Porous alumina for free-standing implants. Part I: Implant design and in vivo animal studies

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

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Modulation of Matrix Metalloproteinases by Plant-Derived Products

Current Cancer Drug Targets ◽

10.2174/1568009620666201120144838 ◽

2020 ◽

Vol 20 ◽

Author(s):

Nur Najmi Mohamad Anuar ◽

Nurul Iman Natasya Zulkafali ◽

Azizah Ugusman

Keyword(s):

Clinical Trials ◽

Natural Products ◽

Matrix Metalloproteinases ◽

Animal Studies ◽

Current Knowledge ◽

In Vitro Models ◽

In Vivo Studies ◽

Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

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Occupational Exposure to Carbon Nanotubes and Carbon Nanofibres: More Than a Cobweb

Nanomaterials ◽

10.3390/nano11030745 ◽

2021 ◽

Vol 11 (3) ◽

pp. 745

Author(s):

Enrico Bergamaschi ◽

Giacomo Garzaro ◽

Georgia Wilson Jones ◽

Martina Buglisi ◽

Michele Caniglia ◽

...

Keyword(s):

Carbon Nanotubes ◽

Animal Studies ◽

Chemical Properties ◽

Biological Behavior ◽

Cross Sectional ◽

Carbon Nanofibres ◽

Material Entity ◽

Cross Sectional Design

Carbon nanotubes (CNTs) and carbon nanofibers (CNFs) are erroneously considered as singular material entities. Instead, they should be regarded as a heterogeneous class of materials bearing different properties eliciting peculiar biological outcomes both in vitro and in vivo. Given the pace at which the industrial production of CNTs/CNFs is increasing, it is becoming of utmost importance to acquire comprehensive knowledge regarding their biological activity and their hazardous effects in humans. Animal studies carried out by inhalation showed that some CNTs/CNFs species can cause deleterious effects such as inflammation and lung tissue remodeling. Their physico-chemical properties, biological behavior and biopersistence make them similar to asbestos fibers. Human studies suggest some mild effects in workers handling CNT/CNF. However, owing to their cross-sectional design, researchers have been as yet unable to firmly demonstrate a causal relationship between such an exposure and the observed effects. Estimation of acceptable exposure levels should warrant a proper risk management. The aim of this review is to challenge the conception of CNTs/CNFs as a single, unified material entity and prompt the establishment of standardized hazard and exposure assessment methodologies able to properly feeding risk assessment and management frameworks.

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Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics

Scientific Reports ◽

10.1038/s41598-021-86110-8 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Hu Zhu ◽

Catherine Z. Chen ◽

Srilatha Sakamuru ◽

Jinghua Zhao ◽

Deborah K. Ngan ◽

...

Keyword(s):

Clinical Trials ◽

High Throughput Screening ◽

Animal Studies ◽

Cytopathic Effect ◽

Mechanisms Of Action ◽

Activity Profile ◽

Pathway Activity ◽

Global Pandemic ◽

Approved Drugs

AbstractThe recent global pandemic of the Coronavirus disease 2019 (COVID-19) caused by the new coronavirus SARS-CoV-2 presents an urgent need for the development of new therapeutic candidates. Many efforts have been devoted to screening existing drug libraries with the hope to repurpose approved drugs as potential treatments for COVID-19. However, the antiviral mechanisms of action of the drugs found active in these phenotypic screens remain largely unknown. In an effort to deconvolute the viral targets in pursuit of more effective anti-COVID-19 drug development, we mined our in-house database of approved drug screens against 994 assays and compared their activity profiles with the drug activity profile in a cytopathic effect (CPE) assay of SARS-CoV-2. We found that the autophagy and AP-1 signaling pathway activity profiles are significantly correlated with the anti-SARS-CoV-2 activity profile. In addition, a class of neurology/psychiatry drugs was found to be significantly enriched with anti-SARS-CoV-2 activity. Taken together, these results provide new insights into SARS-CoV-2 infection and potential targets for COVID-19 therapeutics, which can be further validated by in vivo animal studies and human clinical trials.

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Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽

10.3390/biom9030099 ◽

2019 ◽

Vol 9 (3) ◽

pp. 99 ◽

Cited By ~ 16

Author(s):

Danja J. Den Hartogh ◽

Evangelia Tsiani

Keyword(s):

Insulin Resistance ◽

Animal Studies ◽

Citrus Fruit ◽

Epidemiological Studies ◽

Personal Health ◽

Current Review ◽

Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

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Subinhibitory Antimicrobial Concentrations: A Review of In Vitro and In Vivo Data

Canadian Journal of Infectious Diseases ◽

10.1155/1992/793607 ◽

1992 ◽

Vol 3 (4) ◽

pp. 193-201 ◽

Cited By ~ 14

Author(s):

George G Zhanel ◽

Daryl J Hoban ◽

Godfrey KM Harding

Keyword(s):

Antimicrobial Activity ◽

Animal Studies ◽

Molecular Level ◽

Bacterial Virulence ◽

Antibacterial Effects ◽

Wide Range ◽

Immune Defences

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.

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A Review of Current Noninvasive Imaging Surveillance Practices for Deep Venous Arterialization Procedures

Journal for Vascular Ultrasound ◽

10.1177/1544316721996944 ◽

2021 ◽

pp. 154431672199694

Author(s):

Qi Yan ◽

John A. Treffalls ◽

Lucas Ferrer ◽

Mark G. Davies

Keyword(s):

Animal Studies ◽

Case Reports ◽

Peak Systolic Velocity ◽

Volume Measurement ◽

Free Standing ◽

Common Procedure ◽

Venous Valves ◽

Language Studies ◽

Duplex Imaging ◽

Percutaneous Revascularization

Venous arterialization is an increasingly common procedure performed in patients with critical limb-threatening ischemia (CLTI) where there are no open or percutaneous revascularization options. This study aims to review the imaging follow-up for venous arterialization described in the literature. A systematic review was performed on venous arterialization studies for CLTI using the PRISMA methodology. A literature search was performed on 5 databases from inception. We included all original studies, case reports, and reviews regarding venous arterialization for all pathologies. We excluded free standing abstracts, animal studies, other than lower extremity, and foreign language studies. Our search strategy yielded 23 studies that met inclusion criteria, with 16 studies reporting a specific value from at least one surveillance imaging methodology. Most studies used Duplex imaging (16 studies) and TCPo2 (9 studies). Only 9 studies provided any detail regarding the Duplex findings. One study used focal peak systolic velocity (PSV) gradient (PSV at the lesion in the graft divided by PSV in a proximal segment of the graft) above 2.5 as an indicator for flow-inhibiting venous valves or stenosis in the graft. Another study reported a turbulent flow pattern in the graft, elevating peak velocities to 100 to 200 cm/s throughout the bypass. Four studies reported flow volume measurement through the bypass or in pedal vein ranging from 40 to 437 mL/min. Seven studies reported a mean increase of 18.7 mmHg in TCPo2. Eighty-two percent of patients saw an improvement of TCPo2 in 2 studies. To date, no criteria have been identified that are predictive of the success or failure of deep vein arterialization. Venous arterialization is an increasingly common procedure in the “no-option” diabetic patient. Duplex imaging with TCPo2 offers the most appropriate means of surveillance; however, the literature is sparse with no guidance on normal or critical values.

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In vivo assessment of human vaginal oxygen and carbon dioxide levels during and post menses

Journal of Applied Physiology ◽

10.1152/japplphysiol.01422.2004 ◽

2005 ◽

Vol 99 (4) ◽

pp. 1582-1591 ◽

Cited By ~ 32

Author(s):

Donna R. Hill ◽

Marianne E. Brunner ◽

Deborah C. Schmitz ◽

Catherine C. Davis ◽

Janine A. Flood ◽

...

Keyword(s):

Animal Studies ◽

Pathogenic Bacteria ◽

Sensor Technology ◽

Atmospheric Conditions ◽

Bacterial Virulence Factor ◽

Carbon Dioxide Levels ◽

Kinetics Of ◽

Insertion Process

Previous in vitro and in vivo animal studies showed that O2and CO2concentrations can affect virulence of pathogenic bacteria such as Staphylococcus aureus. The objective of this work was to measure O2and CO2levels in the vaginal environment during tampon wear using newly available sensor technology. Measurements by two vaginal sensors showed a decrease in vaginal O2levels after tampon insertion. These decreases were independent of the type of tampons used and the time of measurement (mid-cycle or during menstruation). These results are not in agreement with a previous study that concluded that oxygenation of the vaginal environment during tampon use occurred via delivery of a bolus of O2during the insertion process. Our measurements of gas levels in menses showed the presence of both O2and CO2in menses. The tampons inserted into the vagina contained O2and CO2levels consistent with atmospheric conditions. Over time during tampon use, levels of O2in the tampon decreased and levels of CO2increased. Tampon absorbent capacity, menses loading, and wear time influenced the kinetics of these changes. Colonization with S. aureus had no effect on the gas profiles during menstruation. Taken collectively, these findings have important implications on the current understanding of gaseous changes in the vaginal environment during menstruation and the potential role(s) they may play in affecting bacterial virulence factor production.

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Self-Powered Multifunctional Instrumented Knee Implant

Volume 2: Mechanics and Behavior of Active Materials; Structural Health Monitoring; Bioinspired Smart Materials and Systems; Energy Harvesting; Emerging Technologies ◽

10.1115/smasis2018-8078 ◽

2018 ◽

Author(s):

Mohsen Safaei ◽

Steven R. Anton

Keyword(s):

Finite Element ◽

Energy Harvesting ◽

Knee Replacement ◽

Center Of Pressure ◽

Experimental Testing ◽

Sensory System ◽

Implant Design ◽

Total Force ◽

Self Powered

Computational modeling, instrumented linkages, optical technologies, MRI, and radiographic techniques have been widely used to study knee motion after total knee replacement (TKR) surgery. Information provided by these methods has helped designers to develop implants with better clinical performance and surgeons to obtain an improved understanding of the stability and mobility of the joint. Correspondingly, overall patient satisfaction with respect to the reduction in pain and recovery of normal functioning of the joint has been improving. However, about 20% of patients are still not fully satisfied with their surgical outcomes. The main obstacle in the current state-of-the-art is that a comprehensive post-operative understanding of knee balance is still unavailable, mostly due to a lack of in vivo data collected from the joint after surgery. This work presents an attempt to develop a self-powered instrumented knee implant for in vivo data acquisition. The knee sensory system in this study utilizes several embedded piezoelectric transducers in the tibial bearing of the knee replacement in order to provide sensing and energy harvesting capabilities. Through a series of analytical modeling, finite element simulation, and experimental testing, the performance of the suggested system is evaluated and a dimensionally optimized design of an instrumented TKR is achieved. More specifically, a comprehensive platform is established in order to combine the knowledge of embedded piezoelectric sensors and energy harvesters, musculoskeletal modeling of the knee joint, multiphysics finite element modeling, additive manufacturing techniques, image processing, and experimental knee loading simulation in order to achieve the experimentally validated and optimized instrumented knee implant design. The cumulative work presented in this article encompasses three main studies performed on the sensing performance of the proposed design: first, preliminary parametric studies of the effect of local dimensional and material parameters on the electromechanical behavior of the embedded sensory system; second, investigation of the ability to sense total force and center of pressure location; and third, evaluation of an enhanced system with the ability to sense compartmental forces and contact locations. Additionally, the energy harvesting capacity of the system is investigated to ensure the achievement of a fully self-powered sensory system. Results obtained from the experimental analysis of the system demonstrate the successful sensing and energy harvesting performance of the designs achieved in this study.

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