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1.
Res Sq ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38645258

RESUMO

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. Despite the variety of animal models of SAH currently available, attempts to translate promising therapeutic strategies from preclinical studies to humans have largely failed. This failure is likely due, at least in part, to poor replication of pathology and disabilities in these preclinical models, especially the long-term neurocognitive deficits that drive poor quality of life / return to work in SAH survivors. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, we developed a standardized mouse model of SAH that reproducibly produced significant and trackable long-term neurobehavioral deficits. SAH was induced by performing double blood injections into the prechiasmatic cistern - a simple modification to the well-characterized single prechiasmatic injection mouse model of SAH. Following SAH, mice recapitulated key characteristics of SAH patients including long-term cognitive impairment as observed by a battery of behavioral testing and delayed pathophysiologic processes assayed by neuroinflammatory markers. We believe that this new SAH mouse model will be an ideal paradigm for investigating the complex pathophysiology of SAH and identifying novel druggable therapeutic targets for treating SAH-associated long-term neurocognitive deficits in patients.

2.
Chemosphere ; 349: 140833, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38043620

RESUMO

New materials' synthesis and utilization have shown many critical challenges in healthcare and other industrial sectors as most of these materials are directly or indirectly developed from fossil fuel resources. Environmental regulations and sustainability concepts have promoted the use of natural compounds with unique structures and properties that can be biodegradable, biocompatible, and eco-friendly. In this context, nanocellulose (NC) utility in different sectors and industries is reported due to their unique properties including biocompatibility and antimicrobial characteristics. The bacterial nanocellulose (BNC)-based materials have been synthesized by bacterial cells and extracted from plant waste materials including pineapple plant waste biomass. These materials have been utilized in the form of nanofibers and nanocrystals. These materials are found to have excellent surface properties, low density, and good transparency, and are rich in hydroxyl groups for their modifications to other useful products. These materials are well utilized in different sectors including biomedical or health care centres, nanocomposite materials, supercapacitors, and polymer matrix production. This review explores different approaches for NC production from pineapple waste residues using biotechnological interventions, approaches for their modification, and wider applications in different sectors. Recent technological developments in NC production by enzymatic treatment are critically discussed. The utilization of pineapple waste-derived NC from a bioeconomic perspective is summarized in the paper. The chemical composition and properties of nanocellulose extracted from pineapple waste may have unique characteristics compared to other sources. Pineapple waste for nanocellulose production aligns with the principles of sustainability, waste reduction, and innovation, making it a promising and novel approach in the field of nanocellulose materials.


Assuntos
Ananas , Nanopartículas , Celulose/química , Biomassa , Nanopartículas/química , Polímeros
3.
Diseases ; 11(4)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37873774

RESUMO

Delayed cerebral ischemia (DCI) is an important contributor to poor outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. We previously showed that volatile anesthetics such as isoflurane, sevoflurane and desflurane provided robust protection against SAH-induced DCI, but the impact of a more commonly used intravenous anesthetic agent, propofol, is not known. The goal of our current study is to examine the neurovascular protective effects of propofol on SAH-induced DCI. Twelve-week-old male wild-type mice were utilized for the study. Mice underwent endovascular perforation SAH or sham surgery followed one hour later by propofol infusion through the internal jugular vein (2 mg/kg/min continuous intravenous infusion). Large artery vasospasm was assessed three days after SAH. Neurological outcome assessment was performed at baseline and then daily until animal sacrifice. Statistical analysis was performed via one-way ANOVA and two-way repeated measures ANOVA followed by the Newman-Keuls multiple comparison test with significance set at p < 0.05. Intravenous propofol did not provide any protection against large artery vasospasm or sensory-motor neurological deficits induced by SAH. Our data show that propofol did not afford significant protection against SAH-induced DCI. These results are consistent with recent clinical studies that suggest that the neurovascular protection afforded by anesthetic conditioning is critically dependent on the class of anesthetic agent.

4.
Crit Rev Biotechnol ; : 1-19, 2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37743323

RESUMO

Owing to the increasing worldwide population explosion, managing waste generated from the food sector has become a cross-cutting issue globally, leading to environmental, economic, and social issues. Circular economy-inspired waste valorization approaches have been increasing steadily, generating new business opportunities developing valuable bioproducts using food waste, especially fruit wastes, that may have several applications in energy-food-pharma sectors. Dragon fruit waste is one such waste resource, which is rich in several value-added chemicals and oils, and can be a renewable resource to produce several value-added compounds of potential applications in different industries. Pretreatment and extraction processes in biorefineries are important strategies for recovering value-added biomolecules. There are different methods of valorization, including green extractions and biological conversion approaches. However, microbe-based conversion is one of the advanced technologies for valorizing dragon fruit waste into bioethanol, bioactive products, pharmaceuticals, and other valued products by reusing or recycling them. This state-of-the-art review briefly overviews the dragon fruit waste management strategies and advanced eco-friendly and cost-effective valorization technologies. Furthermore, various applications of different valuable bioactive components obtained from dragon fruit waste have been critically discussed concerning various industrial sectors. Several industrial sectors, such as food, pharmaceuticals, and biofuels, have been critically reviewed in detail.

5.
J Am Heart Assoc ; 12(14): e029975, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37449587

RESUMO

Background Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide synthase (iNOS) is one of the known major mediators of inflammation. We previously showed that an inhalational anesthetic, isoflurane, provides strong protection against delayed cerebral ischemia after SAH. Our current study aims to define the role of iNOS in isoflurane conditioning-induced protection against delayed cerebral ischemia in a mouse model of SAH. Methods and Results The experiments used 10- to 14-week-old male wild-type (C57BL/6) and iNOS global knockout mice. Anesthetic conditioning was initiated 1 hour after SAH with isoflurane 2% for 1 hour. Isoflurane-induced changes in iNOS expression were measured. N-(3-(aminomethyl) benzyl) acetamidine, a highly selective iNOS inhibitor, was injected intraperitoneally immediately after SAH and then daily. Vasospasm, microvessel thrombosis, and neurological assessment was performed. Data were analyzed by 1-way ANOVA and 2-way repeated measures ANOVA followed by Student Newman Keuls comparison test. Statistical significance was set at P<0.05. Isoflurane conditioning downregulated iNOS expression in naïve and SAH mice. N-(3-(aminomethyl) benzyl) acetamidine attenuated large artery vasospasm and microvessel thrombosis and improved neurological deficits in wild-type animals. iNOS knockout mice were significantly resistant to vasospasm, microvessel thrombosis, and neurological deficits induced by SAH. Combining isoflurane with N-(3-(aminomethyl) benzyl) acetamidine did not offer extra protection, nor did treating iNOS knockout mice with isoflurane. Conclusions Isoflurane conditioning-induced delayed cerebral ischemia protection appears to be mediated by downregulating iNOS. iNOS is a potential therapeutic target to improve outcomes after SAH.


Assuntos
Isquemia Encefálica , Isoflurano , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Camundongos , Masculino , Animais , Óxido Nítrico Sintase Tipo II/metabolismo , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/metabolismo , Isoflurano/farmacologia , Camundongos Endogâmicos C57BL , Isquemia Encefálica/prevenção & controle , Infarto Cerebral , Camundongos Knockout , Vasoespasmo Intracraniano/prevenção & controle
6.
Food Chem ; 428: 136709, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37429239

RESUMO

Protein-polysaccharide nanoconjugates are covalently interactive networks that are currently the subject of intense research owing to their emerging applications in the food nanotechnology field. Due to their biocompatibility and biodegradability properties, they have played a significant role as wall materials for the formation of various nanostructures to encapsulate nutraceuticals. The food-grade protein-polysaccharide nanoconjugates would be employed to enhance the delivery and stability of nutraceuticals for their real use in the food industry. The most common edible polysaccharides (cellulose, chitosan, pectin, starch, carrageenan, fucoidan, mannan, glucomannan, and arabic gum) and proteins (silk fibroin, collagen, gelatin, soy protein, corn zein, and wheat gluten) have been used as potential building blocks in nano-encapsulation systems because of their excellent physicochemical properties. This article broadens the discussion of food-grade proteins and polysaccharides as nano-encapsulation biomaterials and their fabrication methods, along with a review of the applications of protein-polysaccharide nanoconjugates in the delivery of plant-derived nutraceuticals.


Assuntos
Nanoconjugados , Nanoestruturas , Nanoconjugados/química , Polissacarídeos/química , Proteínas , Nanoestruturas/química , Suplementos Nutricionais
7.
Biomedicines ; 11(4)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37189781

RESUMO

Delayed cerebral ischemia (DCI) is the largest treatable cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-kB), a transcription factor known to function as a pivotal mediator of inflammation, is upregulated in SAH and is pathologically associated with vasospasm. We previously showed that a brief exposure to isoflurane, an inhalational anesthetic, provided multifaceted protection against DCI after SAH. The aim of our current study is to investigate the role of NF-kB in isoflurane-conditioning-induced neurovascular protection against SAH-induced DCI. Twelve-week-old wild type male mice (C57BL/6) were divided into five groups: sham, SAH, SAH + Pyrrolidine dithiocarbamate (PDTC, a selective NF-kB inhibitor), SAH + isoflurane conditioning, and SAH + PDTC with isoflurane conditioning. Experimental SAH was performed via endovascular perforation. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. Three doses of PDTC (100 mg/kg) were injected intraperitoneally. NF-kB and microglial activation and the cellular source of NF-kB after SAH were assessed by immunofluorescence staining. Vasospasm, microvessel thrombosis, and neuroscore were assessed. NF-kB was activated after SAH; it was attenuated by isoflurane conditioning. Microglia was activated and found to be a major source of NF-kB expression after SAH. Isoflurane conditioning attenuated microglial activation and NF-kB expression in microglia after SAH. Isoflurane conditioning and PDTC individually attenuated large artery vasospasm and microvessel thrombosis, leading to improved neurological deficits after SAH. The addition of isoflurane to the PDTC group did not provide any additional DCI protection. These data indicate isoflurane-conditioning-induced DCI protection after SAH is mediated, at least in part, via downregulating the NF-kB pathway.

8.
Stroke ; 54(5): 1426-1440, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36866673

RESUMO

Aneurysmal subarachnoid hemorrhage is a devastating condition causing significant morbidity and mortality. While outcomes from subarachnoid hemorrhage have improved in recent years, there continues to be significant interest in identifying therapeutic targets for this disease. In particular, there has been a shift in emphasis toward secondary brain injury that develops in the first 72 hours after subarachnoid hemorrhage. This time period of interest is referred to as the early brain injury period and comprises processes including microcirculatory dysfunction, blood-brain-barrier breakdown, neuroinflammation, cerebral edema, oxidative cascades, and neuronal death. Advances in our understanding of the mechanisms defining the early brain injury period have been accompanied by improved imaging and nonimaging biomarkers for identifying early brain injury, leading to the recognition of an elevated clinical incidence of early brain injury compared with prior estimates. With the frequency, impact, and mechanisms of early brain injury better defined, there is a need to review the literature in this area to guide preclinical and clinical study.


Assuntos
Lesões Encefálicas , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Incidência , Microcirculação , Barreira Hematoencefálica , Lesões Encefálicas/complicações
9.
Cancer Metastasis Rev ; 42(3): 823-845, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36696005

RESUMO

Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality. Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.


Assuntos
Canabinoides , Neoplasias , Humanos , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Canabinoides/metabolismo , Receptores de Canabinoides , Endocanabinoides , Neoplasias/tratamento farmacológico
10.
Neurocrit Care ; 38(3): 622-632, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224490

RESUMO

BACKGROUND: An increase in sirtuin 1 (SIRT1) reportedly attenuates early brain injury, delayed cerebral ischemia, and short-term neurologic deficits in rodent models of subarachnoid hemorrhage (SAH). This study investigates the effect of resveratrol, a SIRT1 activator, on long-term functional recovery in a clinically relevant rat model of SAH. METHODS: Thirty male Wistar rats were subjected to fresh arterial blood injection into the prechiasmatic space and randomized to receive 7 days of intraperitoneal resveratrol (20 mg/kg) or vehicle injections. Body weight and rotarod performance were measured on days 0, 3, 7, and 34 post SAH. The neurologic score was assessed 7 and 34 days post SAH. Morris water maze performance was evaluated 29-33 days post SAH. Brain SIRT1 activity and CA1 neuronal survival were also assessed. RESULTS: Blood pressure rapidly increased in all SAH rats, and no between-group differences in blood pressure, blood gases, or glucose were detected. SAH induced weight loss during the first 7 days, which gradually recovered in both groups. Neurologic score and rotarod performance were significantly improved after resveratrol treatment at 34 days post SAH (p = 0.01 and 0.04, respectively). Latency to find the Morris water maze hidden platform was shortened (p = 0.02). In the resveratrol group, more CA1 neurons survived following SAH (p = 0.1). An increase in brain SIRT1 activity was confirmed in the resveratrol group (p < 0.05). CONCLUSIONS: Treatment with resveratrol for 1 week significantly improved the neurologic score, rotarod performance, and latency to find the Morris water maze hidden platform 34 days post SAH. These findings indicate that SIRT1 activation warrants further investigation as a mechanistic target for SAH therapy.


Assuntos
Lesões Encefálicas , Hemorragia Subaracnóidea , Animais , Masculino , Ratos , Modelos Animais de Doenças , Ratos Wistar , Resveratrol/farmacologia , Sirtuína 1 , Hemorragia Subaracnóidea/tratamento farmacológico
11.
Microbiol Res ; 265: 127180, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36126490

RESUMO

The success of sustainable agricultural practices has now become heavily dependent on the interactions between crop plants and their associated microbiome. Continuous advancement in high throughput sequencing platforms, omics-based approaches, and gene editing technologies has remarkably accelerated this area of research. It has enabled us to characterize the interactions of plants with associated microbial communities more comprehensively and accurately. Furthermore, the genomic and post-genomic era has significantly refined our perspective toward the complex mechanisms involved in those interactions, opening new avenues for efficiently deploying the knowledge in developing sustainable agricultural practices. This review focuses on our fundamental understanding of plant-microbe interactions and the contribution of existing multi-omics approaches, including those under active development and their tremendous success in unraveling different aspects of the complex network between plant hosts and microbes. In addition, we have also discussed the importance of sustainable and eco-friendly agriculture and the associated outstanding challenges ahead.


Assuntos
Fabaceae , Microbiota , Agricultura , Interações Microbianas , Microbiota/genética , Plantas
12.
Phytochem Rev ; : 1-26, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35250414

RESUMO

Algal biomass is a promising feedstock for sustainable production of a range of value-added compounds and products including food, feed, fuel. To further augment the commercial value of algal metabolites, efficient valorization methods and biorefining channels are essential. Algal extracts are ideal sources of biotechnologically viable compounds loaded with anti-microbial, anti-oxidative, anti-inflammatory, anti-cancerous and several therapeutic and restorative properties. Emerging technologies in biomass valorisation tend to reduce the significant cost burden in large scale operations precisely associated with the pre-treatment, downstream processing and waste management processes. In order to enhance the economic feasibility of algal products in the global market, comprehensive extraction of multi-algal product biorefinery is envisaged as an assuring strategy. Algal biorefinery has inspired the technologists with novel prospectives especially in waste recovery, carbon concentration/sequestration and complete utilisation of the value-added products in a sustainable closed-loop methodology. This review critically examines the latest trends in the algal biomass valorisation and the expansive feedstock potentials in a biorefinery perspective. The recent scope dynamics of algal biomass utilisation such as bio-surfactants, oleochemicals, bio-stimulants and carbon mitigation have also been discussed. The existing challenges in algal biomass valorisation, current knowledge gaps and bottlenecks towards commercialisation of algal technologies are discussed. This review is a comprehensive presentation of the road map of algal biomass valorisation techniques towards biorefinery technology. The global market view of the algal products, future research directions and emerging opportunities are reviewed.

13.
J Cereb Blood Flow Metab ; 42(7): 1210-1223, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35137611

RESUMO

Functional connectivity (FC) is a sensitive metric that provides a readout of whole cortex coordinate neural activity in a mouse model. We examine the impact of experimental SAH modeled through endovascular perforation, and the effectiveness of subsequent treatment on FC, through three key questions: 1) Does the endovascular perforation model of SAH induce deficits in FC; 2) Does exposure to hypoxic conditioning provide protection against these FC deficits and, if so, is this neurovascular protection SIRT1-mediated; and 3) does treatment with the SIRT1 activator resveratrol alone provide protection against these FC deficits? Cranial windows were adhered on skull-intact mice that were then subjected to either sham or SAH surgery and either left untreated or treated with hypoxic post-conditioning (with or without EX527) or resveratrol for 3 days. Mice were imaged 3 days post-SAH/sham surgery, temporally aligned with the onset of major SAH sequela in mice. Here we show that the endovascular perforation model of SAH induces global and network-specific deficits in FC by day 3, corresponding with the time frame of DCI in mice. Hypoxic conditioning provides SIRT1-mediated protection against these network-specific FC deficits post-SAH, as does treatment with resveratrol. Conditioning-based strategies provide multifaceted neurovascular protection in experimental SAH.


Assuntos
Sirtuína 1 , Hemorragia Subaracnóidea , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo
14.
Semin Cancer Biol ; 86(Pt 3): 931-950, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-33979677

RESUMO

The success of conventional cancer therapeutics is hindered by associated dreadful side-effects of antibiotic resistance and the dearth of antitumor drugs' selectivity and specificity. Hence, the conceptual evolution of anti-cancerous therapeutic agents that selectively target cancer cells without impacting the healthy cells or tissues, has led to a new wave of scientific interest in microbial-derived bioactive molecules. Such strategic solutions may pave the way to surmount the shortcomings of conventional therapies and raise the potential and hope for the cure of wide range of cancer in a selective manner. This review aims to provide a comprehensive summary of anti-carcinogenic properties and underlying mechanisms of bioactive molecules of microbial origin, and discuss the current challenges and effective therapeutic application of combinatorial strategies to attain minimal systemic side-effects.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
15.
Bioresour Technol ; 346: 126580, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34923076

RESUMO

The processing of sugar beet in the sugar production industry releases huge amounts of sugar beet pulp as waste which can be considered a valuable by-product as a source of cellulose, hemicellulose, and pectin. Valorization of sugar beet pulp into value added products occurs through acid hydrolysis, hydrothermal techniques, and enzymatic hydrolysis. Biochemical conversion of beet pulp into simple fermentable sugars for producing value added products occurs through enzymatic hydrolysis is a cost effective and eco-friendly process. While beet pulp has predominantly been used as a fodder for livestock, recent developments in its biotechnological valorization have unlocked its value as a feedstock in the production of biofuels, biohydrogen, biodegradable plastics, and platform chemicals such as lactic acid, citric acid, alcohols, microbial enzymes, single cell proteins, and pectic oligosaccharides. This review brings forward recent biotechnological developments made in the valorization of sugar beet pulp into valuable products.


Assuntos
Beta vulgaris , Biocombustíveis , Biotecnologia , Hidrólise , Açúcares
16.
Acta Neuropathol Commun ; 9(1): 193, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911575

RESUMO

Previous reports indicate a potential role for signal transducer and activator of transcription 3 (STAT3) in amyloid-ß (Aß) processing and neuritic plaque pathogenesis. In the present study, the impact of STAT3 inhibition on cognition, cerebrovascular function, amyloid pathology, oxidative stress, and neuroinflammation was studied using in vitro and in vivo models of Alzheimer's disease (AD)-related pathology. For in vitro experiments, human brain vascular smooth muscle cells (HBVSMC) and human brain microvascular endothelial cells (HBMEC) were used, and these cultured cells were exposed to Aß peptides followed by measurement of activated forms of STAT3 expression and reactive oxygen species (ROS) generation. Further, 6 months old 5XFAD/APOE4 (5XE4) mice and age-matched negative littermates were used for in vivo experiments. These mice were treated with STAT3 specific inhibitor, LLL-12 for 2 months followed by neurobehavioral and histopathological assessment. In vitro experiments showed exposure of cerebrovascular cells to Aß peptides upregulated activated forms of STAT3 and produced STAT3-mediated vascular oxidative stress. 5XE4 mice treated with the STAT3-specific inhibitor (LLL-12) improved cognitive functions and functional connectivity and augmented cerebral blood flow. These functional improvements were associated with a reduction in neuritic plaques, cerebral amyloid angiopathy (CAA), oxidative stress, and neuroinflammation. Reduction in amyloid precursor protein (APP) processing and attenuation of oxidative modification of lipoprotein receptor related protein-1 (LRP-1) were identified as potential underlying mechanisms. These results demonstrate the broad impact of STAT3 on cognitive functions, parenchymal and vascular amyloid pathology and highlight the therapeutic potential of STAT3 specific inhibition for treatment of AD and CAA.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/farmacologia , Antraquinonas/farmacologia , Transtornos Cerebrovasculares/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Rede Nervosa/diagnóstico por imagem , Placa Amiloide/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Sulfonamidas/farmacologia , Animais , Autopsia , Encéfalo , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Microvasos/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fator de Transcrição STAT3/efeitos dos fármacos
17.
J Am Heart Assoc ; 10(20): e021113, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34622677

RESUMO

Background Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection. Methods and Results In this study, we found that hypoxic postconditioning (8% O2 for 2 hours) initiated 3 hours after SAH provides strong protection against cerebral vasospasm, microvessel thrombi, and neurological deficits. By pharmacologic and genetic inhibition of SIRT1 (sirtuin 1) using EX527 and global Sirt1-/- mice, respectively, we demonstrated that this multifaceted DCI protection is SIRT1 mediated. Moreover, genetic overexpression of SIRT1 using Sirt1-Tg mice, mimicked the DCI protection afforded by hypoxic postconditioning. Finally, we found that post-SAH administration of resveratrol attenuated cerebral vasospasm, microvessel thrombi, and neurological deficits, and did so in a SIRT1-dependent fashion. Conclusions The present study indicates that hypoxic postconditioning provides powerful DCI protection when initiated at clinically relevant time points, and that pharmacologic augmentation of SIRT1 activity after SAH can mimic this beneficial effect. We conclude that conditioning-based therapies administered after SAH hold translational promise for patients with SAH and warrant further investigation.


Assuntos
Isquemia Encefálica , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Animais , Infarto Cerebral , Humanos , Hipóxia/complicações , Camundongos , Sirtuína 1/genética , Hemorragia Subaracnóidea/complicações
18.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638809

RESUMO

Enzyme therapies are attracting significant attention as thrombolytic drugs during the current scenario owing to their great affinity, specificity, catalytic activity, and stability. Among various sources, the application of microbial-derived thrombolytic and fibrinolytic enzymes to prevent and treat vascular occlusion is promising due to their advantageous cost-benefit ratio and large-scale production. Thrombotic complications such as stroke, myocardial infarction, pulmonary embolism, deep venous thrombosis, and peripheral occlusive diseases resulting from blood vessel blockage are the major cause of poor prognosis and mortality. Given the ability of microbial thrombolytic enzymes to dissolve blood clots and prevent any adverse effects, their use as a potential thrombolytic therapy has attracted great interest. A better understanding of the hemostasis and fibrinolytic system may aid in improving the efficacy and safety of this treatment approach over classical thrombolytic agents. Here, we concisely discuss the physiological mechanism of thrombus formation, thrombo-, and fibrinolysis, thrombolytic and fibrinolytic agents isolated from bacteria, fungi, and algae along with their mode of action and the potential application of microbial enzymes in thrombosis therapy.


Assuntos
Bactérias/enzimologia , Proteínas de Bactérias/farmacologia , Fibrinolíticos/farmacologia , Proteínas Fúngicas/farmacologia , Fungos/enzimologia , Trombose/tratamento farmacológico , Proteínas de Bactérias/metabolismo , Proteínas Fúngicas/metabolismo , Humanos , Terapia Trombolítica
19.
Nat Food ; 2(12): 924-925, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-37118249
20.
Brain Sci ; 10(12)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321899

RESUMO

Cognitive impairment, associated with ageing, stress, hypertension and various neurodegenerative disorders including Parkinson's disease and epilepsy, is a major health issue. The present review focuses on Alzheimer's disease (AD), since it is the most important cause of cognitive impairment. It is characterized by progressive memory loss, language deficits, depression, agitation, mood disturbances and psychosis. Although the hallmarks of AD are cholinergic dysfunction, ß-amyloid plaques and neurofibrillary tangle formation, it is also associated with derangement of other neurotransmitters, elevated levels of advanced glycation end products, oxidative damage, neuroinflammation, genetic and environmental factors. On one hand, this complex etiopathology makes a response to commonly used drugs such as donepezil, rivastigmine, galantamine and memantine less predictable and often unsatisfactory. On the other hand, it supports the use of herbal medicines due to their nonspecific antioxidant and anti-inflammatory activity and specific cholinesterase inhibitory activity. The popularity of herbal medicines is also increasing due to their perceived effectiveness, safety and affordability. In the present article, the experimental and clinical evidence have been reviewed for various Indian herbal medicines such as Centella asiatica, Bacopa monnieri, Curcuma longa, Clitoria ternatea, Withania somnifera, Celastrus paniculatus, Evolvulus alsinoides, Desmodium gangeticum, Eclipta alba, Moringa oleifera and Convolvulus pluricaulis, which have shown potential in cognitive impairment. Some commonly available herbal formulations for memory impairment in India have also been reviewed.

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