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1.
Chem Asian J ; : e202400633, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031487

RESUMO

An assembly of metal nanoclusters driven by appropriate surface ligands and solvent environment may engender entirely new photoluminescence (PL). Herein, we first synthesize histidine (His) stabilized copper nanoparticles (CuNPs) and, subsequently, copper nanoclusters (CuNCs) from it using 3-mercaptopropionic acid (MPA) as an etchant. The CuNCs originally emit bluish-green (λem=470 nm) PL with a low quantum yield (QY∼1.8%). However, it transformed into a dual-emissive nanocluster assembly (Zn-CuNCs) in the presence of Zn(II) salt, having a distinct blue emission band (λem = 420 nm) and a red emission band (λem = 615 nm) with eight times QY (∼9.1%) enhancement. Adding dimethyl sulfoxide (DMSO) further modifies the emission intensities; the red band was amplified four times, while the blue band was diminished by 2.5 times. The transmission electron microscopy (TEM) images unveiled that the Zn-CuNCs are a large assembly of tiny nanoclusters, which become more compact in DMSO. The blue emission possesses steady-state fluorescence anisotropy, while the red emission shows no anisotropy. Further, near-perfect white light emission(WLE) was rendered with CIE coordinates of (0.33, 0.32) by combining the dual emission of the Zn-CuNCs with the original green emission of the CuNCs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39023731

RESUMO

Biomass, an organic matter, has gained worldwide attention due to the overconsumption of fossil fuels. Biomass has emerged as a new alternative resource with implications for efficient energy production, environmental benefits and socio-economic impacts. According to the World Bioenergy Association, biomass has accounted for 14% of the energy supply in 2016 and is expected to provide 44% of the energy demand by 2030. This literary endeavour comprises insights into past developments, including biomass types, characterization methods and conversion technologies. This review article aims to facilitate a deeper understanding of agriculture biomass utilization and its significance in achieving sustainable development goals by analysing the latest research findings. Moreover, the emerging role of biosensors in optimizing biomass utilization and monitoring environmental impacts has been documented. The scope embraces the vast realm of bioenergy production, environmental mitigation and the generation of valuable by-products. In conclusion, portraying biomass conversion technologies as the transition towards cleaner, renewable energy, the potential benefits and challenges extend beyond energy production, encompassing effective agricultural residue management and the creation of valuable by-products. This review will guide the researchers and stakeholders towards a deeper understanding of the transformative potential embedded in biomass conversion processes for a sustainable and cleaner energy future.

3.
Indian J Microbiol ; 64(2): 603-617, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39011022

RESUMO

The human microbiome is a diverse consortium of microbial kingdoms that play pivotal roles in host health and diseases. We previously reported a dysbiotic bacteriome in chronic pancreatitis patients with diabetes (CPD) compared with patients with it's nondiabetic (CPND) phenotype. In this study, we extended our exploration to elucidate the intricate interactions between the mycobiome, bacteriome, and hosts' plasma metabolome with the disease phenotypes. A total of 25 participants (CPD, n = 7; CPND, n = 10; healthy control, n = 8) were recruited for the study. We observed elevated species richness in both the bacterial and fungal profiles within the CP diabetic cohort compared to the nondiabetic CP phenotype and healthy control cohorts. Notably, the CP group displayed heterogeneous fungal diversity, with only 40% of the CP nondiabetic patients and 20% of the CP diabetic patients exhibiting common core gut fungal profiles. Specific microbial taxa alterations were identified, including a reduction in Bifidobacterium adolescentis and an increase in the prevalence of Aspergillus penicilloides and Klebsiella sp. in the disease groups. In silico analysis revealed the enrichment of pathways related to lipopolysaccharide (LPS), apoptosis, and peptidase, as well as reduced counts of the genes responsible for carbohydrate metabolism in the CP groups. Additionally, distinct plasma metabolome signatures were observed, with CPD group exhibiting higher concentrations of sugars and glycerolipids, while the CPND cohort displayed elevated levels of amino acids in their blood. The fatty acid-binding protein (FABP) concentration was notably greater in the CPD group than in the HC group (4.220 vs. 1.10 ng/ml, p = 0.04). Furthermore, compared with healthy controls, disease groups exhibited fewer correlations between key fungal taxa (Aspergillus sp., Candida sp.) and bacterial taxa (Prevotella copri, Bifidobacteria sp., Rumminococcaceae). Our study unveils, for the first time, a dysbiotic mycobiome and emphasizes unique host bacterial-mycobial interactions in CP patient with diabetes, potentially influencing disease severity. These findings provide crucial insights for future mechanistic studies aiming to unravel the determinants of disease severity in this complex clinical context. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01207-8.

4.
Int J Biol Macromol ; 266(Pt 2): 131163, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38547950

RESUMO

Novel kinds of starch spectra were generated from a lesser-known plant, making this investigation unique. The recent trend of starch characterization shows the establishment of novel bioresources from nonconventional unexplored databases. The present endeavor was made to obtain the starch fingerprint of Ampelopteris prolifera (rhizome) belonging to seedless vascular plants. For comparison, a commercial local cultivar of potato (Kufri Jyoti) was taken. The starch particle of A. prolifera shows much uniqueness depicting its novelty viz., crystallinity index of 60.04 %, powder diffractogram at (2θ scale)17.57° to 39.78°; this diffractogram pattern is reported from this study as newer one i.e. R type(whereas potato starch is CB type); characteristic peak at 2θ = 20.07° suggests starch-lipid complex formation and V type crystallinity (i.e. RS 5 type); FTIR spectra showing the presence of more short chain branching; high gelatinization temperature(84.62 ±â€¯0.10), particle size and zeta value of A. prolifera is 4.00 ±â€¯0.81 µm and - 18.91 ±â€¯3.58 mV respectively. Bragg's peak from the single crystal X-ray diffraction has been generated for the first time of A. prolifera. Extraction of the starch particle was performed in chilled water. Therefore, the present study suggests wide-spectrum commercial utility and cost-effective production.


Assuntos
Solanum tuberosum , Amido , Solanum tuberosum/química , Amido/química , Difração de Raios X , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Biol Open ; 12(10)2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37787465

RESUMO

Cell cycle regulation in response to biochemical cues is a fundamental event associated with many diseases. The regulation of such responses in complex metabolic environments is poorly understood. This study reveals unknown aspects of the metabolic regulation of cell division in Schizosaccharomyces pombe. We show that changing the carbon source from glucose to lactic acid alters the functions of the cyclin-dependent kinase (CDK) Cdc2 and mitogen-activated protein kinase (MAPK) Sty1, leading to unanticipated outcomes in the behavior and fate of such cells. Functional communication of Cdc2 with Sty1 is known to be an integral part of the cellular response to aberrant Cdc2 activity in S. pombe. Our results show that cross-talk between Cdc2 and Sty1, and the consequent Sty1-dependent regulation of Cdc2 activity, appears to be compromised and the relationship between Cdc2 activity and mitotic timing is also reversed in the presence of lactate. We also show that the biochemical status of cells under these conditions is an important determinant of the altered molecular functions mentioned above as well as the altered behavior of these cells.


Assuntos
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Schizosaccharomyces/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Ácido Láctico/metabolismo , Glucose/metabolismo , Comunicação
6.
Adv Protein Chem Struct Biol ; 136: 415-455, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37437986

RESUMO

Neurodegenerative diseases are characterized by degeneration or cellular atrophy within specific structures of the brain. Neurons are the major target of neurodegeneration. Neurons utilize 75-80% of the energy produced in the brain. This energy is either formed by utilizing the glucose provided by the cerebrovascular blood flow or by the in-house energy producers, mitochondria. Mitochondrial dysfunction has been associated with neurodegenerative diseases. But recently it has been noticed that neurodegenerative diseases are often associated with cerebrovascular diseases. Cerebral blood flow requires vasodilation which to an extent regulated by mitochondria. We hypothesize that when mitochondrial functioning is disrupted, it is not able to supply energy to the neurons. This disruption also affects cerebral blood flow, further reducing the possibilities of energy supply. Loss of sufficient energy leads to neuronal dysfunction, atrophy, and degeneration. In this chapter, we will discuss the metabolic modifications of mitochondria in aging-related neurological disorders and the potential of phytocompounds targeting them.


Assuntos
Mitocôndrias , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Neurônios , Atrofia
7.
Pancreatology ; 23(6): 589-600, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37438173

RESUMO

INTRODUCTION: Infected pancreatic necrosis (IPN) is a major cause of mortality in acute pancreatitis (AP). Currently, no specific strategies are available to predict the development of IPN. Earlier we reported that persistent down-regulation of HLA-DR increases risk of developing IPN. Altered kynurenine pathway (KP) metabolites showed poor prognosis in sepsis. Here we evaluated the role of HLA-DR and KP in IPN. METHODS: Patients with ANP and healthy controls were enrolled. Demographic and clinical parameters were recorded. Circulating interleukin (IL)-8, 6, 1ß, 10, Tumor necrosis factor-α were quantified using flowcytometry. Plasma procalcitonin, endotoxin, and KP (tryptophan, kynurenine) concentrations were estimated using ELISA. qRT-PCR was conducted to evaluate mRNA expression of HLA-DR, IL-10, Toll like receptor-4 (TLR-4), and kynurenine-3-monooxygenase (KMO) genes on peripheral blood mononuclear cells. Plasma metabolites were quantified using gas chromatography mass spectrometry (GC-MS/MS). Standard statistical methods were used to compare study groups. Metaboanalyst was used to analyse/visualize the metabolomics data. RESULTS: We recruited 56 patients in Cohort-1 (IPN:26,Non-IPN:30), 78 in Cohort-2 (IPN:57,Non-IPN:21), 26 healthy controls. Increased cytokines, endotoxin, and procalcitonin were observed in patients with IPN compared to Non-IPN. HLA-DR and KMO gene expressions were significantly down-regulated in IPN groups, showed positive correlation with one another but negatively correlated with IL-6 and endotoxin concentrations. Increased IDO and decreased plasma tryptophan were observed in IPN patients. Metabolome analysis showed significant reduction in several essential amino acids including tryptophan in IPN patients. Tryptophan, at a concentration of 9 mg/ml showed an AUC of 91.9 (95%CI 86.5-97.4) in discriminating IPN. CONCLUSION: HLA-DR downregulation and KP alteration are related to IPN. The KP metabolite plasma tryptophan can act as a potential biomarker for IPN.


Assuntos
Cinurenina , Pancreatite Necrosante Aguda , Humanos , Cinurenina/metabolismo , Triptofano/metabolismo , Pró-Calcitonina , Espectrometria de Massas em Tandem , Doença Aguda , Leucócitos Mononucleares , Biomarcadores , Antígenos HLA-DR/genética , Quinurenina 3-Mono-Oxigenase/genética , Quinurenina 3-Mono-Oxigenase/metabolismo , Necrose , Endotoxinas
8.
ACS Bio Med Chem Au ; 3(3): 283-294, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37363079

RESUMO

Multiplex protein imaging technologies enable deep phenotyping and provide rich spatial information about biological samples. Existing methods have shown great success but also harbored trade-offs between various pros and cons, underscoring the persisting necessity to expand the imaging toolkits. Here we present PACIFIC: photoactive immunofluorescence with iterative cleavage, a new modality of multiplex protein imaging methods. PACIFIC achieves iterative multiplexing by implementing photocleavable fluorophores for antibody labeling with one-step spin-column purification. PACIFIC requires no specialized instrument, no DNA encoding, or chemical treatments. We demonstrate that PACIFIC can resolve cellular heterogeneity in both formalin-fixed paraffin-embedded (FFPE) samples and fixed cells. To further highlight how PACIFIC assists discovery, we integrate PACIFIC with live-cell tracking and identify phosphor-p70S6K as a critical driver that governs U87 cell mobility. Considering the cost, flexibility, and compatibility, we foresee that PACIFIC can confer deep phenotyping capabilities to anyone with access to traditional immunofluorescence platforms.

9.
Microorganisms ; 11(6)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37375003

RESUMO

It is known that alcoholic beverages alter the human gut microbiome. This study focused on the potential impact of non-ethanolic ingredients in whisky on the gut bacteriome. A pilot study was carried out on 15 whisky drinkers, 5 rice beer drinkers, and 9 non-drinkers to determine the effect of alcoholic beverages on the host microbiome and metabolome. Additionally, a mouse model was used to assess the differential impact of three whisky brands (each with an equal ethanol concentration). The results indicate that the non-ethanolic components have an impact on the gut microbiome, as well as on the metabolites in blood and feces. The amount of Prevotella copri, a typical core Indian gut bacterium, decreased in both the human and mouse groups of whisky type 1, but an increase in abundance of Helicobacteriaceae (p = 0.01) was noticed in both groups. Additionally, the alcohol-treated cohorts had lower levels of short-chain fatty acids (SCFAs), specifically butyric acid, and higher amounts of lipids and stress marker IL1-ß than the untreated groups (p = 0.04-0.01). Furthermore, two compounds, ethanal/acetaldehyde (found in all the whisky samples) and arabitol (unique to whisky type 1), were tested in the mice. Similar to the human subjects, the whisky type 1 treated mouse cohort and the arabitol-treated group showed decreased levels of Prevotella copri (p = 0.01) in their gut. The results showed that non-ethanolic compounds have a significant impact on host gut bacterial diversity and metabolite composition, which has a further vital impact on host health. Our work further emphasizes the need to study the impact of non-ethanolic ingredients of alcoholic beverages on host health.

10.
J Am Chem Soc ; 144(44): 20288-20297, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36301712

RESUMO

Delivering cargo molecules across the plasma membrane is critical for biomedical research, and the need to develop molecularly well-defined tags that enable cargo transportation is ever-increasing. We report here a hydrophilic endocytosis-promoting peptide (EPP6) rich in hydroxyl groups with no positive charge. EPP6 can transport a wide array of small-molecule cargos into a diverse panel of animal cells. Mechanistic studies revealed that it entered the cells through a caveolin- and dynamin-dependent endocytosis pathway, mediated by the surface receptor fibrinogen C domain-containing protein 1. After endocytosis, EPP6 trafficked through early and late endosomes within 30 min. Over time, EPP6 partitioned among cytosol, lysosomes, and some long-lived compartments. It also demonstrated prominent transcytosis abilities in both in vitro and in vivo models. Our study proves that positive charge is not an indispensable feature for hydrophilic cell-penetrating peptides and provides a new category of molecularly well-defined delivery tags for biomedical applications.


Assuntos
Peptídeos Penetradores de Células , Endocitose , Animais , Endossomos/metabolismo , Peptídeos Penetradores de Células/metabolismo , Lisossomos/metabolismo , Interações Hidrofóbicas e Hidrofílicas
11.
Pancreatology ; 22(6): 688-697, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35710761

RESUMO

BACKGROUND: To evaluate if altered brain metabolites are connected to pain, depression and affective responses in CP. METHODS: In this prospective study we evaluated pain characteristics, QOL (EORTC QLQc30+PAN28), depression (Beck depression inventory [BDI] II) in 558 patients with CP and 67 healthy controls. Brain metabolites were evaluated using magnetic resonance spectroscopy (MRS) in 49 patients and 5 healthy controls. We measured plasma metabolites using gas chromatography-mass spectrometry (GC-MS/MS). Relationship between metabolomic alterations, pain, depression and QOL components were assessed using statistical/bioinformatics methods. Benjamini-Hochberg FDR correction was applied for multiple testing. RESULTS: 261 (46.8%) patients had depression compared to 5 (7.5%) among healthy controls [n = 67](p < 0.0001). Risk [OR (95% CI) of developing depression in the presence of pain was 1.9 (1.33-1.68); p = 0.0004. The depression scores correlated negatively with functional components and positively with symptom components of EORTC QLQ30. Significant negative correlation, though based on a small sample size, was observed between N-acetyl aspartate in the left hippocampus and choline in the left prefrontal cortex with emotional and cognitive functions. PLS-DA modelling revealed significant alteration in the plasma metabolomic profile among patients with CP who had depression. Six metabolites were significantly different between CP with depression and healthy controls, of which glycine contributed most significantly to the PLS-DA model (VIP score of 3.5). CONCLUSIONS: A significant proportion of patients with CP develops depression that correlate with poor QOL functions. Pain, depression, and emotional components of QOL in patients with CP correlated with N-acetyl aspartate and choline in the left hippocampus and left prefrontal cortex of the brain.


Assuntos
Pancreatite Crônica , Qualidade de Vida , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Colina/metabolismo , Depressão , Humanos , Dor , Pancreatite Crônica/complicações , Pancreatite Crônica/metabolismo , Estudos Prospectivos , Espectrometria de Massas em Tandem
12.
Data Brief ; 42: 108034, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35360049

RESUMO

Schizosaccharomyces pombe has been used as an excellent model for studying eukaryotic cell cycle regulation and stress responses. The bZIP transcription factors Atf1(ATF2 homolog) and Pcr1(CREB homolog) have been shown to be important for regulating the expression of genes related to both stress response and cell cycle. Pcr1 has in fact been implicated as a determining factor in the segregation of the cell cycle and stress response related functions of Atf1. Interestingly Atf1 and Pcr1 levels are known to vary during the cell cycle thus giving rise to the possibility that their relative levels can influence the periodic transcriptional program of the cell. Here we report our observations on the changes in transcriptome of S. pombe cells which have been genetically manipulated to create relative differences in the levels of Atf1 and Pcr1. These results highlight new information regarding the potential role of Atf1 and Pcr1 in orchestrating the integration of the transcriptional programs of cell cycle and stress response.

13.
Methods Mol Biol ; 2394: 65-80, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35094322

RESUMO

Here we present a protocol for interrogating AKT signaling activities in living single cells, using a pair of cyclic peptide-based fluorescent probes. These probes are encapsulated in liposomes and delivered into cells, where they continuously report on AKT signaling activities through a Föster resonance energy transfer mechanism. We describe the use of a microwell chip to achieve single-cell resolution and demonstrate the procedure for on-chip immunostaining. Finally, we provide a method for data extraction, correction, and processing.


Assuntos
Corantes Fluorescentes , Peptídeos Cíclicos , Proteínas Proto-Oncogênicas c-akt , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/química , Peptídeos Cíclicos/química , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
14.
CNS Neurol Disord Drug Targets ; 21(4): 335-342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34455974

RESUMO

BACKGROUND: Dementia correlates with Alzheimer's disease, Parkinson's disease, frontotemporal and cerebrovascular diseases. There are supporting shreds of evidence on the pharmacological activity of curcuma caesia (Zingiberaceae family) for its antioxidant, antidepressant, analgesic, anticonvulsant, and anti-acetylcholinesterase effect. OBJECTIVE: This study aims to analyze the fecal microbial profile in Zederone treated demented rat model. METHODS: In our study, isolation and characterization of Zederone were carried out from curcuma caesia rhizomes, followed by estimation of its memory-enhancing effect on Aluminium-induced demented rat, which was evaluated by behavioural study on radial 8 arm maze. Moreover the detection of amyloid plaque formation was carried out using fluorescent microscopy of the congo red-stained rat brain tissues of the cerebral neocortex region. This study included eighteen female Wistar Albino rats that were divided into three groups that consisted of six rats in each group. The study of fecal microbial profile by metagenomic DNA extraction followed by next-generation sequencing was carried out to establish the correlation between gut microbes and amyloid plaques in dementia. RESULTS: Zederone could be characterized as pale yellow colored, needle-shaped crystals with 96.57% purity. This compound at 10 mg/kg body weight showed cognition improving capacity (p ≤ 0.0001) with a reduction of accumulated amyloid plaques that were detected in the demented group in fluorescence microscope and fecal microbiome study divulged an increased shift towards Lactobacillus genera in the treated group from Bacteroides in the demented group. CONCLUSION: This sesquiterpenoid compound would assist in the modulation of gut bacterial dysbiosis and act as a better therapeutic drug for dementia and other neurological disorders.


Assuntos
Demência/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Disbiose/tratamento farmacológico , Feminino , Placa Amiloide/tratamento farmacológico , Ratos , Ratos Wistar
15.
Analyst ; 146(17): 5307-5315, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34351328

RESUMO

Analyzing intracellular signalling protein activities in living cells promises a better understanding of the signalling cascade and related biological processes. We have previously developed cyclic peptide-based probes for analyzing intracellular AKT signalling activities, but these peptide probes were not cell-permeable. Implementing fusogenic liposomes as delivery vehicles could circumvent the problem when analyzing adherent cells, but it remained challenging to study suspension cells using similar approaches. Here, we present a method for delivering these imaging probes into suspension cells using digitonin, which could transiently perforate the cell membrane. Using U87, THP-1, and Jurkat cells as model systems representing suspended adherent cells, myeloid cells, and lymphoid cells, we demonstrated that low concentrations of digitonin enabled a sufficient amount of probes to enter the cytosol without affecting cell viability. We further combined this delivery method with a microwell single-cell chip and interrogated the AKT signalling dynamics in THP-1 and Jurkat cells, followed by immunofluorescence-based quantitation of AKT expression levels. We resolved the cellular heterogeneity in AKT signalling activities and showed that the kinetic patterns of AKT signalling and the AKT expression levels were related in THP-1 cells, but decoupled in Jurkat cells. We expect that our approach can be adapted to study other suspension cells.


Assuntos
Fenômenos Biológicos , Proteínas Proto-Oncogênicas c-akt , Digitonina , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Análise de Célula Única
16.
J Mol Neurosci ; 71(12): 2608-2617, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34227035

RESUMO

The process of ageing accompanies several metabolic diseases. With ageing, fats accumulate to increase the visceral and abdominal adiposity leading to hyperinsulinemia, insulin resistance, obesity and several other diseases. Drosophila melanogaster is often used to study the ageing process and its related disorders. Therefore, in this study, we performed an in silico analysis to relate the process of ageing and insulin resistance. We analysed the data of insulin-resistant Drosophila from the GEO database and compared it with the data from the literature survey. We observed that 98 genes were common in both the models, and they showed gene modulations related to metabolic pathways, fatty acid metabolism, insulin resistance and neural receptor-ligand binding pathways. Analysis of the REACTOME database against human data revealed that the TRKB signalling pathway is commonly affected. The TRKB-mediated BDNF pathway is a major regulator of memory loss. We further analysed the common genes in Alzheimer's disease and compared the fly data with human data to identify the diseases related to these common genes. Then, we performed a literature survey to provide protective mechanisms for the TRKB signalling pathway activation, mediated through polyphenols. We treated the flies with sesamol-conjugated lipoic acid derivative (a phenolic compound) at hormetic doses to evaluate its effect on the memory of flies.


Assuntos
Envelhecimento/genética , Doença de Alzheimer/genética , Resistência à Insulina/genética , Obesidade/genética , Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Genoma Humano , Genoma de Inseto , Humanos , Obesidade/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo , Transdução de Sinais
17.
J Am Chem Soc ; 143(29): 11191-11198, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34266234

RESUMO

We present a chemical approach to profile fatty acid uptake in single cells. We use azide-modified analogues to probe the fatty acid influx and surface-immobilized dendrimers with dibenzocyclooctyne (DBCO) groups for detection. A competition between the fatty acid probes and BHQ2-azide quencher molecules generates fluorescence signals in a concentration-dependent manner. By integrating this method onto a microfluidics-based multiplex protein analysis platform, we resolved the relationships between fatty acid influx, oncogenic signaling activities, and cell proliferation in single glioblastoma cells. We found that p70S6K and 4EBP1 differentially correlated with fatty acid uptake. We validated that cotargeting p70S6K and fatty acid metabolism synergistically inhibited cell proliferation. Our work provided the first example of studying fatty acid metabolism in the context of protein signaling at single-cell resolution and generated new insights into cancer biology.


Assuntos
Ciclo-Octanos/análise , Dendrímeros/metabolismo , Ácidos Graxos/metabolismo , Glioblastoma/metabolismo , Análise de Célula Única , Azidas/química , Azidas/metabolismo , Proliferação de Células , Ciclo-Octanos/metabolismo , Dendrímeros/química , Ácidos Graxos/química , Fluorescência , Glioblastoma/patologia , Humanos , Estrutura Molecular , Propriedades de Superfície
18.
3 Biotech ; 11(5): 240, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33968583

RESUMO

Scientific pieces of evidence support the pharmacological activity of Curcuma caesia for its antidepressant, analgesic, anticonvulsant and antioxidant effect. Here, we evaluate the bioactivity of essential oil and the various polarity-based solvent partitioned fractions obtained from Curcuma caesia for anti-amnesia, anxiolytic and antidepressant activities using Elevated plus maze and Morris water maze models. The cold maceration technique using methanol was adopted for extraction from dried powdered rhizomes and essential oil was extracted by hydrodistillation method. Partitioning of the methanolic extract based on solvent polarity by hexane, ethyl acetate, and methanol was continued, followed by column chromatography of the ethyl acetate fraction. Suspensions were prepared for fractions (dissolved in distilled water) and essential oil (dissolved in tween 20) at 200 mg/kg and 400 mg/kg after acute toxicity study and were orally administered to Wistar albino female rats after the orientation of hypoxia by sodium nitrite (50 mg/kg) and amnesia by scopolamine (1 mg/kg). Behavioural observations, biochemical and histopathological examinations were carried out for all the treated groups. Diazepam (12 mg/kg) and galantamine (3 mg/kg) were used as standard drugs for this study against hypoxia and amnesia. Data acquired from behavioural, biochemical (acetylcholinesterase, myeloperoxidase, superoxide dismutase, reduced glutathione, catalase) and histopathological studies have illustrated that fraction II acquires highly significant memory-enhancing, anxiolytic and antidepressant effects. Rest fractions (I and III) and essential oil showed moderate efficacy. In prospects, identification of active molecules from the most active fraction (fraction II) and further studies on a molecular basis would substantiate its specific mechanism of neuroprotective action.

19.
Sci Rep ; 11(1): 10978, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34040023

RESUMO

We hypothesized that the gut microbiome in patients with diabetes secondary to chronic pancreatitis (Type 3c) is different from those with Type 1 and Type 2 diabetes. This was a cross-sectional preliminary study that included 8 patients with Type 1, 10 with Type 2, 17 with Type 3c diabetes and 9 healthy controls. Demographic, clinical, biochemical, imaging and treatment data were recorded and sequencing of the V3-V4 region of the bacterial 16SrRNA was done on fecal samples. Bioinformatics and statistical analyses was performed to evaluate the differences in the diversity indices, distance matrices, relative abundances and uniqueness of organisms between the types of diabetes. There was significant difference in the species richness. Beta diversity was significantly different between patients with Type 3c diabetes and the other groups. 31 genera were common to all the three types of diabetes. There was significant differences in the species level taxa between Type 3c diabetes and the other groups. The unique bacterial species signature in Type 3c diabetes compared to Type 1 and Type 2 diabetes included Nesterenkonia sp. AN1, Clostridium magnum, Acinetobacter lwoffii, Clostridium septicum, Porphyromonas somerae, Terrabacter tumescens, and Synechococus sp.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Estudos Transversais , Fezes/microbiologia , Humanos
20.
Analyst ; 146(11): 3474-3481, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-33913937

RESUMO

We present here a cyclic peptide ligand, cy(WQETR), that binds to the terbium ion (Tb3+) and enhances Tb3+ luminescence intensity through the antenna effect. This peptide was identified through screening a cyclic peptide library against Tb3+ with an apparent EC50 of 540 µM. The tryptophan residue from the peptide directly interacts with the Tb3+ ion, which provides access to a low-lying triplet excited state of the tryptophan. Direct excitation of this triplet state enables energy transfer to the Tb3+ ion and enhances Tb3+ luminescence intensity by 150 fold. We further showcase the application of this cy(WQETR)-Tb3+ system by demonstrating the detection of tromethamine with a detection limit of 0.5 mM.


Assuntos
Luminescência , Térbio , Transferência de Energia , Ligantes , Peptídeos Cíclicos
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