RESUMO
Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality. Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.
Assuntos
Canabinoides , Neoplasias , Humanos , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Canabinoides/metabolismo , Receptores de Canabinoides , Endocanabinoides , Neoplasias/tratamento farmacológicoRESUMO
A psychrotolerant yeast strain Mrakia robertii A2-3 isolated from cryoconites of Hamtah glacier, Himalaya, India was investigated for the production of cold-tolerant endoglucanase. Optimum endoglucanase production was found at 15°C with an initial pH of 5.5, and potent inducers were 1% wt/vol of xylose and KNO3 and 0.1% wt/vol of NaCl. Under optimum conditions, the enzyme production was 1.81-fold higher than the unoptimized conditions. Crude enzyme was partially purified by ammonium sulfate precipitation followed by dialysis. The enzyme was purified to 2.53-fold and the yield was 6.03% with specific activity of 17.38 U/mg and molecular weight ~57 kDa. The Km and Vmax values of the partially purified enzyme were found to be 1.57 mg/ml and 142.85 U/mg, respectively. The characterization study revealed that the best temperature was 15°C for activity and stability. Furthermore, the enzyme showed the highest activity at pH 11.0 and was stable at pH 6.0. Fe2+ , Mn2+ , Na2+ , Cu2+ , Co2+ , Ca2+ proved to be activators of endoglucanase. Ethylenediamine tetraacetic acid showed very low effect on the enzyme activity whereas it was active with Tween-80 and sodium deoxycholate. The present study successfully produced a cold-active endoglucanase with novel properties making it promising as a biocatalyst for industrial processes.
Assuntos
Basidiomycota/enzimologia , Celulase/fisiologia , Temperatura Baixa , Camada de Gelo/microbiologia , Basidiomycota/classificação , Basidiomycota/fisiologia , Carboximetilcelulose Sódica/metabolismo , Celulase/química , Celulase/isolamento & purificação , Celulase/metabolismo , DNA Fúngico/genética , DNA Ribossômico/genética , Detergentes , Ativadores de Enzimas , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Índia , Cinética , Peso Molecular , Filogenia , Análise de Sequência de DNARESUMO
Psychrotolerant yeast Rhodotorula sp. Y-23 was isolated from the sediment core sub-samples of Nella Lake, East Antarctica. Isolate was screened for lipase production using plate assay method followed by submerged fermentation. Production optimization revealed the maximum lipase production by using palmolein oil (5% v/v), pH 8.0 and inoculum size of 2.5% v/v at 15 °C. The potential inducers for lipase were 1% w/v of galactose and KNO3 , and MnCl2 (0.1% w/v). Final productions with optimized conditions gave 5.47-fold increase in lipase production. Dialyzed product gave a purification fold of 5.63 with specific activity of 26.83 U mg-1 and 15.67% yields. This lipase was more stable at pH 5.0 and -20 °C whereas more activity was found at pH 8.0 and 35 °C. Stability was more in 50 mM Fe3+ , EDTA-Na (20 mM), sodium deoxycholate (20 mM), H2 O2 (1% v/v), and almost all organic solvents (50% v/v). Tolerance capacity at wider range of pH and temperature with having lower Km value i.e., 0.08 mg ml-1 and higher Vmax 385.68 U mg-1 at 15 °C make the studied lipase useful for industrial applications. Besides this, the lipase was compatible with commercially available detergents, and its addition to them increases lipid degradation performances making it a potential candidate in detergent formulation.
Assuntos
Temperatura Baixa , Proteínas Fúngicas/metabolismo , Sedimentos Geológicos/microbiologia , Lipase/metabolismo , Rhodotorula/enzimologia , Solventes/farmacologia , Regiões Antárticas , Detergentes/química , Estabilidade Enzimática/efeitos dos fármacos , Proteínas Fúngicas/biossíntese , Proteínas Fúngicas/isolamento & purificação , Proteínas Fúngicas/fisiologia , Concentração de Íons de Hidrogênio , Cinética , Lipase/biossíntese , Lipase/isolamento & purificação , Lipase/fisiologia , Óleos de Plantas/metabolismo , Rhodotorula/classificação , Rhodotorula/genética , Rhodotorula/isolamento & purificação , Especificidade por Substrato , TemperaturaRESUMO
Permafrost soils are unique habitats in polar environment and are of great ecological relevance. The present study focuses on the characterization of bacterial communities from permafrost profiles of Svalbard, Arctic. Counts of culturable bacteria range from 1.50 × 103 to 2.22 × 105 CFU g-1 , total bacterial numbers range from 1.14 × 105 to 5.52 × 105 cells g-1 soil. Bacterial isolates are identified through 16S rRNA gene sequencing. Arthrobacter and Pseudomonas are the most dominant genera, and A. sulfonivorans, A. bergeri, P. mandelii, and P. jessenii as the dominant species. Other species belong to genera Acinetobacter, Bacillus, Enterobacter, Nesterenkonia, Psychrobacter, Rhizobium, Rhodococcus, Sphingobacterium, Sphingopyxis, Stenotrophomonas, and Virgibacillus. To the best of our knowledge, genera Acinetobacter, Enterobacter, Nesterenkonia, Psychrobacter, Rhizobium, Sphingobacterium, Sphingopyxis, Stenotrophomonas, and Virgibacillus are the first northernmost records from Arctic permafrost. The present study fills the knowledge gap of culturable bacterial communities and their chronological characterization from permafrost soils of Ny-Ålesund (79°N), Arctic.
Assuntos
Bactérias/classificação , Bactérias/genética , Biota , Pergelissolo/microbiologia , Regiões Árticas , Carga Bacteriana , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , SvalbardRESUMO
Cryoconite holes have biogeochemical, ecological and biotechnological importance. This communication presents results on culturable psychrophilic bacterial diversity from cryoconite holes at Midre Lovénbreen (ML), Austre Brøggerbreen (AB), and Vestre Brøggerbreen (VB) glaciers. The culturable bacterial count ranged from 2.7 × 10(3) to 8.8 × 10(4) CFUs/g while the total bacterial numbers ranged from 5.07 × 10(5) to 1.50 × 10(6) cells at the three glaciers. A total of 35 morphologically distinct bacterial isolates were isolated. Based on 16S rRNA gene sequence data, the identified species belonged to eight genera namely Pseudomonas, Polaromonas, Micrococcus, Subtercola, Agreia, Leifsonia, Cryobacterium and Flavobacterium. The isolates varied in their growth temperature, NaCl tolerance, growth pH, enzyme activities, carbon utilization and antibiotic sensitivity tests. Fatty acid profiles indicate the predominance of branched fatty acids in the isolates. To the best of our knowledge, this is the first record of culturable bacterial communities and their characterization from glacier cryoconites from High Arctic. High amylase and protease activities expressed by Micrococcus sp. MLB-41 and amylase, protease and lipase activities expressed by Cryobacterium sp. MLB-32 provide a clue to the potential applications of these organisms. These cold-adapted enzymes may provide an opportunity for the prospect of biotechnology in Arctic.
Assuntos
Adaptação Fisiológica , Bactérias/isolamento & purificação , Camada de Gelo/microbiologia , Microbiota , Regiões Árticas , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Enzimas/genética , Enzimas/metabolismo , FenótipoRESUMO
A psychrophilic yeast species was isolated from glacier cryoconite holes of Svalbard. Nucleotide sequences of the strains were studied using D1/D2 domain, ITS region and partial sequences of mitochondrial cytochrome b gene. The strains belonged to a clade of psychrophilic yeasts, but showed marked differences from related species in the D1/D2 domain and biochemical characters. Effects of temperature, salt and media on growth of the cultures were also studied. Screening of the cultures for amylase, cellulase, protease, lipase, urease and catalase activities was carried out. The strains expressed high amylase and lipase activities. Freeze tolerance ability of the isolates indicated the formation of unique hexagonal ice crystal structures due to presence of 'antifreeze proteins' (AFPs). FAME analysis of cultures showed a unique trend of increase in unsaturated fatty acids with decrease in temperature. The major fatty acids recorded were oleic acid, linoleic acid, linolenic acid, palmitic acid, stearic acid, myristic acid and pentadecanoic acid. Based on sequence data and, physiological and morphological properties of the strains, we propose a novel species, Rhodotorula svalbardensis and designate strains MLB-I (CCP-II) and CRY-YB-1 (CBS 12863, JCM 19699, JCM 19700, MTCC 10952) as its type strains (Etymology: sval.bar.den'sis. N.L. fem. adj. svalbardensis pertaining to Svalbard).
Assuntos
Citocromos b/classificação , DNA Intergênico/classificação , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Filogenia , Rhodotorula/classificação , Amilases/genética , Amilases/metabolismo , Proteínas Anticongelantes/genética , Proteínas Anticongelantes/metabolismo , Regiões Árticas , Temperatura Baixa , Citocromos b/genética , DNA Intergênico/genética , Ácidos Graxos Insaturados/metabolismo , Proteínas Fúngicas/metabolismo , Camada de Gelo/microbiologia , Lipase/genética , Lipase/metabolismo , Estrutura Terciária de Proteína , Rhodotorula/enzimologia , Rhodotorula/genéticaRESUMO
The Antarctic basidiomycetous yeast Mrakia blollopis SK-4 fermented ethanol between pH 5.0 and pH 10.0 with optimum pH at 8.0-10.0. Knowledge of ethanol fermentability as to the genus Mrakia remains incomplete. Further experiments are required to elucidate the ethanol fermentability of genus e.g., as to optimum fermentation pH, optimum fermentation temperature, and cell viability during fermentation.
Assuntos
Basidiomycota/metabolismo , Etanol/metabolismo , Regiões Antárticas , Basidiomycota/citologia , Sobrevivência Celular , Fermentação , Concentração de Íons de HidrogênioRESUMO
A meat analogue is a casserole in which the primary ingredient is something other than meat. It goes by various other names, such as meat substitute, fake meat, alternative meat, and imitation meat. Consumers growing interest in improving their diets and the future of the planet have contributed to the move towards meat substitutes. This change is due to the growing popularity of low-fat and low-calorie diets, the rise of flexitarians, the spread of animal diseases, the loss of natural resources, and the need to cut down on carbon emissions, which lead to greenhouse effects. Plant-based meat, cultured meat, algal protein-based meat, and insect-based meat substitutes are available on the market with qualities like appearance and flavor similar to those of traditional meat. Novel ingredients like mycoprotein and soybean leg haemoglobin are mixed in with the more traditional soy proteins, cereals, green peas, etc. Plant-based meat is currently more popular in the West, but the growing interest in this product in Asian markets indicates the industry in this region will expand rapidly in the near future. Future growth in the food sector can be anticipated from technologies like lab-grown meat and its equivalents that do not require livestock breeding. Insect-based products also hold great potential as a new source of protein for human consumption. However, product safety and quality should be considered along with other factors such as marketability and affordability.
Assuntos
Dieta Saudável , Melhoramento Vegetal , Animais , Humanos , Carne , Proteínas de Soja , Dieta com Restrição de GordurasRESUMO
The present study deals with whole genome analysis of Fusarium udum, a wilt causing pathogen of pigeon pea. The de novo assembly identified a total of 16,179 protein-coding genes, of which 11,892 genes (73.50%) were annotated using BlastP and 8,928 genes (55.18%) from KOG annotation. In addition, 5,134 unique InterPro domains were detected in the annotated genes. Apart from this, we also analyzed genome sequence for key pathogenic genes involved in virulence, and identified 1,060 genes (6.55%) as virulence genes as per the PHI-BASE database. The secretome profiling of these virulence genes indicated the presence of 1,439 secretory proteins. Of those, an annotation of 506 predicted secretory proteins through CAZyme database indicated maximum abundance of Glycosyl hydrolase (GH, 45%) family proteins followed by auxiliary activity (AA) family proteins. Interestingly, the presence of effectors for cell wall degradation, pectin degradation, and host cell death was found. The genome comprised approximately 895,132 bp of repetitive elements, which includes 128 long terminal repeats (LTRs), and 4,921 simple sequence repeats (SSRs) of 80,875 bp length. The comparative mining of effector genes among different Fusarium species revealed five common and two specific effectors in F. udum that are related to host cell death. Furthermore, wet lab experiment validated the presence of effector genes like SIX (for Secreted in Xylem). We conclude that deciphering the whole genome of F. udum would be instrumental in understanding evolution, virulence determinants, host-pathogen interaction, possible control strategies, ecological behavior, and many other complexities of the pathogen.
RESUMO
The present investigation is on a newly isolated psychrophilic Antarctic filamentous Ascomycetous fungus that has been identified as Thelebolus sp. and given the designation of Thelebolus sp. IITKGP-BT12. The culture was primarily identified through morphological studies, and was further confirmed by 18S rRNA sequencing (GenBank Accession No. KC191572), which revealed its close relatedness with Thelebolus microsporus. The exopolysaccharide (EPS) produced (1.94 g L(-1)) by the fungus was isolated, purified and characterized as glucan having an average molecular mass of 5×10(5)Da. The structure of EPS was determined by gas chromatography with tandem mass spectrometry (GC-MS/MS), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) studies ((1)H, (13)C and HSQC). NMR analysis indicated the presence of (1â3)-linked ß-d-glucan backbone with (1â6)-linked branches of ß-d-glucopyranosyl units. Antiproliferative activity of EPS was demonstrated in B16-F0 cells, with IC50 of 275.42 µg m L(-1). Flow cytometry analysis and DNA fragmentation studies revealed that the cytotoxic action of the EPS mediated apoptosis in cancer cells. This is the first ever report on bioactive EPS thelebolan from Thelebolus sp.
Assuntos
Ascomicetos/química , Polissacarídeos Fúngicos/química , Animais , Regiões Antárticas , Apoptose , Ascomicetos/isolamento & purificação , Ascomicetos/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Espaço Extracelular/química , Polissacarídeos Fúngicos/metabolismo , Polissacarídeos Fúngicos/farmacologia , CamundongosRESUMO
Culturable bacterial abundance at 11 different depths of a 50.26 m ice core from the Tallaksenvarden Nunatak, Antarctica, varied from 0.02 to 5.8 × 10(3) CFU ml(-1) of the melt water. A total of 138 bacterial strains were recovered from the 11 different depths of the ice core. Based on 16S rRNA gene sequence analyses, the 138 isolates could be categorized into 25 phylotypes belonging to phyla Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. All isolates had 16S rRNA sequences similar to previously determined sequences (97.2-100%). No correlation was observed in the distribution of the isolates at the various depths either at the phylum, genus or species level. The 25 phylotypes varied in growth temperature range, tolerance to NaCl, growth pH range and ability to produce eight different extracellular enzymes at either 4 or 18 °C. Iso-, anteiso-, unsaturated and saturated fatty acids together constituted a significant proportion of the total fatty acid composition.