Abstract:
:Induction of premature senescence represents a novel functional strategy to curb the uncontrolled proliferation of malignant cancer cells. This study unveils the regiospecific synthesis of novel isoxazoline derivatives condensed to ring A of medicinal plant product Withaferin-A. Intriguingly, the cis fused products with β-oriented hydrogen exhibited excellent cytotoxic activities against proliferating human breast cancer MCF7 and colorectal cancer HCT-116 cells. The most potent derivative W-2b triggered premature senescence along with increase in senescence-associated β-galactosidase activity, G2/M cell cycle arrest, and induction of senescence-specific marker p21Waf1/Cip1 at its sub-toxic concentration. W-2b conferred a robust increase in phosphorylation of mammalian checkpoint kinase-2 (Chk2) in cancer cells in a dose-dependent manner. Silencing of endogenous Chk2 by siRNA divulged that the amplification of p21 expression and senescence by W-2b was Chk2-dependent. Chk2 activation (either by ectopic overexpression or through treatment with W-2b) suppressed NM23-H1 signaling axis involved in cancer cell proliferation. Finally, W-2b showed excellent in vivo efficacy with 83.8% inhibition of tumor growth at a dose of 25 mg/kg, b.w. in mouse mammary carcinoma model. Our study claims that W-2b could be a potential candidate to limit aberrant cellular proliferation rendering promising improvement in the treatment regime in cancer patients.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Rasool F,Nayak D,Katoch A,Faheem MM,Yousuf SK,Hussain N,Belawal C,Satti NK,Goswami A,Mukherjee Ddoi
10.1038/s41598-017-13664-xsubject
Has Abstractpub_date
2017-10-23 00:00:00pages
13749issue
1issn
2045-2322pii
10.1038/s41598-017-13664-xjournal_volume
7pub_type
杂志文章abstract::Sodium taurocholate cotransporting polypeptide (NTCP) is a recently discovered hepatitis B virus (HBV) receptor. In the present study, we used TK-NOG mice with a humanized liver to examine the impact of endogenous NTCP expression on HBV infection. Upon inoculation with HBV, these mice exhibited clear viremia in 2 week...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep27782
更新日期:2016-06-09 00:00:00
abstract::Gold is a noble metal typically stable as a solid in a face-centered cubic (FCC) structure under ambient conditions; however, under particular circumstances aberrant allotropes have been synthesized. In this work, we document the phase transformation of 25 nm thick nanocrystalline (NC) free-standing gold thin-film via...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-74779-2
更新日期:2020-10-20 00:00:00
abstract::The cholinergic system plays a major anti-inflammatory role in many diseases through acetylcholine (Ach) release after vagus nerve stimulation. Osteoarthritis (OA) is associated with local low-grade inflammation, but the regulatory mechanisms are unclear. Local Ach release could have anti-inflammatory activity since a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-65873-6
更新日期:2020-06-01 00:00:00
abstract::The critical importance of human milk to infants and even human civilization has been well established. Yet our understanding of the milk microbiome has been limited to cataloguing OTUs and computation of community diversity. To the best of our knowledge, there has been no report on the bacterial interactions within t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08275
更新日期:2015-02-05 00:00:00
abstract::Biological invasions are a major threat to biodiversity and ecosystem functioning. Successful invasions depend on the interplay of multiple abiotic and biotic factors, however, the process of the invasion itself is often overlooked. The temporal variation of environmental factors suggests that a 'window of opportunity...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-44737-8
更新日期:2019-06-05 00:00:00
abstract::M2BP (also called 90K) is an interferon-stimulated gene product that is upregulated in HIV-1 infection. A recent study revealed that M2BP reduces the infectivity of HIV-1 by inhibiting the processing of the viral envelope protein. Here we report that in addition to reducing viral infectivity, M2BP inhibits HIV-1 virio...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep32736
更新日期:2016-09-08 00:00:00
abstract::Intracellular endogenous fluorescent co-enzymes, reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), play a pivotal role in cellular metabolism; quantitative assessment of their presence in living cells can be exploited to monitor cellular energetics in Parkinson's disease (PD), a n...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep19145
更新日期:2016-01-13 00:00:00
abstract::Low phase noise mode-locked fiber laser finds important applications in telecommunication, ultrafast sciences, material science, and biology, etc. In this paper, two types of carbon nano-materials, i.e. single-wall carbon nanotube (SWNT) and graphene oxide (GO), are investigated as efficient saturable absorbers (SAs) ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep25266
更新日期:2016-04-29 00:00:00
abstract::Vibrio vulnificus causes fatal infections in humans, and antibiotics are commonly used in treatment regimens against V. vulnificus infection. However, the therapeutic effects of antibiotics are limited by multidrug resistance. In this study, we demonstrated that an antimicrobial peptide (AMP), HPA3PHis, loaded onto a ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-14127-z
更新日期:2017-10-19 00:00:00
abstract::Multimodal polymeric nanoparticles have many exciting diagnostic and therapeutic applications, yet their uptake and passage by the placenta, and applications in the treatment of pregnancy complications have not been thoroughly investigated. In this work, the maternal-fetal-placental biodistribution of anionic and cati...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03128-7
更新日期:2017-06-06 00:00:00
abstract::The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident an...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep26379
更新日期:2016-05-20 00:00:00
abstract::In April 2012 we carried out a 1-year hematological study on a population of wild Japanese monkeys inhabiting the forest area of Fukushima City. This area is located 70 km from the Fukushima Daiichi Nuclear Power Plant (NPP), which released a large amount of radioactive material into the environment following the Grea...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep05793
更新日期:2014-07-24 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-64341-5
更新日期:2020-04-29 00:00:00
abstract::We report the experimental observation of extreme instabilities in a self-pulsing fiber laser under the influence of stimulated Brillouin scattering (SBS). Specifically, we observe temporally localized structures with high intensities that can be referred to as rogue events through their statistical behaviour with hig...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep45868
更新日期:2017-04-04 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-60509-1
更新日期:2020-02-20 00:00:00
abstract::Salt crystallization is a major cause of weathering of rocks, artworks and monuments. Damage can only occur if crystals continue to grow in confinement, i.e. within the pore space of these materials, thus generating mechanical stress. We report the direct measurement, at the microscale, of the force exerted by growing...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep30856
更新日期:2016-08-05 00:00:00
abstract::Results from live cell imaging of fluorescently tagged Cellulose Synthase (CESA) proteins in Cellulose Synthesis Complexes (CSCs) have enhanced our understanding of cellulose biosynthesis, including the mechanisms of action of cellulose synthesis inhibitors. However, this method has been applied only in Arabidopsis th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-18994-4
更新日期:2018-01-15 00:00:00
abstract::Podocyte loss is the initial event in the development of glomerulosclerosis, the structural hallmark of progressive proteinuric nephropathies. Understanding mechanisms underlying glomerular injury is the key challenge for identifying novel therapeutic targets. In mice with protein-overload induced by bovine serum albu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep28445
更新日期:2016-06-27 00:00:00
abstract::Marine blue holes are precious geological heritages with high scientific research values. Their physical and chemical characteristics are unique because of the steep-walled structure and isolated water column which create isolated ecosystems in geographically restricted areas. The Sansha Yongle Blue Hole (SYBH) is the...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-67221-0
更新日期:2020-06-24 00:00:00
abstract::It is believed that motor performance improves when individuals direct attention to movement outcome (external focus, EF) rather than to body movement itself (internal focus, IF). However, our previous study found that an optimal individual attentional strategy depended on motor imagery ability. We explored whether th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep40592
更新日期:2017-01-17 00:00:00
abstract::Although re-sequencing of gene panels and mRNA expression profiling are now firmly established in clinical laboratories, in-depth proteome analysis has remained a niche technology, better suited for studying model systems rather than challenging materials such as clinical trial samples. To address this limitation, we ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34949
更新日期:2016-10-07 00:00:00
abstract::People mimic each other's actions and postures during everyday interactions. It is widely believed this mimicry acts as a social glue, leading to increased rapport. We present two studies using virtual reality to rigorously test this hypothesis. In Study 1, 50 participants interacted with two avatars who either mimick...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep35295
更新日期:2016-10-14 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-020-60910-w
更新日期:2020-02-28 00:00:00
abstract::We propose a homomorphic search protocol based on quantum homomorphic encryption, in which a client Alice with limited quantum ability can give her encrypted data to a powerful but untrusted quantum server and let the server search for her without decryption. By outsourcing the interactive key-update process to a trus...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-61791-9
更新日期:2020-03-20 00:00:00
abstract::To compare the pattern of cause of death of infant mortality rates by urban/rural areas as well as to generate knowledge for potential strategies to decrease this mortality, we carried out a study by analyzing the infant mortality data from the Shenyang Women and Children Health Care Centre. From 1997 to 2014, 970,583...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep24527
更新日期:2016-04-14 00:00:00
abstract::The study of factors influencing animal intake can provide a better understanding of the dynamics of the pasture ecosystem and serve as a basis for managing livestock in a more efficient way. We measured different sward surface heights of tall fescue in the process of short-term intake rate of sheep. There was a signi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-68827-0
更新日期:2020-07-16 00:00:00
abstract::In humans, stress can be contagiously transmitted via chemosignals on a subconscious level. This study investigates how pregnancy affects neural responses to anxiety chemosignals. Using cotton pads, 28 men donated axillary sweat immediately before an academic examination (anxiety sweat) and during ergometer training (...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-07985-0
更新日期:2017-08-23 00:00:00
abstract::We fabricated multi-layered graphene/MoS2 heterostructured devices by positioning mechanically exfoliated bulk graphite and single-crystalline 2H-MoS2 onto Au metal pads on a SiO2/Si substrate via a contamination-free dry transfer technique. We also studied the electrical transport properties of Au/MoS2 junction devic...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep13743
更新日期:2015-09-03 00:00:00
abstract::The helicase Twinkle is indispensable for mtDNA replication in nucleoids. Previously, we showed that Twinkle is tightly membrane-associated even in the absence of mtDNA, which suggests that Twinkle is part of a membrane-attached replication platform. Here we show that this platform is a cholesterol-rich membrane struc...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep15292
更新日期:2015-10-19 00:00:00
abstract::Invasive aspergillosis (IA) is a life-threatening complication among allogeneic hematopoietic stem cell transplant (alloSCT) recipients. Despite well known risk factors and different available assays, diagnosis of invasive aspergillosis remains challenging. 103 clinical variables from patients with hematological malig...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-53504-8
更新日期:2019-11-21 00:00:00