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1.
J Mol Neurosci ; 72(3): 653-676, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34697770

RESUMO

Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington disease, amyotrophic lateral sclerosis, and prion disease affect any part of the brain. The complete mechanism of ND is unknown, but there are some molecular mechanism and chemical process. Natural compounds have better compatibility with the human body along with lesser side effects. Moreover, several studies showed that various natural compounds have significant neuroprotective, potent antioxidant, and anti-inflammatory properties, which are effective for treating the different type of ND. In ND, natural compounds act by various mechanisms such as preventing the generation of reactive oxygen species (ROS), eliminating destructed biomolecules before their accumulation affects cell metabolism, and improving the disease conditions. But due to the presence of the blood-brain barrier (BBB) layer and unfavorable pharmacokinetic properties of natural compounds, their delivery into the brain is limited. To minimize this problem and enhance drug delivery into the brain with an effective therapeutic dose, there is a need to develop a practical novel approach. The various studies showed that nanoformulations and microneedles (MN) containing natural compounds such as quercetin, curcumin, resveratrol, chrysin, piperine, ferulic acid, huperzine A, berberine, baicalein, hesperetin, and retinoic acid effectively improved many ND. In this review, the effect of such natural drug-loaded nanoformulation and MN patches on ND management is discussed, along with their merits and demerits. This review aims to introduce different novel approaches for enhancing natural drug delivery into the brain to manage various neurodegenerative diseases.


Assuntos
Produtos Biológicos , Curcumina , Doenças Neurodegenerativas , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo
2.
Artif Organs ; 46(4): 715-719, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35211997

RESUMO

Our small R&D company created a novel extracorporeal system for the treatment of hepatic coma and drug overdose, in which membrane motion in a screen-plate dialyzer served as a blood pump and also mixed dialysate containing powdered carbon. Early clinical trials of the Biologic-DT™ were successful in the treatment of patients with hepatic coma (especially from A-on-C liver failure) and FDA gave marketing approval. The BioLogic-DT™ was licensed to a venture capital-backed startup. It was marketed too widely and used in some patients without a chance for recovery or transplant. The licensing company failed, and the BioLogic-DT was not remarketed. The MARS™ device included albumin as a sorbent in dialysate, and clinical trials of this device also showed a benefit in the treatment of hepatic coma.


Assuntos
Produtos Biológicos , Encefalopatia Hepática , Falência Hepática , Encefalopatia Hepática/terapia , Humanos , Falência Hepática/terapia , Diálise Renal
3.
Yakugaku Zasshi ; 142(5): 439-446, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35491146

RESUMO

Discovery of natural products that possess novel chemical structures and pharmaceutical activities increases opportunities of drug development. Filamentous fungi have been recognized as an attractive source for pharmaceutically beneficial natural products. Genome sequencing innovation represented by Next-generation sequencer opened fungal genomes one after another, suggesting that one fungal strain has far more biosynthetic gene clusters than that are estimated from the number of previously isolated natural products. In addition, bioinformatics analyses have indicated that most biosynthetic gene clusters are silent under laboratory culture conditions and there are a huge number of natural products hidden in the fungal genome. Therefore, we focused on those silent biosynthetic gene clusters as a potential source for novel natural products and developed methods to activate silent biosynthetic gene clusters by using low molecular weight molecules. In this review, we describe on discovery of novel natural products through activating fungal silent biosynthesis by addition of epigenetic modifiers and plant hormones.


Assuntos
Produtos Biológicos , Produtos Biológicos/química , Epigênese Genética , Fungos/química , Fungos/genética , Genes Fúngicos , Família Multigênica
4.
Dermatol Online J ; 28(1)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35499413

RESUMO

Merkel cell carcinoma (MCC) is a rare neuroendocrine neoplasm, warranting surgical excision with sentinel lymph node biopsy. In later stages, adjuvant chemotherapy and radiation are required owing to its aggressive malignant behavior. We describe a 62-year-old woman who presented with multifocal recurrence of MCC and was not a candidate for immunotherapy or surgery. The patient underwent four treatments of intratumoral talimogene laherparepvec (TVEC) and demonstrated a complete response with no histologic evidence of remaining MCC on four scouting biopsies. Although TVEC therapy is currently approved for the treatment of advanced stage melanoma, it is still being investigated in MCC. This case supports the use of TVEC as monotherapy in select patients with locally advanced MCC who are not candidates for surgery or systemic immunotherapy.


Assuntos
Carcinoma de Célula de Merkel , Melanoma , Terapia Viral Oncolítica , Neoplasias Cutâneas , Produtos Biológicos , Carcinoma de Célula de Merkel/tratamento farmacológico , Feminino , Herpesvirus Humano 1 , Humanos , Pessoa de Meia-Idade , Neoplasias Cutâneas/tratamento farmacológico
5.
ScientificWorldJournal ; 2022: 6573754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35514610

RESUMO

Allium species including garlic and leek exhibits a broad range of medicinal and nutritional properties. Therefore, this study investigates the physicochemical and biological activities of garlic (Allium sativum L.) and leek (A. ampeloprasum L. var. Porrum) oil extracts. The result indicated that physicochemical properties indicated that significantly higher oil yield (21.25%), ACV (2.66 mg/g), FFA (1.34%), and PV (4.10 meq/kg) and also antioxidant activities with respect to 2, 2-diphenyl-1-picrylhydrazyl, DPPH (27.60 ± 1.55%), hydrogen peroxide (12.35 ± 0.92%) free radical scavenging activities, and ascorbic acid content (25.30 ± 3.25%) were obtained for leek leaf oil extract. Stronger antibacterial activity with a maximum zone of inhibition (16.00 mm), minimum inhibitory concentration (MIC) (0.20 µg/ml), and minimum bactericidal concentration (MBC) (0.40 µg/ml) was recorded for leek oil extract against S. pyogenes. However, garlic oil has presented stronger antifungal activity with a maximum zone of inhibition (13.50 mm), MIC (0.40 µg/ml), and minimum fungicidal concentration (MFC) (0.75 µg/ml) against Candida albicans. It is concluded from the results of this investigation that oils extracts of garlic bulb and leek leaves demonstrated significant biological activities that can be used as sources for pharmaceutical and nutraceutical ingredients.


Assuntos
Allium , Produtos Biológicos , Alho , Allium/química , Antioxidantes/análise , Antioxidantes/farmacologia , Alho/química , Óleos/análise , Cebolas/química , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Folhas de Planta/química
6.
Pan Afr Med J ; 41: 135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35519160

RESUMO

In this study, we aimed to evaluate the clinicobiological findings and the biotherapy treatment response of Moroccan patients with juvenile idiopathic arthritis (JIA), and compare our results with those of populations of the same or different ethnicity. This retrospective cross-sectional study included patients aged 1-14 years, diagnosed between 2003 and 2018 with JIA according to the International League of Associations for Rheumatology (ILAR) 2004 revised criteria, who received biologics and who followed up during the year 2018 in the day hospital of our single-center tertiary pediatric rheumatology unit. Among 59 patients, 53% had systemic JIA, 29% seronegative polyarticular JIA, 8% arthritis-related enthesitis, 5% seropositive polyarticular JIA, 3% oligoarthritis and 2% psoriatic arthritis. Tocilizumab was the most prescribed biologic (34 patients), followed by Etanercept (25 patients), Adalimumab (6 patients), Anakinra (3 patients) and biosimilar Infliximab (3 patients). Eleven patients switched biologics. Erythrocyte sedimentation rate, number of active joints and the Juvenile Arthritis Disease Activity Score 27 (JADAS 27) decreased significantly at month three for 56 patients. These results were maintained at the last visit for 31 patients, while there was a slight worsening in 15 of them and no assessment in 13 patients due to lack of data. At the end of the evaluation, 39% of the patients were exclusively on biotherapy, while 61% were still on other disease-modifying antirheumatic drugs (DMARDs). Twenty-eight patients developed lymphopenia, 4 patients had elevated transaminases, 4 patients developed moderate infection, and 2 patients developed macrophage activation syndrome. To the best of our knowledge, this is the first Moroccan study on biotherapy in JIA. Our study population was characterized by a male predominance, a high frequency of the systemic form and a low percentage of positive antinuclear antibodies. We have shown that in the era of biologics, only 67.4% patients are nearly disease-free at the end of the study with a real risk of side effects. Although effective, biotherapy must be closely monitored because of potentially severe side effects, especially with Tocilizumab use.


Assuntos
Antirreumáticos , Artrite Juvenil , Produtos Biológicos , Antirreumáticos/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Terapia Biológica , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
7.
Sci Rep ; 12(1): 7222, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508597

RESUMO

Co-culture is an efficient strategy for natural product discovery. We have used mycolic acid-containing bacteria (MACB) Tsukamurella pumonis TP-B0596 to induce secondary metabolism by actinomycetes and have found several natural products. We also observed that MACB attached to the mycelium of Streptomyces lividans forming coaggregates during combined-culture. This stimulated interest in the interactions among actinomycetes and MACB, and we found that soil isolated cultures contained a mixture of actinomycetes and MACB. Our previously observed interactions were the result of selective screening and combination of bacteria in the lab, which warranted investigation of the existence of these interactions in the natural soil environment. Therefore, in this paper, we report the interaction between a co-isolated natural pair of actinomycetes and MACB in terms of morphology and metabolic changes. A natural pair of actinomycetes and MACB co-aggregated in liquid culture and showed metabolic changes. Interestingly, co-aggregated actinomycetes and MACB were re-isolated from soil with no obvious morphological colony differences from the colony of a single strain. The results demonstrate that there is a stochastic chance of picking colonies containing co-aggregated actinomycetes and MACB, which suggests that the pair can exist in co-aggregate form in the soil environment and interact with each other.


Assuntos
Actinobacteria , Produtos Biológicos , Actinobacteria/metabolismo , Actinomyces/metabolismo , Bactérias/metabolismo , Produtos Biológicos/metabolismo , Ácidos Micólicos/metabolismo , Solo
8.
Ugeskr Laeger ; 184(13)2022 03 28.
Artigo em Dinamarquês | MEDLINE | ID: mdl-35499221

RESUMO

During the past 20 years of the biologic era, remission has become a realistic goal when treating children and adolescents with juvenile idiopathic arthritis (JIA). Studies describing long-term effects and safety are now available for several biologic agents, overall being well tolerated and with acceptable adverse events. No significant association between treatment with biologics and malignancy has been detected. This review finds that although biologics have been a success for most JIA patients, some fail to respond leaving the need for new treatment options and optimal switching between biologics most relevant.


Assuntos
Antirreumáticos , Artrite Juvenil , Produtos Biológicos , Adolescente , Antirreumáticos/efeitos adversos , Artrite Juvenil/induzido quimicamente , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Terapia Biológica , Criança , Humanos , Resultado do Tratamento
9.
J Biomed Sci ; 29(1): 29, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534851

RESUMO

BACKGROUND: Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC. METHODS: In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts. RESULTS: Myricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone. CONCLUSIONS: These results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias de Próstata Resistentes à Castração , Androgênios/farmacologia , Androgênios/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Flavonoides , Glicolatos , Glicóis/farmacologia , Glicóis/uso terapêutico , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/farmacologia , Masculino , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/uso terapêutico
10.
Methods Mol Biol ; 2489: 23-39, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524043

RESUMO

A suite of molecular techniques have been developed in recent decades, which allow gene clusters coding for the biosynthesis of fungal natural products to be investigated and characterized in great detail. Many of these involve the manipulation of the native producer, for example, to increase yields of natural products or investigate the biosynthetic pathway through gene disruptions. However, an alternative and powerful means of investigating biosynthetic pathways, which does not rely on a cooperative native host, is the refactoring and heterologous expression of pathways in a suitable host strain. This protocol aims to walk the reader through the various steps required for the heterologous expression of a fungal biosynthetic gene cluster, specifically using Aspergillus oryzae strain NSAR1 and the pTYGS series of expression vectors. Briefly, this process involves the design and construction of up to four multigene expression vectors using yeast recombination, PEG-mediation transformation of A. oryzae protoplasts, and chemical extraction of the resulting transformants to screen for the presence of metabolites.


Assuntos
Aspergillus oryzae , Produtos Biológicos , Aspergillus oryzae/genética , Aspergillus oryzae/metabolismo , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Expressão Gênica , Genes Fúngicos , Família Multigênica , Saccharomyces cerevisiae/genética
11.
Methods Mol Biol ; 2489: 41-52, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524044

RESUMO

Fungal natural products encompass an important source of pharmaceutically relevant molecules. Heterologous expression of biosynthetic pathways in chassis strains enables the discovery of new secondary metabolites and characterization of pathway enzymes. In our laboratory, biosynthetic genes in a clustered pathway have been refactored in engineered heterologous hosts such as Aspergillus nidulans. Here we describe the assembly of heterologous expression vectors, transformation into A. nidulans, and detection of new compounds in the transformant strains.


Assuntos
Aspergillus nidulans , Produtos Biológicos , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Expressão Gênica , Genes Fúngicos , Família Multigênica
12.
Methods Mol Biol ; 2489: 115-127, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524048

RESUMO

Fungal natural products have extensive biological activities, and thus have been largely commercialized in the pharmaceutical, agricultural, and food industries. Recently, heterologous expression has become an irreplaceable technique to functionalize fungal biosynthetic gene clusters and synthesize fungal natural products in various chassis organisms. This chapter describes the general method of using Pichia pastoris as a chassis host to investigate fungal biosynthetic pathways.


Assuntos
Produtos Biológicos , Saccharomycetales , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Proteínas Fúngicas/metabolismo , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes/metabolismo , Saccharomycetales/metabolismo
13.
Methods Mol Biol ; 2489: 129-155, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524049

RESUMO

Genome mining has become an invaluable tool in natural products research to quickly identify and characterize the biosynthetic pathways that assemble secondary or specialized metabolites. Recently, evolutionary principles have been incorporated into genome mining strategies in an effort to better assess and prioritize novelty and understand their chemical diversification for engineering purposes. Here, we provide an introduction to the principles underlying evolutionary genome mining, including bioinformatic strategies and natural product biosynthetic databases. We introduce workflows for traditional genome mining, focusing on the popular pipeline antiSMASH, and methods to predict enzyme substrate specificity from genomic information. We then provide an in-depth discussion of evolutionary genome mining workflows, including EvoMining, CORASON, ARTS, and others, as adopted by our group for the discovery and prioritization of natural products biosynthetic gene clusters and their products.


Assuntos
Produtos Biológicos , Produtos Biológicos/química , Vias Biossintéticas/genética , Genoma , Genoma Bacteriano , Genômica , Família Multigênica
14.
Methods Mol Biol ; 2489: 157-171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524050

RESUMO

Bacteria produce an impressive array of bioactive specialized metabolites, with Streptomyces (and the actinobacteria more generally) being unusually diverse and prolific producers. However, the biosynthetic potential of these organisms has yet to be fully explored, as many of the biosynthetic gene clusters that direct the synthesis of these natural products are transcriptionally silent under laboratory growth conditions. Here, we describe strategies that can be employed to broadly stimulate the expression of biosynthetic gene clusters in Streptomyces and their relatives, follow the transcription of these genes, and assess the antimicrobial activity of the resulting molecules.


Assuntos
Actinobacteria , Produtos Biológicos , Streptomyces , Actinobacteria/genética , Actinobacteria/metabolismo , Produtos Biológicos/metabolismo , Família Multigênica , Streptomyces/genética , Streptomyces/metabolismo
15.
Methods Mol Biol ; 2489: 315-332, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524058

RESUMO

Cyanobacteria represent an attractive source of natural bioactive compounds, ranging from sunscreens to cancer treatments. While many biosynthetic gene clusters (BGCs) that encode cyanobacterial natural products are known, the slow growth and lack of genetic tools in the native producers hampers their modification, characterization, and large-scale production. By engineering heterologous hosts for the expression of cyanobacterial BGCs, sufficient material can be produced for research or industry. Although several hosts have been evaluated for the expression of cyanobacterial natural products, this work details the process of expressing BGCs in Escherichia coli via promoter exchange.


Assuntos
Produtos Biológicos , Cianobactérias , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Cianobactérias/genética , Cianobactérias/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Família Multigênica , Regiões Promotoras Genéticas
16.
Methods Mol Biol ; 2489: 369-393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524060

RESUMO

Plant natural products (PNPs) are valuable resources for the development of pharmaceuticals and agrochemicals, yet the biosynthesis and metabolism of PNPs are largely unknown. Heterologous pathway reconstitution is a heavily adopted strategy in secondary metabolism characterization. Yeast systems have been broadly utilized in the heterologous production of PNPs and have been considered as a promising platform to investigate plant biosynthetic pathways. Here, we describe the reconstitution and verification of the upstream part of brassinolide biosynthesis in S. cerevisiae using this method.


Assuntos
Produtos Biológicos , Vias Biossintéticas , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Expressão Gênica , Engenharia Metabólica/métodos , Plantas/genética , Plantas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
17.
Methods Mol Biol ; 2489: 333-367, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524059

RESUMO

Cell factories can provide a sustainable supply of natural products with applications as pharmaceuticals, food-additives or biofuels. Besides being an important model organism for eukaryotic systems, Saccharomyces cerevisiae is used as a chassis for the heterologous production of natural products. Its success as a cell factory can be attributed to the vast knowledge accumulated over decades of research, its overall ease of engineering and its robustness. Many methods and toolkits have been developed by the yeast metabolic engineering community with the aim of simplifying and accelerating the engineering process.In this chapter, a range of methodologies are highlighted, which can be used to develop novel natural product cell factories or to improve titer, rate and yields of an existing cell factory with the goal of developing an industrially relevant strain. The addressed topics are applicable for different stages of a cell factory engineering project and include the choice of a natural product platform strain, expression cassette design for heterologous or native genes, basic and advanced genetic engineering strategies, and library screening methods using biosensors. The many engineering methods available and the examples of yeast cell factories underline the importance and future potential of this host for industrial production of natural products.


Assuntos
Produtos Biológicos , Saccharomyces cerevisiae , Biocombustíveis , Produtos Biológicos/metabolismo , Engenharia Metabólica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
18.
Methods Mol Biol ; 2489: 459-468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524065

RESUMO

Chromatography techniques facilitate separation, purification, and identification of secondary compounds (natural products) in lichens and their mycobiont cultures. In particular, high-performance liquid chromatography (HPLC) plays a vital role in the identification of lichen substances because of its high sensitivity, speed, and reliability with the minimal sample. Therefore, we describe the extraction and HPLC protocol for the investigation of secondary compounds with a special focus on lichen mycobiont cultures.


Assuntos
Produtos Biológicos , Líquens , Cromatografia Líquida de Alta Pressão , Reprodutibilidade dos Testes
19.
Arch Bronconeumol ; 58(4): T305-T310, 2022 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35525572

RESUMO

INTRODUCTION: The diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population. METHODS: We conducted a prospective study (May 2015-June 2017) that included 2999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus. RESULTS: The concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ = 0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ = 0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs. CONCLUSIONS: Greater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group.


Assuntos
Produtos Biológicos , Tuberculose Latente , Tuberculose , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Estudos Prospectivos , Teste Tuberculínico/métodos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico
20.
BMC Cancer ; 22(1): 512, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525914

RESUMO

BACKGROUND: Indian natural products have been anecdotally used for cancer treatment but with limited efficacy. To better understand their mechanism, we examined the publicly available data for the activity of Indian natural products in the NCI-60 cell line panel. METHODS: We examined associations of molecular genomic features in the well-characterized NCI-60 cancer cell line panel with in vitro response to treatment with 75 compounds derived from Indian plant-based natural products. We analyzed expression measures for annotated transcripts, lncRNAs, and miRNAs, and protein-changing single nucleotide variants in cancer-related genes. We also examined the similarities between cancer cell line response to Indian natural products and response to reference anti-tumor compounds recorded in a U.S. National Cancer Institute (NCI) Developmental Therapeutics Program database. RESULTS: Hierarchical clustering based on cell line response measures identified clustering of Phyllanthus and cucurbitacin products with known anti-tumor agents with anti-mitotic mechanisms of action. Curcumin and curcuminoids mostly clustered together. We found associations of response to Indian natural products with expression of multiple genes, notably including SLC7A11 involved in solute transport and ATAD3A and ATAD3B encoding mitochondrial ATPase proteins, as well as significant associations with functional single nucleotide variants, including BRAF V600E. CONCLUSION: These findings suggest potential mechanisms of action and novel associations of in vitro response with gene expression and some cancer-related mutations that increase our understanding of these Indian natural products.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias , ATPases Associadas a Diversas Atividades Celulares , Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Humanos , Proteínas de Membrana , Proteínas Mitocondriais , National Cancer Institute (U.S.) , Neoplasias/tratamento farmacológico , Neoplasias/genética , Nucleotídeos , Farmacogenética , Estados Unidos
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