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John D. Loike Anna Plitt Komal Kothari Jona Zumeris Sadna Budhu Kaitlyn Kavalus Yonatan Ray Harold Jacob 《PloS one》2013,8(8)
Biofilms are structured communities of bacteria that play a major role in the pathogenicity of bacteria and are the leading cause of antibiotic resistant bacterial infections on indwelling catheters and medical prosthetic devices. Failure to resolve these biofilm infections may necessitate the surgical removal of the prosthetic device which can be debilitating and costly. Recent studies have shown that application of surface acoustic waves to catheter surfaces can reduce the incidence of infections by a mechanism that has not yet been clarified. We report here the effects of surface acoustic waves (SAW) on the capacity of human neutrophils to eradicate S. epidermidis bacteria in a planktonic state and within biofilms. Utilizing a novel fibrin gel system that mimics a tissue-like environment, we show that SAW, at an intensity of 0.3 mW/cm2, significantly enhances human neutrophil killing of S. epidermidis in a planktonic state and within biofilms by enhancing human neutrophil chemotaxis in response to chemoattractants. In addition, we show that the integrin CD18 plays a significant role in the killing enhancement observed in applying SAW. We propose from out data that this integrin may serve as mechanoreceptor for surface acoustic waves enhancing neutrophil chemotaxis and killing of bacteria. 相似文献
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Komal Raina Chapla Agarwal Ritambhara Wadhwa Natalie J. Serkova Rajesh Agarwal 《Autophagy》2013,9(5):697-713
Small molecules with the potential to initiate different types of programmed cell death could be useful ‘adjunct therapy’ where current anticancer modalities fail to generate significant activity due to a defective apoptotic machinery or resistance of cancer cells to the specific death mechanism induced by that treatment. The current study identified silibinin, for the first time, as one such natural agent, having dual efficacy against colorectal cancer (CRC) cells. First, silibinin rapidly induced oxidative stress in CRC SW480 cells due to reactive oxygen species (ROS) generation with a concomitant dissipation of mitchondrial potential (ΔΨm) and cytochrome c release leading to mild apoptosis as a biological effect. However, with increased exposure to silibinin, cytoplasmic vacuolization intensified within the cells followed by sequestration of the organelles, which inhibits the further release of cytochrome c. Interestingly, this decrease in apoptotic response correlated with increased autophagic events as evidenced by tracking the dynamics of LC3-II within the cells. Mechanistic studies revealed that silibinin strongly inhibited PIK3CA-AKT–MTOR but activated MAP2K1/2-MAPK1/3 pathways for its biological effects. Corroborating these effects, endoplasmic reticulum stress was generated and glucose uptake inhibition as well as energy restriction were induced by silibinin, thus, mimicking starvation-like conditions. Further, the cellular damage to tumor cells by silibinin was severe and irreparable due to sustained interference in essential cellular processes such as mitochondrial metabolism, phospholipid and protein synthesis, suggesting that silibinin harbors a deadly ‘double-edged sword’ against CRC cells thereby further advocating its clinical effectiveness against this malignancy. 相似文献
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Nimra Akram Naheed Khan Mehreen Ameen Shahmeera Mahmood Komal Shamim Marium Amin 《Chronobiology international》2013,30(9):1262-1268
ABSTRACTSeveral studies have focused on determining the effect of chronotype and learning approach on academic achievement separately indicating that morning types have an academic advantage over the evening types and so have the deep learners over the surface learners. But, surprisingly none have assessed the possible relationship between chronotype and learning approach. So, the current study aimed to evaluate this association and their individual influence on academic performance as indicated by the Cumulative Grade Point Average (CGPA) as well as the effect of their interaction on academic performance. The study included 345 undergraduate medical students who responded to reduced Morningness-Eveningness Questionnaire and Biggs Revised Two-Factor Study Process Questionnaire. Morning types indulged in deep learning while evening types in surface learning. Morning and evening types did not differ on academic performance but deep learners had better academic outcomes than their counterparts. The interaction between chronotype and learning approach was significant on determining academic achievement. Our findings gave the impression that chronotype could have an impact on academic performance not directly but indirectly through learning approaches. 相似文献
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Dong Hyun Kim Nitin Puri Komal Sodhi John R. Falck Nader G. Abraham Joseph Shapiro Michal L. Schwartzman 《Journal of lipid research》2013,54(3):786-793
20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome
P450 (CYP)-catalyzed ω-hydroxylation of arachidonic acid, induces
oxidative stress and, in clinical studies, is associated with increased body
mass index (BMI) and the metabolic syndrome. This study was designed to examine
the effects of exogenous 20-HETE on mesenchymal stem cell (MSC)-derived
adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases
in humans) in MSCs decreased during adipocyte differentiation; however,
exogenous administration of 20-HETE (0.1–1 μM) increased adipogenesis
in a dose-dependent manner in these cells (P < 0.05). The
inability of a 20-HETE analog to reproduce these effects suggested the
involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic
effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2
selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by
20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE2, enhanced
adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of
20-HETE and 20-OH-PGE2 resulted in the increased expression of the
adipogenic regulators PPARγ and β-catenin in MSC-derived adipocytes.
Taken together we show for the first time that 20-HETE-derived COX-2-dependent
20-OH-PGE2 enhances mature inflamed adipocyte hypertrophy in MSC
undergoing adipogenic differentiation. 相似文献
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During the fusion of the influenza virus to the host cell, bending of the HA2 chain of hemagglutinin into a hairpin-shaped structure in a pH-dependent manner facilitates the fusion of the viral envelope and the endosomal membrane. To characterize the structural and dynamical responses of the hinge region of HA2 to pH changes and examine the role of a conserved histidine in this region (the hinge histidine), we have performed an extensive set of molecular dynamics (MD) simulations of 26-residue peptides encompassing the hinge regions of several hemagglutinin subtypes under both neutral and low pH conditions, modeled by the change of the protonation state of the hinge histidine. More than 70 sets of MD simulations (collectively amounting to 25.1 μs) were performed in both implicit and explicit solvents to study the effect of histidine protonation on structural dynamics of the hinge region. In both explicit and implicit solvent simulations, hinge bending was consistently observed upon the protonation of the histidine in all the simulations starting with an initial straight helical conformation, whereas the systems with a neutral histidine retained their primarily straight conformation throughout the simulations. Conversely, the MD simulations starting from an initially bent conformation resulted in the formation of a straight helical structure upon the neutralization of the hinge histidine, whereas the bent structure was maintained when the hinge histidine remained protonated. Finally, mutation of the hinge histidine to alanine abolishes the bending response of the peptide altogether. A molecular mechanism based on the interaction of the hinge histidine with neighboring acidic residues is proposed to be responsible for its role in controlling the conformation of the hinge. We propose that this might present a common mechanism for pH-controlled structural changes in helical structures when histidines act as the pH sensor. 相似文献
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Maliheh Moradzadeh Mohamad Reza Kalani Amir Avan 《Journal of cellular biochemistry》2019,120(4):4732-4738
Saffron (Crocus sativus L.), and its main constituents, crocin, and crocetin have shown promising effects as an antileukemic agent in animal models and cell culture systems. Saffron retards the growth of cancer cells via inhibiting nucleic acid synthesis and enhancing antioxidative system. It can induce apoptosis and chemosensitivity via inhibiting multidrug resistance proteins. Saffron also induces differentiation pathways via inhibiting promyelocytic leukemia/retinoic acid receptor-α, histone deacetylase1, and tyrosyl DNA phosphodiesterase-1 as well. The present review highlights the most recent findings on the antileukemic effects of saffron and its underlying molecular targets. The emerging evidence suggests that saffron has a selective toxicity effect against leukemic cells while is safe for the normal cells. 相似文献
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Komal Preet Allagh B. R. Shamanna Gudlavalleti V. S. Murthy Andy R. Ness Pat Doyle Sutapa B. Neogi Hira B. Pant Wellcome Trust- PHFI Folic Acid project team 《PloS one》2015,10(3)
Background
In the last two decades, India has witnessed a substantial decrease in infant mortality attributed to infectious disease and malnutrition. However, the mortality attributed to birth defects remains constant. Studies on the prevalence of birth defects such as neural tube defects and orofacial clefts in India have reported inconsistent results. Therefore, we conducted a systematic review of observational studies to document the birth prevalence of neural tube defects and orofacial clefts.Methods
A comprehensive literature search for observational studies was conducted in MEDLINE and EMBASE databases using key MeSH terms (neural tube defects OR cleft lip OR cleft palate AND Prevalence AND India). Two reviewers independently reviewed the retrieved studies, and studies satisfying the eligibility were included. The quality of included studies was assessed using selected criteria from STROBE statement.Results
The overall pooled birth prevalence (random effect) of neural tube defects in India is 4.5 per 1000 total births (95% CI 4.2 to 4.9). The overall pooled birth prevalence (random effect) of orofacial clefts is 1.3 per 1000 total births (95% CI 1.1 to 1.5). Subgroup analyses were performed by region, time period, consanguinity, and gender of newborn.Conclusion
The overall prevalence of neural tube defects from India is high compared to other regions of the world, while that of orofacial clefts is similar to other countries. The majority of studies included in the review were hospital based. The quality of these studies ranged from low to moderate. Further well-designed, high quality community-based observational studies are needed to accurately estimate the burden of neural tube defects and orofacial clefts in India. 相似文献9.
Background
Illicit drug use increases the risk of cerebrovascular events by a variety of mechanisms. A recent report suggested that universal urine toxicology (UTox) screening of patients with stroke may be warranted. We aimed to evaluate the diagnostic yield of urine drug screening among unselected patients admitted with acute stroke or transient ischemic attack (TIA).Methods
Using a single-center prospective study design, we evaluated consecutive patients with acute ischemic stroke, TIA, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) over one year. Urine samples were collected within 48 hours of admission and analyzed for common classes of abused drugs. Prevalence of positive UTox screening was determined. We evaluated whether baseline demographics and clinical factors were associated with UTox results.Results
Of 483 eligible patients (acute ischemic stroke 66.4%; TIA 18.8%; ICH 7.7%; SAH 7.0%), 414 (85.7%) completed UTox screening. The mean (standard deviation) age was 65.1 (15.6) years, 52.7% were male, and 64.3% were Caucasian. Twenty-two (4.6%) patients had positive screening—cannabinoids were detected in 13 cases (3.1%), cocaine in 5 cases (1.2%), amphetamines in 1 case, and phencyclidine in 1 case. The highest yield (14.1%) was observed in patients < 60 years old with history of tobacco use while it was < 5% in the remaining subgroups (p<0.01).Conclusions
Consistent with current guidelines, a selective approach to UTox screening should be pursued in acute stroke evaluation. The highest diagnostic yield is likely to be for cannabinoids and cocaine testing in younger patients with a history of concurrent tobacco use. 相似文献10.
Komal Sodhi Nitin Puri Gaia Favero Sarah Stevens Charles Meadows Nader G. Abraham Rita Rezzani Hayden Ansinelli Edward Lebovics Joseph I. Shapiro 《PloS one》2015,10(6)