Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology ...of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars.
To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-β-mediated responses in pathologic scars.
The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-β1 signaling through binding with and stabilizing TGF-β receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids.
Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-β signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
MINIThis randomized clinical trial showed different intubation mode in anesthesia did not affect the increase of endotracheal cuff pressure caused by the retractor splay in anterior cervical spine ...surgery. However, nasotracheal intubation improved postoperative dysphonia recovery after anterior cervical spine surgery.
STUDY DESIGN.Prospective, randomized, double-blinded trial.
OBJECTIVE.The aim of this study was to investigate whether the mode of tracheal intubation affects intraoperative endotracheal tube cuff pressure on retractor splay and post-anterior cervical spine surgery (ACSS) voice outcome.
SUMMARY OF BACKGROUND DATA.The combination of endotracheal tube (ETT) and cervical retractors has been implicated in recurrent laryngeal nerve compression and neuropraxia after ACSS. The asymmetric position of the oroETT within the larynx, as being fixed distally by the cuff and proximally by taping on one side of the mouth, may contribute to unilateral vocal palsy.
METHODS.Adult patients undergoing ACSS were randomized to receive either nasotracheal or orotracheal intubation under anesthesia. The primary endpoint was the maximal endotracheal tube cuff pressure (ETCP) when the retractors were set up. After the maximal ETCPs were recorded, then ETCPs were controlled to less than 25 mmHg. Secondary endpoints were self-assessed hoarseness, pitch, and loudness of voice on postoperative days (PODs) 1, 2, 7, and 30.
RESULTS.We equally allocated 110 patients to nasotracheal and orotracheal intubation. The maximal ETCP during retractor splay did not differ for both the means and distributions of pressure range. After the surgery, more patients in the nasotracheal intubation group reported none or mild change of voice than did the orotracheal intubation group on PODs 1 and 2, in terms of hoarseness, pitch, and loudness (P = 0.001, 0.001, and 0.005, respectively, on POD 1; P = 0.002, 0.003, and 0.011, respectively, on POD 2). Mixed model analysis demonstrated that patients with nasotracheal intubation had significantly lower dysphonia scores after surgery (estimate treatment effect−1.62, P < 0.0001). Statistics was adjusted to exclude interaction with ETT sizes.
CONCLUSION.The tracheal intubation modes did not affect ETCP during retractor splay. However, nasotracheal intubation had a beneficial effect on dysphonia recovery after ACSS.Level of Evidence2
Psoriasis is a common, chronic immune-mediated disorder that occurs worldwide. The prevalence of psoriasis in Taiwan is lower than that in Caucasian countries. Nevertheless, an increasing trend in ...the prevalence of psoriasis and psoriatic arthritis has been observed in Taiwan over the past decade. Accumulating studies have also suggested that psoriasis is not a disease limited to the skin and joints but has far-reaching systemic effects, associated with a higher prevalence of comorbid diseases, such as cardiovascular diseases, diabetes mellitus, metabolic syndrome, depression, and chronic kidney disease, than in the normal population. To date, our understanding of the mechanisms linking psoriasis and comorbidities remains far from complete. Psoriasis and its comorbid diseases confer substantial disease and health care burdens and have a significant negative impact on the quality of life of affected patients. The discovery of new, promising drugs has revolutionized psoriasis treatment, but patients still have unmet needs that require further investigation. Studies specifically on the Taiwanese population with psoriasis remain scarce. Herein, we review the medical literature, with a focus on studies examining the Taiwanese population, with regard to epidemiology, comorbidities, and effects of antipsoriatic agents on comorbidities, as well as the efficacy and safety of novel antipsoriatic treatments for patients with psoriasis.
To quit or not to quit Joe, Sheng-Wuu; Hung, Wei-Ting; Chiu, Chou-Kang ...
Personnel review,
08/2018, Letnik:
47, Številka:
5
Journal Article
Recenzirano
Purpose
To deepen our understanding about the development of turnover intention, the purpose of this paper is to develop a model that explains how ethical climate influences turnover intention based ...on the ethical climate theory and social identity theory.
Design/methodology/approach
The hypotheses of this study were statistically tested using a survey of working professionals from Taiwan’s high-tech industry. Of the 400 questionnaires distributed to the working professionals from five large high-tech firms in a well-known science park in Northern Taiwan, 352 usable questionnaires were returned for a questionnaire response rate of 88 percent.
Findings
The test results of this study first show that all three dimensions of ethical climate (i.e. instrumental, benevolent, and principled) are indirectly related to turnover intention via the mediation of firm attractiveness. Moreover, instrumental and benevolent climate directly relate to turnover intention, whereas benevolent climate negatively moderates the relationship between principled climate and firm attractiveness.
Originality/value
This study finds that benevolent climate plays a dual role as an antecedent and a moderator in the formation of turnover intention, complementing prior studies that merely concentrate on the single role of benevolent climate as either an antecedent or a moderator. The effect of principled climate on organizational identification complements the theoretical discussion by Victor and Cullen (1987) about deontology in which an ethical workplace climate (such as legitimacy) drives employees to invest in identity attachments to the organization and influences their future career decision (e.g. turnover).
BARD1 is an ATPase activating protein for OLA1 Chen, Ting; Yeh, Hung-Wei; Chen, Po-Pang ...
Biochimica et biophysica acta. General subjects,
20/May , Letnik:
1866, Številka:
5
Journal Article
Recenzirano
OLA1 is a P-loop ATPase, implicated in centrosome duplication through the interactions with tumor suppressors BRCA1 and BARD1. Disruption of the interaction of OLA1 with BARD1 results in centrosome ...amplification. However, the molecular interplay and mechanism of the OLA1-BARD1 complex remain elusive. Here, we use a battery of biophysical, biochemical, and structural analyses to elucidate the molecular basis of the OLA1-BARD1 interaction. Our structural and enzyme kinetics analyses show this nucleotide-dependent interaction enhances the ATPase activity of OLA1 by increasing the turnover number (kcat). Unlike canonical GTPase activating proteins that act directly on the catalytic G domain, the BARD1 BRCT domain binds to the OLA1 TGS domain via a highly conserved BUDR motif. A cancer related mutation V695L on BARD1 is known to associate with centrosome abnormality. The V695L mutation reduces the BARD1 BRCT-mediated activation of OLA1. Crystallographic snapshot of the BRCT V695L mutant at 1.88 Å reveals this mutation perturbs the OLA1 binding site, resulting in reduced interaction. Altogether, our findings suggest the BARD1 BRCT domain serves as an ATPase activating protein to control OLA1 allosterically.
•BARD1 BRCT domain allosterically activates OLA1 ATPase.•The conserved BUDR motif in the BRCT interacts with OLA1.•Crystal structure reveals the molecular mechanism of disease mutation V695L in BARD1.
Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still ...unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells.
Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or ...even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis.
GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery.
The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV's cornea.
The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.
Poor sleep quality during hospitalization may lead to post-hospital symptoms and increase readmission rates and mortality. Patients in our intensive care unit (ICU) reported low mean scores on the ...Richards-Campbell Sleep Questionnaire (RCSQ) during their third and fifth days of hospitalization (49.7 mm and 51.7 mm, respectively). Therefore, a project to improve sleep quality in the ICU was established.
To increase the mean RCSQ score from 51.7 mm to 76.0 mm on the fifth day. The fifth day timeframe was chosen because of the disease conditions of the patients and related clinical-medical factors.
The project team proposed an evidence-based, sleep care bundle that included non-medication pain control, environmental regulation, improvement of the care process, and individualized sleep care.
After implementing the bundled intervention, the mean RCSQ score of patients in our ICU increased from 49.7 mm to 55.9 mm on the third day and from 51.7 mm to 80.9 mm on the fifth day.
This application of a sleep care bundle
Highlights • A novel approach for visualization of temporal patterns focused on the association of cancers with other diseases. • A dynamic animation of cancer-disease association across different ...age groups and gender. • Identifying comorbidity relationships and providing more information for medical researchers.
A genetic algorithm for the optimization of composite laminates is proposed in this work. The well-known roulette selection criterion, one-point crossover operator, and uniform mutation operator are ...used in this genetic algorithm to create the next population. To improve the hill-climbing capability of the algorithm, adaptive mechanisms designed to adjust the probabilities of the crossover and mutation operators are included, and the elite strategy is enforced to ensure the quality of the optimum solution. The proposed algorithm includes a new operator called the elite comparison, which compares and uses the differences in the design variables of the two best solutions to find possible combinations. This genetic algorithm is tested in four optimization problems of composite laminates. Specifically, the effect of the elite comparison operator is evaluated. Results indicate that the elite comparison operator significantly accelerates the convergence of the algorithm, which thus becomes a good candidate for the optimization of composite laminates.
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