Sunday, January 24, 2021

Endothelium-dependent remote signaling in ischemia and reperfusion: alterations in the cardiometabolic continuum

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Publication date: Available online 23 January 2021

Source: Free Radical Biology and Medicine

Author(s): Ralf Erkens, Matthias Totzeck, Amanda Brum, Dragos Duse, Hans Erik Bøtker, Tienush Rassaf, Malte Kelm

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Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1α (HIF-1α)/HO-1 signaling pathway

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Publication date: Available online 23 January 2021

Source: Free Radical Biology and Medicine

Author(s): Xiangyun Li, Jianbo Yu, Lirong Gong, Yuan Zhang, Shuan Dong, Jia Shi, Cui Li, Yuting Li, Yanfang Zhang, Haibo Li

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Muscles in and around the ear as the source of “physiological noise” during auditory selective attention: a review and novel synthesis

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Abstract

The sensitivity of the auditory system is regulated via two major efferent pathways: the medial olivocochlear system that connects to the outer hair cells, and by the middle ear muscles – the tensor tympani and stapedius. The role of the former system in suppressing otoacoustic emissions has been extensively studied, but that of the complementary network has not. In studies of selective attention, decreases in otoacoustic emissions from contralateral stimulation have been ascribed to the medial olivocochlear system, but the acknowledged problem is that the results can be confounded by parallel muscle activity. Here, the potential role of the muscle system is examined through a wide but not exhaustive review of the selective attention literature, and the unifying hypothesis is made that the prominent "physiological noise" detected in such experiments, which is reduced during attention, is the sound produced by the muscles in proximity to the ear – including the middle ear m uscles. All muscles produce low‐frequency sound during contraction, but the implications for selective attention experiments – in which muscles near the ear are likely to be active – have not been adequately considered. This review and synthesis suggests that selective attention may reduce physiological noise in the ear canal by reducing the activity of muscles close to the ear. Indeed, such an experiment has already been done, but the significance of its findings have not been widely appreciated. Further sets of experiments are needed in this area.

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Aesthetic and therapeutic outcome of fat grafting for localized Scleroderma treatment: From basic study to clinical application

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Abstract

Background

Localized scleroderma (LoS) is a rare autoimmune disease characterized by skin fibrosis and subcutaneous tissue atrophy, resulting in aesthetic impairment on patients. Fat grafting has been used to treat LoS patients, achieving aesthetic and therapeutic improvement.

Aims

This article summarized the epidemiology and pathophysiology of LoS and the current progress and thorny questions of basic and clinical research on fat grafting treating LoS.

Methods

The literature of the last 20 years concerning fat grafting of treating LoS was reviewed.

Results

Fat grafting has been proved to produce aesthetic and therapeutic outcomes on LoS patients, including the improvement of soft tissue atrophy, skin fibrosis and pigmentation. Due to the inflammatory microenvironment of scleroderma, however, fat grafting still faces many difficulties, such as low fat retention. Novel fat grafting methods in order to supplement the deficiency of adipose‐derived stem cells and improve fat retention in LoS groups have been proposed whose effectiveness and feasibility is still needed further study.

Conclusion

Currently, fat grafting has been regarded as an effective treatment with a combination of aesthetic and therapeutic outcomes on LoS patients.

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Targeting ubiquitin-specific protease-7 in plasmacytoid dendritic cells triggers anti-myeloma immunity

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Periodontitis is a Factor Associated with Dyslipidemia

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Abstract

Objective

To investigate the association between the severity of periodontitis (exposure) and dyslipidemia (outcome).

Methods

This was a cross‐sectional study of users of public health services. Periodontitis was defined using the Center for Disease Prevention and Control and the American Academy of Periodontology criteria. Lipid evaluation used data on systemic biomarkers. Dyslipidemia diagnosis was based on the Guidelines of total cardiovascular risk of the World Health Organization. Weight, height, waist circumference, and blood pressure were measured, and socioeconomic‐demographic, lifestyle behavior factors, general and oral health conditions of the participants were collected. Hierarchical and logistic regression analyzes were used to determine the association between the exposures and the outcome. Odds Ratios, unadjusted and adjusted, and 95% confidence intervals were estimated.

Results

Of 1,011 individuals examined, 75.17% had dyslipidemia, and 84.17% had periodontitis, 0.2% with mild, 48.56% moderate and 35.41% severe disease. The association between periodontitis and dyslipidemia was maintained through hierarchical analysis and in the multiple regression modeling, showing that the occurrences of dyslipidemia in the group with periodontitis, and its moderate and severe levels, were, respectively, 14%, 30%, and 16% higher compared with those without periodontitis.

Conclusions

The results showed a positive association between moderate and severe periodontitis and dyslipidemia.

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Effects of ibuprofen administration timing on oral surgery pain: A randomized clinical trial

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Abstract

Objective

This study aimed to compare the analgesic effect of ibuprofen 400 mg given 30 minutes before or immediately after third molars surgery under local anaesthesia.

Materials and Methods

The single‐center, randomized, split‐mouth, triple‐blind, clinical trial involved 38 outpatients, for a total of 76 bilateral symmetrical fully bone impacted mandibular third molars. Each patient was undergone to separate surgical sessions for the right and left side, and ibuprofen was randomly administered 30 minutes before or immediately after the intervention. Study participants recorded pain intensity using Numerical Rating Scale‐11, the timing of rescue therapy intake, and overall tablets consumption over three days.

Results

The overall pain intensity score was lower in the group receiving ibuprofen immediately after (3.13 ± 2.46) than before (3.58 ± 2.40) surgery, with statistically significant differences only on the second and third day. The mean time to the first using rescue therapy was longer in the postoperative (598.33 ± 422.62 minutes) than in the preoperative (406.25 ± 149.79 minutes) analgesic treatment group (p=0.123). The number of supplemented ibuprofen tablets did not differ (p=0.530) between both groups.

Conclusions

Within the limits of the present study, ibuprofen administration immediately after surgery seemed to be more effective than preoperative administration.

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The systemic inflammation response index predicts the survival of patients with clinical T1‐2N0 oral squamous cell carcinoma

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Abstract

Objective

The systemic inflammation response index (SIRI) is an independent prognostic factor for many malignant tumors. However, the value of this factor in patients with clinical T1‐2N0 (cT1‐2N0) oral squamous cell carcinoma (OSCC) is still unclear.

Methods

We calculated SIRI of 235 cT1‐2N0 OSCC patients from 2013 to 2017. Multivariate cox regression analysis was applied to verify the prognostic significance of SIRI. Kaplan‐Meier curves were plotted to analyze the overall survival (OS) and disease‐specific survival (DSS) for cT1‐2N0 OSCC patients.

Results

According to the optimal cutoff point of SIRI, we divided cT1‐2N0 OSCC patients into high SIRI group (SIRI ≥ 1.3) and low SIRI group (SIRI < 1.3). SIRI was an independent prognostic indicator for OS (HR = 2.87; 95% CI = 1.35‐6.10; P = 0.006) and DSS (HR = 2.17; 95% CI = 1.10‐4.27; P = 0.025). High SIRI had a significantly poorer OS (P = 0.001) and DSS (P = 0.007) in survival analysis than the low SIRI. Moreover, the prognostic value of SIRI was significantly stronger than neutrophil‐to‐lymphocyte ratio (NLR) and monocyte‐to‐lymphocyte ratio (MLR).

Conclusions

Preoperative SIRI can be regarded as a meaningful indicator for poor survival of cT1‐2N0 OSCC patients, and it is a promising tool to formulate the best individualized treatment for high‐risk patients.

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Age‐related dental phenotypes and tooth characteristics of FAM83H‐associated hypocalcified amelogenesis imperfect

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Abstract

Objectives

Autosomal‐dominant hypocalcified amelogenesis imperfecta (ADHCAI) shows phenotypic heterogeneity. Our aim was to characterise the ADHCAI phenotypes, tooth properties, and genotypes.

Methods

Three unrelated ADHCAI probands and seven additional affected members of the three families were recruited. Mutations were identified by exome and Sanger sequencing, and haplotypes by SNP array. Tooth colour, roughness, density, nanohardness, minerals, and ultrastructure were investigated.

Results

Ten participants were heterozygous for the FAM83H mutation c.1387C>T (p.Gln463*). All shared a 3.43 Mbp region on chromosome 8q24.3 encompassing the FAM83H variant, indicating a common ancestry. The c.1387C>T was estimated to be 23.8 generations or 600 years. The FAM83H enamel had higher roughness and lower lightness, density, nanohardness, and calcium and phosphorus levels than controls. Blunted enamel rods, wide interrod spaces, and disorganized dentinoenamel junctions were observed. Evaluating the patients with the same mutation and reviewing others with different mutations in FAM83H revealed that the FAM83H heterogeneous phenotypes are age‐influenced. Tooth colour and surface texture change with aging.

Conclusions

FAM83H enamel demonstrated decreased lightness, density, hardness, calcium, phosphorus, and defective ultrastructure. We have identified that the phenotypic variation in FAM83H‐associated ADHCAI is age‐related. Awareness of the correlation between age and clinical features of FAM83H‐ADHCAI can help dentists make an accurate diagnosis.

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Efficacy and safety of sorafenib plus vitamin K treatment for hepatocellular carcinoma: A phase II, randomized study

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Efficacy and safety of sorafenib plus vitamin K treatment for hepatocellular carcinoma: A phase II, randomized study

Vitamin K dosing during sorafenib treatment against HCC showed higher ORR and prolonged PFS significantly. The vitamin K dosing might enhance the antitumor action of sorafenib by suppressing des‐γ‐carboxy prothrombin, which is a factor that promotes angiogenesis and tumor growth.


Abstract

The previous retrospective study suggested that dosing vitamin K may enhance the anticancer action of sorafenib against hepatocellular carcinoma. To confirm it, we performed a phase II, randomized, open‐label study. Patients with hepatocellular carcinoma were randomly assigned to receive sorafenib + vitamin K2 (menatetrenone, 45 mg daily, orally) or sorafenib only. Between 1 May 2012 and 1 May 2016, 68 patients were screened. Forty‐four eligible patients were assigned at a 1:1 ratio to each cohort. The objective response rate in the vitamin K‐dosed group was significantly higher than that in the sorafenib only group (27.3% vs 4.5%, respectively; p = 0.039). The median time of progression‐free survival was significantly extended in the vitamin K‐dosed group compared with the sorafenib only group (4.9 months vs 2.7 months, respectively; hazard ratio (HR), 0.44; 95% confidence interval (CI): 0.21–0.89; p = 0.018). Although there was no significant difference between the two groups in the median time of overall survival, patients in the vitamin K‐dosed group with a complete response or partial response achieved a significantly extended median time of overall survival compared with the other patients in the vitamin K‐dosed group or the patients in the sorafenib only group (26.1 months vs 9.0 months; HR, 0.34; 95% CI: 0.11–0.95; p = 0.046 or 11.5 months; HR, 0.16; 95% CI: 0.034–0.70; p = 0.006, respectively). Dosing vitamin K could augment the anticancer action of sorafenib against HCC.

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Circ_0008305‐mediated miR‐660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis

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Circ_0008305‐mediated miR‐660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis

circ_0008305 was greatly increased in HCC tissues and cells. circ_0008305 can act as a sponge of miR‐660. miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5).


Abstract

Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR‐660 while miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR‐660, which resulted in an upregulated expression of BA G5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR‐660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305‐mediated miR‐660‐5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression.

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Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases

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Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases

In our study of the National Cancer Data Base (NCBD), addition of immunotherapy to radiation therapy improves survival in patients with melanoma with brain metastases when added to SBRT or WBRT, with the best survival observed for IT with SBRT. Concurrrent versus Noncurrent immunotherapy combined with radiation had no significantly different survival.


Abstract

Introduction

Immunotherapy (IT) and radiotherapy (RT) have improved overall survival in patients with melanoma with brain metastasis (MBM). We examined the real‐world survival impact of IT and RT combination and timing strategies.

Materials and Methods

From the facility‐based National Cancer Database (NCDB) data set, 3008 cases of MBM were identified between 2011 and 2015. Six treatment cohorts were identified: stereotactic radiosurgery (SRS) + IT, SRS alone, whole brain radiotherapy (WBRT) + IT, WBRT alone, IT alone, and none. Concurrent therapy was defined as IT given within 28 days before or after RT; nonconcurrent defined as IT administered within 28–90 days of RT. The co‐primary outcomes were propensity score‐adjusted overall survival by treatment regimen and overall survival by RT and IT timing.

Results

Median overall survival (mOS) was performed for each treatment category; SRS +IT 15.77 m; (95%CI 12.13–21.29), SRS alone (9.33 m; 95%CI: 8.0–11.3), IT alone (7.29 m; 95%CI: 5.35–12.91), WBRT +IT (4.89 m; 95%CI: 3.65–5.92), No RT or IT (3.29 m; 95%CI: 2.96–3.75), and WBRT alone (3.12 m; 95%CI 2.79–3.52). By propensity score matching, mOS for SRS +IT (15.5 m; 95%CI: 11.5–20.2) was greater than SRS alone (10.1 m; 95%CI: 8.4–11.8) (p = 0.010), and median survival for WBRT +IT (4.6 m; 95%CI: 3.4–5.6) was greater than WBRT alone (2.9 m; 95%CI: 2.5–3.5) (p < 0.001). In the SRS +IT group, 24‐month landmark survival was 47% (95%CI; 42–52) for concurrent versus 37% (95%CI; 30–44) for nonconcurrent (p = 0.40).

Conclusion

Those who received IT in addition to WBRT and SRS experienced longer survival compared to RT modalities alone, while those receiving concurrent SRS and IT trended toward improved survival versus nonconcurrent therapy.

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