Collagen in Wound Healing Mathew-Steiner, Shomita S; Roy, Sashwati; Sen, Chandan K
Bioengineering,
05/2021, Letnik:
8, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Normal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in ...the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Impairments in any of these phases stall the wound in a chronic, non-healing state that typically requires some form of intervention to guide the process back to completion. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components caused by elevated metalloproteinases and other enzymes and improper activation of soluble mediators of the wound healing process. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. In this work the significance of collagen in different biological processes relevant to wound healing are reviewed and a summary of the current literature on the use of collagen-based products in wound care is provided.
These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician ...judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.
Fundamental to all living organisms is the capacity to coordinate cell division and cell differentiation to generate appropriate numbers of specialized cells. Whereas eukaryotes use cyclins and ...cyclin-dependent kinases to balance division with cell fate decisions, equivalent regulatory systems have not been described in bacteria. Moreover, the mechanisms used by bacteria to tune division in line with developmental programs are poorly understood. Here we show that Caulobacter crescentus, a bacterium with an asymmetric division cycle, uses oscillating levels of the second messenger cyclic diguanylate (c-di-GMP) to drive its cell cycle. We demonstrate that c-di-GMP directly binds to the essential cell cycle kinase CckA to inhibit kinase activity and stimulate phosphatase activity. An upshift of c-di-GMP during the G1-S transition switches CckA from the kinase to the phosphatase mode, thereby allowing replication initiation and cell cycle progression. Finally, we show that during division, c-di-GMP imposes spatial control on CckA to install the replication asymmetry of future daughter cells. These studies reveal c-di-GMP to be a cyclin-like molecule in bacteria that coordinates chromosome replication with cell morphogenesis in Caulobacter. The observation that c-di-GMP-mediated control is conserved in the plant pathogen Agrobacterium tumefaciens suggests a general mechanism through which this global regulator of bacterial virulence and persistence coordinates behaviour and cell proliferation.
These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician ...judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.
Forkhead box P3 (FOXP3) is currently thought to be the most specific marker for naturally occurring CD4+CD25+ T regulatory cells (nTregs). In mice, expression of FoxP3 is strictly correlated with ...regulatory activity, whereas increasing evidence suggests that in humans, activated T effector cells (Teffs) may also express FOXP3. In order to better define the role of FOXP3 in human Teff cells, we investigated the intensity and kinetics of expression in ex vivo Teff cells, suppressed Teff cells and Teff cell lines. We found that all dividing Teff cells expressed FOXP3, but only transiently, and at levels that were significantly lower than those in suppressive nTregs. This temporary expression in Teff cells was insufficient to suppress expression of reported targets of FOXP3 repressor activity, including CD127, IL-2 and IFN-γ, and was not correlated with induction of a nTreg phenotype. Thus expression of FOXP3 is a normal consequence of CD4+ T cell activation and, in humans, it can no longer be used as an exclusive marker of nTregs. These data indicate that our current understanding of how FOXP3 contributes to immune tolerance in humans needs to be re-evaluated.
Summary Background Cancer-induced muscle wasting begins early in the course of a patient's malignant disease, resulting in declining physical function and other detrimental clinical consequences. ...This randomised, double-blind, placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm, a selective androgen receptor modulator, in patients with cancer. Methods We enrolled male (>45 years) and female (postmenopausal) patients with cancer who were not obese and who had at least 2% weight loss in the previous 6 months. Participants were randomly assigned (1:1:1 ratio, by computer generated list, block size three, stratified by cancer type) to receive once-daily oral enobosarm 1 mg, 3 mg, or placebo for up to 113 days at US and Argentinian oncology clinics. The sponsor, study personnel, and participants were masked to assignment. The primary endpoint was change in total lean body mass from baseline, assessed by dual-energy x-ray absorptiometry. Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol-specified window of within 10 days before baseline or first study drug, and within 10 days of day 113 or end of study (evaluable efficacy population). Adverse events and other safety measurements were assessed in the intention-to-treat (safety) population. This trial is registered with ClinicalTrials.gov , number NCT00467844. Findings Enrolment started on July 3, 2007, and the last patient completed the trial on Aug 1, 2008. 159 patients were analysed for safety (placebo, n=52; enobosarm 1 mg, n=53; enobosarm 3 mg, n=54). The evaluable efficacy population included 100 participants (placebo, n=34; enobosarm 1 mg, n=32; enobosarm 3 mg, n=34). Compared with baseline, significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups (enobosarm 1 mg median 1·5 kg, range −2·1 to 12·6, p=0·0012; enodosarm 3 mg 1·0 kg, −4·8 to 11·5, p=0·046). Change in total lean body mass within the placebo group (median 0·02 kg, range −5·8 to 6·7) was not significant (p=0·88). The most common serious adverse events were malignant neoplasm progression (eight of 52 15% with placebo vs five of 53 9% with enobosarm 1 mg vs seven of 54 13% with enobosarm 3 mg), pneumonia (two 4% vs two 4% vs three 6%), and febrile neutropenia (three 6% vs one 2% vs none). None of these events were deemed related to study drug. Interpretation Cancer cachexia is an unmet medical need and our data suggest that use of enobosarm might lead to improvements in lean body mass, without the toxic effects associated with androgens and progestational agents. Funding GTx.
High-elevation neotropical environments of the Andes include the Páramo, a biodiversity hotspot with fast speciation rates. The genus
Espeletia
is distinctive of this ecosystem in the northern Andes. ...Its southern distribution limit lies in Ecuador, with the endemic
E
.
pycnophylla
subsp.
llanganatensis
being the only known representative south of the equator. This study presents the distribution, population structure and co-occurring flora of the subspecies
llanganatensi
s in the Valle de los Frailejones (VFL), Cordillera de los Llanganates. Four clusters totalling ~ 20 ha could be identified at elevations of 3400–3550 m above sea level.
Espelatia
pycnophylla
subsp.
llanganatensis
occurred amidst the sub-Páramo upper elevational limits of montane forests and within transitional areas between forest margins and waterlogged terrains. This habitat preference was a distinguishing ecological difference to the nearest (200 km) congener,
E. pycnophylla
subsp.
angelensis
. Plants (
N
= 781 measured) were skewed towards the smallest size classes ≤ 20 cm (28% of the population, including 17% recruits ≤ 10 cm) and reaching a total plant height of 900 cm. Synflorescences were observed in specimens ≥ 110 cm and in 51% of the mature population. The oldest specimens grew on terrains with higher edaphic stability. While local recruitment appears healthy, geographic distribution is limited suggesting vulnerability to local extinction. Co-occurring vegetation encompassed ~ 70 species, with grasses (Poaceae) and mosses (Bryophyta) dominating the ground cover, resulting in homogenous vegetation. Although
E. pycnophylla
subsp.
llanganatensis
is currently not exposed to direct human disturbance, clandestine mining activities intruding the region pose a potential threat to the survival of this Ecuadorian endemic.
Of the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal ...of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10-30 minutes of administration and sustained for at least 24 hours.
Coherent Diffractive Imaging (CDI) is an algorithmic imaging technique where intricate features are reconstructed from measurements of the freely diffracting intensity pattern. An important goal of ...such lensless imaging methods is to study the structure of molecules that cannot be crystallized. Ideally, one would want to perform CDI at the highest achievable spatial resolution and in a single-shot measurement such that it could be applied to imaging of ultrafast events. However, the resolution of current CDI techniques is limited by the diffraction limit, hence they cannot resolve features smaller than one half the wavelength of the illuminating light. Here, we present sparsity-based single-shot subwavelength resolution CDI: algorithmic reconstruction of subwavelength features from far-field intensity patterns, at a resolution several times better than the diffraction limit. This work paves the way for subwavelength CDI at ultrafast rates, and it can considerably improve the CDI resolution with X-ray free-electron lasers and high harmonics.
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