Biomolecular Concepts最新文献

The single nucleotide polymorphism (SNP) of the promoter region of MMP-1 (at 1607 bp) and MMP-3 (at 1171 bp) create Ets binding sites. Correlations between these SNPs and sensitivity to several biological processes such as metastasis and recurrence of cancer have been reported in several studies. In this case-control study, we looked for these SNPs in women infected with or not with high-risk human papillomaviruses (HR-HPV). The frequency, distribution and correlation of these SNPs with the presence or absence of HR-HPV infection were evaluated. Genotypes 1G1G, 1G2G and 2G2G for MMP1 and genotypes 5A5A, 5A6A, 6A6A for MMP3 were found in our study population. In general, we noted that the 1G (40.8%) and 2G (64.8%) alleles were more frequent in non-infected women and infected women, respectively, and more specifically this difference was significant in women from Côte d'Ivoire. These results, although yet to be reaffirmed with assays for quantifying the mRNA of these genes, suggest that the SNP of the MMP-1 promoter could promote infection with HR-HPV.

Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs. We show how this effect can be utilised in structural studies of nano-sized upward convex objects such as spherical or filamentous molecular assemblies deposited on a flat surface, because it causes 'magnification' of such objects in AFM topographs. Subsequently, this enhancement effect is harnessed through contact-point based deconvolution of AFM topographs. Here, the application of this approach is demonstrated through the 3D reconstruction of the surface envelope of individual helical amyloid filaments without the need of cross-particle averaging using the contact-deconvoluted AFM topographs. Resolving the structural variations of individual macromolecular assemblies within inherently heterogeneous populations is paramount for mechanistic understanding of many biological phenomena such as amyloid toxicity and prion strains. The approach presented here will also facilitate the use of AFM for high-resolution structural studies and integrative structural biology analysis of single molecular assemblies.

Objectives Natural products commonly used in traditional medicine, such as essential oils (EOs), are attractive sources for the development of molecules with anti-proliferative activities for future treatment of human cancers, e.g., prostate and cervical cancer. In this study, the chemical composition of the EO from Cymbopogon nardus was characterized, as well as its antioxidativeproperties and anti-inflammatory and antiproliferative activities on LNCaP cells derived from prostate cancer. Methods The chemical composition of the EO was determined by GC/FID and GC/MS analyses. The antioxidative properties were assessed using DPPH radical scavenging assay and ABTS+• radical cation decolorization assay, and the anti-inflammatory capacity was determined by the inhibition of the lipoxygenase activity. Antiproliferative activity was evaluated by MTT assay. Results Collectively, our data show that the major constituents of C. nardus EO are citronellal (33.06 %), geraniol (28.40 %), nerol (10.94 %), elemol (5.25 %) and delta-elemene (4.09 %). C. nardus EO shows modest antioxidant and anti-inflammatory activity compared to the standard galic acid. C. nardus EO exhibits the best antiproliferative activity on the prostate cancer cell line LNCaP with an IC50 of 58.0 ± 7.9 μg/mL, acting through the induction of the cell cycle arrest. Conclusions This study has determined that C. nardus EO efficiently triggers cytotoxicity and pens a new field of investigation regarding the putative use of this EO in vivo.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Persistence infection can lead to the development of cervical cancer potentially due to some genetic factors such as polymorphisms in regulatory and coding regions of cytokine genes. The purpose of this study was to determine whether there is a relationship between TNF-308 G/A or IL18 polymorphisms and high-risk HPV infection among sexually active women from Burkina Faso. Ninety-one HPV infected and two hundred and nine HPV negative women (the latter used as healthy controls) were screened. TNFA-308 G/A and IL18-607 C/A polymorphisms were detected using the TaqMan allelic discrimination. HPV 52 (21.19%), HPV 39 (11.86%) and HPV 33 (11.02%) were the most common HPV genotypes. The TNFA-308A and IL18-607 C alleles were predominant in all women in the study. None of the TNFA and IL18 alleles were associated with HPV infection. The results suggest that there is no relationship between TNF-308 G/A or IL18-607C/A polymorphisms and HPV infection among women in the study.

Interferon-gamma (IFN-γ) is a key cytokine that mediates immunity to tuberculosis (TB). Mycobacterium tuberculosis (M. tb) is known to downregulate the surface expression of IFN-γ receptor (IFN-γR) on macrophages and peripheral blood mononuclear cells (PBMCs) of patients with active TB disease. Many M. tb antigens also downmodulate IFN-γR levels in macrophages when compared with healthy controls. In the current study, we aimed at deciphering key factors involved in M. tb mediated downregulation of IFN-γR levels on macrophage surface. Our data showed that both M. tb H37Rv and M. bovis BCG infections mediate downmodulation of IFN-γR on human macrophages. This downmodulation is regulated at the level of TLR signaling pathway, second messengers such as calcium and cellular kinases i.e. PKC and ERK-MAPK, indicating that fine tuning of calcium response is critical to maintaining IFN-γR levels on macrophage surface. In addition, genes in the calcium and cysteine protease pathways which were previously identified by us to play a negative role during M. tb infection, also regulated IFN-γR expression. Thus, modulations in IFN-γR levels by utilizing host machinery may be a key immune suppressive strategy adopted by the TB pathogen to ensure its persistence and thwart host defense.

Background Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine abnormalities in women. Due to the side effects of drugs, the tendency to use natural antioxidants and anti-inflammatory agents to regulate metabolism, hyperinsulinemia, and hyperlipidemia in PCOS patients has been increased. This review aimed to investigate the role of herbal substances on the treatment of PCOS. Methods The present review was carried out using keywords such as polycystic ovary syndrome and/or PCOS and/or herb. Databases including Web of Science, PubMed, and Science Direct were used to collect all related articles published from 1990 to 2019. We excluded studies unrelated to the PCOS and medical herbs. Results Overall, 361 records were identified through database searching. After primary screening and the full-texts assessment, 323 records were excluded, and 38 articles were finally included. The results indicate that some medicinal herbs may have a key role in treating PCOS. The compounds in these medical herbs can affect lipid profiles (Aloe vera, chamomile, and cinnamon), insulin resistance (cinnamon, chamomile, Aloe vera, and Camellia sinensis), blood glucose (Aloe vera, cinnamon, and Camellia sinensis), hormones (Aloe vera, silymarin, chamomile, fenugreek, Camellia sinensis, Heracleum persicum, Potentilla, Mentha spicata, Foeniculum vulgar, licorice, and Marrubium), and ovarian tissue (Aloe vera, chamomile, Camellia sinensis, Mentha spicata, and silymarin). Conclusion Natural substances such as Aloe vera, cinnamon, green tea, fenugreek, and silymarin can be used as a new supportive care for PCOS. Further clinical trials are warranted to confirm their benefits and safety.

The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN's mg/Kg LD50 (μM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN. In vitro mechanistic probing of CN-mediated inhibition of hemeFe reductionist systems was explored as a murburn model for mitochondrial oxidative phosphorylation (mOxPhos). The effect of CN in haloperoxidase catalyzed chlorine moiety transfer to small organics was considered as an analogous probe for phosphate group transfer in mOxPhos. Similarly, inclusion of CN in peroxidase-catalase mediated one-electron oxidation of small organics was used to explore electron transfer outcomes in mOxPhos, leading to water formation. The free energy correlations from a Hammett study and IC50/Hill slopes analyses and comparison with ligands ( CO/ H 2 S/ N 3 - ) $left( {text{CO}}/{{{{text{H}}_{2}}text{S}}/{text{N}_{3}^{text{-}}};}; right)$ provide insights into the involvement of diffusible radicals and proton-equilibriums, explaining analogous outcomes in mOxPhos chemistry. Further, we demonstrate that superoxide (diffusible reactive oxygen species, DROS) enables in vitro ATP synthesis from ADP+phosphate, and show that this reaction is inhibited by CN. Therefore, practically instantaneous CN ion-radical interactions with DROS in matrix catalytically disrupt mOxPhos, explaining the acute lethal effect of CN.

The ability to construct a functional system from its individual components is foundational to understanding how it works. Synthetic biology is a broad field that draws from principles of engineering and computer science to create new biological systems or parts with novel function. While this has drawn well-deserved acclaim within the biotechnology community, application of synthetic biology methodologies to study biological systems has potential to fundamentally change how biomedical research is conducted by providing researchers with improved experimental control. While the concepts behind synthetic biology are not new, we present evidence supporting why the current research environment is conducive for integration of synthetic biology approaches within biomedical research. In this perspective we explore the idea of synthetic biology as a discovery science research tool and provide examples of both top-down and bottom-up approaches that have already been used to answer important physiology questions at both the organismal and molecular level.

Two decades of evidence-based exploratory pursuits in heme-flavin enzymology led to the formulation of a new biological electron/moiety transfer paradigm, called murburn concept. Murburn is a novel literary abstraction from "mured burning" or "mild unrestricted burning". This concept was invoked to explain the longstanding conundrum of maverick physiological dose responses and also applied to remodel the prevailing understanding of drug metabolism and cellular respiration. A conglomeration of simple ideas grounded in the known principles of thermodynamics and reaction chemistry, murburn concept invokes catalytic/functional roles for diffusible reactive species or radicals. Hitherto, diffusible reactive species were primarily seen as toxic agents of chaos, non-conducible to the maintenance of life-order. Since the murburn paradigm offers a distinctly different perspective for several biological phenomena, researchers holding conventional views of cellular metabolism pose a direct conflict of interests to the advancement of murburn concept. Murburn schemes are poised to integrate numerous metabolic motifs with holistic physiological outcomes; redefining pursuits in biology and medicine. To advance this agenda, I present a brief account of murburn concept and point out how redundant ideas are still advocated in some prestigious journals.

Here we have proposed a new biological definition of life based on the function and reproduction of existing genes and creation of new ones, which is applicable to both unicellular and multicellular organisms. First, we coined a new term "genetic information metabolism" comprising functioning, reproduction, and creation of genes and their distribution among living and non-living carriers of genetic information. Encompassing this concept, life is defined as organized matter that provides genetic information metabolism. Additionally, we have articulated the general biological function of life as Tetz biological law: "General biological function of life is to provide genetic information metabolism" and formulated novel definition of life: "Life is an organized matter that provides genetic information metabolism". New definition of life and Tetz biological law allow to distinguish in a new way living and non-living objects on Earth and other planets based on providing genetic information metabolism.