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1.
Entropy (Basel) ; 26(5)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38785657

RESUMO

Lid-driven cavity (LDC) flow is a significant area of study in fluid mechanics due to its common occurrence in engineering challenges. However, using numerical simulations (ANSYS Fluent) to accurately predict fluid flow and mixed convective heat transfer features, incorporating both a moving top wall and a heated hemispherical obstruction at the bottom, has not yet been attempted. This study aims to numerically demonstrate forced convection in a lid-driven square cavity (LDSC) with a moving top wall and a heated hemispherical obstacle at the bottom. The cavity is filled with a Newtonian fluid and subjected to a specific set of velocities (5, 10, 15, and 20 m/s) at the moving wall. The finite volume method is used to solve the governing equations using the Boussinesq approximation and the parallel flow assumption. The impact of various cavity geometries, as well as the influence of the moving top wall on fluid flow and heat transfer within the cavity, are evaluated. The results of this study indicate that the movement of the wall significantly disrupts the flow field inside the cavity, promoting excellent mixing between the flow field below the moving wall and within the cavity. The static pressure exhibits fluctuations, with the highest value observed at the top of the cavity of 1 m width (adjacent to the moving wall) and the lowest at 0.6 m. Furthermore, dynamic pressure experiences a linear increase until reaching its peak at 0.7 m, followed by a steady decrease toward the moving wall. The velocity of the internal surface fluctuates unpredictably along its length while other parameters remain relatively stable.

2.
Methods Cell Biol ; 183: 187-202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38548412

RESUMO

Dendritic cells (DC) are professional antigen presenting cells (APCs) that can efficiently present captured antigens to cytotoxic T cells and initiate powerful antigen-specific responses. Therefore, DC have been explored for cancer immunotherapy. However, due to the scarcity of DCs in the peripheral blood, ex-vivo expansion is required to generate sufficient DCs before use. The majority of DC-based tumor vaccines utilize monocyte-derived DC (mo-DC) that are generated with GM-CSF and IL-4. Here, we describe the generation of a novel type of DC, CD137L-DC, which are generated from monocytes by stimulation with a CD137 ligand agonist, and that proved to be more potent than classical mo-DC in inducing cytotoxic responses against tumor associated viruses, such as EBV and HBV in vitro. In a phase I clinical trial on patients with locally recurrent or metastatic NPC, a CD137L-DC-EBV vaccine showed good tolerability and prolonged patient survival, providing a basis for further development of CD137L-DC vaccines for immunotherapy.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Herpesvirus Humano 4 , Vacinas Anticâncer/uso terapêutico , Células Dendríticas , Neoplasias/terapia , Monócitos
3.
Antimicrob Agents Chemother ; 68(3): e0107223, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319085

RESUMO

Current antiretroviral therapy for HIV-1 infection does not represent a cure for infection as viral rebound inevitably occurs following discontinuation of treatment. The "block and lock" therapeutic strategy is intended to enforce proviral latency and durably suppress viremic reemergence in the absence of other intervention. The transcription-associated cyclin-dependent protein kinases (tCDKs) are required for expression from the 5´ HIV-1 long-terminal repeat, but the therapeutic potential of inhibiting these kinases for enforcing HIV-1 latency has not been characterized. Here, we expanded previous observations to directly compare the effect of highly selective small molecule inhibitors of CDK7 (YKL-5-124), CDK9 (LDC000067), and CDK8/19 (Senexin A), and found each of these prevented HIV-1 provirus expression at concentrations that did not cause cell toxicity. Inhibition of CDK7 caused cell cycle arrest, whereas CDK9 and CDK8/19 inhibitors did not, and could be continuously administered to establish proviral latency. Upon discontinuation of drug administration, HIV immediately rebounded in cells that had been treated with the CDK9 inhibitor, while proviral latency persisted for several days in cells that had been treated with CDK8/19 inhibitors. These results identify the mediator kinases CDK8/CDK19 as potential "block and lock" targets for therapeutic suppression of HIV-1 provirus expression.


Assuntos
HIV-1 , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Quinases Ciclina-Dependentes/farmacologia , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , Ciclinas/metabolismo , Ciclinas/farmacologia
4.
J Med Biochem ; 42(4): 706-713, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-38084237

RESUMO

Background: Glycolipid metabolism disorders (dysglycolipidemia) are characterized by elevated levels of glycolipid profile components and fasting blood glucose. Dysglycolipidemia are major threats to human health and life. Therefore, the aim of this cross-sectional study is to estimate the prevalence of dysglycolipidemia and the existence of association of TSH and T4 and glycolipid profiles. Methods: Cross-sectional data were obtained from the medical laboratory of Ma'an Governmental Hospital. A total of 141 patients' results were collected (18-60 years). Differences in the glycolipidemic profiles according to age and sex and TSH and T4 were compared. Different statistical analyses were used to analyze the prevalence of dysglycolipidemia and the correlation with the levels of TSH and T4. Results: The study involved results of 141 patients (54.7% males and 45.3% females) in Ma'an Province (Jordan), who visited the internal medicine clinic at Ma'an Governmental Hospital. Patients have overweight and BMI of more than 25 kg/m2. The overall results of the prevalence of dyslipidemia indicated that patients have 42.5% of hypercholesterolemia, 48.2% of high LDL-C, 34.1% of hypertriglyceridemia, and 41.8% of low HDL-C. The prevalence of isolated lipid profiles showed that 10 patients have mixed dyslipidemia. The association of dyslipidemia with age indicated a positive significance between triglyceride and older people (≥40 years), while HDL levels have a significance with gender (p=0.025). The overall ANOVA model yielded non-statistical significant results between levels of any components of lipid profile and levels of TSH and T4 hormones. Welch test (p=0.036) showed positive significance between levels of fasting blood glucose and triglyceride levels. Conclusions: Our results showed and confirmed the presence of a high percentage of hyperlipidemia in Ma'an province and there was no relationship with levels of TSH and T4. A relationship exists between levels of triglycerides and blood glucose concentrations.

5.
J Nutr Sci ; 12: e80, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37528831

RESUMO

Relatively little is known about how the diet of chronically undernourished children may impact cardiometabolic biomarkers. The objective of this exploratory study was to characterise relationships between dietary patterns and the cardiometabolic profile of 153 3-5-year-old Peruvian children with a high prevalence of chronic undernutrition. We collected monthly dietary recalls from children when they were 9-24 months old. At 3-5 years, additional dietary recalls were collected, and blood pressure, height, weight, subscapular skinfolds and fasting plasma glucose, insulin and lipid profiles were assessed. Nutrient intakes were expressed as average density per 100 kcals (i) from 9 to 24 months and (ii) at follow-up. The treelet transform and sparse reduced rank regress'ion (RRR) were used to summarize nutrient intake data. Linear regression models were then used to compare these factors to cardiometabolic outcomes and anthropometry. Linear regression models adjusting for subscapular skinfold-for-age Z-scores (SSFZ) were then used to test whether observed relationships were mediated by body composition. 26 % of children were stunted at 3-5 years old. Both treelet transform and sparse RRR-derived child dietary factors are related to protein intake and associated with total cholesterol and SSFZ. Associations between dietary factors and insulin were attenuated after adjusting for SSFZ, suggesting that body composition mediated these relationships. Dietary factors in early childhood, influenced by protein intake, are associated with cholesterol profiles, fasting glucose and body fat in a chronically undernourished population.


Assuntos
Doenças Cardiovasculares , Humanos , Criança , Pré-Escolar , Lactente , Peru , Doenças Cardiovasculares/epidemiologia , Ingestão de Alimentos , Colesterol , Biomarcadores , Insulina
6.
Antiviral Res ; 217: 105689, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37516154

RESUMO

Human cytomegalovirus (HCMV) is a herpesvirus that causes life-threatening infections in newborns or immunosuppressed patients. For viral replication, HCMV establishes a network of cellular interactions, among others cyclin-dependent kinases (CDK). Furthermore, HCMV encodes pUL97, a viral kinase, which is a CDK-homologue. HCMV uses pUL97 in order to phosphorylate and thereby antagonize SAMHD1, an antiviral host cell factor. Since HCMV has several mechanisms to evade restriction by SAMHD1, we first analyzed the kinetics of SAMHD1-inactivation and found that phosphorylation of SAMHD1 by pUL97 occurs directly after infection of macrophages. We hence hypothesized that inhibition of this process qualifies as efficient antiviral target and FDA approved CDK-inhibitors (CDKIs) might be potent antivirals that prevent the inactivation of SAMHD1. Indeed, Abemaciclib, a 2nd generation CDKI exhibited superior IC50s against HCMV in infected macrophages and the antiviral activity largely relied on its ability to block pUL97-mediated SAMHD1-phosphorylation. Altogether, our study highlights the therapeutic potential of clinically-approved CDKIs as antivirals against HCMV, sheds light on their mode of action and establishes SAMHD1 as a valid and highly potent therapeutic target.


Assuntos
Antivirais , Citomegalovirus , Recém-Nascido , Humanos , Fosforilação , Proteína 1 com Domínio SAM e Domínio HD , Antivirais/farmacologia , Replicação Viral
7.
Front Immunol ; 14: 1117310, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063846

RESUMO

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.


Assuntos
Lesões Encefálicas , Gasderminas , Hemorragia Subaracnóidea , Humanos , Lesões Encefálicas/metabolismo , Inflamassomos/metabolismo , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Piroptose , Hemorragia Subaracnóidea/metabolismo , Gasderminas/antagonistas & inibidores
8.
Transp Res E Logist Transp Rev ; 172: 103082, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36915804

RESUMO

Since the outbreak of COVID-19, its impacts have been envisaged in multi-dimensional ways, including global supply chains, international logistics, and transportation. Owing to a series of virus variants since 2020, several Belt and Road Initiative (BRI) projects have been halted along the Belt and Road (B&R), and their implementation progress has been affected. In addition, China, which initiated the BRI in 2013, has been facing challenges which are caused by its economic, socio-demographic, and international political structural changes. Moreover, growing conflicts and tensions in international trade and politics, such as the war between Russia and Ukraine, China-US trade conflicts, foreign companies' reshoring the production lines from China, and diplomatic disputes between China and Australia, have been interwoven with the impacts of COVID-19 on the supply chains, international trade, and transportation in the world. Having considered the above, this study explores a new research-driven approach to reignite the BRI momentum in the transitional period towards the post-COVID-19 era from a Chinese economic perspective. In doing so, this paper proposes nine research agendas, such as the optimization network of transportation and logistics distribution centers (LDCs) along the B&R, priority development and performance of LDCs, greening the B&R with green shipping corridors, revisiting port devolution continuum, humanitarian logistics in association with COVID-19, security and risk analysis of China's energy supply chains, and export of the 6th Generation Ports (6GP) model with smart ports to major container ports along the port supply chains. Each research agenda is addressed with its motivation, significance, and applicable and representative methods.

9.
Front Pharmacol ; 14: 1281067, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38293667

RESUMO

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates showed that the compound was well distributed in a spontaneous HCC mouse model. Therefore, a rationale design was developed for chemically synthesizing a linoleate-pazopanib conjugate (LAPC). The LAPC showed a significantly improved cytotoxicity compared to the parental drug pazopanib. Pazopanib's angiogenic suppressing signals were not observed in LAPC-treated HCC cells, potentially suggesting an altered mechanism of action (MOA). In an efficacy trial comparing placebo, oral pazopanib, and LAPC treatments in the hepatitis B virus transgene-related spontaneous HCC mouse model (HBVtg-HCC), the LAPC treatment demonstrated superior tumor ablating capacity in comparison to both placebo and pazopanib treatments, without any discernible systemic toxicity. The LAPC exposure is associated with an apoptosis marker (Terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) and an enhanced ferroptosis (glutathione peroxidase 4 [GPX4]) potential in HBVtg-HCC tumors. Therefore, the LAPC showed excellent HCC ablative efficacy with altered MOA. The molecular mechanisms of the LAPC and LDCs for HCC therapeutics are of great academic interest. Further comprehensive preclinical trials (e.g., chemical-manufacture-control, toxicity, distribution, and pharmacokinetics/pharmacodynamics) are expected.

10.
Sensors (Basel) ; 22(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36015994

RESUMO

An edge displacement sensor is one of the key technologies for building large segmented mirror astronomical optical telescopes. A digital interface is one novel approach for sensor technologies, digital transformation and the Internet of Things (IoT) in particular. Frequency output sensors and inductance-to-digital converter (LDC) demonstrated significant advantages in comparison with conventional sensors with analog-to-digital converter (ADC) interfaces. In order for the differential inductive frequency output displacement (DIFOD) sensor to meet the high-stability requirements of segmented mirror astronomical telescopes, it is important to understand the factors for time drift of the sensor. This paper focuses on the investigation of key factors of sensor structure and material, signal conditioning and interface, and fixtures for time drift to permanently installed applications. First, the measurement principle and probe structural characteristics of the sensor are analyzed. Then, two kinds of signal conditioning and digitalization methods using resonance circuits and LDC chips are implemented and compared. Finally, the time drift stability experiments are performed on the sensors with different signal conditioning methods and fixtures under controlled temperature. Experimental results show that the magnetic shield ring effectively improves the sensitivity and quality factor of the sensors, the time drift stability of the sensor using the signal conditioning based on resonance circuits is better than that of the sensors using LDC chips, and the root mean square (RMS) of the sensor time drift meets the requirement of 0.01 µm/24 h. This study will help further development of high-stability of frequency output sensors and IoT-based systems for scaled-up applications in the future.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35886241

RESUMO

A better understanding of river capacity for contaminants (i.e., water environmental capacity, WEC) is essential for the reasonable utilization of water resources, providing government's with guidance about sewage discharge management, and allocating investments for pollutant reduction. This paper applied a new framework integrating a modified hydro-environmental model, Soil and Water Assessment Tool (SWAT) model, and load-duration curve (LDC) method for the dynamic estimation of the NH3-N WEC of the data-scarce Luanhe River basin in China. The impact mechanisms of hydrological and temperature conditions on WEC are discussed. We found that 77% of the WEC was concentrated in 40% hydrological guarantee flow rates. While the increasing flow velocity promoted the pollutant decay rate, it shortened its traveling time in streams, eventually reducing the river WEC. The results suggest that the integrated framework combined the merits of the traditional LDC method and the mechanism model. Thus, the integrated framework dynamically presents the WEC's spatiotemporal distribution under different hydrological regimes with fewer data. It can also be applied in multi-segment rivers to help managers identify hot spots for fragile water environmental regions and periods at the basin scale.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , China , Monitoramento Ambiental/métodos , Rios , Água , Poluentes Químicos da Água/análise
12.
Molecules ; 27(5)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35268828

RESUMO

Pharmaceuticals carried into space are subjected to different gravitational conditions. Hypergravity is encountered in the first stage, during spacecraft launching. The stability of medicines represents a critical element of space missions, especially long-duration ones. Therefore, stability studies should be envisaged before the implementation of drugs for future deep space travel, where the available pharmaceuticals would be limited and restocking from Earth would be impossible. Multipurpose drugs should be proposed for this reason, such as phenothiazine derivatives that can be transformed by optical methods into antimicrobial agents. Within this preliminary study, promethazine and thioridazine aqueous solutions were exposed to UV laser radiation that modified their structures and generated a mixture of photoproducts efficient against particular bacteria. Subsequently, they were subjected to 20 g in the European Space Agency's Large Diameter Centrifuge. The aim was to evaluate the impact of hypergravity on the physico-chemical and spectral properties of unirradiated and laser-irradiated medicine solutions through pH assay, UV-Vis/FTIR absorption spectroscopy, and thin-layer chromatography. The results revealed no substantial alterations in centrifuged samples when compared to uncentrifuged ones. Due to their stability after high-g episodes, laser-exposed phenothiazines could be considered for future space missions.


Assuntos
Tioridazina
13.
BMC Vet Res ; 18(1): 85, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246131

RESUMO

BACKGROUND: Left displacement of the third gastric compartment (LDC3) in alpacas is an extremely rare condition and has not been reported thus far. Therefore, we describe the clinical diagnosis and treatment of LDC3 in an alpaca. CASE PRESENTATION: A 2-year-old brown female alpaca (Vicugna pacos) was presented to evaluate a 3-day history of abdominal distension causing loss of both appetite and thirst, along with oliguria and low to no defecation. Clinical examination, X-ray examination, surgical exploration, and determination of gastric pH (pH ~ 2.35) confirmed that LDC3 resulted in abdominal distension. The gastric wall of the displaced third gastric compartment was incised for the expulsion of pneumatosis, and a medical-grade silicone tube was inserted into the incision to remove the effusion by siphoning. Surgical treatment proved to effectively alleviate the abdominal distension caused by LDC3 without apparent side effects. CONCLUSIONS: To our knowledge, this case is the first known report of LDC3 in an alpaca in China. A similar condition, left displaced abomasum, has previously been described in cattle and sheep.


Assuntos
Camelídeos Americanos , Animais , Bovinos , China , Feminino , Radiografia , Ovinos
14.
Methods Mol Biol ; 2368: 241-265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34647260

RESUMO

Simulated microgravity and partial gravity research on Earth is a necessary complement to space research in real microgravity due to limitations of access to spaceflight. However, the use of ground-based facilities for reduced gravity simulation is far from simple. Microgravity simulation usually results in the need to consider secondary effects that appear in the generation of altered gravity. These secondary effects may interfere with gravity alteration in the changes observed in the biological processes under study. In addition to microgravity simulation, ground-based facilities are also capable of generating hypergravity or fractional gravity conditions whose effects on biological systems are worth being tested and compared with the results of microgravity exposure. Multiple technologies (2D clinorotation, random positioning machines, magnetic levitators, or centrifuges) and experimental hardware (different containers and substrates for seedlings or cell cultures) are available for these studies. Experimental requirements should be collectively and carefully considered in defining the optimal experimental design, taking into account that some environmental parameters, or life-support conditions, could be difficult to be provided in certain facilities. Using simulation facilities will allow us to anticipate, modify, or redefine the findings provided by the scarce available spaceflight opportunities.


Assuntos
Voo Espacial , Ausência de Peso , Hipergravidade , Plântula , Simulação de Ausência de Peso
15.
Cancer Immunol Immunother ; 71(6): 1531-1543, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34661709

RESUMO

INTRODUCTION: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), and provides a target for a dendritic cell (DC) vaccine. CD137 ligand (CD137L) expressed on antigen presenting cells, costimulates CD137-expressing T cells, and reverse CD137L signaling differentiates monocytes to CD137L-DC, a type of DC, which is more potent than classical DC in stimulating T cells. METHODS: In this phase I study, patients with locally recurrent or metastatic NPC were administered CD137L-DC pulsed with EBV antigens (CD137L-DC-EBV-VAX). RESULTS: Of the 12 patients treated, 9 received full 7 vaccine doses with a mean administered cell count of 23.9 × 106 per dose. Treatment was well tolerated with only 4 cases of grade 1 related adverse events. A partial response was obtained in 1 patient, and 4 patients are still benefitting from a progression free survival (PFS) of currently 2-3 years. The mean pre-treatment neutrophil: lymphocyte ratio was 3.4 and a value of less than 3 was associated with prolonged median PFS. Progressors were characterized by a high frequency of naïve T cells but a low frequency of CD8+ effector T cells while patients with a clinical benefit (CB) had a high frequency of memory T cells. Patients with CB had lower plasma EBV DNA levels, and a reduction after vaccination. CONCLUSION: CD137L-DC-EBV-VAX was well tolerated. The use of CD137L-DC-EBV-VAX is demonstrated to be safe. Consistent results were obtained from all 12 patients, indicating that CD137L-DC-EBV-VAX induces an anti-EBV and anti-NPC immune response, and warranting further studies in patients post effective chemotherapy. PRECIS: The first clinical testing of CD137L-DC, a new type of monocyte-derived DC, finds that CD137L-DC are safe, and that they can induce an immune response against Epstein-Barr virus-associated nasopharyngeal carcinoma that leads to tumor regression or prevents tumor progression.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Ligante 4-1BB/genética , Células Dendríticas , Herpesvirus Humano 4 , Humanos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia
16.
Cell ; 184(17): 4480-4494.e15, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34320407

RESUMO

In neutrophils, nicotinamide adenine dinucleotide phosphate (NADPH) generated via the pentose phosphate pathway fuels NADPH oxidase NOX2 to produce reactive oxygen species for killing invading pathogens. However, excessive NOX2 activity can exacerbate inflammation, as in acute respiratory distress syndrome (ARDS). Here, we use two unbiased chemical proteomic strategies to show that small-molecule LDC7559, or a more potent designed analog NA-11, inhibits the NOX2-dependent oxidative burst in neutrophils by activating the glycolytic enzyme phosphofructokinase-1 liver type (PFKL) and dampening flux through the pentose phosphate pathway. Accordingly, neutrophils treated with NA-11 had reduced NOX2-dependent outputs, including neutrophil cell death (NETosis) and tissue damage. A high-resolution structure of PFKL confirmed binding of NA-11 to the AMP/ADP allosteric activation site and explained why NA-11 failed to agonize phosphofructokinase-1 platelet type (PFKP) or muscle type (PFKM). Thus, NA-11 represents a tool for selective activation of PFKL, the main phosphofructokinase-1 isoform expressed in immune cells.


Assuntos
Fagocitose , Fosfofrutoquinase-1 Hepática/metabolismo , Explosão Respiratória , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo , Regulação Alostérica/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Cinética , Viabilidade Microbiana/efeitos dos fármacos , Modelos Moleculares , NADPH Oxidases/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fagocitose/efeitos dos fármacos , Proteínas de Ligação a Fosfato/metabolismo , Fosfofrutoquinase-1 Hepática/antagonistas & inibidores , Fosfofrutoquinase-1 Hepática/ultraestrutura , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Recombinantes/isolamento & purificação , Explosão Respiratória/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia
17.
J Digit Imaging ; 34(4): 986-1004, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34241789

RESUMO

There are various efforts in de-identifying patient's radiation oncology data for their uses in the advancement of research in medicine. Though the task of de-identification needs to be defined in the context of research goals and objectives, existing systems lack the flexibility of modeling data and normalization of names of attributes for accomplishing them. In this work, we describe a de-identification process of radiation and clinical oncology data, which is guided by a data model and a schema of dynamically capturing domain ontology and normalization of terminologies, defined in tune with the research goals in this area. The radiological images are obtained in DICOM format. It consists of diagnostic, radiation therapy (RT) treatment planning, RT verification, and RT response images. During the DICOM de-identification, a few crucial pieces of information are taken about the dataset. The proposed model is generic in organizing information modeling in sync with the de-identification of a patient's clinical information. The treatment and clinical data are provided in the comma-separated values (CSV) format, which follows a predefined data structure. The de-identified data is harmonized throughout the entire process. We have presented four specific case studies on four different types of cancers, namely glioblastoma multiforme, head-neck, breast, and lung. We also present experimental validation on a few patients' data in these four areas. A few aspects are taken care of during de-identification, such as preservation of longitudinal date changes (LDC), incremental de-identification, referential data integrity between the clinical and image data, de-identified data harmonization, and transformation of the data to an underlined database schema.


Assuntos
Objetivos , Radiologia , Bases de Dados Factuais , Humanos , Modelos Teóricos
18.
Drug Deliv ; 28(1): 1080-1092, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34114924

RESUMO

The principal goal of the present investigation was to enterprise new and effective drug delivery vesicle for the sustained delivery of local anesthetic lidocaine hydrochloride (LDC), using a novel combination of copolymeric hydrogel with tetrahydroxyborate (COP-THB) to improve bioactivity and therapeutic potential. To support this contention, the physical and mechanical properties, rheological characteristics, and component release of candidate formulations were investigated. An optimized formulation of COP-THB containing LDC to an upper maximum concentration of 1.5% w/w was assessed for drug crystallization. The biocompatibility of the prepared COP-THB hydrogel was exhibited strong cell survival (96%) and growth compatibility on L929 fibroblast cell lines, which was confirmed by using methods of MTT assay and microscopic observations. The COP-THB hydrogel release pattern is distinct from that of COP-THB/LDC hydrogels by the slow-release rate and the low percentage of cumulative release. In vivo evaluations were demonstrated the anesthetic effects and toxicity value of treated samples by using mice models. In addition, COP-THB/LDC hydrogels significantly inhibit in vivo tumor growth in mice model and effectively reduced it is in vivo toxicity. The pharmacological evaluation showed that encapsulation of LDC in COP-THB hydrogels prolonged its anesthetic action with favorable in vitro and in vivo compatibility. This novel design may theoretically be used in promising studies involving the controlled release of local anesthetics.HighlightsDevelopment a modified sustained release system for the local anesthetic lidocaine.PVP-THB hydrogel to improve the pharmacological properties of the drug and their anesthetic activities.Profiles of PVP-THB/LDC showed that the effective release of associated lidocaine.This new formulation could potentially be used in future local anesthetics.


Assuntos
Anestésicos Locais/farmacologia , Hidrogéis/química , Lidocaína/farmacologia , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Animais , Sobrevivência Celular , Química Farmacêutica , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Fibroblastos , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Distribuição Aleatória , Reologia
19.
Bioresour Technol ; 331: 125066, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33812140

RESUMO

The degradation of lignin is the main rate-limiting step in the bio-pulping of rice straw. A lignin-degrading bacterial consortium LDC, which can efficiently degrade lignin of reed, was screened in the early stage of our laboratory work. In present study, 7-day incubation of LDC can degrade rice straw lignin by 31.18% in mineral salt medium. The communities' structure of different incubation phases varied greatly, in which high abundance (44.78%) of Anaerocolumna was first found. The expression levels of lignin degradation enzyme class II peroxidase (AA2), vanillyl alcohol oxidase (AA4) and 1,4-benzoquinone reductase (AA6) during peak phase (48 h) were significantly up-regulated than initial phase (24 h), increasing by 112%, 165% and 67%, respectively, and 42.86% AA2 was from Thaurea; 100% AA4 was from Clostridium; 62.5% AA6 was from Pseudomonas. These provide microbial resources and data support for the industrialization of rice straw bio-pulping.


Assuntos
Lignina , Oryza , Bactérias , Consórcios Microbianos
20.
Artigo em Inglês | MEDLINE | ID: mdl-33804085

RESUMO

Least developed countries (LDCs) are home to over a billion people throughout Africa, Asia-Pacific, and the Caribbean. The people who live in LDCs represent just 13% of the global population but 40% of its growth rate. Characterised by low incomes and low education levels, high proportions of the population practising subsistence living, inadequate infrastructure, and lack of economic diversity and resilience, LDCs face serious health, environmental, social, and economic challenges. Many communities in LDCs have very limited access to adequate sanitation, safe water, and clean cooking fuel. LDCs are environmentally vulnerable; facing depletion of natural resources, the effects of unsustainable urbanization, and the impacts of climate change, leaving them unable to safeguard their children's lifetime health and wellbeing. This paper reviews and describes the complexity of the causal relationships between children's health and its environmental, social, and economic influences in LDCs using a causal loop diagram (CLD). The results identify some critical feedbacks between poverty, family size, population growth, children's and adults' health, inadequate water, sanitation and hygiene (WASH), air pollution, and education levels in LDCs and suggest leverage points for potential interventions. A CLD can also be a starting point for quantitative systems science approaches in the field, which can predict and compare the effects of interventions.


Assuntos
Saúde da Criança , Países em Desenvolvimento , África , Ásia , Região do Caribe , Criança , Saúde Ambiental , Humanos
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