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1.
Kidney Int ; 103(2): 264-281, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36481180

RESUMO

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.


Assuntos
Complicações na Gravidez , Insuficiência Renal Crônica , Gravidez , Feminino , Humanos , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Complicações na Gravidez/etiologia , Tomada de Decisão Clínica , Incerteza , Rim , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Resultado da Gravidez
2.
Inorg Chem ; 61(2): 968-981, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-34961320

RESUMO

A new quaternary telluride, Ba4Ge2Sb2Te10, was synthesized at high temperature via the reaction of elements. A single-crystal X-ray diffraction study shows that the title compound crystallizes in its own structure type in the monoclinic P21/c space group having cell dimensions of a = 13.984(3) Å, b = 13.472(3) Å, c = 13.569(3) Å, and ß = 90.16(3)° with four formula units per unit cell (Z = 4). The pseudo-one-dimensional crystal structure of Ba4Ge2Sb2Te10 consists of infinite 1∞[Ge2Sb2Te10]8- stripes, which are separated by Ba2+ cations. Each of the Ge(1) atoms is covalently bonded to four Te atoms, whereas the Ge(2) atom is covalently bonded with one Sb(2) and three Te atoms in a distorted tetrahedral geometry. The title compound is the first example of a chalcogenide that shows Ge-Sb bonding. The Sb(1) atom is present at the center of the seesaw geometry of four Te atoms. In contrast, the Sb(2) atom forms a seesaw geometry by coordinating with one Ge(2) and three Te atoms. Condensation of these Ge and Sb centered polyhedral units lead to the formation of 1∞[Ge2Sb2Te10]8- stripes. The temperature-dependent resistivity study suggests the semimetallic/degenerate semiconducting nature of polycrystalline Ba4Ge2Sb2Te10. The positive sign of Seebeck coefficient values indicates that the predominant charge carriers are holes in Ba4Ge2Sb2Te10. An extremely low lattice thermal conductivity of ∼0.34 W/mK at 773 K was observed for polycrystalline Ba4Ge2Sb2Te10, which is presumably due to the lattice anharmonicity induced by the stereochemically active 5s2 lone pair of Sb. The electronic structure of Ba4Ge2Sb2Te10 and the bonding of atom pairs in the structure have been analyzed by means of ELF analysis and crystal orbital Hamilton population (COHP) analysis.

3.
Environ Res ; 214(Pt 1): 113761, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35793724

RESUMO

Green synthesis of nanoparticles (NPs) provides economic and environmental benefits as an alternative to chemical or physical methods. Furthermore, the surface properties of such NPs can be modulated by means of the functionalization with different groups making them suitable for various advanced functional applications including water pollutants removal using adsorption technique. In the present work, an eco-friendly synthesis route for nano-adsorbent SiO2 NPs and subsequent surface modifications for enhanced adsorption capacity in removal of Cr(VI) ions from aqueous solution are reported. The green synthesis of SiO2 NPs was carried out using simple bamboo leaves followed by surface modification with amine (A-SiO2) and carboxylic (C-SiO2) functional groups with aim to study the effect of functionalization on adsorption capacity. These nano-adsorbents were characterized by FTIR, SEM, XPS, BET, and zeta potential. and adsorption of Cr(VI) was studied at varying parameters i.e. NPs mass, contact time, and solution pH. The investigation shows interesting results revealing the importance of interactions between the surface functional groups on SiO2 NPs and Cr(VI) species as well as experimental conditions for the choice of surface modifier to achieve a maximum adsorption capacity. The adsorption mechanism has been studied using Langmuir, Freundlich and Temkin adsorption isotherms. The maximum adsorption capacity has been achieved in the case of A-SiO2 NPs which was found to 174 mg/g and much higher than that of SiO2 and C-SiO2 NPs attributed to the selective adsorption and pH conditions. Additionally, A-SiO2 NPs exhibit excellent recyclability indicating their suitability for promising and long term potential applications. This study provides a novel, simple and cost-effective synthesis/surface engineering technology for producing high performance recyclable nano-adsorbents for adsorptive removal of Cr(VI).


Assuntos
Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Adsorção , Cromo , Concentração de Íons de Hidrogênio , Cinética , Dióxido de Silício , Água
4.
Environ Res ; 212(Pt C): 113328, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35483413

RESUMO

Green synthesis of nanomaterials is a sustainable, biologically safe, reliable, and eco-friendly approach. Green synthesis is beneficial to reduce the devastating effects of the traditional chemical synthesis methods and particularly aims at decreasing the usage of toxic chemicals. This review deals with the green synthesis of silica nanoparticles (SiO2 NPs) with emphasis on the engineering surface properties for enhanced adsorption capability and their applications as novel nano-adsorbents for water pollutants removal. Green synthesized SiO2 NPs have shown excellent adsorption properties with higher adsorption capacity of 150-200 mg/g and more than 95% removal for various toxic water pollutants along with reusability for more than 5 cycles. These SiO2 NPs show fascinating physical and chemical properties i.e. tunable size (5 nm to more than 100 nm), low toxicity, biocompatibility, high porosity, higher specific surface area (500--700 m2/g) making them attractive/suitable for several applications in biomedical, agriculture, catalysis, construction, water treatment, etc. Commonly, highly pure SiO2 NPs are synthesized from organic chemicals (very expensive and highly toxic in nature) as a precursor that led to high production costs, high energy consumption, and environmental hazards. On the other hand, green synthesis of SiO2 NPs from natural resources like biomass that includes rice husk, bamboo leaves/stem, sugarcane bagasse, corn cobs, wheat straw, etc. is cost-effective, less toxic, and eco-friendly which has been discussed in detail. Furthermore, the effect of key synthesis parameters (i.e., temperature, time, concentration, pH, etc.) on the morphology, size, purity, and specific surface area of SiO2 NPs have been summarized. Finally, the applications of SiO2 NPs as nano-adsorbents for the removal of toxic water pollutants (i.e., heavy metal cations, anions, dyes, etc.) including the adsorption mechanisms along with the future scope, challenges, and suggestions have been discussed.


Assuntos
Nanopartículas , Saccharum , Poluentes Químicos da Água , Poluentes da Água , Adsorção , Celulose , Nanopartículas/química , Dióxido de Silício/química , Poluentes Químicos da Água/química
5.
Environ Res ; 212(Pt D): 113550, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35654159

RESUMO

Titanium dioxide (TiO2) has been considered as one of the most promising photocatalysts nanomaterials and is being used in a variety of fields of energy and environment under sunlight irradiation via photocatalysis. Highly efficient photocatalytic materials require the design of the proper structure with excellent morphology, interfacial structures, optical and surface properties, etc. Which are the key points to realize effective light-harvesting for photocatalytic applications. Hierarchical TiO2 based nanoflower structures (i.e., 3D nanostructures) possess such characteristics and have attracted much attention in recent years. The uniqueness of TiO2 nanoflowers (NFs) with a coarse texture and arranged structures demonstrates higher photocatalytic activity. This review deals with the hydrothermal synthesis of 3D TiO2 NFs and effect of shape/size as well as various key synthesis parameters to improve their optoelectronic and photocatalytic properties. Furthermore, to improve their photocatalytic properties, various strategies such as doping engineering and heterojunction/nanocomposite formation with other functional nanomaterials have been discussed followed by their potential applications in photocatalytic degradation of various emerging pollutants discharged into the wastewater from various sources. Importance of such 3D nanoarchitecutres and future research in other fields of current interest in environments are discussed.


Assuntos
Poluentes Ambientais , Nanocompostos , Purificação da Água , Catálise , Nanocompostos/química , Titânio/química
6.
Biologicals ; 78: 17-26, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35840492

RESUMO

This online workshop Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps was organized on October 14th, 2021, by the Animal Free Safety Assessment Collaboration (AFSA), the Humane Society International (HSI), the European Federation of Pharmaceutical Industries and Associations (EFPIA), in collaboration with the International Alliance of Biological Standardization (IABS). The workshop saw a participation of over a hundred representatives from international organizations, pharmaceutical industries and associations, and regulatory authorities of 28 countries. Participants reported on country- and region-specific regulatory requirements and, where present, on the perspectives on the waiving and elimination of the Abnormal Toxicity Test. With AFSA, HSI, EFPIA and IABS representatives as facilitators, the participants also discussed specific country/global actions to further secure the deletion of ATT from all regulatory requirements worldwide.


Assuntos
Testes de Toxicidade , Vacinas , Indústria Farmacêutica , Humanos , Padrões de Referência , Vacinas/efeitos adversos
7.
Adv Exp Med Biol ; 1379: 171-203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35760992

RESUMO

Organs-on-chips are microfluidic tissue-engineered models that offer unprecedented dynamic control over cellular microenvironments, emulating key functional features of organs or tissues. Sensing technologies are increasingly becoming an essential part of such advanced model systems for real-time detection of cellular behavior and systemic-like events. The fast-developing field of organs-on-chips is accelerating the development of biosensors toward easier integration, thus smaller and less invasive, leading to enhanced access and detection of (patho-) physiological biomarkers. The outstanding combination of organs-on-chips and biosensors holds the promise to contribute to more effective treatments, and, importantly, improve the ability to detect and monitor several diseases at an earlier stage, which is particularly relevant for complex diseases such as cancer. Biosensors coupled with organs-on-chips are currently being devised not only to determine therapy effectiveness but also to identify emerging cancer biomarkers and targets. The ever-expanding use of imaging modalities for optical biosensors oriented toward on-chip applications is leading to less intrusive and more reliable detection of events both at the cellular and microenvironment levels. This chapter comprises an overview of hybrid approaches combining organs-on-chips and biosensors, focused on modeling and investigating solid tumors, and, in particular, the tumor microenvironment. Optical imaging modalities, specifically fluorescence and bioluminescence, will be also described, addressing the current limitations and future directions toward an even more seamless integration of these advanced technologies.


Assuntos
Técnicas Biossensoriais , Neoplasias , Microambiente Celular , Humanos , Microfluídica/métodos , Neoplasias/diagnóstico , Engenharia Tecidual/métodos , Microambiente Tumoral
8.
Sensors (Basel) ; 22(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36501821

RESUMO

Vehicle teleoperation has the ability to bridge the gap between completely automated driving and manual driving by remotely monitoring and operating autonomous vehicles when their automation fails. Among many challenges related to vehicle teleoperation, the considered ones in this work are variable time delay, saturation of actuators installed in vehicle, and environmental disturbance, which together limit the teleoperation performance. State-of-the-art predictive techniques estimate vehicle states to compensate for the delays, but the predictive states do not account for sudden disturbances that the vehicle observes, which makes the human-picked steer inadequate. This inadequacy of steer deteriorates the path-tracking performance of vehicle teleoperation. In the proposed successive reference-pose-tracking (SRPT) approach, instead of transmitting steering commands, the reference trajectory, in the form of successive reference poses, is transmitted to the vehicle. This paper introduces a method of generation of successive reference poses with a joystick steering wheel and compares the human-in-loop path-tracking performance of the Smith predictor and SRPT approach. Human-in-loop experiments (with 18 different drivers) are conducted using a simulation environment that consists of the integration of a real-time 14-DOF Simulink vehicle model and Unity game engine in the presence of bidirectional variable delays. Scenarios for performance comparison are low adhesion ground, strong lateral wind, tight corners, and sudden obstacle avoidance. Result shows significant improvement in reference tracking and in reducing human effort in all scenarios using the SRPT approach.


Assuntos
Condução de Veículo , Humanos , Automação , Simulação por Computador
9.
J Assoc Physicians India ; 70(8): 11-12, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36082725

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is an important and catastrophic complication of diabetes mellitus (DM). Kidney disease has heterogeneity in histology in diabetes patients and includes both diabetic kidney disease (DKD) (albuminuric or nonalbuminuric) and nondiabetic kidney disease (NDKD) either in isolation or in coexistence with DN. Diabetic nephropathy is hard to overturn. While NDKD is treatable and reversible. MATERIALS AND METHODS: We enrolled a total of 50 type 2 diabetes mellitus (T2DM) patients with clinical kidney disease, of both genders and age >18 years, who underwent kidney biopsy from October 2016 to October 2018. Patients with proteinuria <30 mg per day were excluded from the study. The indications of the renal biopsy were nephrotic syndrome (NS), active urinary sediment, rapid decline in renal function, asymptomatic proteinuria, and hematuria. RESULT: A total of 50 (males: 42 and females: eight) patients with T2DM who underwent kidney biopsy were enrolled. The clinical presentation was: NS 26 (52%), chronic kidney disease (CKD) 11 (22%), asymptomatic proteinuria and hematuria six (12%), acute kidney injury (AKI) four (8%), and acute nephritic syndrome (ANS) three (6%). Diabetic retinopathy (DR) was noted in 19 (38%) cases. Kidney biopsy revealed isolated DN, isolated NDKD, and NDKD superimposed on DN in 26 (52%), 14 (28%), and 10 (20%) cases, respectively. Idiopathic membranous nephropathy (MN) (4) and amyloidosis (2) were the most common forms of NDKD, whereas diffuse proliferative glomerulonephritis (DPGN) was the main form of NDKD superimposed on DN. Diabetic nephropathy was observed in 15 (79%) cases in presence of DR and also in 11 (35.5%) cases even in absence of DR. Of eight patients with microalbuminuria four (50%) cases have biopsy-proven DN. CONCLUSION: About 48% of patients had NDKD either in isolation or in coexistence with DN. Diabetic nephropathy was found in absence of DR and in patients with a low level of proteinuria. The level of proteinuria and presence of DR does not help to distinguish DN vs NDKD. Hence, renal biopsy may be useful in selected T2DM patients with clinical kidney disease to diagnose NDKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Retinopatia Diabética , Glomerulonefrite , Síndrome Nefrótica , Adolescente , Biópsia , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Feminino , Glomerulonefrite/complicações , Hematúria , Humanos , Rim/patologia , Masculino , Síndrome Nefrótica/complicações , Proteinúria/etiologia , Estudos Retrospectivos
10.
Nanotechnology ; 32(34)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-33962405

RESUMO

Plasmonic nanostructures exhibiting high optical nonlinearities are widely used in the rapidly growing modern nanotechnology of nonlinear optics including biomedical applications due to their tunable plasmonic behavior. In this work, we investigate the nonlinear optical properties of uniformly distributed Au nanoparticles (NPs) embedded in pre-synthesized sodium-zinc borate glass by the well-known ion-exchange technique for optical limiting (OL) applications. Various techniques such as optical absorption spectroscopy, x-ray photoelectron spectroscopy, Transmission Electron Microscope (TEM), Photoluminescence, Time of Flight secondary mass spectroscopy and the Z scan technique were used for the characterization of these NPs. TEM confirmed spherically shaped Au NPs with varying sizes of up to 16 nm, in agreement with optical absorption spectroscopy. Nonlinear optical (NLO) properties of these Au NPs were investigated by using an open as well as close aperture Z scan technique which exhibited enhanced optical nonlinearities. The two-photon absorption (2PA) coefficients demonstrated an increasing trend while the OL threshold values demonstrated a decreasing trend as a function of heat treatment. The improved 2PA coefficients and decreased OL threshold values endorsed the Au NPs containing glasses as contending materials for the fabrication of promising optical limiters for the protection of eyes and other sensitive instruments from laser induced damages.

11.
Antonie Van Leeuwenhoek ; 114(8): 1245-1258, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34076810

RESUMO

Plant growth promoting rhizobacteria offer an effective and eco-sustainable solution to protect crops against phytopathogens. In the present study, Bacillus safensis STJP (NAIMCC-B-02323) from the rhizospheric soil of Stevia rebaudiana showed strong biocontrol activity against phytopathogen, Alternaria alternata. B. safensis STJP produced antifungal volatile organic compounds (AVOC). In the presence of AVOC, there was no conidia germination, mycelium growth was inhibited, and hyphae ruptured as observed by scanning electron microscopy. When mycelium of the fungus from bacterial treated plate was transferred into fresh potato dextrose agar plate, A. alternata could not grow. Extracted AVOC from B. safensis STJP were identified by thin-layer chromatography (TLC), Fourier-transform-infrared (FTIR) spectroscopy and gas-chromatography-mass spectrometry (GC-MS). In total 25 bacterial metabolites were identified by GC-MS analysis having alcohol, alkane, phenol, alkyl halide and aromatic compounds. Five of these (phenol, 2,4-bis (1,1-dimethylethyl)-, 3-hexadecanol, pyrrolo(1,2-a)pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)-, 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo(1,2-a:1',2'-d)pyrazine and hexadecanoic acid) inhibited the mycelium growth, controlling spore formation and conidia germination of A. alternata. This study concluded that AVOC producing B. safensis can be used as a green-fungicide against A. alternata. Bacterial metabolites could pave the way for the development of next generation biopesticides. This can be a reliable technology to enhance the quality and reliability of biopesticides.


Assuntos
Alternaria , Antifúngicos , Antifúngicos/farmacologia , Bacillus , Reprodutibilidade dos Testes
12.
Angew Chem Int Ed Engl ; 60(38): 20991-20998, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34292639

RESUMO

In this study, a methyl group on the classic tetramethylcyclam (TMC) ligand framework is replaced with a benzylic group to form the metastable [FeIV (Osyn )(Bn3MC)]2+ (2-syn; Bn3MC=1-benzyl-4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane) species at -40 °C. The decay of 2-syn with time at 25 °C allows the unprecedented monitoring of the steps involved in the intramolecular hydroxylation of the ligand phenyl ring to form the major FeIII -OAr product 3. At the same time, the FeII (Bn3MC)2+ (1) precursor to 2-syn is re-generated in a 1:2 molar ratio relative to 3, accounting for the first time for all the electrons involved and all the Fe species derived from 2-syn as shown in the following balanced equation: 3 [FeIV (O)(LPh )]2+ (2-syn)→2 [FeIII (LOAr )]2+ (3)+[FeII (LPh )]2+ (1)+H2 O. This system thus serves as a paradigm for aryl hydroxylation by FeIV =O oxidants described thus far. It is also observed that 2-syn can be intercepted by certain hydrocarbon substrates, thereby providing a means to assess the relative energetics of aliphatic and aromatic C-H hydroxylation in this system.


Assuntos
Hidrocarbonetos Aromáticos/química , Compostos de Ferro/síntese química , Oxigênio/química , Hidroxilação , Compostos de Ferro/química , Estrutura Molecular
13.
FASEB J ; 33(5): 6609-6621, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30808244

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is the deadliest tumor due to its highly abundant tumor stroma. Pancreatic stellate cells (PSCs) are considered precursor cells of cancer-associated fibroblasts (CAFs), which induce tumor progression, invasion, and metastasis. In this study, we investigated the role of integrin subunit α (ITGA) 11, the receptor for collagen type I, in tumor stroma interaction. Clinical sample analysis showed that ITGA11 was overexpressed by CAFs in PDAC stroma, as shown with colocalization immunostaining with α-smooth muscle actin. In contrast, there was no expression in healthy pancreas. Public transcriptomic data confirmed a reduced expression of ITGA11 in healthy pancreas and adjacent nontumoral tissues compared with human tumor tissues. Primary human PSCs (hPSCs) activated with either TGF-ß or pancreatic cancer cell (PANC-1)-conditioned medium (CM) resulted in the significant up-regulation of ITGA11 and various CAF markers. Furthermore, short hairpin RNA (shRNA)-mediated stable ITGA11 knockdown (shITGA11) in hPSCs significantly inhibited TGF-ß- and PANC-1 CM-mediated activation at both gene and protein levels of extracellular matrix, cytokines, and adhesion molecules. Additionally, shITGA11 hPSCs had a reduced migration and contractility compared with shRNA control (shCTR) PSCs. Furthermore, we investigated the effect of ITGA11 on the paracrine effects of hPSCs. Interestingly, the CM from shITGA11 hPSCs, activated with either TGF-ß or PANC-1 CM, caused tumor cells to migrate and invade lesser compared with their counterpart, activated shCTR PSCs. In summary, this study presents ITGA11 as an interesting stromal therapeutic target that plays a crucial role in the regulation of the differentiation of PSCs into CAFs and paracrine effects.-Schnittert, J., Bansal, R., Mardhian, D. F., van Baarlen, J., Östman, A., Prakash, J. Integrin α11 in pancreatic stellate cells regulates tumor stroma interaction in pancreatic cancer.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Matriz Extracelular/metabolismo , Cadeias alfa de Integrinas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Células Estreladas do Pâncreas/metabolismo , Microambiente Tumoral , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Matriz Extracelular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia
14.
FASEB J ; 33(8): 9466-9475, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31100032

RESUMO

Hepatic fibrosis, characterized by an excessive extracellular matrix (ECM) accumulation, leading to scar-tissue formation is a growing health problem worldwide. Hepatocellular damage due to liver injury triggers inflammation and transdifferentiation of quiescent hepatic stellate cells (HSCs) into proliferative, contractile, and ECM-producing myofibroblasts. Involvement of the Janus kinase (JAK)-2 pathway in the pathogenesis of fibrosis has been reported earlier. However, in this study, we have investigated the effect of selective JAK2 antagonist TG101348 in fibroblasts and inflammatory macrophages and in vivo in an acute carbon tetrachloride-induced liver injury mouse model. In vitro, TG101348 significantly inhibited TGF-ß-induced collagen I expression in murine 3T3 fibroblasts. In human HSCs (LX2 cells), TG101348 potently attenuated TGF-ß-induced contractility and the protein and gene expression of major fibrotic parameters (collagen I, vimentin, and α-smooth muscle actin). In LPS- and IFN-γ-stimulated inflammatory macrophages, TG101348 significantly reduced the NO release and strongly inhibited the expression of inflammatory markers (inducible nitric oxide synthase, C-C motif chemokine ligand 2, IL-1ß, IL-6, and C-C chemokine receptor type 2). In vivo in an acute liver injury mouse model, TG101348 significantly attenuated collagen accumulation and HSC activation. Interestingly, TG101348 drastically inhibited macrophage infiltration and intrahepatic inflammation. Pharmacological inhibition of the JAK2 signaling pathway in activated HSCs and inflammatory macrophages using TG101348 suggests a potential therapeutic approach for the treatment of liver fibrosis.-Akcora, B. O., Dathathri, E., Ortiz-Perez, A., Gabriël, A. V., Storm, G., Prakash, J., Bansal, R. TG101348, a selective JAK2 antagonist, ameliorates hepatic fibrogenesis in vivo.


Assuntos
Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pirrolidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Células 3T3 , Animais , Tetracloreto de Carbono/toxicidade , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Células Hep G2 , Humanos , Cirrose Hepática/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Óxidos de Nitrogênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia
15.
Inorg Chem ; 59(17): 12276-12285, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32845626

RESUMO

Standard solid-state methods produced black crystals of the compounds BaCu0.43(3)Te2 and BaAg0.77(1)Te2 at 1173 K; the crystal structures of each were established using single-crystal X-ray diffraction data. Both crystal structures are modulated. The compound BaCu0.43(3)Te2 crystallizes in the monoclinic superspace group P2(αß1/2)0, having cell dimensions of a = 4.6406(5) Å, b = 4.6596(5) Å, c = 10.362(1) Å, ß = 90.000(9)°, and Z = 2 and an incommensurate vector of q = 0.3499(6)b* + 0.5c*. The compound BaAg0.77(1)Te2 crystallizes in the orthorhombic P21212(α00)000 superspace group with cell dimensions of a = 4.6734(1) Å, b = 4.6468(1) Å, c = 11.1376(3) Å, and Z = 2 and an incommensurate vector of q = 0.364(2)a*. The asymmetric unit of the BaCu0.43(3)Te2 structure comprises eight crystallographically independent sites; that for BaAg0.77(1)Te2 comprises four. In these two structures, each of the M (M = Cu, Ag) atoms is connected to four Te atoms to make two-dimensional layers of [MxTe4/4]n- that are separated by layers of Ba atoms and square nets of Te. A Raman spectroscopic study at 298(2) K on a pelletized polycrystalline sample of BaAg0.8Te2 shows the presence of Ag-Te (83, 116, and 139 cm-1) and Ba-Te vibrations (667 and 732 cm-1). A UV-vis-NIR spectroscopic study on a powdered sample of BaAg0.8Te2 shows the semiconducting nature of the compound with a direct band gap of 1.0(2) eV, consistent with its black color. DFT calculations give a pseudo bandgap with a weak value of the DOS at the Fermi level.

16.
Inorg Chem ; 59(4): 2434-2442, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31999109

RESUMO

A new ternary telluride, Ba3ScTe5, with a pseudo-one-dimensional structure, was synthesized at 1173 K by standard solid-state methods. A single-crystal X-ray diffraction study at 100(2) K shows the structure to be modulated. The structure of the subcell of Ba3ScTe5 crystallizes with two formula units in the hexagonal space group D6h3-P63/mcm with unit cell dimensions of a = b = 10.1190(5) Å and c = 6.8336(3) Å. The asymmetric unit of the subcell structure consists of four crystallographically independent sites: Ba1 (site symmetry: m2m), Sc1 (-3.m), Te1 (m2m), and Te2 (3.2). Its structure is made up of chains of ∞1[ScTe33-] that are separated by Ba2+ cations. The Sc atoms are bonded to six Te1 atoms that form a slightly distorted octahedral geometry. The structure of the subcell also contains linear infinite chains of Te2 with intermediate Te···Te interactions. The superstructure of Ba3ScTe5 is incommensurate and was solved in the hexagonal superspace group P-6(00γ)0 with a = 10.1188(3) Å and c = 6.8332(3) Å and a modulation vector of q = 0.3718(2)c*. The arrangement and coordination geometries of the atoms in the superstructure are very similar to those in the substructure. However, the main difference is that the infinite chains of Te atoms in the superstructure are distorted owing to the formation of long- and short-bonded pairs of Te atoms. The presence of these chains with intermediate Te···Te interactions makes assignment of the formal oxidation states arbitrary. The optical absorption study of a polycrystalline sample of Ba3ScTe5 that was synthesized by the stoichiometric reaction of elements at 1173 K reveals a direct band gap of 1.1(2) eV. The temperature-dependent resistivity study of polycrystalline Ba3ScTe5 shows semiconducting behavior corroborating the optical studies, while density functional theory calculations report a pseudo band gap of 1.3 eV.

17.
Small ; 15(23): e1805510, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31033203

RESUMO

Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high-resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms.


Assuntos
Bioimpressão/métodos , Impressão Tridimensional , Medicina Regenerativa/tendências , Pesquisa Translacional Biomédica , Biomimética/métodos , Biomimética/tendências , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Pesquisa Translacional Biomédica/métodos , Pesquisa Translacional Biomédica/tendências
18.
FASEB J ; 32(2): 969-978, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29066614

RESUMO

Tumor-associated macrophages (TAMs) are the key effector cells in the tumor microenvironment and induce neoangiogenesis, matrix remodeling, and metastasis while suppressing the tumor immune system. These protumoral macrophages display an M2 phenotype induced by IL-4 and IL-13 cytokines. In this study, we hypothesized that the inhibition of the signal transducer and activator of transcription 6 (Stat6) pathway, a common downstream signaling pathway of IL-4 and IL-13, may be an interesting strategy by which to inhibit TAM differentiation and, thus, their protumorigenic activities. In vitro inhibition of the Stat6 pathway by using small interfering RNA or the pharmacologic inhibitor, AS1517499, inhibited the differentiation of mouse RAW264.7 macrophages into the M2 phenotype, as demonstrated by the reduction of Arg-1 (arginase-1) and Mrc-1 (mannose receptor 1) expression and arginase activity. In vivo, AS1517499 significantly attenuated tumor growth and early liver metastasis in an orthotopic 4T1 mammary carcinoma mouse model. Furthermore, in another experiment, we observed an increase in the intrahepatic mRNA expression of F4/80 (EGF-like module-containing mucin-like hormone receptor-like 1; total macrophages) and M2 macrophage markers [ Ym-1 (chitinase 3-like protein 3) and Mrc-1] and metastatic niche markers [ Mmp-2 (matrix metalloproteinase-2), Postn (periostin), and Cd34] in mice with increasing growth of primary tumors. Of interest, these markers were found to be reduced after treatment with AS1517499. In summary, inhibition of the Stat6 pathway in TAMs is a vital therapeutic approach to attenuate tumor growth and metastasis by inhibiting TAM-induced protumorigenic and prometastatic activities.-Binnemars-Postma, K., Bansal, R., Storm, G., Prakash, J. Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer.


Assuntos
Macrófagos/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Proteínas de Neoplasias/metabolismo , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Feminino , Macrófagos/patologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Pirimidinas/farmacologia , Células RAW 264.7
19.
Inorg Chem ; 58(1): 535-539, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30525530

RESUMO

The structure of Ag5U(PS4)3 is unique, as in the literature there are no other structures of the type MAnPQ (M = transition metal, An = actinide, Q = S, Se, or Te). The compound has been synthesized at 1123 K by standard solid-state methods, and its single-crystal X-ray structure has been determined at 100(2) K. Ag5U(PS4)3 crystallizes in a remarkable new structure type in space group P3221 of the trigonal system with three formula units in a hexagonal cell of dimensions a = b = 9.6635(2) Å, c = 17.1834(4) Å, and γ = 120°. In the structure, each U atom is coordinated to eight S atoms in a bicapped trigonal prismatic manner. Each P atom is tetrahedrally coordinated to four S atoms. Two of the three unique Ag atoms are connected to four S atoms in a distorted tetrahedral manner, whereas the third unique Ag atom forms an Ag2S6 species. The overall structure consists of U polyhedra connected to each other via PS4 tetrahedra through edge-sharing in a zigzag fashion along the c axis to form infinite layers. PS4 groups and the Ag atoms pack these layers. From density functional theory calculations, the total density of states of Ag5U(PS4)3 is asymmetric with respect to spin and has finite spin polarization in the crystal cell: the magnetic moments of two of the U atoms are parallel, whereas the magnetic moment of the third U atom is antiparallel.

20.
Inorg Chem ; 58(12): 7837-7844, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31185552

RESUMO

Single crystals and a polycrystalline sample of Ba2Ag2Se2(Se2) were synthesized by standard solid-state chemistry methods at 1173 and 973 K, respectively. The crystal structure of this ternary compound was established by single-crystal X-ray diffraction studies at 100(2) K. The superstructure of this compound is commensurate and crystallizes in the space group P21/ c of a monoclinic system with cell constants of a = 6.1766(2) Å, b = 6.1788(2) Å, c = 21.5784(8) Å, and ß = 90.02(1)° ( Z = 4). The asymmetric unit of the superstructure comprises eight atoms occupying general positions: two Ba atoms, two Ag atoms, and four Se atoms. In this structure, each Ag atom is tetrahedrally coordinated with four adjacent Se atoms to form distorted AgSe4 units that share edges with the neighboring tetrahedra to form a two-dimensional [AgSe4/4]- layer. These layers are separated by Ba2+ and Se22- units. The presence of the Se22- unit is also supported by an intense band at around 247 cm-1 in the Raman spectrum of Ba2Ag2Se2(Se2). A density functional theory study shows that the compound is a semiconductor with a calculated band gap of 1.1 eV. As determined by UV-visible spectroscopy, the direct and indirect band gaps are 1.23(2) and 1.10(2) eV, respectively, in good agreement with the theory and consistent with the black color of the compound. A temperature-dependent resistivity study also confirms the semiconducting nature of Ba2Ag2Se2(Se2).

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