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1.
Artigo em Inglês | MEDLINE | ID: mdl-32364084

RESUMO

Background - Obesity has become a global disease, leading to the enhanced risk of metabolic syndrome which includes diabetes, cardiovascular disease, stroke, hypertension and certain cancers but it is difficult to control only by diet and exercise as they are difficult to implement. Objective- The objective of this review is to bring into light the active constituents that can be obtained from various natural sources which act as anti-obesity agents because with a global rise in the prevalence of obesity, an urgent need to prevent and control it has arisen. Method- For this review, we have compiled information about natural anti-obesity products, by an electronic search of the articles available on PubMed, Scopus and other internet sources for the duration of1975-2019and added my own research too. We have analyzed and organized data on various natural products in popular use and pharmacognostical and biological studies of them. Their mechanisms of action have also been studied. Conclusion-Consumption of diets comprising high amounts of active anti-obesity natural compounds is a promising strategy for the suppression of lipid accumulation and adipogenesis in obese individuals.

2.
Future Med Chem ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32349522

RESUMO

Cancer, characterized by uncontrolled malignant neoplasm, is a leading cause of death in both advanced and emerging countries. Although, ample drugs are accessible in the market to intervene with tumor progression, none are totally effective and safe. Natural anthraquinone (AQ) equivalents such as emodin, aloe-emodin, alchemix and many synthetic analogs extend their antitumor activity on different targets including telomerase, topoisomerases, kinases, matrix metalloproteinases, DNA and different phases of cell lines. Nano drug delivery strategies are advanced tools which deliver drugs into tumor cells with minimum drug leakage to normal cells. This review delineates the way AQ derivatives are binding on these targets by abolishing tumor cells to produce anticancer activity and purview of nanoformulations related to AQ analogs.

3.
QJM ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374836
4.
J Neurosci ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376783

RESUMO

Age-related cognitive impairments are associated with differentially expressed genes (DEGs) linked to defined neural systems; however, studies examining multiple regions of the hippocampus fail to find links between behavior and transcription in the dentate gyrus (DG). We hypothesized that use of a task requiring intact DG function, would emphasize molecular signals in the DG associated with a decline in performance. We used a water maze beacon discrimination task to characterize young and middle-age male F344 rats, followed by a spatial reference memory probe trial test. Middle-age rats showed increased variability in discriminating two identical beacons. Use of an allocentric strategy and formation of a spatial reference memory was not different between age groups; however, older animals compensated for impaired beacon discrimination through greater reliance on spatial reference memory. mRNA sequencing of hippocampal subregions indicated DEGs in the DG of middle-age rats, linked to synaptic function and neurogenesis, correlated with beacon discrimination performance, suggesting that senescence of the DG underlies the impairment. Few genes correlated with spatial memory across age groups, with a greater number in region CA1. Age-related CA1 DEGs, correlated with spatial memory, were linked to regulation of neural activity. These results indicate that the beacon task is sensitive to impairment in middle-age, and distinct gene profiles are observed in neural circuits that underlie beacon discrimination performance and allocentric memory. The use of different strategies in older animals and associated transcriptional profiles could provide an animal model for examining cognitive reserve and neural compensation of aging.Significance StatementHippocampal subregions are thought to differentially contribute to memory. We took advantage of age-related variability in performance on a water maze beacon task and next generation sequencing to test the hypothesis that aging of the dentate gyrus (DG) is linked to impaired beacon discrimination and compensatory use of allocentric memory. The DG expressed synaptic function and neurogenesis genes correlated with beacon discrimination in middle-age animals. Spatial reference memory was associated with CA1 transcriptional correlates linked to regulation of neural activity and use of an allocentric strategy. This is the first study examining transcriptomes of multiple hippocampal subregions to link age-related impairments associated with discrimination of feature overlap and alternate response strategies to gene expression in specific hippocampal subregions.

5.
Asian Cardiovasc Thorac Ann ; : 218492320927200, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418436

RESUMO

Isolated cardiac hydatid cyst is a rare entity. It warrants early surgical repair because cyst rupture is potentially fatal. We report the case of a 32-year-old lady with an epicardial ventricular hydatid cyst, which was managed successfully by complete cyst excision.

7.
Med Leg J ; : 25817220923653, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32437298

RESUMO

Hunger strike is a protest where an informed person refuses essential nourishment with the intention of accomplishing a specific goal. Hunger strikes conflict with medical, ethical, humanitarian and legal values. A multidisciplinary approach is important when dealing with hunger strike patients. On one hand, there is the wish to preserve life, and on the other to respect the strikers' autonomy and their wishes, values and advanced directives (or living will). Most hunger strikes are short-lived, but in complex and prolonged circumstances, legal advice must be sought from health service solicitors and a doctor's medical indemnity organisation. There is an emergent need to have defined guidelines for the management of these hunger strikes to be followed.

8.
Exp Eye Res ; : 108079, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32454039

RESUMO

Previously, we have shown that Staphylococcus (S) aureus induces a glycolytic response in retinal residential (microglia) and infiltrated cells (neutrophils and macrophages) during endophthalmitis. In this study, we sought to investigate the physiological role of glycolysis in bacterial endophthalmitis using a glycolytic inhibitor, 2-deoxyglucose (2DG). Our data showed that 2DG treatment attenuated the inflammatory responses of mouse bone marrow-derived macrophages (BMDM) and neutrophils (BMDN) when challenged with either live or heat-killed S. aureus (HKSA). Among the inflammatory mediators, 2DG caused a significant reduction in levels of cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CXCL1 and CXCL2). Western blot analysis of 2DG treated cells showed downregulation of bacterial-induced MEK/ERK pathways. In vivo, intravitreal administration of 2DG both pre- and post-bacterial infection resulted in a significant reduction in intraocular inflammation in C57BL/6 mouse eyes and downregulation of ERK phosphorylation in retinal tissue. Collectively, our study demonstrates that 2DG attenuates inflammatory response in bacterial endophthalmitis and cultured innate immune cells via inhibition of ERK signaling. Thus glycolytic inhibitors in combination with antibiotics could mitigate inflammation-mediated tissue damage in ocular infections.

10.
Clin Med (Lond) ; 20(3): e24-e25, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32414737

RESUMO

Presence of human leucocyte antigen (HLA) B27 in a patient with lower-back pain should not be considered synonymous with axial spondyloarthritis. Other causes of back pain should be ruled-out by careful evaluation. Lumbosacral transitional vertebra is a common congenital malformation of spine which frequently leads to mechanical back pain. We present a young man with lower-back pain who had HLA B27. He was labelled with axial spondyloarthritis elsewhere and was given etanercept without benefit. Further evaluation revealed that he had lumbosacral transitional vertebra and spina bifida occulta. No evidence of sacroiliitis was found. Etanercept was stopped and he was started on physiotherapy protocol for transitional vertebra, with which he improved remarkably. This case highlights the need for greater awareness among clinicians about lumbosacral transitional vertebra, a finding which is frequently missed. Presence of HLA B27 can be coincidental, as in our case.

11.
Biomaterials ; 249: 120020, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32305816

RESUMO

Lack of oxygen, reduced vascularization, elevated oxidative stress, and infection are critical clinical hallmarks of non-healing chronic diabetic wounds. Therefore, delivering oxygen, inducing angiogenesis, and management of oxidative stress and infection may provide newer and improved therapeutic avenues for better clinical outcomes in diabetic wound healing. Here, we report the development and evaluation of an exosome laden oxygen releasing antioxidant wound dressing OxOBand to promote wound closure and skin regeneration in diabetic wounds. OxOBand is composed of antioxidant polyurethane (PUAO), as highly porous cryogels with sustained oxygen releasing properties and supplemented with adipose-derived stem cells (ADSCs) exosomes. Exosomes engulfed by the cells enhanced the migration of human keratinocytes and fibroblasts and increased the survival of human neuroblastoma cells under hyperglycemic conditions. OxOBand facilitated faster wound closure, enhanced collagen deposition, faster re-epithelialization, increased neo-vascularization, and decreased oxidative stress within two weeks as compared to untreated diabetic control wounds. The dressing promoted the development of mature epithelial structures with hair follicles and epidermal morphology similar to that of healthy skin. In clinically challenging infected diabetic wounds, these dressings prevented infection and ulceration, improved wound healing with increased collagen deposition, and re-epithelialization. Altogether, OxOBand is a remarkably newer treatment strategy for enhanced diabetic wound healing and may lead to novel therapeutic interventions for the treatment of diabetic ulcers.

12.
Int J Biol Macromol ; 155: 572-580, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32246958

RESUMO

Xylanase is a versatile tool in the food, fiber biobleaching and biofuel industries. Here, to discover new enzyme with special properties, we cloned three xylanases (Xyn11A, Xyn11B, and Xyn11C) by mining the genome of the xylanase producing fungus strain Fusarium sp. 21, biochemically characterized these enzyme and explored their potential application in juice processing. Both Xyn11A and Xyn11B had an optimal pH of 6.0 and optimal temperature of 45 °C, and retained >90% of the residual activity at pH range of 5-10.5 for 24 h. Xyn11C displayed the maximum activity at pH 5.0 and 45 °C and outstanding pH stability with a minimal loss of activity in the pH range of 2.0-10.5. These three xylanases displayed a strong specificity towards beechwood and corncob xylan, with no activity for other substrates. Xyn11A showed much a higher activity against corncob xylan, while Xyn11B and Xyn11C presented higher activities against beechwood xylan. Xyn11A catalyzed the hydrolysis of beechwood xylan with a Km of 4.25 ± 0.29 mg·mL-1 and kcat/Km of 30.34 ± 0.65 mL·s-1·mg-1, while the hydrolysis of corncob xylan had Km and kcat/Km values of 14.73 ± 1.43 mg·mL-1and 26.48 ± 0.11 mL·s-1·mg-1, respectively. Xyn11B and Xyn11C hydrolyzed beechwood xylan with Km of 9.8 ± 0.69 mg·mL-1, and 4.89 ± 0.38 mg·mL-1and kcat/Km values of 45.07 ± 1.66 mL-1·mg-1, and 26.95 ± 0.67 mL·s-1·mg-1, respectively. Beechwood xylan hydrolysates catalyzed by these three xylanases contained xylobiose, xylotriose and xylooligosaccharides (XOS). The clarification of orange juice was improved when treated with these three xylanases. Conclusively, the desirable pH stability and substrate specificity make Xyn11A, Xyn11B and Xyn11C have high potential for application in fiber biobleaching, wine and fruit juice clarification, as well as probiotic XOS production.

13.
Tissue Eng Part A ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32242474

RESUMO

Osteoporosis often leads to fragility fractures of the hip resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) using a calcium sulphate/hydroxyapatite (CaS/HA) biomaterial. A defect was created by reaming the femoral neck canal of osteoporotic (OVX) rats and they were treated as follows: G1. Empty, G2. CaS/HA, G3. CaS/HA + Systemic ZA, G4. CaS/HA + Local ZA and G5. CaS/HA + Local ZA + rhBMP-2. Bone formation was evaluated 6 months after treatment. Furthermore, radioactively labelled 14C-ZA was used to study the bioavailability of ZA at the defect location, which was determined using scintillation counting. Micro-CT indicated significantly higher bone volume (BV) in groups G4 and G5 compared to the other treatment groups. This was confirmed qualitatively by histological assessment. Addition of rhBMP-2 gave no additional benefit in this model. Local delivery of ZA performed better than systemic administration of ZA. Mechanical testing showed no differences between the groups, likely reflecting that the addition of bioactive molecules had limited effect on cortical bone or the choice of mechanical testing setup was not optimal. Scintillation counting revealed higher amounts of 14C-ZA present in the treated leg of G4 compared to its contralateral control and compared to G3 indicating that local ZA delivery can be used to achieve high local concentrations without causing a systemic effect. This long-term study shows that local delivery of ZA using a CaS/HA carrier can regenerate cancellous bone in the femoral neck canal and has clear implications for enhancing implant integration and fixation in fragile bone.

14.
J Clin Neurosci ; 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32317191

RESUMO

Clopidogrel (CLP) is a second generation thienopyridine drug commonly used in secondary prevention of ischemic stroke (IS). Its antiplatelet response maybe variable due to genetic and non-genetic factors. Adipokines may affect platelet aggregation through ADP mediated platelet signalling. However, the combined effect of CYP genetic variants and adipokines on antiplatelet response of clopidogrel is unclear. Patients of IS/Transient ischemic attack (TIAs) within 3 months were prospectively screened following clopidogrel treatment. Major exclusions were cardioembolic and non atherosclerotic strokes. Antiplatelet effect of clopidogrel along with adipokine (Leptin and adiponectin) levels and genotyping of CYP, P2Y12 gene were investigated. Rare genetic variants were confirmed by DNA sequencing. 204 patients with ischemic stroke/TIAs were screened and 163 were recruited. 85 (52.1%) patients were poor responders to clopidogrel. Antiplatelet response to clopidogrel was weaker in females [Median 8.0 (IQR: 3.0-14.0)] compared to males [Median 5.0 (IQR: 2.0-10.0)]. In female subgroup analysis, association was found among high leptin levels and PPI (+) usage in poor responders. None of the genetic variants (CYP2C19*2,*3,*4*, CYP2C9*3, CYP2B6 and P2Y12) were found to influence the antiplatelet effects (p > 0.05). On multivariable logistic regression, a poor clopidogrel response was associated with female gender (Adjusted OR 2.55, 95% CI: 1.05-6.18) and PPI usage (Adjusted OR 2.42, 95% CI: 1.09-5.34). Despite a high prevalence of clopidogrel resistance in the North Indian stroke patients, female gender rather than genetic polymorphisms of CYP and P2Y12 genes may influence its antiplatelet effect. Further research may ascertain the role of gender on clopidogrel response.

15.
Glia ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32275335

RESUMO

During aging humans lose midbrain dopamine neurons, but not all dopamine regions exhibit vulnerability to neurodegeneration. Microglia maintain tissue homeostasis and neuronal support, but microglia become senescent and likely lose some of their functional abilities. Since aging is the greatest risk factor for Parkinson's disease, we hypothesized that aging-related changes in microglia and neurons occur in the vulnerable substantia nigra pars compacta (SNc) but not the ventral tegmental area (VTA). We conducted stereological analyses to enumerate microglia and dopaminergic neurons in the SNc and VTA of 1-, 6-, 9-, 18-, and 24-month-old C57BL/J6 mice using sections double-stained with tyrosine hydroxylase (TH) and Iba1. Both brain regions show an increase in microglia with aging, whereas numbers of TH+ cells show no significant change after 9 months of age in SNc and 6 months in VTA. Morphometric analyses reveal reduced microglial complexity and projection area while cell body size increases with aging. Contact sites between microglia and dopaminergic neurons in both regions increase with aging, suggesting increased microglial support/surveillance of dopamine neurons. To assess neurotrophin expression in dopaminergic neurons, BDNF and TH mRNA were quantified. Results show that the ratio of BDNF to TH decreases in the SNc, but not the VTA. Gait analysis indicates subtle, aging-dependent changes in gait indices. In conclusion, increases in microglial cell number, ratio of microglia to dopamine neurons, and contact sites suggest that innate biological mechanisms compensate for the aging-dependent decline in microglia morphological complexity (senescence) to ensure continued neuronal support in the SNc and VTA.

16.
Nanotechnology ; 31(32): 325702, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32330912

RESUMO

Electronic structure calculations based on density functional theory were performed to investigate structural, mechanical, and electronic properties of phosphorene-based large honeycomb dumbbell (LHD) hybrid structures and a new phosphorene allotrope, referred to as ψ″-P. The LHD hybrids (i.e., X6P4; X being C or Si or Ge or Sn) and ψ″-P have significantly higher bandgaps than the corresponding pristine LHD structures, except the case of C6P4, which is metallic. ψ″-P is found to be a highly flexible p-type material which shows strain-engineered photocatalytic activity in a highly alkaline medium. The carrier mobility of the considered systems is as high as 105 cm2 V-1 s-1 (specifically the electron mobility of LHD structures). The calculated STM images display the surface morphologies of the LHD hybrids and ψ″-P. The predicted phosphorus-based 2D structures with novel electronic properties may be candidate materials for nanoscale devices.

17.
Biomed Mater ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272467

RESUMO

Withania somnifera (Ashwagandha) has been used in Indian traditional medicine for various health benefits. Withaferrin-A, a steroidal lactone present in this herb has shown proteosomal inhibition based enhancement in bone mineralization. In present work chitosan microparticles blending total methanolic root extract of Withania somnifera were incorporated as porogen in calcium phosphate based hydroxyapatite bone filler. The controlled release of bioactive molecules enabled enhanced pre-osteoblast proliferation and differentiation. Microparticle percentages were optimized to have minimum effect on setting time, mechanical strength, and degradability of hydroxyapatite bone filler. In vitro cell adhesion, proliferation and differentiation were evaluated to determine biocompatibility of the composites. Based on desirable results obtained, we provide preliminary rationale for the use of methanolic extract blended chitosan microparticles impregnated calcium phosphate filler for enhanced bone regeneration.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32219719

RESUMO

The present study examines the trend in distribution of Candida species and their antifungal resistance patterns in hospitals across Haryana, a North Indian state with poorly addressed epidemiology of fungal infections. In our collection of 228 Candida isolates, Candida albicans dominated in both high vaginal swab (HVS) and urine samples while Candida glabrata and Candida tropicalis were the second-highest non-albicans Candida species (NAC), respectively. Of note, in blood samples, C. tropicalis and C. albicans were present in equal numbers. All 228 isolates were subjected to antifungal susceptibility tests, whereby 51% of C. albicans recovered from HVS samples displayed fluconazole resistance. To understand its mechanistic basis, expression profiling of efflux pump genes CDR1, CDR2, MDR1 and azole drug target, ERG11 was performed in 20 randomly selected resistant isolates, wherein many isolates elicited higher expression. Further, ERG11 gene sequencing suggested that most of the isolates harbored mutations, which are not reported with azole resistance. However, one isolate, RPCA9 (MIC 64 µg/mL) harbored triple mutation (Y132C, F145L, A114V), wherein Y132 and F145 sites were previously implicated in azole resistance. Interestingly, one isolate, (RPCA61) having MIC > 128 µg/mL harbored a novel mutation, G129R. Of note, HVS isolates RPCA 21, RPCA 22, and RPCA 44 (MICs 64 to > 128 µg/mL) did not show any change in alteration in ERG11 or overexpression of efflux pump genes. Together, this study presents a first report of Candida infections in selected hospitals of Haryana State.

19.
Dermatol Ther ; : e13312, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32173966

RESUMO

Normal human cultured melanocytes were exposed to various glutathione concentrations (0.1, 0.5, 1.0, 5.0, and 10.0 mg/mL) for 72 hours. At the end of the experiment, proliferation, viability, migration, and ultrastructural changes were monitored. Glutathione at the doses of 0.5 to 10.0 mg/mL reduced the viability of melanocytes significantly as compared to the control (P < .05). Glutathione significantly reduced the proliferation of melanocytes at the doses of 0.5 to 10.0 mg/mL as compared to the control (P < .001). Glutathione at 0.5 to 10.0 mg/mL significantly reduced the migration of melanocytes as compared to the control (P < .001). The percentage of mature melanosomes was 53.43% in control and 50.58%, 41.83%, 33.4%, and 8.95% in 0.1, 0.5, 1.0, and 5.0 mg/mL glutathione exposed cells, respectively. This reduction in the number of mature melanosomes was statistically significant as compared to the control. However, no cytotoxic effects were recognized by electron micrographs. These results encourage the potential implementation of glutathione as a skin-lightening agent. However, this study is limited by cell culture and ultrastructural. It should therefore be expanded in the future to include patients with pigmentary disorders.

20.
Nat Neurosci ; 23(4): 544-555, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32203499

RESUMO

Dopaminergic neurons (DANs) drive learning across the animal kingdom, but the upstream circuits that regulate their activity and thereby learning remain poorly understood. We provide a synaptic-resolution connectome of the circuitry upstream of all DANs in a learning center, the mushroom body of Drosophila larva. We discover afferent sensory pathways and a large population of neurons that provide feedback from mushroom body output neurons and link distinct memory systems (aversive and appetitive). We combine this with functional studies of DANs and their presynaptic partners and with comprehensive circuit modeling. We find that DANs compare convergent feedback from aversive and appetitive systems, which enables the computation of integrated predictions that may improve future learning. Computational modeling reveals that the discovered feedback motifs increase model flexibility and performance on learning tasks. Our study provides the most detailed view to date of biological circuit motifs that support associative learning.

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