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1.
Proc Natl Acad Sci U S A ; 120(49): e2315096120, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38011564

RESUMO

Hidradenitis suppurativa (HS) is a complex inflammatory skin disease with undefined mechanistic underpinnings. Here, we investigated HS epithelial cells and demonstrated that HS basal progenitors modulate their lineage restriction and give rise to pathogenic keratinocyte clones, resulting in epidermal hyperproliferation and dysregulated inflammation in HS. When comparing to healthy epithelial stem/progenitor cells, in HS, we identified changes in gene signatures that revolve around the mitotic cell cycle, DNA damage response and repair, as well as cell-cell adhesion and chromatin remodeling. By reconstructing cell differentiation trajectory and CellChat modeling, we identified a keratinocyte population specific to HS. This population is marked by S100A7/8/9 and KRT6 family members, triggering IL1, IL10, and complement inflammatory cascades. These signals, along with HS-specific proinflammatory cytokines and chemokines, contribute to the recruitment of certain immune cells during the disease progression. Furthermore, we revealed a previously uncharacterized role of S100A8 in regulating the local chromatin environment of target loci in HS keratinocytes. Through the integration of genomic and epigenomic datasets, we identified genome-wide chromatin rewiring alongside the switch of transcription factors (TFs), which mediated HS transcriptional profiles. Importantly, we identified numerous clinically relevant inflammatory enhancers and their coordinated TFs in HS basal CD49fhigh cells. The disruption of the S100A enhancer using the CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators. Our study not only uncovers the plasticity of epidermal progenitor cells in HS but also elucidates the epigenetic mechanisms underlying HS pathogenesis.


Assuntos
Hidradenite Supurativa , Humanos , Hidradenite Supurativa/genética , Pele/metabolismo , Epigenômica , Epigênese Genética , Células-Tronco/metabolismo , Cromatina/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-39313361

RESUMO

Alcohol-associated liver disease (ALD), including alcoholic fatty liver, is a serious problem in many countries, and its economic costs to society are enormous. There is evidence indicating the relations between gut environments and liver disease, and thus, improvement of gut environment is expected to be an effective approach for ALD prevention. In this study, we explored the preventive effect of partially hydrolyzed guar gum (PHGG) on ALD focusing on the gut-liver axis. Two weeks of PHGG pre-feeding suppressed the liver fat accumulation in the experimental binge alcohol model mouse. In cecal microbiome, PHGG pre-feeding increased beneficial Bifidobacterium with its metabolite acetate concentration and suppressed the alcohol-induced increase in the potential pathobiont Streptococcus. PHGG pre-feeding increased colonic gene expression of angiogenin genes, which act as antimicrobial peptides and decreased expression of genes for mast cell protease, which suggests a potential involvement in leaky gut. Correlation network analysis based on evaluated parameters revealed four relations worth noticing. (i) The abundance of Bifidobacterium positively correlated with cecal acetate. (ii) Cecal acetate negatively correlated with Streptococcus via colonic angiogenin expression. (iii) Streptococcus positively correlated with liver fat area. (iv) Cecal acetate had direct negative correlation with liver fat area. Considering these relations comprehensively, acetate produced by Bifidobacterium may be a key mediator in ALD prevention; it inhibited growth of potential pathobiont Streptococcus and also directly regulated liver lipid metabolism reaching through portal vein. This study demonstrated that regularly intake of PHGG may be effective in reducing the risk of alcoholic fatty liver via gut-liver axis.

3.
Environ Res ; 261: 119697, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39068969

RESUMO

Although river water is vital for drinking, irrigation and domestic needs, it faces threats from natural processes and human activities. Small and medium-sized rivers, especially in Nepal, remain understudied despite their vital importance in providing water to densely populated areas. This study evaluated the suitability for drinking and irrigation and the hydro-chemical characteristics of the Biring and Tangting rivers in Koshi province, Nepal. The results showed that turbidity, pH, EC, TDS, TH, NH4+, K+, Ca2+, Mg2+, Na+, Cl-, SO42-, HCO3- and NO3- values of all sampling sites in the Biring and Tangting rivers, except for the turbidity value of 10.39 NTU recorded in the PT9 site of the Tangting River, did not exceed maximum limit values set for drinking water. However, according to Water Quality Index results, the water of both rivers was in poor condition for drinking due to domestic wastewater discharges and cremation activities which caused high NH4+ levels. The major cations in both rivers were listed as Ca2⁺ > Na⁺ > K⁺ > Mg2⁺, while the major anions were listed as HCO3⁻ > Cl⁻ > SO42⁻ > NO3⁻. Gibbs and Piper diagrams showed that geogenic weathering of carbonate rocks prevailing in the region affected the hydrochemistry in both rivers. Evaluation based on seven different irrigation indices and US salinity laboratory diagram revealed that the water of both rivers was suitable for irrigation despite some magnesium-related limitations.


Assuntos
Irrigação Agrícola , Rios , Qualidade da Água , Rios/química , Nepal , Água Potável/análise , Água Potável/química , Monitoramento Ambiental/métodos , Abastecimento de Água , Poluentes Químicos da Água/análise
4.
Chem Biodivers ; 21(4): e202301820, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38372508

RESUMO

As a part of novel discovery of drugs from natural resources, present study was undertaken to explore the antibacterial potential of chalcone Indl-2 in combination with different group of antibiotics. MIC of antibiotics was reduced up to eight folds against the different cultures of E. coli by both chalcones. Among the two compounds, the i. e. 1-(3', 4,'5'-trimethoxyphenyl)-3-(3-Indyl)-prop-2-enone (6, Indl-2), a chalcone derivative of gallic acid (Indl-2) was better along with tetracycline (TET) worked synergistically and was found to inhibit efflux transporters as obvious by ethidium bromide efflux confirmed by ATPase assays and docking studies. In combination, Indl-2 kills the MDREC-KG4 cells, post-antibiotic effect (PAE) of TET was prolonged and mutant prevention concentration (MPC) of TET was also decreased. In-vivo studies revealed that Indl-2 reduces the concentration of TNF-α. In acute oral toxicity study, Indl-2 was non-toxic and well tolerated up-to dose of 2000 mg/kg. Perhaps, the study is going to report gallic acid derived chalcone as synergistic agent acting via inhibiting the primary efflux pumps.


Assuntos
Chalcona , Chalconas , Chalcona/farmacologia , Chalconas/farmacologia , Escherichia coli , Ácido Gálico/farmacologia , Antibacterianos/farmacologia , Tetraciclina/farmacologia , Proteínas de Membrana Transportadoras , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/metabolismo
5.
Biosci Biotechnol Biochem ; 87(7): 771-776, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37133406

RESUMO

Diosmin (DSN) is found mainly in citrus fruits, and has potent antioxidant effects. This study aimed to evaluate pharmacokinetics of diosmetin-7-glucoside-γ-cyclodextrin (DIOSG-CD) inclusion complex. The area under the curve values from AUC0-24 of DIOSG-CD, prepared by reacting DSN and naringinase with γ-CD, were approximately 800-fold higher than those of DSN following their administration in Sprague-Dawley rats.


Assuntos
Diosmina , gama-Ciclodextrinas , Ratos , Animais , Ratos Sprague-Dawley , Diosmina/farmacocinética , Disponibilidade Biológica
6.
Arch Toxicol ; 97(7): 1847-1858, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37166470

RESUMO

Arsenic trioxide (ATO), an inorganic arsenical, is a toxic environmental contaminant. It is also a widely used chemical with industrial and medicinal uses. Significant public health risk exists from its intentional or accidental exposure. The pulmonary pathology of acute high dose exposure is not well defined. We developed and characterized a murine model of a single inhaled exposure to ATO, which was evaluated 24 h post-exposure. ATO caused hypoxemia as demonstrated by arterial blood-gas measurements. ATO administration caused disruption of alveolar-capillary membrane as shown by increase in total protein and IgM in the bronchoalveolar lavage fluid (BALF) supernatant and an onset of pulmonary edema. BALF of ATO-exposed mice had increased HMGB1, a damage-associated molecular pattern (DAMP) molecule, and differential cell counts revealed increased neutrophils. BALF supernatant also showed an increase in protein levels of eotaxin/CCL-11 and MCP-3/CCL-7 and a reduction in IL-10, IL-19, IFN-γ, and IL-2. In the lung of ATO-exposed mice, increased protein levels of G-CSF, CXCL-5, and CCL-11 were noted. Increased mRNA levels of TNF-a, and CCL2 in ATO-challenged lungs further supported an inflammatory pathogenesis. Neutrophils were increased in the blood of ATO-exposed animals. Pulmonary function was also evaluated using flexiVent. Consistent with an acute lung injury phenotype, respiratory and lung elastance showed significant increase in ATO-exposed mice. PV loops showed a downward shift and a decrease in inspiratory capacity in the ATO mice. Flow-volume curves showed a decrease in FEV0.1 and FEF50. These results demonstrate that inhaled ATO leads to pulmonary damage and characteristic dysfunctions resembling ARDS in humans.


Assuntos
Lesão Pulmonar Aguda , Arsenicais , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Pulmão/patologia , Líquido da Lavagem Broncoalveolar/química
7.
Int J Toxicol ; 42(1): 50-62, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36280476

RESUMO

Hesperetin glucosides such as hesperidin and hesperetin-7-glucoside are abundantly present in citrus fruits and have various pharmacological properties. However, the potential toxicity of hesperetin glucosides remains unclear. An initial assessment of the safety of hesperetin-7-glucoside-ß-cyclodextrin inclusion complex (HPTGCD) as a functional food ingredient was undertaken to assess toxicity and mutagenic potential. A bacterial reverse mutation assay (Ames test) using Salmonella typhimurium (strains TA98, TA1535, TA100, and TA1537) and Escherichia coli (strain WP2 uvrA) with HPTGCD (up to 5000 µg/plate) in the absence and presence of metabolic activation was negative. In a single oral (gavage) toxicity study in male and female rats, HPTGCD at dose up to 2000 mg/kg did not produce mortality nor clinical signs of toxicity or change in body weight. In a subchronic oral (dietary admix) toxicity study in rats receiving 0, 1.5, 3, and 5% HPTGCD for 13 weeks, no adverse effects were noted and the no-observed-adverse-effect level (NOAEL) was 5% in the diet (equivalent to 3267.7 mg/kg/day for males and to 3652.4 mg/kg/day for females). These results provide initial evidence of the safety of HPTGCD.


Assuntos
Hesperidina , Mutagênicos , Ratos , Masculino , Feminino , Animais , Testes de Mutagenicidade/métodos , Hesperidina/toxicidade , Mutação
8.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674505

RESUMO

Cellulose of bacterial origin, known as bacterial cellulose (BC), is one of the most versatile biomaterials that has a huge potential in tissue engineering due to its favourable mechanical properties, high hydrophilicity, crystallinity, and purity. Additional properties such as porous nano-fibrillar 3D structure and a high degree of polymerisation of BC mimic the properties of the native extracellular matrix (ECM), making it an excellent material for the fabrication of composite scaffolds suitable for cell growth and tissue development. Recently, the fabrication of BC-based scaffolds, including composites and blends with nanomaterials, and other biocompatible polymers has received particular attention owing to their desirable properties for tissue engineering. These have proven to be promising advanced materials in hard and soft tissue engineering. This review presents the latest state-of-the-art modified/functionalised BC-based composites and blends as advanced materials in tissue engineering. Their applicability as an ideal biomaterial in targeted tissue repair including bone, cartilage, vascular, skin, nerve, and cardiac tissue has been discussed. Additionally, this review briefly summarises the latest updates on the production strategies and characterisation of BC and its composites and blends. Finally, the challenges in the future development and the direction of future research are also discussed.


Assuntos
Materiais Biocompatíveis , Engenharia Tecidual , Materiais Biocompatíveis/química , Celulose/química , Alicerces Teciduais/química , Polímeros , Bactérias/química
9.
J Clin Biochem Nutr ; 72(2): 189-197, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36936875

RESUMO

Partially hydrolyzed guar gum dietary fiber is well recognized for a number of health benefits. In the present study, we aim to investigate the effects of partially hydrolyzed guar gum on constipation, intestinal microbiota as well as mental health in healthy subjects. In the randomized, parallel, double-blind, and placebo-controlled study the enrolled healthy men and women volunteers took either 3 g/day (T3) or 5 g/day (T5) of dietary fiber intakes for eight consecutive weeks compared to placebo (T0). The fecal characteristics, fecal microbiota, defecation characteristics, and quality of life (QOL) questionnaire were investigated. The results revealed a significant suppression in fecal potent harmful mucolytic bacteria in the T3 and T5 groups compared to the T0 group. The defecation frequency, excretory feeling, and scores of sleep and motivation questionnaire were also improved in the dietary fiber intake groups, showing a significant difference in the T5 group compared to the T0 group. In summary, the consumption of partially hydrolyzed guar gum dietary fiber is found effective in suppressing the potent harmful mucolytic bacteria that could be associated with the improvement of constipation-related symptoms including mental health in terms of sleep and motivation among the healthy subjects.

10.
Medicina (Kaunas) ; 59(6)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37374226

RESUMO

Metabolic syndrome is a multifaceted pathophysiologic condition that is largely caused by an imbalance between caloric intake and energy expenditure. The pathogenesis of metabolic syndrome is determined by an individual's genetic/epigenetics and acquired factors. Natural compounds, notably plant extracts, have antioxidant, anti-inflammatory, and insulin-sensitizing properties and are considered to be a viable option for metabolic disorder treatment due to their low risk of side effects. However, the limited solubility, low bioavailability, and instability of these botanicals hinder their performance. These specific limitations have prompted the need for an efficient system that reduces drug degradation and loss, eliminates unwanted side effects, and boosts drug bioavailability, as well as the percentage of the drug deposited in the target areas. The quest for an enhanced (effective) drug delivery system has led to the formation of green-engineered nanoparticles, which has increased the bioavailability, biodistribution, solubility, and stability of plant-based products. The unification of plant extracts and metallic nanoparticles has helped in the development of new therapeutics against metabolic disorders such as obesity, diabetes mellitus, neurodegenerative disorders, non-alcoholic fatty liver, and cancer. The present review outlines the pathophysiology of metabolic diseases and their cures with plant-based nanomedicine.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Metabólicas , Síndrome Metabólica , Nanopartículas Metálicas , Nanopartículas , Humanos , Distribuição Tecidual , Nanopartículas/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
11.
Mediators Inflamm ; 2022: 3300903, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248189

RESUMO

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.


Assuntos
Microbioma Gastrointestinal , Microbiota , Doenças Neurodegenerativas , Encéfalo , Microbioma Gastrointestinal/fisiologia , Humanos
13.
Drug Chem Toxicol ; 45(3): 1131-1139, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32838564

RESUMO

The effluents from textile dyeing industry are causing water pollution and may transform into more toxic and carcinogenic chemical species by environmental conditions. Therefore systemic toxicity of textile dyes is major health concern. Hence, this study sought to examine the toxic effect of disperse textile dyes on important systemic enzymes in the larvae of wild type Drosophila melanogaster (Oregon R+). Drosophila larvae were fed with corn-sugar-yeast diets containing two disperse dyes, Disperse blue-124 and Disperse black-9 (1, 10 and 100 mg/mL) for 2 days (48 h) and subsequent the enzymatic estimations were carried out using larval homogenate. In silico molecular docking studies were also performed to analyze the binding interaction of these dyes with acetyl choline esterase enzyme. Disperse black 9 shows more strong binding by occupying a groove and forming one hydrogen bond with Tyr465 of acetyl choline esterase enzyme while Disperse blue-124 shows surface binding without forming any hydrogen bond. Drosophila larvae fed on these dyes exhibited a dose-dependent increase in acetyl choline esterase enzymatic activity (1.8 fold increase with Disperse black-9, 100 mg/mL) while 4.4-folds Disperse blue-124, 100 mg/mL). Both Disperse Blue and Disperse Black dyes altered the activities of antioxidant enzymes Catalase (CAT, increased more than 2.5 fold), Superoxide dismutase (SOD, increased more than two folds) and showed a dose-dependent increase in Xanthine oxidase and lipid peroxidation (LPO) levels (more than 3 folds). Therefore both the disperse dyes were found to dysregulate the activities of antioxidant enzymes which may be the underlying mechanism for their toxic effects.


Assuntos
Drosophila melanogaster , Poluentes Químicos da Água , Animais , Antioxidantes , Colina , Colinesterases , Corantes/toxicidade , Esterases , Simulação de Acoplamento Molecular , Oregon , Têxteis , Poluentes Químicos da Água/toxicidade
14.
Molecules ; 27(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36080157

RESUMO

Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7-O-glucoside inclusion complex with ß-cyclodextrin (HEPT7G/ßCD; SunActive® HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with naringinase enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis. The objective of this study was to investigate the stability, solubility, and spectroscopic features of the HEPT7G/ßCD inclusion complex using Fourier-transform infrared (FTIR), Raman, ultraviolet-visible absorption (UV-vis), 1H- and 13C- nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC-MS), scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) spectroscopic techniques including zeta potential, Job's plot, and phase solubility measurements. The effects of complexation on the profiles of supramolecular interactions in analytic features, especially the chemical shifts of ß-CD protons in the presence of the HEPT7G moiety, were evaluated. The stoichiometric ratio, stability, and solubility constants (binding affinity) describe the extent of complexation of a soluble complex in 1:1 stoichiometry that exhibits a greater affinity and fits better into the ß-CD inner cavity. The NMR spectroscopy results identified two different configurations of the HEPT7G moiety and revealed that the HEPT7G/ßCD inclusion complex has both -2S and -2R stereoisomers of hesperetin-7-O-glucoside possibly in the -2S/-2R epimeric ratio of 1/1.43 (i.e., -2S: 41.1% and -2R: 58.9%). The study indicated that encapsulation of the HEPT7G moiety in ß-CD is complete inclusion, wherein both ends of HEPT7G are included in the ß-CD inner hydrophobic cavity. The results showed that the water solubility and thermal stability of HEPT7G were apparently increased in the inclusion complex with ß-CD. This could potentially lead to increased bioavailability of HEPT7G and enhanced health benefits of this flavonoid.


Assuntos
Hesperidina , beta-Ciclodextrinas , Varredura Diferencial de Calorimetria , Flavonoides/química , Glucosídeos , Prótons , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X , beta-Ciclodextrinas/química
15.
Molecules ; 27(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36500720

RESUMO

Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.


Assuntos
Antioxidantes , Urtica dioica , Humanos , Antioxidantes/química , Células Hep G2 , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectroscopia de Infravermelho com Transformada de Fourier , Fenóis/química , Flavonoides/farmacologia , Flavonoides/análise , Quercetina
16.
Indian J Palliat Care ; 28(1): 37-42, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35673384

RESUMO

Objectives: Increased levels of psychological distress and burnout in cancer palliative care professionals have implications on their psychological well-being, quality of patient care they provide and for their employing organisations. There is a dearth of studies on psychological well-being with no published study available on psychological well-being amongst cancer palliative care professionals in India. The aim of the present study was to assess psychological well-being amongst cancer palliative care professionals. Materials and Methods: The study was cross-sectional and quantitative which was carried out at four cancer palliative care centers (one hospice and three hospitals) in Bengaluru city of India. The tools sociodemographic and professional datasheet and psychological well-being (PWB-20) scale were administered with 65 participants (Mean Age = 32.5, SD = 11.78). Purposive sampling method was used to recruit the participants working full-time at respective centers after obtaining permissions and ethical approvals. Descriptive, correlational, and inferential analysis of the quantitative data was carried out based on normality of the distribution. Results: The results revealed above average levels of self-acceptance and engagement and growth, below average levels of mastery and competence, while average levels of positive relations and PWB (total score). Significant differences in PWB domains based on age (P < 0.05) and self-care practices (P < 0.05) were seen. Sense of engagement and growth was found to be positively correlated with age and income earned per month (P = 0.01). Conclusion: Findings from the present study suggest that cancer palliative care professionals had moderate levels of PWB with implications in training and future research.

17.
Bioorg Chem ; 106: 104454, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33213895

RESUMO

Being crucial part of plant-based novel discovery of drug from natural resources, a study was done to explore the antibacterial potential of curcumin mimics in combination with antibiotics against multidrug resistant isolates of Pseudomonas aeruginosa. The best candidate Van D, a curcumin mimics reduced the MIC of tetracycline (TET) up to 16 folds against multidrug resistant clinical isolates. VanD further inhibited the efflux pumps as evident by ethidium bromide efflux and by in-silico docking studies. In another experiment, it was also found that Van D inhibits biofilm synthesis. This derivative kills the KG-P2, an isolate of P. aeruginosa in a time dependent manner, the post-antibiotic effect (PAE) of tetracycline was extended as well as mutant prevention concentration (MPC) of TET was also decreased. In Swiss albino mice, Van D reduced the proinflammatory cytokines concentration. In acute oral toxicity study, this derivative was well tolerated and found to be safe up to 1000 mg/kg dose. To the best of our knowledge, this is the first report on curcumin mimics as synergistic agent via inhibition of efflux pump.


Assuntos
Antibacterianos/uso terapêutico , Chalconas/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/metabolismo , Antibacterianos/toxicidade , Proteínas da Membrana Bacteriana Externa/metabolismo , Biofilmes/efeitos dos fármacos , Chalconas/síntese química , Chalconas/metabolismo , Chalconas/toxicidade , Curcumina/química , Curcumina/farmacologia , Desenho de Fármacos , Sinergismo Farmacológico , Feminino , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Ligação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Tetraciclina/farmacologia
18.
Biosci Biotechnol Biochem ; 85(10): 2195-2199, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34347032

RESUMO

The pharmacokinetics of compounds comprising hesperetin-7-glucoside with ß-cyclodextrin and physically mixed hesperidin/dextrin was compared in 8 healthy adult male subjects in a nonrandomized, double-blind, cross-over, controlled study. For 0-24 h, the area under the curve of the total plasma hesperetin concentration after hesperetin-7-glucoside with ß-cyclodextrin consumption was >100-fold higher than that after hesperidin/dextrin consumption.


Assuntos
Hesperidina/análogos & derivados , Adulto , Disponibilidade Biológica , Humanos
19.
Molecules ; 26(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204433

RESUMO

Catechins are a part of the chemical family of flavonoids, a naturally occurring antioxidant, and a secondary metabolite in certain plants. Green tea catechins are well recognized for their essential anti-inflammatory, photo-protective, antioxidant, and chemo-preventive functions. Ultraviolet radiation is a principal cause of damage to the skin. Studies observed that regular intake of green tea catechins increased the minimal dose of radiation required to induce erythema. The objectives of this systematic review and meta-analysis are to determine the effectiveness of green tea catechins in cutaneous erythema and elucidate whether green tea catechin consumption protects against erythema (sunburn) inflammation. A comprehensive literature search was conducted to identify the relevant studies. Two researchers carried out independent screening, data extraction, and quality assessment according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The pooled effect of green tea catechins on protection against erythema was assessed using approaches fixed-effects or random-effects model to quantify the effectiveness of green tea catechins in the erythema dose-response. Studies not be included in meta-analyses were summarized narratively. Six randomized controlled studies of enrolled studies regularly administrated green tea catechins orally for 6 to 12 weeks involving healthy volunteers comprising a total of 100 participants were included in the analysis. The results revealed green tea catechins have favorable protection against erythema inflammation even at increased minimal erythema dose (MED) of ultraviolet radiation. Meta-analysis results confirm oral supplementation of green tea catechins is highly effective at low-intensity ultraviolet radiation-induced erythema response (MED range; 1.25-1.30) compared to placebo, showing a significant pooling difference (p = 0.002) in erythema index (SMD: -0.35; 95% CI, -0.57 to -0.13; I2 = 4%, p = 0.40) in the random-effects model. The pro-inflammatory signaling pathways through oral supplementation with green tea catechins are an attractive strategy for photo-protection in healthy human subjects and could represent a complementary approach to topical sunscreens. Therefore, studies that involved green tea catechin in topical applications to human subjects were also evaluated separately, and their meta-analysis is presented as a reference. The evidence indicates that regular green tea catechin supplementation is associated with protection against UV-induced damage due to erythema inflammation.


Assuntos
Catequina/farmacologia , Eritema/tratamento farmacológico , Chá/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Catequina/química , Eritema/metabolismo , Eritema/prevenção & controle , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Inflamação/tratamento farmacológico , Pele/metabolismo , Protetores Solares/farmacologia , Chá/metabolismo , Raios Ultravioleta/efeitos adversos
20.
Indian J Palliat Care ; 27(4): 544-551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34898950

RESUMO

OBJECTIVES: Cancer palliative care professionals face a plethora of challenges related to death, dying and suffering apart from limited workforce and other resources in India. However, the grief held by them is underappreciated and psychological needs are under explored. The aim of the present study was to explore felt needs of cancer palliative care professionals working in India. MATERIALS AND METHODS: The study was cross-sectional, qualitative and in-depth in nature. It was conducted across four cancer palliative care centers in Bengaluru city of India. sample consisted of 15 professionals (mean age = 42 years and standard deviation = 8.41) with at least six months of experience, involved in direct patient care who gave an additional consent for audio-recording. The tools used were sociodemographic and professional datasheet and semi-structured interview guide, which were developed for the present study and validated from five experts. Thematic analysis was used to generate and analyze patterns within the qualitative data. RESULTS: Five themes were identified, namely, death and grief; challenges in practice; strategies for self-care; positive professional experiences; and vision for palliative care. CONCLUSION: The cancer palliative care professionals need regular support in coping with death and grief, regular trainings and supervision across workplace to deal with occupational challenges, and to address their self-care and spiritual needs. The study highlights need to introduce more specialized training courses in handling pediatric patients, increase palliative care workforce, and hospice units. This can have implications in future research and training with development of innovative interventions to address these needs and challenges.

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