The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes ...permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.
Hunger and chronic undernourishment impact over 800 million people, which translates to ≈10.7% of the world's population. While countries are increasingly making efforts to reduce poverty and hunger ...by pursuing sustainable energy and agricultural practices, a third of the food produced around the globe still is wasted and never consumed. Reducing food shortages is vital in this effort and is often addressed by the development of genetically modified produce or chemical additives and inedible coatings, which create additional health and environmental concerns. Herein, a multifunctional bio‐nanocomposite comprised largely of egg‐derived polymers and cellulose nanomaterials as a conformal coating onto fresh produce that slows down food decay by retarding ripening, dehydration, and microbial invasion is reported. The coating is edible, washable, and made from readily available inexpensive or waste materials, which makes it a promising economic alternative to commercially available fruit coatings and a solution to combat food wastage that is rampant in the world.
A conformal bio‐nanocomposite coating based on cellulose nanocrystals and poly(albumen) is developed that increases the shelf‐life of fresh produce by retarding ripening, dehydration, and microbial attack. The coating is edible, easily washable, and made from readily available inexpensive materials, which makes it a promising solution to combat food wastage.
The pregnancy microbiome and preterm birth Bayar, Erna; Bennett, Phillip R.; Chan, Denise ...
Seminars in immunopathology,
08/2020, Letnik:
42, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Preterm birth is a global health concern and continues to contribute to substantial neonatal morbidity and mortality despite advances in obstetric and neonatal care. The underlying aetiology is ...multi-factorial and remains incompletely understood. In this review, the complex interplay between the vaginal microbiome in pregnancy and its association with preterm birth is discussed in depth. Advances in the study of bacteriology and an improved understanding of the human microbiome have seen an improved awareness of the vaginal microbiota in both health and in disease.
Both non-alcoholic fatty liver disease (NAFLD) and the multitarget complexity of microRNA (miR) suppression have recently raised much interest, but the in vivo impact and context-dependence of ...hepatic miR-target interactions are incompletely understood. Assessing the relative in vivo contributions of specific targets to miR-mediated phenotypes is pivotal for investigating metabolic processes.
We quantified fatty liver parameters and the levels of miR-132 and its targets in novel transgenic mice overexpressing miR-132, in liver tissues from patients with NAFLD, and in diverse mouse models of hepatic steatosis. We tested the causal nature of miR-132 excess in these phenotypes by injecting diet-induced obese mice with antisense oligonucleotide suppressors of miR-132 or its target genes, and measured changes in metabolic parameters and transcripts.
Transgenic mice overexpressing miR-132 showed a severe fatty liver phenotype and increased body weight, serum low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and liver triglycerides, accompanied by decreases in validated miR-132 targets and increases in
. Likewise, liver samples from both patients with NAFLD and mouse models of hepatic steatosis or non-alcoholic steatohepatitis (NASH) displayed dramatic increases in miR-132 and varying decreases in miR-132 targets compared with controls. Furthermore, injecting diet-induced obese mice with anti-miR-132 oligonucleotides, but not suppressing its individual targets, reversed the hepatic miR-132 excess and hyperlipidemic phenotype.
Our findings identify miR-132 as a key regulator of hepatic lipid homeostasis, functioning in a context-dependent fashion via suppression of multiple targets and with cumulative synergistic effects. This indicates reduction of miR-132 levels as a possible treatment of hepatic steatosis.
Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall ...design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.
The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to ...augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. Transplanted epicardial cells formed persistent fibroblast grafts in infarcted hearts. Cotransplantation of hESC-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo, resulting in 2.6-fold greater cardiac graft size and simultaneously augmenting graft and host vascularization. Notably, cotransplantation improved systolic function compared with hearts receiving either cardiomyocytes alone, epicardial cells alone or vehicle. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant therapeutic for cardiac repair.
Anti‐fibrotic actions of relaxin Samuel, C S; Royce, S G; Hewitson, T D ...
British journal of pharmacology,
20/May , Letnik:
174, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Fibrosis refers to the hardening or scarring of tissues that usually results from aberrant wound healing in response to organ injury, and its manifestations in various organs have collectively been ...estimated to contribute to around 45–50% of deaths in the Western world. Despite this, there is currently no effective cure for the tissue structural and functional damage induced by fibrosis‐related disorders. Relaxin meets several criteria of an effective anti‐fibrotic based on its specific ability to inhibit pro‐fibrotic cytokine and/or growth factor‐mediated, but not normal/unstimulated, fibroblast proliferation, differentiation and matrix production. Furthermore, relaxin augments matrix degradation through its ability to up‐regulate the release and activation of various matrix‐degrading matrix metalloproteinases and/or being able to down‐regulate tissue inhibitor of metalloproteinase activity. Relaxin can also indirectly suppress fibrosis through its other well‐known (anti‐inflammatory, antioxidant, anti‐hypertrophic, anti‐apoptotic, angiogenic, wound healing and vasodilator) properties. This review will outline the organ‐specific and general anti‐fibrotic significance of exogenously administered relaxin and its mechanisms of action that have been documented in various non‐reproductive organs such as the cardiovascular system, kidney, lung, liver, skin and tendons. In addition, it will outline the influence of sex on relaxin's anti‐fibrotic actions, highlighting its potential as an emerging anti‐fibrotic therapeutic.
Linked Articles
This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc
Locally aromatic alkyl-
N
-substituted squarephaneic tetraimide (SqTI) conjugated macrocycles are four-electron reducible, owing to global aromaticity and presumed global Baird aromaticity of the ...dianion and tetraanion states, respectively. However, their good solubility inhibits their application as a battery electrode material. By applying sidechain removal as a strategy to reduce SqTI solubility, we report the development of its unsubstituted derivative SqTI-H, which was obtained directly from squarephaneic tetraanhydride by facile treatment with hexamethyldisilazane and MeOH. Compared to alkyl-
N
-substituted SqTI-Rs, SqTI-H exhibited further improved thermal stability and low neutral state solubility in most common organic solvents, owing to computationally demonstrated hydrogen-bonding capabilities emanating from each imide position on SqTI-H. Reversible solid state electrochemical reduction of SqTI-H to the globally aromatic dianion state was also observed at −1.25 V
vs.
Fc/Fc
+
, which could be further reduced in two stages. Preliminary testing of SqTI-H in composite electrodes for lithium-organic half cells uncovered imperfect cycling performance, which may be explained by persistent solubility of reduced states, necessitating further optimisation of electrode fabrication procedures to attain maximum performance.
Unsubstituted squarephaneic tetraimide with reduced solubility due to H-bonding interactions is synthesised, characterised, and tested as a battery electrode material.
Abstract Posttraumatic stress disorder (PTSD) is a debilitating condition associated with mild to moderate cognitive impairment and with a prevalence rate of up to 22% in veterans. This systematic ...review and quantitative meta-analysis explore volumetric differences of three key structural brain regions (hippocampus, amygdala and anterior cingulate cortex (ACC)), all of which have been implicated in dysfunction of both salience network (SN) and default mode network (DMN) in PTSD sufferers. A literature search was conducted in Embase, Medline, PubMed and PsycINFO in May 2013. Fifty-nine volumetric analyses from 44 articles were examined and included (36 hippocampus, 14 amygdala and nine ACC) with n =846 PTSD participants, n =520 healthy controls (HCs) and n =624 traumatised controls (TCs). Nine statistical tests were performed for each of the three regions of interest (ROIs), measuring volume differences in PTSD subjects, healthy and traumatised controls. Hippocampal volume was reduced in subjects with PTSD, with a greater reduction in the left hippocampus. A medium effect size reduction was found in bilateral amygdala volume when compared with findings in healthy controls; however, no significant differences in amygdala volume between PTSD subjects and trauma-exposed controls were found. Significant volume reductions were found bilaterally in the ACC. While often well matched with their respective control groups, the samples of PTSD subjects composed from the source studies used in the meta-analyses are limited in their homogeneity. The current findings of reduced hippocampal volume in subjects with PTSD are consistent with the existing literature. Amygdala volumes did not show significant reductions in PTSD subjects when compared with volumes in trauma-exposed controls—congruous with reported symptoms of hypervigilance and increased propensity in acquisition of conditioned fear memories—but a significant reduction was found in the combined left and right hemisphere volume analysis when compared with healthy controls. Bilateral volume reductions in the ACC may underpin the attentional deficits and inabilities to modulate emotions that are characteristically associated with PTSD patients.
The nucleus is physically linked to the cytoskeleton, adhesions, and extracellular matrix-all of which sustain forces, but their relationships to DNA damage are obscure. We show that nuclear rupture ...with cytoplasmic mislocalization of multiple DNA repair factors correlates with high nuclear curvature imposed by an external probe or by cell attachment to either aligned collagen fibers or stiff matrix. Mislocalization is greatly enhanced by lamin A depletion, requires hours for nuclear reentry, and correlates with an increase in pan-nucleoplasmic foci of the DNA damage marker γH2AX. Excess DNA damage is rescued in ruptured nuclei by cooverexpression of multiple DNA repair factors as well as by soft matrix or inhibition of actomyosin tension. Increased contractility has the opposite effect, and stiff tumors with low lamin A indeed exhibit increased nuclear curvature, more frequent nuclear rupture, and excess DNA damage. Additional stresses likely play a role, but the data suggest high curvature promotes nuclear rupture, which compromises retention of DNA repair factors and favors sustained damage.
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