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Psoriasis, a prevalent inflammatory skin condition impacting millions globally, continues to pose treatment challenges, despite the availability of multiple therapies. This underscores the demand for innovative treatments. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their capacity to modulate the immune system and facilitate tissue healing. Recent research indicates that MSCs don't just work through direct cell-to-cell interactions but also release extracellular vesicles (EVs), containing various bioactive substances like proteins, lipids, and nucleic acids. This article explores our current knowledge of psoriasis's origins and the potential utilization of MSCs and their EVs, particularly exosomes, in managing the condition. Additionally, we delve into how MSCs and EVs function in therapy, including their roles in regulating immune responses and promoting tissue repair. Lastly, we discuss the obstacles and opportunities associated with translating MSC-based treatments for psoriasis into clinical practice.
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BACKGROUND: Coronary artery disease (CAD) is a leading cause of death in women. Epicardial adipose tissue (EAT) secretes cytokines to modulate coronary artery function, and the release of fatty acids from EAT serves as a readily available energy source for cardiomyocytes. However, despite having beneficial functions, excessive amounts of EAT can cause the secretion of proinflammatory molecules that increase the instability of atherosclerotic plaques and contribute to CAD progression. Although exercise mitigates CAD, the mechanisms by which exercise impacts EAT are unknown. The Yucatan pig is an excellent translational model for the effects of exercise on cardiac function. Therefore, we sought to determine if chronic aerobic exercise promotes an anti-inflammatory microenvironment in EAT from female Yucatan pigs. METHODS: Sexually mature, female Yucatan pigs (n = 7 total) were assigned to sedentary (Sed, n = 3) or exercise (Ex, n = 4) treatments, and coronary arteries were occluded (O) with an ameroid to mimic CAD or remained non-occluded (N). EAT was collected for bulk (n = 7 total) and single nucleus transcriptomic sequencing (n = 2 total, 1 per exercise treatment). RESULTS: Based on the bulk transcriptomic analysis, exercise upregulated S100 family, G-protein coupled receptor, and CREB signaling in neurons canonical pathways in EAT. The top networks in EAT affected by exercise as measured by bulk RNA sequencing were SRC kinase family, fibroblast growth factor receptor, Jak-Stat, and vascular endothelial growth factor. Single nucleus transcriptomic analysis revealed that exercise increased the interaction between immune, endothelial, and mesenchymal cells in the insulin-like growth factor pathway and between endothelial and other cell types in the platelet endothelial cell adhesion molecule 1 pathway. Sub-clustering revealed nine cell types in EAT, with fibroblast and macrophage populations predominant in O-Ex EAT and T cell populations predominant in N-Ex EAT. Unlike the findings for exercise alone as a treatment, there were not increased interactions between endothelial and mesenchymal cells in O-Ex EAT. Coronary artery occlusion impacted the most genes in T cells and endothelial cells. Genes related to fatty acid metabolism were the most highly upregulated in non-immune cells from O-Ex EAT. Sub-clustering of endothelial cells revealed that N-Ex EAT separated from other treatments. CONCLUSIONS: According to bulk transcriptomics, exercise upregulated pathways and networks related to growth factors and immune cell communication. Based on single nucleus transcriptomics, aerobic exercise increased cell-to-cell interaction amongst immune, mesenchymal, and endothelial cells in female EAT. Yet, exercise was minimally effective at reversing alterations in gene expression in endothelial and mesenchymal cells in EAT surrounding occluded arteries. These findings lay the foundation for future work focused on the impact of exercise on cell types in EAT.
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Tecido Adiposo Epicárdico , Pericárdio , Condicionamento Físico Animal , Transcriptoma , Animais , Feminino , Imunidade Adaptativa/genética , Núcleo Celular/metabolismo , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/genética , Tecido Adiposo Epicárdico/metabolismo , Imunidade Inata , Pericárdio/metabolismo , Suínos , Transcriptoma/genéticaRESUMO
Drought stress is one of the most severe natural disasters in terms of its frequency, length, impact intensity, and associated losses, making it a significant threat to agricultural productivity. Sorghum (Sorghum bicolor), a C4 plant, shows a wide range of morphological, physiological, and biochemical adaptations in response to drought stress, paving the way for it to endure harsh environments. In arid environments, sorghum exhibits enhanced water uptake and reduced dissipation through its morphological activity, allowing it to withstand drought stress. Sorghum exhibits physiological and biochemical resistance to drought, primarily by adjusting its osmotic potential, scavenging reactive oxygen species, and changing the activities of its antioxidant enzymes. In addition, certain sorghum genes exhibit downregulation capabilities in response to drought stress. Therefore, in the current review, we explore drought tolerance in sorghum, encompassing its morphological characteristics and physiological mechanisms and the identification and selection of its functional genes. The use of modern biotechnological and molecular biological approaches to improving sorghum resistance is critical for selecting and breeding drought-tolerant sorghum varieties.
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Secas , Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio , Sorghum , Fatores de Transcrição , Sorghum/genética , Sorghum/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Adaptação Fisiológica/genéticaRESUMO
Past few years have seen a paradigm shift towards ecofriendly, green and biological fabrication of metal nanoparticles (MNPs) for diverse nanomedicinal applications especially in cancer nanotheranostics. Besides, the well-known green synthesis methods of plant materials, the potential of the microbial world (bacteria, fungi, alga, etc.) in biofabrication is equally realized. Biomolecules and enzymes in the microbial cells are capable of catalyzing the biosynthesis process. These microbial derived inorganic nanoparticles have been frequently evaluated as potential agents in cancer therapies revealing exciting results. Through, cellular and molecular pathways, these microbial derived nanoparticles are capable of killing the cancer cells. Considering the recent developments in the anticancer applications of microbial derived inorganic MNPs, a dire need was felt to bring the available information to a single document. This manuscript reviews not only the mechanistic aspects of the microbial derived MNPs but also include the diverse mechanisms that governs their anticancer potential. Besides, an updated literature review is presented that includes studies of 2019-onwards.
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Nanopartículas Metálicas , Neoplasias , Humanos , Nanopartículas Metálicas/uso terapêutico , Fungos/metabolismo , Bactérias/metabolismo , Neoplasias/tratamento farmacológicoRESUMO
Schizophrenia is a mental illness affecting the normal lifestyle of adults and early adolescents incurring major symptoms as jumbled speech, involvement in everyday activities eventually got reduced, patients always struggle with attention and memory, reason being both the genetic and environmental factors responsible for altered brain chemistry and structure, resulting in schizophrenia and associated orphan diseases. The network biology describes the interactions among genes/proteins encoding molecular mechanisms of biological processes, development, and diseases. Besides, all the molecular networks, protein-protein Interaction Networks have been significant in distinguishing the pathogenesis of diseases and thereby drug discovery. The present meta-analysis prioritizes novel disease indications viz. rare and orphan diseases associated with target Glutamate Ionotropic Receptor NMDA Type Subunit 1, GRIN1 using text mining knowledge-based tools. Furthermore, ZINC database was virtually screened, and binding conformation of selected compounds was performed and resulted in the identification of Narciclasine (ZINC04097652) and Alvespimycin (ZINC73138787) as potential inhibitors. Furthermore, docked complexes were subjected to MD simulation studies which suggests that the identified leads could be a better potential drug to recuperate schizophrenia.
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Receptores de N-Metil-D-Aspartato , Esquizofrenia , Humanos , Simulação por Computador , Ácido Glutâmico/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Doenças Raras , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Esquizofrenia/metabolismoRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is an invasive phenotype with undesirable clinical features, poor prognosis, and therapy resistance. Ketoprofen is a Non-steroidal anti-inflammatory drug (NSAID) with anti-tumor properties. AIM: To investigate the effects of Ketoprofen on apoptosis and autophagy in TNBC cell line MDA-MB-231. METHODS: The cytotoxic activity of Ketoprofen was assayed by the MTS method. Flowcytometry was utilized to measure the number of apoptotic MDA-MB-231 cells. The expression levels of apoptosis and autophagy markers, JAK2 and STAT3 were determined using quantitative real time-PCR (qRT-PCR) and western blotting methods. RESULTS: Ketoprofen significantly decreased the proliferation of MDA-MB-231 cells compared to control cells. It also considerably induced apoptosis and apoptotic markers in these cells in comparison to controls. Treating the MADA-MB-231 cell line with Ketoprofen had an inhibitory effect on autophagy markers in this cell line. The use of FasL, as a death ligand, and ZB4, as an antibody that blocks the extrinsic pathway of apoptosis, revealed the involvement of the extrinsic pathway in the apoptosis-stimulating effect of Ketoprofen in the MADA-MB-231 cell line. Ketoprofen also hindered the phosphorylation and activation of JAK2 and STAT molecules leading to the inhibition of the JAK/STAT pathway in this TNBC cell line. CONCLUSION: The outcomes of this study uncovered the anti-TNBC activity of Ketoprofen by inducing apoptosis and inhibiting viability and autophagy in MADA-MB-231 cells. Our data also suggested that Ketoprofen impedes apoptosis in TNBC cells by two different mechanisms including the induction of the extrinsic apoptotic pathway and inhibition of the JAK/STAT signaling.
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Cetoprofeno , Neoplasias de Mama Triplo Negativas , Humanos , Cetoprofeno/farmacologia , Cetoprofeno/uso terapêutico , Neoplasias de Mama Triplo Negativas/genética , Transdução de Sinais , Janus Quinases/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição STAT/metabolismo , Apoptose , Proliferação de Células , AutofagiaRESUMO
Membranes are receiving significant attention to remove emerging organic micropollutants (OMPs) from wastewater and natural water sources. Herein, we report the facile preparation of a novel thin-film nanocomposite (TFN) membrane with high permeability and efficient removal of OMPs. ZnO nanoparticles were first synthesized using the co-precipitation method and functionalized with N1-(3-Trimethoxysilylpropyl)diethylenetriamine to make the surface rich with amine groups and then synthesized nanomaterials were covalently cross-linked into the active layer during the interfacial polymerization (IP) process. The performance of the membranes containing the cross-linked ZnO was significantly better than the non-cross-linked ZnO NPs containing membranes. Adding multiple hydrophilic groups and entities on the surface significantly decreased the contact angle (from â¼60° to 20°). SEM images confirmed the uniform presence and homogeneous distribution of the functionalized NPs throughout the entire membrane surface. Zeta potential measurements showed the modified membranes have a lower negative charge than the pristine membranes. Filtration studies revealed a significant increase in permeability ascribed to the creation of nanochannels in the membrane's active layer. The modified membranes outperformed commercial NF membranes in removing four common OMPs with rejection efficiencies of â¼30%, 64%, 60%, and 70% for Sulfamethoxazole, Amitriptyline, Omeprazole, and Loperamide HCl, respectively. The higher removal efficiency was attributed to the weakened hydrophobic interactions due to the presence of hydrophilic moieties and a stronger size exclusion effect. Moreover, the modified membranes showed high resistance to bacterial adhesion in static conditions.
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Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, 1 H-NMR, and 13 C-NMR spectroscopy. The inâ vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC50 =19.8â µM), DR9 (IC50 =24.8â µM) and DR3 (IC50 =47.2â µM) as compared with Dexibuprofen (IC50 =156.6â µM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3â V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %).
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Antioxidantes , Pró-Fármacos , Antioxidantes/farmacologia , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Anti-Inflamatórios/farmacologia , Ésteres , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. Sulforaphane, derived from broccoli and other members of the Brassica genus, is a phytochemical shown to have anticancer properties. Numerous studies have shown that sulforaphane prevents the development and progression of prostatic tumors. This review evaluates the most recent published reports on prevention of the progression of prostate cancer by sulforaphane in vitro, in vivo and in clinical settings. A detailed description of the proposed mechanisms of action of sulforaphane on prostatic cells is provided. Furthermore, we discuss the challenges, limitations and future prospects of using sulforaphane as a therapeutic agent in treatment of prostate cancer.
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Brassica , Neoplasias da Próstata , Masculino , Humanos , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/prevenção & controle , Brassica/química , SulfóxidosRESUMO
Phyto-melatonin improves crop yield by mitigating the negative effects of abiotic stresses on plant growth. Numerous studies are currently being conducted to investigate the significant performance of melatonin in crops in regulating agricultural growth and productivity. However, a comprehensive review of the pivotal performance of phyto-melatonin in regulating plant morpho-physiological and biochemical activities under abiotic stresses needs to be clarified. This review focused on the research on morpho-physiological activities, plant growth regulation, redox status, and signal transduction in plants under abiotic stresses. Furthermore, it also highlighted the role of phyto-melatonin in plant defense systems and as biostimulants under abiotic stress conditions. The study revealed that phyto-melatonin enhances some leaf senescence proteins, and that protein further interacts with the plant's photosynthesis activity, macromolecules, and changes in redox and response to abiotic stress. Our goal is to thoroughly evaluate phyto-melatonin performance under abiotic stress, which will help us better understand the mechanism by which phyto-melatonin regulates crop growth and yield.
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Melatonina , Melatonina/farmacologia , Melatonina/metabolismo , Desenvolvimento Vegetal , Estresse Fisiológico , Produtos Agrícolas/metabolismo , FotossínteseRESUMO
Cotton growth and yield are severely affected by abiotic stress worldwide. Mepiquate chloride (MC) and melatonin (MT) enhance crop growth and yield by reducing the negative effects of abiotic stress on various crops. Numerous studies have shown the pivotal role of MC and MT in regulating agricultural growth and yield. Nevertheless, an in-depth review of the prominent performance of these two hormones in controlling plant morpho-physiological activity and yield in cotton under abiotic stress still needs to be documented. This review highlights the effects of MC and MT on cotton morpho-physiological and biochemical activities; their biosynthetic, signaling, and transduction pathways; and yield under abiotic stress. Furthermore, we also describe some genes whose expressions are affected by these hormones when cotton plants are exposed to abiotic stress. The present review demonstrates that MC and MT alleviate the negative effects of abiotic stress in cotton and increase yield by improving its morpho-physiological and biochemical activities, such as cell enlargement; net photosynthesis activity; cytokinin contents; and the expression of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase. MT delays the expression of NCED1 and NCED2 genes involved in leaf senescence by decreasing the expression of ABA-biosynthesis genes and increasing the expression of the GhYUC5, GhGA3ox2, and GhIPT2 genes involved in indole-3-acetic acid, gibberellin, and cytokinin biosynthesis. Likewise, MC promotes lateral root formation by activating GA20x genes involved in gibberellin catabolism. Overall, MC and MT improve cotton's physiological activity and antioxidant capacity and, as a result, improve the ability of the plant to resist abiotic stress. The main purpose of this review is to present an in-depth analysis of the performance of MC and MT under abiotic stress, which might help to better understand how these two hormones regulate cotton growth and productivity.
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Gossypium , Melatonina , Gossypium/genética , Melatonina/farmacologia , Cloretos , Antioxidantes/farmacologia , Giberelinas , Citocininas , Estresse FisiológicoRESUMO
Rice is one of the staple foods for the majority of the global population that depends directly or indirectly on it. The yield of this important crop is constantly challenged by various biotic stresses. Rice blast, caused by Magnaporthe oryzae (M. oryzae), is a devastating rice disease causing severe yield losses annually and threatening rice production globally. The development of a resistant variety is one of the most effective and economical approaches to control rice blast. Researchers in the past few decades have witnessed the characterization of several qualitative resistance (R) and quantitative resistance (qR) genes to blast disease as well as several avirulence (Avr) genes from the pathogen. These provide great help for either breeders to develop a resistant variety or pathologists to monitor the dynamics of pathogenic isolates, and ultimately to control the disease. Here, we summarize the current status of the isolation of R, qR and Avr genes in the rice-M. oryzae interaction system, and review the progresses and problems of these genes utilized in practice for reducing rice blast disease. Research perspectives towards better managing blast disease by developing a broad-spectrum and durable blast resistance variety and new fungicides are also discussed.
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Magnaporthe , Oryza , Resistência à Doença/genética , Virulência/genética , Magnaporthe/genética , Oryza/genética , Doenças das Plantas/genéticaRESUMO
This study aimed to evaluate 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl butanoic acid-based ester derivatives as a new class of angiotensin-II receptor antagonists. For this purpose, a series of compounds were synthesized using a variety of phenols. Their chemical characterization was established by FTIR, 1HNMR, and 13CNMR techniques. The biological activities including antioxidant potentials using the DPPH assay, the antihypertensive assay, the urease enzyme inhibition assay, and the antibacterial assay using agar well diffusion methods were performed. All the new compounds showed significant free radical scavenging potentials more than the parent drug while retaining antihypertensive potentials along with urease inhibition properties. However, the AV2 test compound was found to be the most potent against hypertension. Most of the synthesized analogs showed urease inhibitory actions. Molecular docking studies were performed for all the active analogs to decode the binding detail of the ligands with receptors of the enzyme's active site.
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Anti-Hipertensivos , Urease , Ácido Butírico , Simulação de Acoplamento Molecular , Tetrazóis , Relação Estrutura-AtividadeRESUMO
The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.
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Complexos de Coordenação , Metformina , Cobre/química , Metformina/farmacologia , Zinco/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Simulação de Acoplamento Molecular , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Espectroscopia de Infravermelho com Transformada de Fourier , alfa-Glucosidases/químicaRESUMO
Background and Objectives: Analyzing the cardiac autonomic function in COVID-19 patients can provide insights into the impact of the virus on the heart's regulatory mechanisms and its recovery. The autonomic nervous system plays a crucial role in regulating the heart's functions, such as heart rate, blood pressure, and cardiac output. This study aimed to investigate the impact of COVID-19 on heart rate variability (HRV) during a 6-min walk test (6MWT). Materials and Methods: The study included 74 participants, consisting of 37 individuals who had recovered from mild to moderate COVID-19 and 37 healthy controls. The study assessed heart rate variability (HRV) and blood pressure both before and after a 6-min walk test (6MWT). Results: The study found significant differences in a few time domains (SDNN and pNN50) and all frequency domain measures, whereas there were no significant differences in demographic characteristics or blood pressure between COVID-19-recovered individuals and healthy controls at rest. There were significant 6MWT effects on average HR, time-domain (SDNN and pNN50) measures of HRV, and all frequency domain measures of HRV. A significant group × 6MWT interaction was found for SDNN, pNN50, total power, Ln total power, LF, HF, Ln LF, Ln HF, and LF nu. Conclusions: Cardiac Autonomic analysis through HRV is essential to ensure the continued health and well-being of COVID-19 survivors and to minimize the potential long-term impacts of the disease on their cardiovascular system. This suggests that HRV analysis during the recovery phase following exercise could serve as a valuable tool for evaluating the physiological effects of COVID-19 and monitoring the recovery process.
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COVID-19 , Humanos , Coração , Pressão Sanguínea , Frequência Cardíaca , Sistema Nervoso AutônomoRESUMO
The effects of androgens have been extensively studied in a variety of organs and cell types with an increasing focus on the sexually dimorphic role androgens play not only with respect to cellular functions but also in metabolism. Although the classical mechanism of androgen action is via ligand-dependent binding with the nuclear transcription factor, androgen receptor (AR), cytosolic AR can also activate second messenger signaling pathways. Given that cytosolic AR can signal in this manner, there has been increased interest in the mechanisms by which androgens may control cellular organelle function. This review highlights the effects that androgens have on mitochondrial structure and function with emphasis on biogenesis, fusion/fission, mitophagy, bioenergetics (oxidative phosphorylation), and reactive oxygen species production. There are a number of publications on the effects of androgens in these general areas of mitochondrial function. However, the precise mechanisms by which androgens cause these effects are not known. In addition, given that the nucleus and mitochondria work in tandem to control mitochondrial function and the mitochondria have their own DNA, future research efforts should focus on the direct, mechanistic effects of androgens on mitochondrial function.
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Androgênios , Receptores Androgênicos , Androgênios/metabolismo , Androgênios/farmacologia , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de SinaisRESUMO
Acinetobacter baumannii has rapidly emerged as a major cause of gram-negative hospital infections worldwide. A. baumannii encodes for the transport protein AceI, which confers resistance to chlorhexidine, a widely used antiseptic. AceI is also the prototype for the recently discovered proteobacterial antimicrobial compound efflux (PACE) family of transport proteins that confer resistance to a range of antibiotics and antiseptics in many gram-negative bacteria, including pathogens. The gene encoding AceI is conserved in the core genome of A. baumannii, suggesting that it has an important primordial function. This is incongruous with the sole characterized substrate of AceI, chlorhexidine, an entirely synthetic biocide produced only during the last century. Here we investigated a potential primordial function of AceI and other members of the PACE family in the transport of naturally occurring polyamines. Polyamines are abundant in living cells, where they have physiologically important functions and play multifaceted roles in bacterial infection. Gene expression studies revealed that the aceI gene is induced in A. baumannii by the short-chain diamines cadaverine and putrescine. Membrane transport experiments conducted in whole cells of A. baumannii and Escherichia coli and also in proteoliposomes showed that AceI mediates the efflux of these short-chain diamines when energized by an electrochemical gradient. Assays conducted using 8 additional diverse PACE family proteins identified 3 that also catalyze cadaverine transport. Taken together, these results demonstrate that short-chain diamines are common substrates for the PACE family of transport proteins, adding to their broad significance as a novel family of efflux pumps.
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Acinetobacter baumannii , Antibacterianos , Proteínas de Bactérias , Diaminas , Farmacorresistência Bacteriana , Proteínas de Membrana Transportadoras , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Clorexidina/farmacologia , Diaminas/química , Diaminas/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismoRESUMO
CRISPR-based targeted genome editing is bringing revolutionary changes in the research arena of biological sciences. CRISPR/Cas9 has been explored as an efficient therapeutic tool for the treatment of genetic diseases. It has been widely used in ophthalmology research by using mouse models to correct pathogenic mutations in the eye stem cells. In recent studies, CRISPR/Cas9 has been used to correct a large number of mutations related to inherited retinal disorders. In vivo therapeutic advantages for retinal diseases have been successfully achieved in some rodents. Current advances in the CRISPR-based gene-editing domain, such as modified Cas variants and delivery approaches have optimized its application to treat blindness. In this review, recent progress and challenges of the CRISPR-Cas system have been discussed to cure blindness and its prospects.
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Sistemas CRISPR-Cas , Edição de Genes , Animais , Cegueira/genética , Sistemas CRISPR-Cas/genética , Terapia Genética , CamundongosRESUMO
The presence of phyto-hormones in plants at relatively low concentrations plays an indispensable role in regulating crop growth and yield. Salt stress is one of the major abiotic stresses limiting cotton production. It has been reported that exogenous phyto-hormones are involved in various plant defense systems against salt stress. Recently, different studies revealed the pivotal performance of hormones in regulating cotton growth and yield. However, a comprehensive understanding of these exogenous hormones, which regulate cotton growth and yield under salt stress, is lacking. In this review, we focused on new advances in elucidating the roles of exogenous hormones (gibberellin (GA) and salicylic acid (SA)) and their signaling and transduction pathways and the cross-talk between GA and SA in regulating crop growth and development under salt stress. In this review, we not only focused on the role of phyto-hormones but also identified the roles of GA and SA responsive genes to salt stress. Our aim is to provide a comprehensive review of the performance of GA and SA and their responsive genes under salt stress, assisting in the further elucidation of the mechanism that plant hormones use to regulate growth and yield under salt stress.
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Reguladores de Crescimento de Plantas , Estresse Salino , Regulação da Expressão Gênica de Plantas , Gossypium/genética , Gossypium/metabolismo , Hormônios , Desenvolvimento Vegetal/genética , Reguladores de Crescimento de Plantas/metabolismo , Plantas/metabolismo , Ácido Salicílico/metabolismo , Estresse Fisiológico/genéticaRESUMO
The agent responsible for the COVID-19 pandemic was the newly discovered coronavirus SARS-CoV-2. A trimeric spike protein on the SARS-CoV-2 virion binds to the ACE2 receptor on host cells. In this study we performed a structure-based virtual screening and molecular docking of existing drugs against a high-resolution structure of the SARS-CoV-2 spike protein-ACE2 receptor complex. The 2.5-Å crystal structure of the C-terminal domain of the SARS-CoV-2 spike protein (residues 319-541) in complex with human ACE2 (SARS-CoV-2-S-CTD/hACE2) (PDB ID: 6LZG) was used as the target for screening 4,374 FDA-approved drugs from the ZINC15 database using PyRx software. Molecular docking was performed using BIOVIA Discovery Studio Visualizer. The top twenty highest affinity drugs had binding energies of -7.0 to -8.8 kcal/mol. The highest affinity drug was the selective vasopressin V2-receptor antagonist Tolvaptan, for which molecular docking identified drug-amino acid residue interactions with ACE2. Other drugs displaying binding energies better than -8.0 kcal/mol were Nizoral, Amaryl, Accolate, Sorafenib, Glipizide and Azelastine. The predicted interactions of these highest affinity drugs with residues in ACE2 were at positions that could disrupt the spike protein-ACE2 complex, so these drugs have the potential to be repurposed as inhibitors of the SARS-CoV-2 virus.