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Drought stress (DS) is a significant abiotic stress that limits agricultural productivity worldwide. In semi-arid climates, one potential solution to alleviate the deleterious effects of drought is the use of soil amendments such as nanoparticles. The current research was conducted out to probe the sway of drought at critical growth stages (CGS) of wheat crop (D0: Control, D1: Drought at tillering stage, and D2: Drought at anthesis stage) and the application of Cu-nanoparticles (T0: 0 mg L-1, T1: 300 mg L-1, T2: 700 mg L-1, and T3: 950 mg L-1) in order to improve drought resilience. Results of the study revealed that DS considerably decreased the wheat growth and yield during CGS. However, Cu-nanoparticles application alleviated the detrimental backlash of DS and led to improvements in various aspects of wheat growth and yield, including plant height, spike length, 1000 grain weight, stomatal conductance, leaf chlorophyll content, water use efficiency, leaf turgor potential, relative water content, and ultimately the grain yield. The use of principal component analysis allowed us to integrate and interpret the diverse findings of our study, elucidating the impact of Cu-nanoparticle treatment on wheat growth and yield under drought. Overall, the study concluded that DS during the anthesis stage had the most significant negative impact on crop yield. However, applying Cu-nanoparticles at the rate of 300 mg L-1 proved to be an effective strategy for improving crop productivity by reducing the harmful effects of drought.
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Cobre , Secas , Triticum , Triticum/crescimento & desenvolvimento , Triticum/efeitos dos fármacos , Nanopartículas Metálicas/química , Estresse Fisiológico , Água/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/efeitos dos fármacos , Clorofila/metabolismo , Solo/químicaRESUMO
New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis.
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Leishmaniose Visceral , Leishmaniose , Ratos , Animais , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Modelos Animais de DoençasRESUMO
Giardia duodenalis is the causative agent of the neglected diarrhoeal disease giardiasis. While often self-limiting, giardiasis is ubiquitous and impacts hundreds of millions of people annually. It is also a common gastro-intestinal disease of domestic pets, wildlife, and livestock animals. However, despite this impact, there is no vaccine for Giardia currently available. In addition, treatment relies on chemotherapies that are associated with increasing failure rates. To identify new treatment options for giardiasis we recently screened the Compounds Australia Scaffold Library for new chemotypes with selective anti-Giardia activity, identifying three compounds with sub-µM activity and promising selectivity. Here we extended these studies by examining the anti-Giardia activity of series CL9569 compounds. This compound series was of interest given the promising activity (IC50 1.2 µM) and selectivity demonstrated by representative compound, SN00798525 (1). Data from this work has identified an additional three thieno [3,2-b]pyrrole 5-carboxamides with anti-Giardia activity, including 2 which displayed potent cytocidal (IC50 ≤ 10 nM) and selective activity against multiple Giardia strains, including representatives from both human-infecting assemblages and metronidazole resistant parasites. Preclinical studies in mice also demonstrated that 2 is well-tolerated, does not impact the normal gut microbiota and can reduce Giardia parasite burden in these animals.
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Giardia lamblia , Giardíase , Parasitos , Humanos , Animais , Camundongos , Giardíase/tratamento farmacológico , Giardíase/veterinária , Giardíase/parasitologia , Giardia , Metronidazol/uso terapêutico , Fezes/parasitologiaRESUMO
Introduction: Tumour-emitted molecules induce immunosuppression in the tumour microenvironment. An immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO/IDO1), facilitates immune escape in several malignant tumours, including osteosarcoma. Upregulation of IDO establishes a tolerogenic environment in the tumour and the tumour-draining lymph nodes. IDO-induced downregulation of effector T-cells and upregulation of local regulatory T-cells creates immunosuppression and promotes metastasis. Observations: Osteosarcoma is the most common bone tumour characterised by immature bone formation by the tumour cells. Almost 20% of osteosarcoma patients present with pulmonary metastasis at the time of diagnosis. The improvement in therapeutic modalities for osteosarcoma has been in a stagnant phase for two decades. Therefore, the development of novel immunotherapeutic targets for osteosarcoma is emergent. High IDO expression is associated with metastasis and poor prognosis in osteosarcoma patients. Conclusion and Relevance: At present, only a few studies are available describing IDO's role in osteosarcoma. This review describes the prospects of IDO not only as a prognostic marker but also as an immunotherapeutic target for osteosarcoma.
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Silicon nanoparticles (Si-NPs) have shown their potential for use in farming under water-deficient conditions. Thus, the experiment was accomplished to explore the impacts of seed priming of Si-NPs on wheat (Triticum aestivum L.) growth and yield under different drought levels. The plants were grown in pots under natural ecological environmental conditions and were harvested on 25th of April, 2020. The results revealed that seed priming of Si-NPs (0, 300, 600, and 900 mg/L) suggestively improved, the spike length, grains per spike, 1000 grains weight, plant height, grain yield, and biological yield by 12-42%, 14-54%, 5-49%, 5-41%, 17-62%, and 21-64%, respectively, relative to the control. The Si-NPs improved the leaf gas trade ascribes and chlorophyll a and b concentrations, though decreased the oxidative pressure in leaves which was demonstrated by the diminished electrolyte leakage and upgrade in superoxide dismutase and peroxidase activities in leaf under Si-NPs remedies over the control. The outcomes proposed that Si-NPs could improve the yield of wheat under a dry spell. In this manner, the utilization of Si-NPs by seed priming technique is a practical methodology for controlling the drought stress in wheat. These findings will provide the basis for future research and helpful to improve the food security under drought and heat related challenges.
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Silício , Triticum , Silício/farmacologia , Secas , Clorofila A , AntioxidantesRESUMO
Lung cancer has the highest incidence of morbidity and mortality throughout the globe. A large number of patients are diagnosed with lung cancer at the later stages of the disease. This eliminates surgery as an option and places complete dependence on radiotherapy or chemotherapy, and/or a combination of both, to halt disease progression by targeting the tumor cells. Unfortunately, these therapies have rarely proved to be effective, and this necessitates the search for alternative preventive approaches to reduce the mortality rate of lung cancer. One of the effective therapies against lung cancer comprises targeting the tumor microenvironment. Like any other cancer cells, lung cancer cells tend to use multiple pathways to maintain their survival and suppress different immune responses from the host's body. This review comprehensively covers the role and the mechanisms that involve the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lung adenocarcinoma and methods of treating it by altering the tumor microenvironment. It focuses on the insight and understanding of the lung cancer tumor microenvironment and chemokines, cytokines, and activating molecules that take part in angiogenesis and metastasis. The review paper accounts for the novel and current immunotherapy and targeted therapy available for lung cancer in clinical trials and in the research phases in depth. Special attention is being paid to mark out single or multiple genes that are required for malignancy and survival while developing targeted therapies for lung cancer treatment.
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Drought is a major abiotic factor and affects cereal-based staple food production and reliability in developing countries such as Pakistan. To ensure a sustainable and consistent food supply, holistic production plans involving the integration of several drought mitigation approaches are required. Using a randomized complete block design strategy, we examined the drought-ameliorating characteristics of plant growth-promoting rhizobacteria (PGPR) and nanoparticles (NPs) exclusively or as a combined application (T4) through three stages (D1, D2, and D3) of wheat growth (T1, control). Our field research revealed that Azospirillum brasilense alone (T2) and zinc oxide NPs (T3) improved wheat plant water relations, chlorophyll, proline, phenolics and grain quality, yield, and their allied traits over the stressed treatments. Specifically, the best outcome was observed in the combined treatment of PGPR and ZnO NPs (T4). Interestingly, the combined treatment delivered effective drought mitigation through enhanced levels of antioxidants (15% APX, 27% POD, 35% CAT, 38% PPO and 44% SOD) over controls at the grain-filling stage (GFS, D3 × T1). The 40% improvements were recorded under the combined treatment at GFS over their respective controls. Their combined usage (PGPR and ZnO NPs) was concluded as an effective strategy for building wheat resilience under drought, especially in arid and semi-arid localities.
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Drought stress is a major limitation in wheat production around the globe. Organic amendments could be the possible option in semi-arid climatic conditions to mitigate the adverse effects of drought at critical growth stages. Wheat straw biochar (BC0 = Control, BC1 = 3% biochar and BC2 = 5% biochar) was used to alleviate the drought stress at tillering (DTS), flowering (DFS), and grain filling (DGFS) stages. Drought stress significantly reduced the growth and yield of wheat at critical growth stages, with DGFS being the most susceptible stage, resulting in significant yield loss. Biochar application substantially reduced the detrimental effects of drought by improving plant height (15.74%), fertile tiller count (17.14%), spike length (16.61%), grains per spike (13.89%), thousand grain weight (10.4%), and biological yield (13.1%) when compared with the control treatment. Furthermore, physiological parameters such as water use efficiency (38.41%), stomatal conductance (42.76%), chlorophyll a (19.3%), chlorophyll b (22.24%), transpiration rate (39.17%), photosynthetic rate (24.86%), electrolyte leakage (-42.5%) hydrogen peroxide (-18.03%) superoxide dismutase (24.66%), catalase (24.11%) and peroxidase (-13.14%) were also improved by biochar application. The use of principal component analysis linked disparate scales of our findings to explain the changes occurred in wheat growth and yield in response to biochar application under drought circumstances. In essence, using biochar at 5% rate could be a successful strategy to promote wheat grain production by reducing the hazardous impacts of drought stress.
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Secas , Triticum , Antioxidantes , Carvão Vegetal , Clorofila A , Mecanismos de Defesa , Grão ComestívelRESUMO
INTRODUCTION: Cutaneous, muco-cutaneous and visceral leishmaniasis occur due to an infection with the protozoan parasite Leishmania. The current therapeutic options are limited mainly due to extensive toxicity, emerging resistance and variation in efficacy based on species and strain of the Leishmania parasite. There exists a high unmet medical need to identify new chemical starting points for drug discovery to tackle the disease. AREAS COVERED: The authors have highlighted the recent progress, limitations and successes achieved in assay development for leishmaniasis drug discovery. EXPERT OPINION: It is true that sophisticated and robust phenotypic in vitro assays have been developed during the last decade, however limitations and challenges remain with respect to variation in activity reported between different research groups and success in translating in vitro outcomes in vivo. The variability is not only due to strain and species differences but also a lack of well-defined criteria and assay conditions, e.g. culture media, host cell type, assay formats, parasite form used, multiplicity of infection and incubation periods. Thus, there is an urgent need for more physiologically relevant assays that encompass multi-species phenotypic approaches to identify new chemical starting points for leishmaniasis drug discovery.
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Antiprotozoários , Leishmania , Leishmaniose Visceral , Leishmaniose , Antiprotozoários/farmacologia , Descoberta de Drogas/métodos , Humanos , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Leishmaniose Visceral/tratamento farmacológicoRESUMO
Therapeutic manipulation of the immune system in cancer has been an extensive area of research in the field of oncoimmunology. Immunosuppression regulates antitumour immune responses. An immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO) mediates tumour immune escape in various malignancies including breast cancer. IDO upregulation in breast cancer cells may lead to the recruitment of regulatory T (T-regs) cells into the tumour microenvironment, thus inhibiting local immune responses and promoting metastasis. Immunosuppression induced by myeloid derived suppressor cells activated in an IDO-dependent manner may enhance the possibility of immune evasion in breast cancer. IDO overexpression has independent prognostic significance in a subtype of breast cancer of emerging interest, basal-like breast carcinoma. IDO inhibitors as adjuvant therapeutic agents may have clinical implications in breast cancer. This review proposes future prospects of IDO not only as a therapeutic target but also as a valuable prognostic marker for breast cancer.
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Phenotypic screening of a 900 compound library of antitubercular nitroimidazole derivatives related to pretomanid against the protozoan parasite Trypanosoma cruzi (the causative agent for Chagas disease) identified several structurally diverse hits with an unknown mode of action. Following initial profiling, a first proof-of-concept in vivo study was undertaken, in which once daily oral dosing of a 7-substituted 2-nitroimidazooxazine analogue suppressed blood parasitemia to low or undetectable levels, although sterile cure was not achieved. Limited hit expansion studies alongside counter-screening of new compounds targeted at visceral leishmaniasis laid the foundation for a more in-depth assessment of the best leads, focusing on both drug-like attributes (solubility, metabolic stability and safety) and maximal killing of the parasite in a shorter timeframe. Comparative appraisal of one preferred lead (58) in a chronic infection mouse model, monitored by highly sensitive bioluminescence imaging, provided the first definitive evidence of (partial) curative efficacy with this promising nitroimidazooxazine class.
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Doença de Chagas/tratamento farmacológico , Nitroimidazóis/química , Nitroimidazóis/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos , Camundongos , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/fisiologiaRESUMO
The first approaches to the 10'-anthronyl-2-anthraquinone skeleton have been devised, allowing two syntheses of the marine natural product albopunctatone. Both routes involve regioselective addition of a nucleophilic masked anthraquinone to a protected chrysazin derivative; the best affords albopunctatone in five steps and 35% overall yield. Albopunctatone exhibits potent inhibitory activity against Plasmodium falciparum and negligible toxicity to a range of other microbial pathogens and mammalian cells.
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Antraquinonas/química , Antraquinonas/síntese química , Antimaláricos/química , Antimaláricos/síntese química , Urocordados/química , Animais , Antraquinonas/farmacologia , Antimaláricos/farmacologia , Linhagem Celular , Técnicas de Química Sintética , Humanos , Modelos Moleculares , Conformação Molecular , Plasmodium falciparum/efeitos dos fármacosRESUMO
Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world's lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC50 values of the natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC50 values of ≤ 10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC50 values < 5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified.
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Antiprotozoários/farmacologia , Produtos Biológicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Kinetoplastida/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas , Animais , Produtos Biológicos/química , Linhagem Celular , Descoberta de Drogas , Humanos , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Parasitária , Trypanosoma brucei gambiense/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Tripanossomíase Africana/tratamento farmacológicoRESUMO
Leishmaniasis, caused by the trypanosomatid protozoan Leishmania, is endemic in 98 countries worldwide, with morbidity and mortality increasing daily. Despite available drugs, leishmaniasis faces the challenge of emerging resistance and toxicity concerns for current drug regimes. Identification of anti-leishmanial compounds representing new chemistry and novel mechanisms of action is essential to populate the drug discovery pipeline. The in vitro assays currently available have shown poor translational outcomes, with high compound attrition rates. It is therefore imperative that more physiologically relevant assays are developed to identify anti-leishmanial compounds. This review provides an overview of the disease, current treatment options and compares the various technologies and assay formats currently available for leishmanial drug discovery.
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Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Leishmaniose/tratamento farmacológico , Animais , Descoberta de Drogas/métodos , Humanos , Leishmania/efeitos dos fármacosRESUMO
Brassinosteroids (BRs) are steroidal plant hormones involved in regulation of physiological and molecular processes to ameliorate various biotic and abiotic stresses. Exogenous application of BRs to improve stress tolerance in plants has recently become a high research priority. Several studies have revealed the involvement of these steroidal hormones in upregulation of stress-related defense genes and their cross talk with other metabolic pathways. This is likely to stimulate research on many unanswered questions regarding their role in enhancing the ability of plants to tolerate adverse environmental conditions. Thus, this review appraises new insights on mechanisms mediating BR-regulated changes in plants, focused mainly on their involvement in regulation of physiological and molecular mechanisms under stress conditions. Herein, examples of BR-stimulated modulation of antioxidant defense system and upregulation of transcription factors in plants exposed to various biotic (bacterial, viral, and fungal attack) and abiotic stresses (drought, salinity, heat, low temperature, and heavy metal stress) are discussed. Based on these insights, future research in the current direction can be helpful to increase our understanding of BR-mediated complex and interrelated processes under stress conditions.
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Brassinosteroides , Plantas , Estresse Fisiológico , Secas , Regulação da Expressão Gênica de Plantas , Transdução de SinaisRESUMO
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis. HCC associated fibroblasts stimulate natural killer cells dysfunction through prostaglandin E2 and subsequently IDO promotes favorable condition for tumor metastasis. IDO up-regulation induces immunosuppression and may enhance the risk of hepatitis C virus and hepatitis B virus induced HCC. Therefore, IDO inhibitors as adjuvant therapeutic agents may have clinical implications in HCC. This review proposes future prospects of IDO not only as a therapeutic target but also as a prognostic marker for HCC.
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Carcinoma Hepatocelular/enzimologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Neoplasias Hepáticas/enzimologia , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Hepatite B/complicações , Hepatite C/complicações , Humanos , Imunoterapia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Terapia de Alvo MolecularRESUMO
BACKGROUND: Accumulation of lead (Pb) in agricultural soils has become a major factor for reduced crop yields and poses serious threats to humans consuming agricultural products. The present study investigated the effects of KNO3 seed priming (0 and 0.5% KNO3 ) on growth of maize (Zea mays L.) seedlings exposed to Pb toxicity (0, 1300 and 2550 mg kg-1 Pb). RESULTS: Pb exposure markedly reduced the growth of maize seedlings and resulted in higher Pb accumulation in roots than shoots. Pretreatment of seeds with KNO3 significantly improved the germination percentage and increased physiological indices. A stimulating effect of KNO3 seed priming was also observed on pigments (chlorophyll a, b, total chlorophyll and carotenoid contents) of Pb-stressed plants. Low translocation of Pb from roots to shoots caused an increased accumulation of total free amino acids and higher activities of catalase, peroxidase, superoxide dismutase and ascorbate peroxidase in roots as compared to shoot, which were further enhanced by exogenous KNO3 supply to prevent Pb toxicity. CONCLUSION: Maize accumulates more Pb in roots than shoot at early growth stages. Priming of seeds with KNO3 prevents Pb toxicity, which may be exploited to improve seedling establishment in crop species grown under Pb contaminated soils. © 2017 Society of Chemical Industry.
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Chumbo/toxicidade , Nitratos/farmacologia , Compostos de Potássio/farmacologia , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Zea mays/efeitos dos fármacos , Antioxidantes/análise , Antioxidantes/metabolismo , Carotenoides/análise , Clorofila/análise , Contaminação de Alimentos/prevenção & controle , Germinação/efeitos dos fármacos , Chumbo/análise , Raízes de Plantas/química , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Poluentes do Solo/análise , Zea mays/crescimento & desenvolvimentoRESUMO
Nanomedicine application in cancer immunotherapy is currently one of the most challenging areas in cancer therapeutic intervention. Innovative solutions have been provided by nanotechnology to deliver cytotoxic agents to the cancer cells partially affecting the healthy cells of the body during the process. Nanoparticle-based drug delivery is an emerging approach to stimulate the immune responses against cancer. The inhibition of indoleamine 2,3-dioxygenase (IDO) is a pivotal area of research in cancer immunotherapy. IDO is a heme-containing immunosuppressive enzyme, which is responsible for the degradation of tryptophan while increasing the concentration of kynurenine metabolites. Various preclinical studies showed that IDO inhibition in certain diseases may result in significant therapeutic effects. Here, we provide a review of the natural and synthetic inhibitors of IDO. These inhibitors are classified according to their source, inhibitory concentrations, the chemical structure, and the mechanism of action. Tumor-targeted chemotherapy is an advanced technique and has more advantages as compared to the conventional chemotherapy. Search for more efficient and less toxic nanoparticles in conjunction with compounds to inhibit IDO is still an area of interest for several research groups worldwide, especially revealing to be an extensive and a promising area in cancer therapeutic innovations.
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Climate change is one of the most complex challenges that pose serious threats to livelihoods of poor people who rely heavily on agriculture and livestock particularly in climate-sensitive developing countries of the world. The negative effects of water scarcity, due to climate change, are not limited to productivity food crops but have far-reaching consequences on livestock feed production systems. Selenium (Se) is considered essential for animal health and has also been reported to counteract various abiotic stresses in plants, however, understanding of Se regulated mechanisms for improving nutritional status of fodder crops remains elusive. We report the effects of exogenous selenium supply on physiological and biochemical processes that may influence green fodder yield and quality of maize (Zea mays L.) under drought stress conditions. The plants were grown in lysimeter tanks under natural conditions and were subjected to normal (100% field capacity) and water stress (60% field capacity) conditions. Foliar spray of Se was carried out before the start of tasseling stage (65 days after sowing) and was repeated after 1 week, whereas, water spray was used as a control. Drought stress markedly reduced the water status, pigments and green fodder yield and resulted in low forage quality in water stressed maize plants. Nevertheless, exogenous Se application at 40 mg L-1 resulted in less negative leaf water potential (41%) and enhanced relative water contents (30%), total chlorophyll (53%), carotenoid contents (60%), accumulation of total free amino acids (40%) and activities of superoxide dismutase (53%), catalase (30%), peroxidase (27%), and ascorbate peroxidase (27%) with respect to control under water deficit conditions. Consequently, Se regulated processes improved fodder yield (15%) and increased crude protein (47%), fiber (10%), nitrogen free extract (10%) and Se content (36%) but did not affect crude ash content in water stressed maize plants. We propose that Se foliar spray (40 mg L-1) is a handy, feasible and cost-effective approach to improve maize fodder yield and quality in arid and semi-arid regions of the world facing acute shortage of water.
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Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C virus (HCV) has infected more than 12 million individuals in Pakistan. The aim of the present study was to assess the expression and activity of IDO in HCV-infected patients. The functional enzymatic activity of IDO was measured by colorimetric assay. Serum samples from 100 HCV-infected patients were taken to examine IDO activity and samples from 100 healthy volunteers were used as controls. Liver sections from patients with HCV (n=35) and healthy controls (n=5) were used for immunohistochemical studies. Immunohistochemical analysis revealed that IDO was overexpressed in 28 of 35 (80%) cirrhotic liver samples, whereas 5 of 35 (14.2%) cases presented moderate and 2 of 35 (5.7%) cases presented mild expression of IDO. The enzymatic activity of IDO was significantly higher in the serum samples of HCV-infected patients as compared with those in the control. These data indicate that the expression of IDO correlated with the pathogenesis of disease. In summary, it is suggested that the high expression of IDO in the progressively cirrhotic livers of HCV-infected patients might contribute to the development of hepatocellular carcinoma. IDO may characterize a novel therapeutic target against HCV.