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1.
Virology ; 592: 109998, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38301447

RESUMEN

Plant viruses are responsible for nearly 47 % of all crop losses brought by plant diseases, which have a considerable negative impact on agricultural output. Nanoparticles have the potential to greatly raise agricultural output due to their wonderful applications in the fields of highly sensitive biomolecular detection, disease diagnostics, antimicrobials, and therapeutic compounds. The application of nanotechnology in plant virology is known as nanophytovirology, and it involves biostimulation, drug transport, genetic manipulation, therapeutic agents, and induction of plant defenses. The inactivation and denaturation of capsid protein, nucleic acids (RNA or DNA), and other protein constituents are involved in the underlying mechanism. To determine the precise mechanism by which nanoparticles affect viral mobility, reproduction, encapsidation, and transmission, more research is however required. Nanoparticles can be used to precisely detect plant viruses using nanobiosensors or as biostimulants. The varieties of nanoparticles employed in plant virus control and their methods of virus suppression are highlighted in this review.


Asunto(s)
Nanopartículas , Virus de Plantas , Virus de Plantas/genética , Proteínas de la Cápside/genética , ARN Viral/genética , Enfermedades de las Plantas/prevención & control
2.
Pharm Nanotechnol ; 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37877511

RESUMEN

The ever-growing demand for safe and nutritious food has activated the scrutinization of innovative approaches to enhance food preservation and extended shelf life. Nanotechnology has progressed by making a significant contribution to the food industry at the nanoscale level and appeared as a promising avenue for these challenges. Various nanomaterials have been employed to preserve and extend the shelf life of a variety of food products. Since most harvested fruits and vegetables have a perishable nature, they cannot be preserved in natural circumstances for a long period. Due to a range of unique qualities, nanotechnology-related shelf life extension technologies can compensate for the limitations of normal preservation procedures. The encapsulation of nutraceuticals increases their stability and bioavailability, resulting in beneficial effects on humans. Nanoparticles are used as carriers of health-promoting and/or functional substances in product formulations. They have shown excellent effectiveness in encapsulating bioactive substances and retaining their qualities to ensure their functioning (antioxidant and antibacterial) in food products. This review focuses on the current developments in nanotechnology and their application for improving shelf life and food preservation techniques. Here we excavated the implementation of different types and forms of nanostructured materials (NSMs), from inorganic metals, metal oxides, and their nanocomposites to nano-organic materials incorporating bioactive chemicals in the food system. This review also focuses on exploring the slow and sustainable release of the bioactive compounds, and nutrients enriching the taste and sensory characteristics of the food. Throughout the paper, we dug deep into the regulatory, food safety, and assessment concerns about nanotechnology. The review provides a deep understanding of the developing landscape of nanotechnological applications, challenges, and future opportunities revolutionizing the preservation and extended shelf life of food products.

3.
Plant Physiol Biochem ; 203: 108007, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37714028

RESUMEN

Drought and high temperature stress may occur concomitantly or individually in succession causing cellular dysfunctions. Abscisic acid (ABA) is a key stress regulator, and its responsive genes are controlled by ABRE (Abscisic acid Responsive Element)-binding factors (ABFs)and G-Box Regulatory factors (GRFs). Here, we identify ABFs, GRFs and targeting miRNAs in desi and kabuli chickpea. To validate their role after drought priming and subsequent high temperature stress, two contrasting chickpea varieties (PBG1 and PBG5) were primed and exposed to 32 °C, 35 °C and 38 °C for 12, 6 and 2 h respectively and analyzed for Physio-biochemical, expression of ABFs, GRFs and MiRNAs, and GC-MS based metabolite analysis. To ascertain the ABF-GRF protein-protein interactions, docking studies were carried out between the ABF3 and GRF14. Genome-wide analysis identified total 9 & 11 ABFs, and 11 GRFsin desi and kabuli respectively. Their gene structure, and motif composition were conserved in all subfamilies and only 10 and 12 genes have undergone duplication in both desi and kabuli chickpea respectively. These genes were differentially expressed in-silico. MiR172 and miR396 were identified to target ABFs and GRFs respectively. Protein-protein interaction (ABF3 and GRF14) might be successful only when the ABF3 was phosphorylated. Drought priming downregulated miR172 and miR396 and eventually upregulated targeting ABFs, and GRFs. Metabolite profiling (GC-MS) revealed the accumulation of 87 metabolites in Primed (P) and Non-Primed (NP) Chickpea plants. Tolerant cultivar (PBG5) responded better in all respects however both severity of stress and exposure are important factors and can produce broadly similar cellular response.

4.
Front Oncol ; 13: 1199105, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37492478

RESUMEN

Triple-negative breast cancer (TNBC) is one of the deadliest subtypes of breast cancer (BC) for its high aggressiveness, heterogeneity, and hypoxic nature. Based on biological and clinical observations the TNBC related mortality is very high worldwide. Emerging studies have clearly demonstrated that hypoxia regulates the critical metabolic, developmental, and survival pathways in TNBC, which include glycolysis and angiogenesis. Alterations to these pathways accelerate the cancer stem cells (CSCs) enrichment and immune escape, which further lead to tumor invasion, migration, and metastasis. Beside this, hypoxia also manipulates the epigenetic plasticity and DNA damage response (DDR) to syndicate TNBC survival and its progression. Hypoxia fundamentally creates the low oxygen condition responsible for the alteration in Hypoxia-Inducible Factor-1alpha (HIF-1α) signaling within the tumor microenvironment, allowing tumors to survive and making them resistant to various therapies. Therefore, there is an urgent need for society to establish target-based therapies that overcome the resistance and limitations of the current treatment plan for TNBC. In this review article, we have thoroughly discussed the plausible significance of HIF-1α as a target in various therapeutic regimens such as chemotherapy, radiotherapy, immunotherapy, anti-angiogenic therapy, adjuvant therapy photodynamic therapy, adoptive cell therapy, combination therapies, antibody drug conjugates and cancer vaccines. Further, we also reviewed here the intrinsic mechanism and existing issues in targeting HIF-1α while improvising the current therapeutic strategies. This review highlights and discusses the future perspectives and the major alternatives to overcome TNBC resistance by targeting hypoxia-induced signaling.

5.
Plant Physiol Biochem ; 201: 107840, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37379659

RESUMEN

In wheat (Triticum aestivum L.), terminal heat stress obstructs reproductive functioning eventually leading to yield loss. Drought priming during the vegetative stage can trigger a quicker and effective defense response against impending high temperature stress and improve crop production. In the present study, two contrasting wheat cultivars (PBW670 and C306) were subjected to moderate drought stress of 50-55% field capacity for eight days during the jointing stage to generate drought priming (DP) response. Fifteen days after anthesis heat stress (36 °C) was imposed for three days and physiological response of primed, and non-primed plants was assessed by analyzing membrane damage, water status and antioxidative enzymes. Heat shock transcription factors (14 TaHSFs), calmodulin (TaCaM5), antioxidative genes (TaSOD, TaPOX), polyamine biosynthesis genes and glutathione biosynthesis genes were analyzed. GC-MS based untargeted metabolite profiling was carried out to underpin the associated metabolic changes. Yield related parameters were recorded at maturity to finally assess the priming response. Heat stress response was visible from day one of exposure in terms of membrane damage and elevated antioxidative enzymes activity. DP reduced the impact of heat stress by lowering the membrane damage (ELI, MDA & LOX) and enhancing antioxidative enzyme activity except APX in both the cultivars. Drought priming upregulated the expression of HSFs, calmodulin, antioxidative genes, polyamines, and the glutathione biosynthesis genes. Drought priming altered key amino acids, carbohydrate, and fatty acid metabolism in PBW670 but also promoted thermotolerance in C306. Overall, DP provided a multifaceted approach against heat stress and positive association with yield.


Asunto(s)
Termotolerancia , Triticum , Triticum/metabolismo , Sequías , Calmodulina/metabolismo , Respuesta al Choque Térmico , Glutatión/metabolismo
6.
Front Cell Infect Microbiol ; 13: 1104615, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36926513

RESUMEN

The use of nanomaterials in several fields of science has undergone a revolution in the last few decades. It has been reported by the National Institutes of Health (NIH) that 65% and 80% of infections are accountable for at least 65% of human bacterial infections. One of their important applications in healthcare is the use of nanoparticles (NPs) to eradicate free-floating bacteria and those that form biofilms. A nanocomposite (NC) is a multiphase stable fabric with one or three dimensions that are much smaller than 100 nm, or systems with nanoscale repeat distances between the unique phases that make up the material. Using NC materials to get rid of germs is a more sophisticated and effective technique to destroy bacterial biofilms. These biofilms are refractory to standard antibiotics, mainly to chronic infections and non-healing wounds. Materials like graphene and chitosan can be utilized to make several forms of NCs, in addition to different metal oxides. The ability of NCs to address the issue of bacterial resistance is its main advantage over antibiotics. This review highlights the synthesis, characterization, and mechanism through which NCs disrupt Gram-positive and Gram-negative bacterial biofilms, and their relative benefits and drawbacks. There is an urgent need to develop materials like NCs with a larger spectrum of action due to the rising prevalence of human bacterial diseases that are multidrug-resistant and form biofilms.


Asunto(s)
Infecciones Bacterianas , Nanocompuestos , Nanopartículas , Humanos , Biopelículas , Antibacterianos/farmacología , Bacterias
7.
Plant Physiol Biochem ; 194: 418-439, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36493590

RESUMEN

Chickpea (Cicer arietinum L.) suffers from chilling stress at the reproductive stage (<15 °C) which leads to significant yield loss. This study presents a comprehensive plant response to drought priming and its effect on chilling tolerance during the reproductive stage in two chickpea cultivars PBG1 and PBG5. Lipidome profiling (Fatty acid methyl esters analysis), metabolome profiling (GC-MS based untargeted analysis), fatty acid desaturases and antioxidative gene expression (qRT-PCR) were analyzed to monitor physiological and biochemical events after priming during flowering, podding and seed filling stages. Drought priming alleviated membrane damage and chlorophyll degradation by increasing membrane unsaturated fatty acids (18:3) along with up-regulation of various fatty acid desaturases (CaFADs) genes and antioxidative machinery during flowering and improved seed yield in PBG5. PCA, HCA, and KEGG pathway analysis of 87 identified metabolites showed that metabolites were regulated differently in both cultivars under non-primed and primed conditions. The plant response was more apparent at flowering and podding stages which coincided with chilling temperature (<15 °C). Drought priming stimulated many important genes, especially FADs, antioxidative proteins and accumulation of key metabolites (proline and TCA intermediates) required for defense especially in PBG5. This explains that plant's response to drought priming not only depends on developmental stage, and temperature regime (<15 °C) but also on the genotypic-specificity.


Asunto(s)
Cicer , Cicer/metabolismo , Sequías , Raíces de Plantas/metabolismo , Antioxidantes/metabolismo , Metaboloma
8.
Plant Cell Rep ; 41(10): 2005-2022, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35916939

RESUMEN

KEY MESSAGE: Priming alleviates membrane damage, chlorophyll degradation along with cryoprotectants accumulation during chilling stress that leads to improved reproductive functioning and increased seed yield. Chilling temperatures below 15 °C have severe implications on the reproductive growth and development of chickpea. The abnormal reproductive development and subsequent reproductive failure lead to substantial yield loss. We exposed five chickpea cultivars (PBG1, GPF2, PDG3, PDG4, and PBG5) to drought stress (Priming) during the vegetative stage and analyzed for chilling tolerance during the reproductive stage. These varieties were raised in the fields in two sets: one set of plants were subjected to drought stress at the vegetative stage for 30 days (priming) and the second set of plants were irrigated regularly (non-primed). The leaf samples were harvested at the flowering, podding, and seed filling stage and analyzed for membrane damage, water status, chlorophyll content, cellular respiration, and certain cryoprotective solutes. The reproductive development was analyzed by accessing pollen viability, in vivo and in vitro germination, pollen load, and in vivo pollen tube growth. Principal component analysis (PCA) revealed that priming improved membrane damage, chlorophyll b degradation, and accumulation of cryoprotectants in GPF2, PDG3, and PBG5 at the flowering stage (< 15 °C). Pearson's correlation analysis showed a negative correlation with the accumulation of proline and carbohydrates with flower, pod, and seed abortion. Only, PBG5 responded best to priming while PBG1 was worst. In PBG5, priming resulted in reduced membrane damage and lipid peroxidation, improved water content, reduced chlorophyll degradation, and enhanced cryoprotective solutes accumulation, which led to increased reproductive functioning and finally improved seed yield and harvest index. Lastly, the priming response is variable and cultivar-specific but overall improve plant tolerance.


Asunto(s)
Cicer , Carbohidratos , Clorofila/metabolismo , Sequías , Prolina/metabolismo , Agua/metabolismo
9.
Plant Physiol Biochem ; 184: 26-39, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35623111

RESUMEN

Arsenic is a hazardous metalloid that causes detrimental effects on plant growth and metabolism. Plants accumulate arsenic in edible parts that consequently enter the food chain leading to many health problems. Metal tolerant plant growth-promoting bacteria (PGPB) ameliorate heavy metal toxicity. In this study, the effect of arsenic (As5+) and the role of PGPB Pseudomonas citronellolis (PC) in mitigating As5+ toxicity and associated metabolic alterations in chickpea were assessed. Five chickpea varieties (PBG1, GPF2, PDG3, PDG4 and PBG5) were evaluated for arsenic accumulation, translocation, and its interference with metabolic and defense processes. As5+ (40 mg kg-1) interfered with plant metabolism and enhanced the antioxidative and carbohydrate metabolizing enzyme's activity but PC treatment maintained the activity at par with control. PC also facilitated the accumulation of As5+ in the root system and restricted its translocation to the shoot. Further, to map the metabolic changes, Gas chromatography Mass Spectroscopy (GC-MS) based metabolite profiling and gene expression analysis (qRT-PCR) were performed in the best and worst-performing chickpea varieties (PBG1 and PBG5). 48 metabolites of various metabolic pathways (amino acid, carbohydrate, and fatty acid) were altered in As5+ and PC treatment. Gene expressions showed correlation with biochemical analysis of the antioxidative enzymes and carbohydrate metabolizing enzymes while PC treatment improved chlorophyll biosynthesis enzyme CaDALA expression in As5+ treated plants. Therefore, PC mitigates As5+ toxicity by restricting it in the roots thereby maintaining the cellular homeostasis under As5+ stress in chickpeas.


Asunto(s)
Arsénico , Cicer , Arsénico/metabolismo , Carbohidratos/farmacología , Cicer/genética , Homeostasis , Pseudomonas
10.
Plant Physiol Biochem ; 180: 91-105, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35398655

RESUMEN

Drought and high temperature stress affect chickpea growth and productivity. Often these stresses occur simultaneously in the field and lead to a wide range of molecular and metabolic adaptations. Two chickpea varieties; GPF2 (heat sensitive) and PDG4 variety (heat tolerant) were exposed to 35 °C for 24 h individually and along with drought stress. Five heat responsive signalling genes and 11 structural genes were analyzed using qPCR along with untargeted metabolites analysis using GC MS. Expression of antioxidant genes (CaSOD and CaGPX, CaAPX and CaCAT), transcription factors (CaHSFB2, CaHSFB2A, CaHSFB2B, CaHSP17.5 and CaHSP22.7) and signalling genes (CaCAM, CaGAD, and CaMAPK) were upregulated in GPF2 as compared to PDG4 variety. Principal component analysis (PCA), partial least-square discriminant analysis (PLS-DA), and heat map analysis were applied to the metabolomics data to identify the differential response of metabolites in two chickpea varieties. GC-MS analysis identified 107 and 83 metabolites in PDG4 and GPF2 varieties respectively. PDG4 variety accumulated more sugars, amino acids, sugar alcohols, TCA cycle intermediates which provided heat resistance. Additionally, the differential metabolic pathways involved in heat tolerance were alanine, aspartate, and glutamate metabolism, pantothenate CoA biosynthesis, fructose and mannose metabolism and pentose phosphate pathway in PDG4 variety. There was less accumulation of metabolites in the primed plants of both varieties as compared to the non-primed plants indicating less damage due to heat stress. The present study gives an overview of the molecular changes occurring in response to heat stress in sensitive and tolerant chickpea.

11.
Artículo en Inglés | MEDLINE | ID: mdl-35410623

RESUMEN

Allergies have been known to be an abnormally vigorous immune response in which the immune system fights off an allergen or antigen, initiating mast cells to release histamine into the blood. Substances that prevent mast cells from releasing histamine are considered antiallergic agents. The drugs utilized to treat allergy are mast cell stabilizers, steroids, anti-histamine, leukotriene receptor antagonists, and decongestants. Anti-histamine drugs have side effects such as drowsiness, confusion, constipation, difficulty urinating, blurred vision, etc. The use of medicinal plants for the effective and safe management of diseases has recently received much attention. Various herbs are utilized for their antiallergic and anti-histaminic properties. Some of the herbs useful in the management of allergic diseases of the respiratory tract, like Piper longum, Ocimum tenuiflorum, Solanum xanthocarpum have been discussed. Ample scientific evidence is available for the anti-histaminic and antiallergic activity of Azadirachta indica, Aloe vera, Tinospora cordifolia, and many other such herbs are safer to use as antiallergic agents have been reported. The review summarizes a wide variety of herbs and botanical ingredients with their common scientific names and distribution for easy identification and usage as safe antiallergic agents and discusses their molecular mechanisms involved in combating allergic reactions.


Asunto(s)
Antialérgicos , Hipersensibilidad , Humanos , Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Estabilizadores de Mastocitos , Antagonistas de Leucotrieno/uso terapéutico , Descongestionantes Nasales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Hipersensibilidad/tratamiento farmacológico , Histamina/uso terapéutico , Alérgenos
12.
Artículo en Inglés | MEDLINE | ID: mdl-34115206

RESUMEN

NO (nitric oxide) is an important regulator of neutrophil functions and has a key role in diverse pathophysiological conditions. NO production by nitric oxide synthases (NOS) is under tight control at transcriptional, translational, and post-translational levels including interactions with heterologous proteins owing to its potent chemical reactivity and high diffusibility; this limits toxicity to other cellular components and promotes signaling specificity. The protein-protein interactions govern the activity and spatial distribution of NOS isoform to regulatory proteins and to their intended targets. In comparison with the vast literature available for endothelial, macrophages, and neuronal cells, demonstrating neuronal NOS (nNOS) interaction with other proteins through the PDZ domain, neutrophil nNOS, however, remains unexplored. Neutrophil's key role in both physiological and pathological conditions necessitates the need for further studies in delineating the NOS mediated NO modulations in signaling pathways operational in them. nNOS has been linked to depression, schizophrenia, and Parkinson's disease, suggesting the importance of exploring nNOS/NO-mediated neutrophil physiology in relation to such neuronal disorders. The review thus presents the scenario of neutrophil nNOS from the genetics to the functional level, including protein-protein interactions governing its intracellular sequestration in diverse cell types, besides speculating possible regulation in neutrophils and also addressing their clinical implications.


Asunto(s)
Neutrófilos , Óxido Nítrico Sintasa de Tipo I/metabolismo , Humanos , Neuronas , Óxido Nítrico
13.
J Leukoc Biol ; 105(1): 49-61, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30285282

RESUMEN

Neutrophils play a key role in innate immune responses against foreign intrusion and influence the subsequent instigation of adaptive immune response. Nitric oxide (NO) synthesized by neutrophil nitric oxide synthase (NOS) profoundly modulates their diverse physiological responsibilities furthermore encompassing pathological implications. Neutrophils are the active participants in diverse inflammatory and cardiovascular disorders but neutrophil nitric oxide synthase (NOS) remains enigmatic on various aspects. This review focuses on inducible NOS (iNOS) and makes an attempt to address its potential impact in neutrophil pathophysiology, their differentiation, functionality, and survival. We described the scenario from its expressional modulation, by pro- and anti-inflammatory cytokines governing the extent and duration of neutrophil immune response, to iNOS catalysis, the intracellular compartmentalization, and protein-protein interactions determining its microenvironment, activity and its contribution as a potential signaling protein apart from its role as signal transducer. Further, the relevance of investigating the unexplored facets of iNOS biology in neutrophils and possible prototypes of iNOS regulation is also exemplified in related cellular systems.


Asunto(s)
Neutrófilos/enzimología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Animales , Biocatálisis , Supervivencia Celular , Enfermedad , Humanos , Mitocondrias/metabolismo , Neutrófilos/citología
14.
Biotechnol Adv ; 29(6): 949-60, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21856405

RESUMEN

CO2 fixing microbes are the species primarily engaged in complexing the inorganic carbon dioxide to organic carbon compounds. There are many microorganisms from archaeal and bacterial domain that can fix carbon dioxide through six known CO2 fixing pathways. These organisms are ubiquitous and can survive in wide range of aerobic and anaerobic habitats. This review focuses on the prior research, that has been conducted in this field and presents a summarized overview of all the mechanisms (along with their genes and enzymes) used by these microbes for CO2 incorporation. In addition, this review provides a better understanding of diversity and taxonomy of CO2 fixing microorganisms. The information presented here will motivate researchers to further explore the diversity of CO2 fixing microorganisms as well as to decipher the underlying mechanisms of CO2 utilization.


Asunto(s)
Archaea/metabolismo , Bacterias/metabolismo , Dióxido de Carbono/metabolismo , Calentamiento Global , Redes y Vías Metabólicas
15.
Cell Tissue Res ; 340(2): 381-8, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20232214

RESUMEN

The involvement of nitric oxide (NO) as both pro and anti-inflammatory agent in allergic, airway inflammatory, and asthmatic diseases and the active participation of eosinophils in such ailments have been previously suggested. NO modulates eosinophil number, migration and their survival. The microenvironment of NO synthase (NOS) in subcellular organelles determines its rate and efficiency of catalysis, which in turn influences NO generation at distinct intracellular locales. The present study was undertaken to assess the intracellular distribution of NOS isoforms by transmission electron microscopy followed by morphometric analysis in human and rat eosinophils. Rat eosinophils were explored in parallel, and since they are widely used as model systems to mimic human diseases, a comparative study on NOS localization patterns might provide useful information in deciphering NO role in diverse aspects of eosinophil-related inflammatory ailments. The results demonstrated predominance of neuronal NOS (nNOS) in the eosinophilic granules and even distribution of inducible NOS (iNOS) and nNOS in the cytoplasm and nucleus of human eosinophils. In rat eosinophils, however, iNOS was mainly localized in the eosinophilic granules and nucleus, while nNOS was distributed evenly in cytoplasm and nucleus. Distribution of endothelial NOS (eNOS) in eosinophils was scanty. Differences in NOS isoforms and their localization in human and rat cells might have implications in differential mode of catalysis and functional contribution to eosinophil physiology and pathology, warranting detailed investigations. The present study highlights species-specific differences in the relative abundance and distribution pattern of NOS isoforms in rat and human eosinophils, which should be considered cautiously in interpreting the rat data to humans.


Asunto(s)
Eosinófilos/enzimología , Eosinófilos/ultraestructura , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa/ultraestructura , Animales , Humanos , Inmunohistoquímica , Isoenzimas/metabolismo , Isoenzimas/ultraestructura , Masculino , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo I/ultraestructura , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/ultraestructura , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico Sintasa de Tipo III/ultraestructura , Transporte de Proteínas , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie
16.
J Neuroinflammation ; 1(1): 3, 2004 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-15285799

RESUMEN

BACKGROUND: Ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARgamma agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS. CASE PRESENTATION: The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32%) and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events. CONCLUSIONS: In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events. Pioglitazone should therefore be considered for further testing of therapeutic potential in MS patients.

17.
J Leukoc Biol ; 75(6): 1070-8, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15039465

RESUMEN

Recent studies from our laboratory have demonstrated that ascorbate potentiated enzymatic synthesis of nitric oxide (NO) from polymorphonuclear leukocytes (PMNs). NO is known to modulate various function of PMNs such as chemotaxis, adherence, aggregation, and generation of reactive oxygen species (ROS). The role of ascorbate in the PMN phagocytosis, ROS generation, and apoptosis was thus evaluated in the present study. Ascorbate and its oxidized and cell-permeable analog, dehydroascorbate (DHA), did not affect the phagocytosis but enhanced ROS generation and apoptosis following treatment with Escherichia coli or arachidonic acid. A detailed investigation on the DHA-mediated response indicated that inhibitors of DHA uptake, reduced nicotinamide adenine dinucleotide phosphate oxidase, NO synthase, or ROS scavengers attenuated ROS generation. In DHA-treated cells, enhanced generation of peroxynitrite was also observed; thus, ascorbate-mediated ROS and reactive nitrogen species generation might mediate cytotoxicity toward the ingested microbes and subsequently, augmented PMN apoptosis. Results of the present study have helped in delineating the role of ascorbate in the modulation of NO-mediated ROS generation from PMNs.


Asunto(s)
Ácido Ascórbico/farmacología , Neutrófilos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Ácido Araquidónico/farmacología , Células Cultivadas/citología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/microbiología , Ácido Deshidroascórbico/farmacología , Escherichia coli/metabolismo , Depuradores de Radicales Libres/farmacología , Humanos , Macaca mulatta , Masculino , NADPH Oxidasas/antagonistas & inhibidores , Neutrófilos/metabolismo , Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Oxidación-Reducción , Oxígeno/metabolismo , Ácido Peroxinitroso/metabolismo , Fagocitosis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/antagonistas & inhibidores
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