Correlative light and soft X-ray tomography of in situ mesoscale heterochromatin structure in intact cells.

Heterochromatin organization is critical to many genome-related programs including transcriptional silencing and DNA repair. While super-resolution imaging, electron microscopy, and multiomics methods have provided indirect insights into the heterochromatin organization, a direct measurement of mesoscale heterochromatin ultrastructure is still missing. We use a combination of correlative light microscopy and cryo-soft X-ray tomography (CLXT) to analyze heterochromatin organization in the intact hydrated state of human mammary fibroblast cells.

Exergames for falls prevention in sheltered homes: a feasibility study.

Introduction: Falls prevention is a global priority given its substantial impact on older adults and cost to healthcare systems. Advances in telerehabilitation technology such as `exergaming' show potential for delivering accessible, engaging exercise programs for older adults. This study aimed to establish the feasibility, acceptability and usability of exergaming in sheltered housing.

Implanting mechanically reprogrammed fibroblasts for aged tissue regeneration and wound healing.

Cell-based therapies are essential for tissue regeneration and wound healing during aging. Autologous transplantation of aging cells is ineffective due to their increased senescence and reduced tissue remodeling capabilities. Alternatively, implanting reprogrammed aged cells provides unique opportunities.

Lateral confined growth of cells activates Lef1 dependent pathways to regulate cell-state transitions.

Long-term sustained mechano-chemical signals in tissue microenvironment regulate cell-state transitions. In recent work, we showed that laterally confined growth of fibroblasts induce dedifferentiation programs. However, the molecular mechanisms underlying such mechanically induced cell-state transitions are poorly understood.

Novel fragment-derived colchicine-site binders as microtubule-destabilizing agents.

Microtubules (MTs) are dynamic filaments of the cytoskeleton, which are formed by the polymerization of their building block tubulin. Perturbation of MT dynamics by MT-targeting agents (MTAs) leads to cell cycle arrest or cell death, a strategy that is pursued in chemotherapy. We recently performed a combined computational and crystallographic fragment screening approach and identified several tubulin-binding fragments.

Rational Design of a Novel Tubulin Inhibitor with a Unique Mechanism of Action.

In this study, we capitalized on our previously performed crystallographic fragment screen and developed the antitubulin small molecule Todalam with only two rounds of straightforward chemical synthesis. Todalam binds to a novel tubulin site, disrupts microtubule networks in cells, arrests cells in G2/M, induces cell death, and synergizes with vinblastine. The compound destabilizes microtubules by acting as a molecular plug that sterically inhibits the curved-to-straight conformational switch in the α-tubulin subunit, and by sequestering tubulin dimers into assembly incompetent oligomers.

A multicenter randomized controlled trial comparing gamification with remote monitoring against standard rehabilitation for patients after arthroscopic shoulder surgery.

Background: Gamification has become increasingly popular in rehabilitation and is viewed as a tool to improve patient activation, motivation, and engagement. The aim of this study was to compare the efficacy of validated exergames played through a system using "depth sensor" and bespoke software against standard physiotherapy in patients treated with arthroscopic shoulder surgery. This included the following common conditions: subacromial impingement syndrome, calcific tendinopathy, and rotator cuff tear.

Fibroblast rejuvenation by mechanical reprogramming and redifferentiation.

Over the course of the aging process, fibroblasts lose contractility, leading to reduced connective-tissue stiffness. A promising therapeutic avenue for functional rejuvenation of connective tissue is reprogrammed fibroblast replacement, although major hurdles still remain. Toward this, we recently demonstrated that the laterally confined growth of fibroblasts on micropatterned substrates induces stem-cell-like spheroids.

What Do U.K. Orthopedic Surgery Patients Think About PROMs? Evaluating the Evaluation and Explaining Missing Data.

The NHS routinely evaluates the quality of life of patients receiving hip or knee replacement surgery using patient-reported outcome measures (PROMs), but some hospital completion rates are only 30%, restricting data usefulness. Statistics limit insights into how and why data are missing, so qualitative methods were used to explore this issue. Observation periods preceded semistructured interviews with 34 preoperative patients attending an orthopedic outpatient clinic.

Frequency-induced morphology alterations in microconfined biological cells.

Low-intensity therapeutic ultrasound has demonstrated an impetus in bone signaling and tissue healing for decades now. Though this technology is clinically well proven, still there are breaches in studies to understand the fundamental principle of how osteoblast tissue regenerates physiologically at the cellular level with ultrasound interaction as a form of acoustic wave stimuli. Through this article, we illustrate an analysis for cytomechanical changes of cell membrane periphery as a basic first physical principle for facilitating late downstream biochemical pathways.

Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors.

Cells in tissues undergo transdifferentiation programs when stimulated by specific mechanical and biochemical signals. While seminal studies have demonstrated that exogenous biochemical factors can reprogram somatic cells into pluripotent stem cells, the critical roles played by mechanical signals in such reprogramming process have not been well documented. In this paper, we show that laterally confined growth of fibroblasts on micropatterned substrates induces nuclear reprogramming with high efficiency in the absence of any exogenous reprogramming factors.

Platelet rich plasma injections for lateral epicondylitis of the elbow reduce the need for surgical intervention.

Objective: We aimed to assess the effectiveness of PRP injections in lateral epicondylitis of the elbow as it was felt after PRP introduction the numbers of patients requiring surgery for had reduced.

Methods: We conducted a retrospective review of cases from the 1 January 2008 to 31st December 2015. The numbers of patients undergoing surgical release and the numbers of patients requiring PRP injections were recorded each year and the numbers of patients requiring surgery was compared pre and post PRP injection to ascertain if PRP introduction reduced surgical intervention.

Can shoulder range of movement be measured accurately using the Microsoft Kinect sensor plus Medical Interactive Recovery Assistant (MIRA) software?

Background: This study compared the accuracy of measuring shoulder range of movement (ROM) with a simple laptop-sensor combination vs. trained observers (shoulder physiotherapists and shoulder surgeons) using motion capture (MoCap) laboratory equipment as the gold standard.

Methods: The Microsoft Kinect sensor (Microsoft Corp.

Abrus Agglutinin, a type II ribosome inactivating protein inhibits Akt/PH domain to induce endoplasmic reticulum stress mediated autophagy-dependent cell death.

Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG-mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis.

Cobalt doped proangiogenic hydroxyapatite for bone tissue engineering application.

The present study delineates the synthesis and characterization of cobalt doped proangiogenic-osteogenic hydroxyapatite. Hydroxyapatite samples, doped with varying concentrations of bivalent cobalt (Co(2+)) were prepared by the ammoniacal precipitation method and the extent of doping was measured by ICP-OES. The crystalline structure of the doped hydroxyapatite samples was confirmed by XRD and FTIR studies.

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network.

Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug-elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device consisting of a network of interconnected microchannels which replicates the architectural properties of microvascular systems.

Assessing the immunomodulatory role of heteroglycan in a tumor spheroid and macrophage co-culture model system.

The therapeutic benefits of glycans have garnered much attention over the last few decades with most studies being reported in 2D cultures or in animal models. The present work is therefore aimed to assess the effects of an immunomodulatory heteroglycan in a 3D milieu. Briefly, HT29 tumor spheroids were incubated with THP-1 macrophages at 1:1 ratio in a culture medium supplemented with immune stimulants such as heteroglycans or LPS.

Abrus precatorius agglutinin-derived peptides induce ROS-dependent mitochondrial apoptosis through JNK and Akt/P38/P53 pathways in HeLa cells.

10kDAGP, a tryptic digest of Abrus precatorius lectin 'Agglutinin' is known to induce apoptosis by mitochondria-dependent pathways in human cervical cancer (HeLa) cells. The present study was focused on deciphering the detailed molecular mechanism of apoptosis induction in vitro by 10kDAGP and also its in vivo therapeutic efficacy. For in vivo model, HeLa cell encapsulated hollow fiber was implanted in Swiss Albino mice and treated with 10kDAGP.

On-chip lectin microarray for glycoprofiling of different gastritis types and gastric cancer.

An on-chip lectin microarray based glycomic approach is employed to identify glyco markers for different gastritis and gastric cancer. Changes in protein glycosylation have impact on biological function and carcinogenesis. These altered glycosylation patterns in serum proteins and membrane proteins of tumor cells can be unique markers of cancer progression and hence have been exploited to diagnose various stages of cancer through lectin microarray technology.

Oscillatory shear stress induced calcium flickers in osteoblast cells.

The dynamic physical microenvironment of bone affects the activity of osteoblast cells, yet little is known about how osteoblast mechanotransduction depends on different features of a dynamic stimulus. Here we investigated the effect of physiologically relevant oscillatory flow shear stress on the calcium mobility in osteoblast cells within a microfluidic platform that mimics the confined environment of bone matrix. We characterized the spatiotemporal evolution of intracellular calcium 'flickers', an important signature of cell activation, in response to steady, pulsatile, and oscillatory shear stress.

Role of PI3K/Akt/mTOR and MEK/ERK pathway in Concanavalin A induced autophagy in HeLa cells.

Concanavalin A (Con A), a mannose or glucose specific legume lectin, is well known for its anti-proliferative and cytotoxic effect on different types of cancer cells, through its binding to the membrane receptors leading to a major stimulus for the induction of distinct metabolic responses. Recently it has been also been proved that, Con A induces autophagy in hepatoma cells through internalization and mitochondria mediated pathway involving a mitochondrial interacting protein named Bcl2/E1B-19kDa protein-interacting protein 3 (BNIP3). Through this current endeavor, we propose a membrane associated pathway involved in Con A induced autophagy, taking Human cervical cancer (HeLa) cell as a cancer model.

Characterization and lectin microarray of an immunomodulatory heteroglucan from Pleurotus ostreatus mycelia.

Glucans isolated from various mushroom and mycelia sources are interestingly being studied nowadays as a potent therapeutic agent. The present work was focused on the isolation, characterization and immunomodulatory study of a novel water soluble glucan from the pure mycelia of Pleurotus ostreatus. The extracted glucan was found to have a high molecular weight of ∼2.

Effect of fluidic transport on the reaction kinetics in lectin microarrays.

Lectins are the proteins which can distinguish glycosylation patterns. They are frequently used as biomarkers for progressions of several diseases including cancer. As the lectin microarray based prognosis devices miniaturize the process of glycoprofiling, it is anticipated that their performance can be augmented by integration with microfluidic framework.