesqueleto de Actina/química , Citoesqueleto de Actina/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Movimento Celular , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Camundongos Knockout , Ligação Proteica , Multimerização Proteica , Receptores Imunológicos/genética , Proteína cdc42 de Ligação ao GTP/metabolismoRESUMO
In this study, the electrochemical behavior of zinc meso-substituted porphyrins in the presence of imidazole is examined by using both cyclic voltammetry (CV) and density functional theory (DFT) methods. The results show that the first half-wave oxidation potentials (1st E1/2) of zinc porphyrins complexed with imidazole all move to the negative side, while the second ones (2nd E1/2) move to the positive side, resulting in larger half-wave oxidation potential splittings of the two oxidation states (ΔE = second E1/2 - first E1/2) comparing with the zinc porphyrins. By employing DFT calculations, we have found that both sterically controlled inter π-conjugation between porphyrin rings and meso-substituted phenyl groups and deformation of porphyrin rings do play important roles in contributing to the half-wave oxidation potentials. Imidazole exhibits strong effects on the deformation of porphyrin rings which is dominant in determining the first E1/2 while the inter π-conjugation between porphyrin rings and meso-substituted phenyl groups mainly contributes to the second E1/2. Without imidazole, the inter π-conjugation between porphyrin rings and meso-substituted phenyl groups is the only important criterion which effects both first E1/2 and second E1/2 of zinc porphyrins.
RESUMO
Retinoblastoma (RB) protein inactivation during tumor progression is often associated with acquisition of immature phenotypes and resistance to therapy. Determination of an RB inactivation signature in a context of gaining undifferentiated phenotype in a p53-null sarcoma system revealed a critical role for interleukin (IL)-6. Using a Gene Set Enrichment Analysis (GSEA), we discovered that poorly differentiated breast cancers are enriched for this RB inactivation signature. Accelerated IL-6 secretion following RB inactivation in an RB-intact luminal-type breast cancer cell line MCF-7 promoted a positive feed forward loop between IL-6 and STAT3 driving tumor growth and endocrine therapy resistance. In addition, some of RB-intact basal-like type breast cancer cell lines exhibited a similar phenotype following RB depletion. The mechanism whereby RB inactivation increases IL-6 production in MCF-7 cells appeared to involve fatty acid oxidation (FAO)-dependent mitochondrial metabolism and c-Jun NH(2)-terminal kinase (JNK). In addition, IL-6, via STAT3-mediated feedback to mitochondria, autonomously adjusts mitochondrial superoxide to levels suitable to maintain stem cell-like activity. The gene expression profile of luminal-type breast cancer patients with low RB expression revealed high enrichment of genes involved in mitochondrial respiration and downstream targets of IL-6. These findings unveiled an unexpected strategy whereby RB suppresses malignant features of cancer cells through metabolic reprogramming and cell-autonomous inflammation.
Assuntos
Neoplasias da Mama/patologia , Autorrenovação Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Interleucina-6/metabolismo , Mitocôndrias/patologia , Proteína do Retinoblastoma/metabolismo , Tamoxifeno/farmacologia , Animais , Antineoplásicos Hormonais/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Feminino , Humanos , Interleucina-6/genética , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína do Retinoblastoma/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/fisiologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In this study, the electrochemical behavior of free base and zinc meso-substituted porphyrins is examined by cyclic voltammetry (CV) and density functional theory (DFT). The results show that the half-wave oxidation potential splitting of the two oxidation states (ΔE= second E1/2 - first E1/2) of tetraphenylporphyrin (H2TPP) and its zinc complex (ZnTPP) are higher than those of porphyrins and their zinc complexes with meso-substituted five-membered heterocylic rings. The ΔE values follow the trend of TPP > T(3'-thienyl)P > T(3'-furyl)P > T(2'-thienyl)P for both meso-porphyrins and their respective zinc complexes. By employing DFT calculations, we have found that the trend of ΔE values is consistent with that of highest spin density (HSD) distribution and HOMO-LUMO energy gaps of cationic radicals as well as the π-conjugation between central porphyrin and meso-substituted rings. Also, they exhibit the better resonance between the porphyrin ring with meso-substituted rings as moving from porphyrins and their zinc complexes with phenyl rings to five-membered heterocyclic rings. A good agreement between calculated and experimental results indicates that cationic radicals, especially their spin density distribution, do play an important role in half-wave oxidation potential splitting of meso-porphyrins and their zinc complexes.
RESUMO
An efficient and facile size- and shape-selective separation of gold nanorod (GNR) solutions is developed using a fractionated precipitation strategy. This convenient method has the benefit of eliminating nanoparticulate side products that can substantially deteriorate the quality of self-assembled nanostructures. The fabrication of advanced plasmonic metamaterials crucially depends on the capacity to supply feedstocks of high-purity building blocks.