Cancer is the second deadliest disease worldwide. Although recent advances applying precision treatments with targeted (molecular and immune) agents are promising, the histological and molecular ...heterogeneity of cancer cells and huge mutational burdens (intrinsic or acquired after therapy) leading to drug resistance and treatment failure are posing continuous challenges. These recent advances do not negate the need for alternative approaches such as chemoprevention, the pharmacological approach to reverse, suppress or prevent the initial phases of carcinogenesis or the progression of premalignant cells to invasive disease by using non-toxic agents. Although data are limited, the success of several clinical trials in preventing cancer in high-risk populations suggests that chemoprevention is a rational, appealing and viable strategy to prevent carcinogenesis. Particularly among higher-risk groups, the use of safe, non-toxic agents is the utmost consideration because these individuals have not yet developed invasive disease. Natural dietary compounds present in fruits, vegetables and spices are especially attractive for chemoprevention and treatment because of their easy availability, high margin of safety, relatively low cost and widespread human consumption. Hundreds of such compounds have been widely investigated for chemoprevention and treatment in the last few decades. Previously, we reviewed the most widely studied natural compounds and their molecular mechanisms, which were highly exploited by the cancer research community. In the time since our initial review, many promising new compounds have been identified. In this review, we critically review these promising new natural compounds, their molecular targets and mechanisms of anticancer activity that may create novel opportunities for further design and conduct of preclinical and clinical studies.
•Table of natural compounds studied through preclinical and early clinical studies.•Comprehensive review of new promising natural compounds and their anticancer effects.•Summary of cellular processes affected by new promising compounds.•Comprehensive review of the molecular targets of promising new compounds.•Assessment of the future perspectives about these compounds.
Background Current cell-free DNA assessment of fetal chromosomes does not analyze and report on all chromosomes. Hence, a significant proportion of fetal chromosomal abnormalities are not detectable ...by current noninvasive methods. Here we report the clinical validation of a novel noninvasive prenatal test (NIPT) designed to detect genomewide gains and losses of chromosomal material ≥7 Mb and losses associated with specific deletions <7 Mb. Objective The objective of this study is to provide a clinical validation of the sensitivity and specificity of a novel NIPT for detection of genomewide abnormalities. Study Design This retrospective, blinded study included maternal plasma collected from 1222 study subjects with pregnancies at increased risk for fetal chromosomal abnormalities that were assessed for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), fetal sex, genomewide copy number variants (CNVs) ≥7 Mb, and select deletions <7 Mb. Performance was assessed by comparing test results with findings from G-band karyotyping, microarray data, or high coverage sequencing. Results Clinical sensitivity within this study was determined to be 100% for T21 (95% confidence interval CI, 94.6–100%), T18 (95% CI, 84.4–100%), T13 (95% CI, 74.7–100%), and SCAs (95% CI, 84–100%), and 97.7% for genomewide CNVs (95% CI, 86.2–99.9%). Clinical specificity within this study was determined to be 100% for T21 (95% CI, 99.6–100%), T18 (95% CI, 99.6–100%), and T13 (95% CI, 99.6–100%), and 99.9% for SCAs and CNVs (95% CI, 99.4–100% for both). Fetal sex classification had an accuracy of 99.6% (95% CI, 98.9–99.8%). Conclusion This study has demonstrated that genomewide NIPT for fetal chromosomal abnormalities can provide high resolution, sensitive, and specific detection of a wide range of subchromosomal and whole chromosomal abnormalities that were previously only detectable by invasive karyotype analysis. In some instances, this NIPT also provided additional clarification about the origin of genetic material that had not been identified by invasive karyotype analysis.
Nanomaterials for Cardiac Tissue Engineering R Amin, Devang; Sink, Eric; Narayan, Suguna P ...
Molecules (Basel, Switzerland),
11/2020, Letnik:
25, Številka:
21
Journal Article
Recenzirano
Odprti dostop
End stage heart failure is a major cause of death in the US. At present, organ transplant and left-ventricular assist devices remain the only viable treatments for these patients. Cardiac tissue ...engineering presents the possibility of a new option. Nanomaterials such as gold nanorods (AuNRs) and carbon nanotubes (CNTs) present unique properties that are beneficial for cardiac tissue engineering approaches. In particular, these nanomaterials can modulate electrical conductivity, hardness, and roughness of bulk materials to improve tissue functionality. Moreover, they can deliver bioactive cargo to affect cell phenotypes. This review covers recent advances in the use of nanomaterials for cardiac tissue engineering.
Motivation: Experiments such as ChIP-chip, ChIP-seq, ChIP-PET and DamID (the four methods referred herein as ChIP-X) are used to profile the binding of transcription factors to DNA at a genome-wide ...scale. Such experiments provide hundreds to thousands of potential binding sites for a given transcription factor in proximity to gene coding regions. Results: In order to integrate data from such studies and utilize it for further biological discovery, we collected interactions from such experiments to construct a mammalian ChIP-X database. The database contains 189 933 interactions, manually extracted from 87 publications, describing the binding of 92 transcription factors to 31 932 target genes. We used the database to analyze mRNA expression data where we perform gene-list enrichment analysis using the ChIP-X database as the prior biological knowledge gene-list library. The system is delivered as a web-based interactive application called ChIP Enrichment Analysis (ChEA). With ChEA, users can input lists of mammalian gene symbols for which the program computes over-representation of transcription factor targets from the ChIP-X database. The ChEA database allowed us to reconstruct an initial network of transcription factors connected based on shared overlapping targets and binding site proximity. To demonstrate the utility of ChEA we present three case studies. We show how by combining the Connectivity Map (CMAP) with ChEA, we can rank pairs of compounds to be used to target specific transcription factor activity in cancer cells. Availability: The ChEA software and ChIP-X database is freely available online at: http://amp.pharm.mssm.edu/lib/chea.jsp Contact: avi.maayan@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Estimating potential gains from mergers is an important strategic decision-making problem. This paper introduces a new inverse data envelopment analysis (DEA) based on a cost efficiency model for ...estimating potential gains from mergers. There are restructuring scenarios for firms that want to minimize cost. The existing inverse DEA technical efficiency models are not appropriate for estimating merger gains in these situations. It is also shown that the proposed inverse DEA cost efficiency model can reveal more merger gains than the inverse DEA technical efficiency model. The applicability of the proposed method is shown through an application in Canada’s banking sector to determine the required level of inputs and outputs for a merged bank to achieve target levels of cost and technical efficiencies. The results highlight the potential financial gains to improving both technical and cost efficiencies as efficiency-seeking banks increasingly become large and complex institutions through growth, mergers and acquisitions in a financial environment that is being shaped by reforms and technological innovation.
In integrated photonics, specific wavelengths such as 1,550 nm are preferred due to low-loss transmission and the availability of optical gain in this spectral region. For chip-based photodetectors, ...two-dimensional materials bear scientifically and technologically relevant properties such as electrostatic tunability and strong light–matter interactions. However, no efficient photodetector in the telecommunication C-band has been realized with two-dimensional transition metal dichalcogenide materials due to their large optical bandgaps. Here we demonstrate a MoTe2-based photodetector featuring a strong photoresponse (responsivity 0.5 A W–1) operating at 1,550 nm in silicon photonics enabled by strain engineering the two-dimensional material. Non-planarized waveguide structures show a bandgap modulation of 0.2 eV, resulting in a large photoresponse in an otherwise photoinactive medium when unstrained. Unlike graphene-based photodetectors that rely on a gapless band structure, this photodetector shows an approximately 100-fold reduction in dark current, enabling an efficient noise-equivalent power of 90 pW Hz–0.5. Such a strain-engineered integrated photodetector provides new opportunities for integrated optoelectronic systems.A strain-induced absorption-enhanced MoTe2-based silicon photonic microring-integrated photodetector is demonstrated, featuring high responsivity of ~0.5 A W–1 at 1,550 nm, with a low noise-equivalent power of 90 pW Hz–0.5.
Cancer is the second leading cause of death in the United States. Despite the estimated 565,650 deaths in 2008 of Americans as a result of cancer, it is mostly a preventable disease. Simply by ...modification of diet, maintenance of optimum body weight, and regular physical activity, 30% to 40% of all instances of cancer could be prevented. Modification of diet alone by increasing vegetable and fruit intake could prevent 20% or more of all cases of cancer and may potentially prevent approximately 200,000 cancer-related deaths annually. Because of their safety, low toxicity, antioxidant properties, and general acceptance as dietary supplements, fruits, vegetables, and other dietary elements (phytochemicals and minerals) are being investigated for the prevention of cancer. Extensive research over the past several decades has identified numerous dietary and botanical natural compounds that have chemopreventive potential. In this review, we discuss promising natural chemopreventive compounds, their molecular targets, and their mechanisms, which may help the further design and conduct of preclinical and clinical trials.
As the first laboratory to offer massively parallel sequencing-based noninvasive prenatal testing (NIPT) for fetal aneuploidies, Sequenom Laboratories has been able to collect the largest clinical ...population experience data to date, including >100,000 clinical samples from all 50 U.S. states and 13 other countries. The objective of this study is to give a robust clinical picture of the current laboratory performance of the MaterniT21 PLUS LDT.
The study includes plasma samples collected from patients with high-risk pregnancies in our CLIA-licensed, CAP-accredited laboratory between August 2012 to June 2013. Samples were assessed for trisomies 13, 18, 21 and for the presence of chromosome Y-specific DNA. Sample data and ad hoc outcome information provided by the clinician was compiled and reviewed to determine the characteristics of this patient population, as well as estimate the assay performance in a clinical setting.
NIPT patients most commonly undergo testing at an average of 15 weeks, 3 days gestation; and average 35.1 years of age. The average turnaround time is 4.54 business days and an overall 1.3% not reportable rate. The positivity rate for Trisomy 21 was 1.51%, followed by 0.45% and 0.21% rate for Trisomies 18 and 13, respectively. NIPT positivity rates are similar to previous large clinical studies of aneuploidy in women of maternal age ≥ 35 undergoing amniocentesis. In this population 3519 patients had multifetal gestations (3.5%) with 2.61% yielding a positive NIPT result.
NIPT has been commercially offered for just over 2 years and the clinical use by patients and clinicians has increased significantly. The risks associated with invasive testing have been substantially reduced by providing another assessment of aneuploidy status in high-risk patients. The accuracy and NIPT assay positivity rate are as predicted by clinical validations and the test demonstrates improvement in the current standard of care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we ...demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin(+) MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent 'mesenspheres' that can self-renew and expand in serial transplantations. Nestin(+) MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or beta3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin(+) cells and favours their osteoblastic differentiation, in vivo nestin(+) cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin(+) MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin(+) cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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