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1.
Org Lett ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941620

RESUMO

A light-mediated cyclization reaction initiated by an atom transfer radical addition (ATRA) of haloalkanes onto alkenes was exploited for the synthesis of functionalized dihydrobenzofurans. Initial investigation indicated that the dimeric gold catalyst [Au2(µ-dppm)2Cl2] can effectively be used for intermolecular ATRA reactions. Further, the reactivity was applied in a cascade-like cyclization for the preparation of dihydrobenzofuran derivatives. With the presented photochemical approach, the functionalization can be achieved directly from ortho-allylphenols in yields of up to 96% under mild conditions.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38881368

RESUMO

PURPOSE: The present study aimed to compare the clinical outcomes and safety at a 1-year follow-up after 5 or 6 weeks of non-weight bearing after a Talar OsteoPeriostic grafting from the Iliac Crest (TOPIC) for a medial osteochondral lesion of the talus (OLT). METHODS: A retrospective comparative case-control analysis of prospectively followed patients who underwent a TOPIC procedure with medial malleolus osteotomy was performed. Patients were matched in two groups with either 5 or 6 weeks of non-weight bearing. Clinical outcomes were evaluated using the Numeric Rating Scale (NRS) during walking, rest, running, and stairclimbing. Additionally, the Foot and Ankle Outcome Score (FAOS) and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were assessed. Moreover, radiology and complications were assessed. RESULTS: Eleven patients were included in the 5-week non-weight bearing group and 22 in the 6-week non-weight bearing group. No significant differences were found in any of the baseline variables. The NRS during walking in the 5-week group improved by 3.5 points and 4 points for the 6-week group (p = 0.58 at 1-year post-operatively). In addition, all other NRS scores, FAOS subscales and the AOFAS scores improved (all n.s. at 1 year follow-up). No significant differences in radiological (osteotomy union and cyst presence in the graft) were found. Moreover, no significant differences were found in terms of complications and reoperations. CONCLUSION: No statistical significant differences were found in terms of clinical, radiological and safety outcomes between 5 or 6 weeks of non-weight bearing following a TOPIC for a medial OLT. LEVEL OF EVIDENCE: Level III, Therapeutic.

3.
Biochim Biophys Acta Bioenerg ; 1865(4): 149150, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906313

RESUMO

Photosystem II (PS II) assembly is a stepwise process involving preassembly complexes or modules focused around four core PS II proteins. The current model of PS II assembly in cyanobacteria is derived from studies involving the deletion of one or more of these core subunits. Such deletions may destabilize other PS II assembly intermediates, making constructing a clear picture of the intermediate events difficult. Information on plastoquinone exchange pathways operating within PS II is also unclear and relies heavily on computer-aided simulations. Deletion of PsbX in [S. Biswas, J.J. Eaton-Rye, Biochim. Biophys. Acta - Bioenerg. 1863 (2022) 148519] suggested modified QB binding in PS II lacking this subunit. This study has indicated the phenotype of the ∆PsbX mutant arose by disrupting a conserved hydrogen bond between PsbX and the D2 (PsbD) protein. We mutated two conserved arginine residues (D2:Arg24 and D2:Arg26) to further understand the observations made with the ∆PsbX mutant. Mutating Arg24 disrupted the interaction between PsbX and D2, replicating the high-light sensitivity and altered fluorescence decay kinetics observed in the ∆PsbX strain. The Arg26 residue, on the other hand, was more important for either PS II assembly or for stabilizing the fully assembled complex. The effects of mutating both arginine residues to alanine or aspartate were severe enough to render the corresponding double mutants non-photoautotrophic. Our study furthers our knowledge of the amino-acid interactions stabilizing plastoquinone-exchange pathways while providing a platform to study PS II assembly and repair without the actual deletion of any proteins.

4.
Chemistry ; : e202401850, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853595

RESUMO

Molecular building blocks, capable of adopting several strongly deviating conformations, are of particular interest in the development of stimuli-responsive self-assemblies. The pronounced structural flexibility of a short acridone-based bridging ligand, equipped with two monodentate isoquinoline donors, is herein exploited to assemble a surprisingly diverse series of coordination-driven Pd(II) architectures. First, it can form a highly twisted Pd2L4 helicate, transformable into the corresponding mesocate, controlled by temperature, counter anion and choice of solvent. Second, it also allows the formation of heteroleptic cages, either from a mix of ligands with Pd(II) cations or by cage-to-cage transformation from homoleptic assemblies. Here, the acridone-based ligand tolerates counter ligands that carry their donors either in a diverging or converging arrangement, as it can rotate its own coordination sites by 90° and structurally adapt to both situations via shape complementarity. Third, by a near 180° rotation of only one of its arms, the ligand can adopt an S-shape conformation and form an unprecedented C6h-symmetric Pd6L12 saw-toothed six-membered ring.

5.
Environ Res ; 256: 119247, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38815719

RESUMO

The incorporation of organic groups into sol-gel silica materials is known to have a noticeable impact on the properties and structure of the resulting xerogels due to the combination of the properties inherent to the organic fragments (functionality and flexibility) with the mechanical and structural stability of the inorganic matrix. However, the reduction of the inorganic content in the materials could be detrimental to their thermal stability properties, limiting the range of their potential applications. Therefore, this work aims to evaluate the thermal stability of hybrid inorganic-organic silica xerogels prepared from mixtures of tetraethoxysilane and organochlorinated triethoxysilane precursors. To this end, a series of four materials with a molar percentage of organochlorinated precursor fixed at 10%, but differing in the type of organic group (chloroalkyls varying in the alkyl-chain length and chlorophenyl), has been selected as model case study. The gases and vapors released during the thermal decomposition of the samples under N2 atmosphere have been analyzed and their components determined and quantified using a thermogravimetric analyzer coupled to a Fourier-transform infrared spectrophotometer and to a gas chromatography-mass spectrometry unit. These analyses have allowed to identify up to three different thermal events for the pyrolysis of the organochlorinated xerogel materials and to elucidate the reaction pathways associated with such processes. These mechanisms have been found to be strongly dependent on the specific nature of the organic group.


Assuntos
Dióxido de Silício , Dióxido de Silício/química , Adsorção , Hidrocarbonetos Clorados/química , Géis/química , Poluentes Atmosféricos/química , Poluentes Atmosféricos/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Temperatura Alta , Volatilização , Cromatografia Gasosa-Espectrometria de Massas
6.
J Immunother Cancer ; 12(5)2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724462

RESUMO

BACKGROUND: Tumor-associated antigens and their derived peptides constitute an opportunity to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. A performant and rational antigen selection pipeline would lay the foundation for immunotherapy trials with the potential to enhance treatment, tremendously benefiting patients suffering from rare, understudied cancers. METHODS: We present an experimentally validated, data-driven computational pipeline that selects and ranks antigens in a multipronged approach. In addition to minimizing the risk of immune-related adverse events by selecting antigens based on their expression profile in tumor biopsies and healthy tissues, we incorporated a network analysis-derived antigen indispensability index based on computational modeling results, and candidate immunogenicity predictions from a machine learning ensemble model relying on peptide physicochemical characteristics. RESULTS: In a model study of uveal melanoma, Human Leukocyte Antigen (HLA) docking simulations and experimental quantification of the peptide-major histocompatibility complex binding affinities confirmed that our approach discriminates between high-binding and low-binding affinity peptides with a performance similar to that of established methodologies. Blinded validation experiments with autologous T-cells yielded peptide stimulation-induced interferon-γ secretion and cytotoxic activity despite high interdonor variability. Dissecting the score contribution of the tested antigens revealed that peptides with the potential to induce cytotoxicity but unsuitable due to potential tissue damage or instability of expression were properly discarded by the computational pipeline. CONCLUSIONS: In this study, we demonstrate the feasibility of the de novo computational selection of antigens with the capacity to induce an anti-tumor immune response and a predicted low risk of tissue damage. On translation to the clinic, our pipeline supports fast turn-around validation, for example, for adoptive T-cell transfer preparations, in both generalized and personalized antigen-directed immunotherapy settings.


Assuntos
Antígenos de Neoplasias , Imunoterapia , Humanos , Antígenos de Neoplasias/imunologia , Imunoterapia/métodos , Redes Reguladoras de Genes
7.
ACS Appl Mater Interfaces ; 16(20): 26195-26208, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38722801

RESUMO

To complement or outperform lithium-ion batteries with liquid electrolyte as energy storage devices, a high-energy as well as high-power anode material must be used in solid-state batteries. An overlooked class of anode materials is the one of conversion/alloy active materials (e.g., SnO2, which is already extensively studied in liquid electrolyte-based batteries). Conversion/alloy active materials offer high specific capacities and often also fast lithium-ion diffusion and reaction kinetics, which are required for high C-rates and application in high-energy and high-power devices such as battery electric vehicles. To date, there are only very few reports on conversion/alloy active materials─namely, SnO2─as anode material in sulfide-based solid-state batteries, with a relatively complex electrode design. Otherwise, conversion-alloy active materials are used as a seed layer or interlayer for a homogeneous Li deposition or to mitigate the formation and growth of the SEI, respectively. Within this work, four different conversion/alloy active materials─SnO2, Sn0.9Fe0.1O2, ZnO, and Zn0.9Fe0.1O─are synthesized and incorporated as negative active materials ("anodes") in composite electrodes into SSBs with Li6PS5Cl as solid electrolyte. The structure and the microstructure of the as-synthesized active materials and composite electrodes are investigated by XRD, SEM, and FIB-SEM. All active materials are evaluated based on their C-rate performance and long-term cyclability by galvanostatic cycling under a constant pressure of 40 MPa. Furthermore, light is shed on the degradation processes that take place at the interface between the active material and solid electrolyte. It is evidenced that the decomposition of Li6PS5Cl to LiCl, Li2S, and Li3P at the anode is amplified by Fe substitution. Lastly, a 2D sheet electrode is designed and cycled to tackle the interfacial degradation processes. This approach leads to an improved C-rate performance (factor of 3) as well as long-term cyclability (factor of 2.3).

8.
J Am Chem Soc ; 146(21): 14521-14527, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38743878

RESUMO

Herein, the development of a light-mediated synthesis of functionalized indolines and tetrahydroquinolines is reported. These structural motifs are considered as highly valuable targets, attributed to their widespread occurrence in pharmaceuticals and natural products. The gold-mediated approach offers a direct route to functionalized indolines in yields of up to 81% under mild photochemical conditions. Thereby, easily accessible Boc-protected N-aryl-allylamine and homoallylamine derivatives were reacted with sp3-hybridized haloalkanes in an intermolecular cascade cyclization reaction. A broad scope of substrates, including a variety of different substituents on the aromatic backbone as well as various haloalkanes, could be utilized. Indoline derivatives, which are functionalized in position 2, are also accessible by applying ortho-allylic anilines. Moreover, the synthetic appeal was demonstrated for a total synthesis of the anti-inflammatory agent AN669 in three reaction steps in an overall yield of 64%.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38796727

RESUMO

PURPOSE: The purpose of the present study is to assess the gender-specific differences in the presentation and outcomes following Talar OsteoPeriostic grafting from the Iliac Crest (TOPIC) between male and female patients. METHODS: A prospective comparative analysis was performed comparing consecutive female and male patients having been treated by the press-fit TOPIC procedure. Clinical comparative assessment preoperatively and at 12 months of follow-up included determination of the Numeric Rating Scale (NRS) scores for pain during walking (primary outcome), at rest and during stair-climbing. The Foot and Ankle Outcome Score (FAOS) was also assessed. A computed tomography (CT) scan was performed for lesion size, morphology and localization determination preoperatively as well as 10-12 weeks postoperatively to assess the union of the osteotomy site and at 1 year postoperatively to assess consolidation of the graft as well as intra-graft cyst development. RESULTS: A total of 48 patients (30 women, 18 men) were eligible for inclusion. Both men and women demonstrated significant functional improvements postoperatively concerning the clinical outcomes with no significant differences between men and women (n.s.) except for a significantly greater improvement in postoperative FAOS pain scores in women. Men presented with OLTs significantly larger in both surface area (208 mm2 for males versus 155 mm2 for females, p < 0.05) as well as lesion volume (3.0 cm3 for males versus 1.8 cm3 for females, p < 0.05). At 1-year postoperatively, all patients showed graft consolidation. Cyst formation was present in 11 females (37% of the group) and 10 males (59% of the group), respectively (n.s.). CONCLUSION: Both males and females showed clinically relevant improvements in the clinical outcomes after undergoing the TOPIC procedure with significant differences in preoperative lesion size. The TOPIC procedure is a good treatment strategy for large OLTs in both men and women. LEVEL OF EVIDENCE: Level III, comparative prospective clinical cohort.

10.
Methods Mol Biol ; 2782: 65-80, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38622392

RESUMO

Maintaining immune homeostasis is instrumental for host health. Immune cells, such as T cells, are instrumental for the eradication of pathogenic bacteria, fungi and viruses. Furthermore, T cells also play a major role in the fight against cancer. Through the formation of immunological memory, a pool of antigen-experienced T cells remains in the body to rapidly protect the host upon reinfection or retransformation. In order to perform their protective function, T cells produce cytolytic molecules, such as granzymes and perforin, and cytokines such as interferon γ and tumor necrosis factor α. Recently, it has become evident that posttranscriptional regulatory events dictate the kinetics and magnitude of cytokine production by murine and human CD8+ T cells. Here, the recent literature regarding the role posttranscriptional regulation plays in maintaining immune homeostasis of antigen-experienced CD8+ T cells is reviewed.


Assuntos
Linfócitos T CD8-Positivos , Glicoproteínas de Membrana , Humanos , Animais , Camundongos , Proteínas Citotóxicas Formadoras de Poros , Citocinas , Perforina , Granzimas , Homeostase
11.
Methods Mol Biol ; 2782: 195-208, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38622404

RESUMO

As part of the adaptive immune system, T cells are critical to maintain immune homeostasis. T cells provide protective immunity by killing infected cells and combatting cancerous cells. To do so, T cells produce and secrete effector molecules, such as granzymes, perforin, and cytokines such as tumor necrosis factor α and interferon γ. However, in immune suppressive environments, such as tumors, T cells gradually lose the capacity to perform their effector function. One way T cell effector function can be enhanced is through genetic engineering with tools such as clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9). This protocol explains in a step-by-step fashion how to perform a controlled electroporation-based CRISPR experiment to enhance human T cell effector function. Of note, these steps are suitable for CRISPR-mediated genome editing in T cells in general and can thus also be used to study proteins of interest that do not influence T cell effector function.


Assuntos
Sistemas CRISPR-Cas , Linfócitos T , Humanos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Engenharia Genética/métodos , Citocinas/genética
12.
Methods Mol Biol ; 2782: 209-226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38622405

RESUMO

T cells are instrumental in protecting the host against invading pathogens and the development of cancer. To do so, they produce effector molecules such as granzymes, interleukins, interferons, and perforin. For the development and immunomonitoring of therapeutic applications such as cell-based therapies and vaccines, assessing T cell effector function is paramount. This can be achieved through various methods, such as 51Cr release assays, flow cytometry, and enzyme-linked immune absorbent spot (ELISpot) assays. For T cell ELISpots, plates are coated with antibodies directed against the effector molecule of interest (e.g., IFN-g). Subsequently, peripheral blood mononuclear cells (PBMCs) or isolated T cells are cultured on the plate together with stimuli of choice, and the production of effector molecules is visualized via labeled detection antibodies. For clinical studies, ELISpot is currently the gold standard to determine antigen-specific T cell frequencies. In contrast to 51Cr release assays, ELISpot allows for the exact enumeration of responding T cells, and compared to flow cytometry, ELISpot is more cost-effective and high throughput. Here, we optimize and describe, in a step-by-step fashion, how to perform a controlled IFN-γ ELISpot experiment to determine the frequency of responding or antigen-specific T cells in healthy human volunteers. Of note, this protocol can also be employed to assess the frequency of antigen-specific T cells induced in, e.g., vaccination studies or present in cellular products.


Assuntos
Leucócitos Mononucleares , Linfócitos T , Humanos , ELISPOT/métodos , Antígenos , Granzimas , Ensaio de Imunoadsorção Enzimática/métodos
13.
J Pers Soc Psychol ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602791

RESUMO

Commitment strategies are effective mechanisms individuals can use to overcome self-control problems. Across seven studies (and two supplemental studies), we explore the negative interpersonal consequences of commitment strategy choice and use. In Study 1, using an incentivized trust game, we demonstrate that individuals trust people who choose to use a commitment strategy less than those who choose to use willpower to achieve their goals. Study 2 shows this relationship holds across four domains and for integrity-based trust in particular. Study 3 provides evidence that it is the choice to use the strategy rather than strategy use itself that incurs this integrity penalty. In Studies 4-5b, we demonstrate that this effect is driven, at least in part, by the fact that people infer past performance from strategy choice. Finally, Study 6 provides evidence that people select commitment strategies more in private than in public, which is consistent with the notion that people anticipate the negative consequences of commitment strategy choice. Thus, we establish the role of willpower as a positive signal in impression formation as well as the negative interpersonal consequences of choosing to rely on external aides when faced with temptation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

14.
Elife ; 132024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591541

RESUMO

Collective cell migration is fundamental for the development of organisms and in the adult for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact inhibition of locomotion (CIL), a local repulsive force, can propel the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell (SC) collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin is required to present the repulsive Slit2/Slit3 signal at the cell surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, nonmigratory cell clusters. Moreover, analysis of ex vivo explants from mice following sciatic nerve injury showed that inhibition of Slit2 decreased SC collective migration and increased clustering of SCs within the nerve bridge. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.


Assuntos
Caderinas , Movimento Celular , Inibição de Contato , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas de Membrana , Regeneração Nervosa , Proteínas do Tecido Nervoso , Células de Schwann , Células de Schwann/metabolismo , Células de Schwann/fisiologia , Animais , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Camundongos , Caderinas/metabolismo , Caderinas/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Regeneração Nervosa/fisiologia , Locomoção/fisiologia , Adesão Celular , Transdução de Sinais
15.
Bioethics ; 38(5): 410-418, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38669606

RESUMO

Recent advances in human brain organoid systems have raised serious worries about the possibility that these in vitro 'mini-brains' could develop sentience, and thus, moral status. This article considers the relative moral status of sentient human brain organoids and research animals, examining whether we have moral reasons to prefer using one over the other. It argues that, contrary to common intuitions, the wellbeing of sentient human brain organoids should not be granted greater moral consideration than the wellbeing of nonhuman research animals. It does so not by denying that typical humans have higher moral status than animals, but instead by arguing that none of the leading justifications for granting humans higher moral status than nonhuman animals apply to brain organoids. Additionally, it argues that there are no good reasons to be more concerned about the well-being of human brain organoids compared to those generated from other species.


Assuntos
Encéfalo , Status Moral , Organoides , Humanos , Animais , Princípios Morais , Pesquisa Biomédica/ética
16.
Angew Chem Int Ed Engl ; 63(24): e202404682, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38573026

RESUMO

While metal-mediated self-assembly is a popular technique to construct discrete nanosized objects, highly symmetric structures, built from one type of ligand at a time, are dominating reported systems. The tailored integration of a set of different ligands requires sophisticated approaches to avoid narcissistic separation or formation of statistical mixtures. Here, we demonstrate how the combination of three structure-guiding effects (metal-templated macrocyclization, additional bridging ligands and shape-complementarity) based on Co(III)salphen metal nodes allows for a rational and high-yielding synthesis of structurally complex, lantern-shaped cages with up to four differentiable bridges. Three new heteroleptic coordination cages based on dinuclear Co(III)salphen macrocycles were synthesized in a one-pot reaction approach and fully characterized, including single crystal X-ray analyses. One cage groups two of the same ligands, another two different ligands around a symmetric Co2-bis-salphen ring. In the most complex structure, this ring is unsymmetric, rendering all four connections between the two metal centers distinguishable. While heteroleptic assembly around Pd(II) nodes has been shown to be dynamic, beneficial for cage-to-cage transformations, assembly cascades and adaptive systems, the herein introduced cages based on kinetically more inert Co(III)salphen will be advantageous for applications in enzyme-like catalysis and molecular machinery that require enhanced structural and chemical stability.

17.
Analyst ; 149(10): 2864-2876, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38619825

RESUMO

Radiation-induced lung injury (RILI) is a dose-limiting toxicity for cancer patients receiving thoracic radiotherapy. As such, it is important to characterize metabolic associations with the early and late stages of RILI, namely pneumonitis and pulmonary fibrosis. Recently, Raman spectroscopy has shown utility for the differentiation of pneumonitic and fibrotic tissue states in a mouse model; however, the specific metabolite-disease associations remain relatively unexplored from a Raman perspective. This work harnesses Raman spectroscopy and supervised machine learning to investigate metabolic associations with radiation pneumonitis and pulmonary fibrosis in a mouse model. To this end, Raman spectra were collected from lung tissues of irradiated/non-irradiated C3H/HeJ and C57BL/6J mice and labelled as normal, pneumonitis, or fibrosis, based on histological assessment. Spectra were decomposed into metabolic scores via group and basis restricted non-negative matrix factorization, classified with random forest (GBR-NMF-RF), and metabolites predictive of RILI were identified. To provide comparative context, spectra were decomposed and classified via principal component analysis with random forest (PCA-RF), and full spectra were classified with a convolutional neural network (CNN), as well as logistic regression (LR). Through leave-one-mouse-out cross-validation, we observed that GBR-NMF-RF was comparable to other methods by measure of accuracy and log-loss (p > 0.10 by Mann-Whitney U test), and no methodology was dominant across all classification tasks by measure of area under the receiver operating characteristic curve. Moreover, GBR-NMF-RF results were directly interpretable and identified collagen and specific collagen precursors as top fibrosis predictors, while metabolites with immune and inflammatory functions, such as serine and histidine, were top pneumonitis predictors. Further support for GBR-NMF-RF and the identified metabolite associations with RILI was found as CNN interpretation heatmaps revealed spectral regions consistent with these metabolites.


Assuntos
Aprendizado de Máquina , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Análise Espectral Raman , Animais , Análise Espectral Raman/métodos , Camundongos , Metabolômica/métodos , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Pneumonite por Radiação/metabolismo , Pneumonite por Radiação/patologia , Pulmão/efeitos da radiação , Pulmão/patologia , Pulmão/metabolismo , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Análise de Componente Principal , Redes Neurais de Computação
18.
J Tradit Complement Med ; 14(2): 182-190, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38481545

RESUMO

Background: Gomphrena perennis L. is a native plant of South America whose pharmacological properties have not been studied yet. Aim: To evaluate the cardiovascular and intestinal pharmacological effects of Gomphrena perennis L. leaves tincture (GphT) and the mechanisms involved. Experimental procedure: The chromatographic profile of GphT was done. Its ex vivo effects were evaluated by contractile concentration-response curves (CRCs) obtained from the agonist carbachol or calcium found in isolated rat small intestine, as well as in the relaxant CRCs. Cardiac effects were evaluated on isolated rat hearts exposed to ischemia/reperfusion (I/R). Experiments in vivo were performed to evaluate the diuretic activity in conscious rats and the hypotensive effect in anaesthetised rats. Results: Fifteen flavonoids were identified in GphT by HPLC-UV, including diosmin. GphT induced a non-competitive inhibition in both carbachol and calcium CRCs on rat small intestine. The first was not affected by indomethacin. Moreover, GphT, unlike diosmin, relaxed the contracture produced by a high-potassium solution in a dose-dependently way. Neither propranolol nor l-NAME changed it. GphT did not show diuretic activity but induced hypotension insensitive to l-NAME. While GphT perfusion of isolated hearts increased injury consequent to I/R, oral administration was cardioprotective and reversed by l-NAME. However, diosmin did not improve the post-ischemic recovery. Conclusions: This study supports the use of Gomphrena perennis L. tincture as an antispasmodic and hypotensive agent. Moreover, it has been demonstrated to be preventive of post-ischemic cardiac dysfunction. However, diosmin would not be responsible for these effects.

19.
Photosynth Res ; 160(2-3): 61-75, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38488942

RESUMO

The low-molecular-weight PsbM and PsbT proteins of Photosystem II (PS II) are both located at the monomer-monomer interface of the mature PS II dimer. Since the extrinsic proteins are associated with the final step of assembly of an active PS II monomer and, in the case of PsbO, are known to impact the stability of the PS II dimer, we have investigated the potential cooperativity between the PsbM and PsbT subunits and the PsbO, PsbU and PsbV extrinsic proteins. Blue-native polyacrylamide electrophoresis and western blotting detected stable PS II monomers in the ∆PsbM:∆PsbO and ∆PsbT:∆PsbO mutants that retained sufficient oxygen-evolving activity to support reduced photoautotrophic growth. In contrast, the ∆PsbM:∆PsbU and ∆PsbT:∆PsbU mutants assembled dimeric PS II at levels comparable to wild type and supported photoautotrophic growth at rates similar to those obtained with the corresponding ∆PsbM and ∆PsbT cells. Removal of PsbV was more detrimental than removal of PsbO. Only limited levels of dimeric PS II were observed in the ∆PsbM:∆PsbV mutant and the overall reduced level of assembled PS II in this mutant resulted in diminished rates of photoautotrophic growth and PS II activity below those obtained in the ∆PsbM:∆PsbO and ∆PsbT:∆PsbO strains. In addition, the ∆PsbT:∆PsbV mutant did not assemble active PS II centers although inactive monomers could be detected. The inability of the ∆PsbT:∆PsbV mutant to grow photoautotrophically, or to evolve oxygen, suggested a stable oxygen-evolving complex could not assemble in this mutant.


Assuntos
Complexo de Proteína do Fotossistema II , Synechocystis , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/genética , Synechocystis/metabolismo , Synechocystis/genética , Synechocystis/crescimento & desenvolvimento , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Mutação , Subunidades Proteicas/metabolismo , Oxigênio/metabolismo
20.
Photosynth Res ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502256

RESUMO

The 11th International Photosynthesis Conference on Hydrogen Energy Research and Sustainability 2023 was organized in honor of Robert Blankenship, Gyozo Garab, Michael Grätzel, Norman Hüner, and Gunnar Öquist, in Istanbul, Türkiye at Bahçesehir University Future Campus from 03 to 09 July 2023. It was jointly supported by the International Society of Photosynthesis Research (ISPR) and the International Association for Hydrogen Energy (IAHE). In this article we provide brief details of the conference, its events, keynote speakers, and the scientific contribution of scientists honored at this conference. Further, we also describe the participation of young researchers, their talks, and their awards.

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