Αρχειοθήκη ιστολογίου

Πέμπτη 7 Απριλίου 2022

miR-199a-5p Plays a Pivotal Role on Wound Healing via Suppressing VEGFA and ROCK1 in Diabetic Ulcer Foot

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Diabetes mellitus (DM) is a growing health problem. As a common complication of DM, diabetic foot ulcer (DFU) results in delayed wound healing and is a leading cause of nontraumatic amputation. miR-199a-5p, a short noncoding RNA, had abnormal expression in DFU wound tissues. The expression of miR-199a-5p was significantly increased in DFU wound tissues, skin tissues of diabetic rats, and high glucose-induced cells. Vascular endothelial growth factor A (VEGFA) and Rho-associated kinase 1 (ROCK1) are directly targets of miR-199a-5p. Inhibiting the expression of miR-199a-5p alleviated the inhibition of VEGFA and ROCK1, thereby rescued impaired proliferation and migration of HG-induced cells, and restored the normal function of the cells to some extent. In diabetic rats, inhibition of miR-199a-5p significantly increased the expression of VEGFA and ROCK1, significantly promoted wound healing, and rescued impaired wound healing. miR-199a-5p and its targets showed therapeutic effect on diabetic wounds.
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Glycyrrhizin Attenuates Hypoxic-Ischemic Brain Damage by Inhibiting Ferroptosis and Neuroinflammation in Neonatal Rats via the HMGB1/GPX4 Pathway

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With unknown etiology and limited treatment options, neonatal hypoxic-ischemic brain damage (HIBD) remains a major cause of mortality in newborns. Ferroptosis, a recently discovered type of cell death triggered by lipid peroxidation, is closely associated with HIBD. High-mobility group box 1 (HMGB1), a molecule associated with inflammation damage, can induce neuronal death in HIBD. However, it remains unknown whether HMGB1 contributes to neuronal ferroptosis in patients with HIBD. Herein, glycyrrhizin (GL), an HMGB1 inhibitor, was used to investigate the relationship between ferroptosis and HMGB1. RAS-selective lethal 3(RSL3), a ferroptosis agonist, was administered to further confirm the changes in the signaling pathway between HMGB1 and ferroptosis. Western blot analysis revealed that GL mar kedly suppressed the expression of HMGB1 and increased the level of GPX4 in the context of HIBD. We observed changes in neuronal ultrastructure via transmission electron microscopy to further confirm the occurrence of ferroptosis. Real-time PCR indicated that GL inhibited the expression of ferroptosis-related genes and inflammatory factors. Immunofluorescence and immunohistochemistry staining confirmed GL inhibition of neuronal damage and ferroptosis in HIBD associated with GPX4 and ROS. GL not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by HIBD in vivo. More importantly, GL may improve oxidative stress imbalance and mitochondrial damage, alleviate the downstream production of inflammatory factors, and ultimately reduce ferroptosis and damage to cortical neurons following HIBD via the HMGB1/GPX4 pathway. In conclusion, we showed for the first time that GL could suppress the occurrence of neuronal ferroptos is and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway. These findings highlight the potential of HMGB1 signaling antagonists to treat neuronal damage by suppressing ferroptosis, provide new and unique insights into GL as a neuroprotective agent, and suggest new prevention and treatment strategies for HIBD.
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Integrated Network Pharmacology and Gut Microbiota Study on the Mechanism of Huangqin Decoction in Treatment Diabetic Enteritis

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Objective. Using network pharmacology and gut microbiota sequencing to investigate the probable mechanism of Huangqin decoction in the treatment of Diabetic enteritis (DE). Methods. The mechanism of Huangqin decoction on DE was studied by combining network pharmacology and gut microbiota sequencing analysis. The core components and possible targets of Huangqin decoction were analyzed by network pharmacology. The effect of Huangqin decoction on microorganisms was investigated by gut microbiota sequencing. Results. The results of gut microbiota sequencing analysis showed the abundance of TM7, Tenericutes, Chloroflexi, Cyanobacteria, Acidobacteria, WS6, [Prevotella], Helicobacter, Prevotella, Lactococcus, and Anaeroplasma in the Huangqin decoction group had a significant downward. Using a network ph armacology-related database, 141 main active components of Huangqin decoction were identified, as well as 256 corresponding component targets and 1777 corresponding disease targets; the disease targets and component targets were mapped, and topological analysis was used to determine the potential of Huangqin decoction in the treatment of DE. There were 156 targets, of which the top 20 genes were selected for GO and KEGG. The KEGG results showed that 134 pathways were enriched, which was partially consistent with the metabolic pathways of gut microbiota sequencing analysis. Conclusion. The results show that Huangqin decoction can inhibit the expression of inflammatory factors and related inflammatory pathways in intestinal epithelial cells, thereby regulating the structure of intestinal flora. Using picurst2 for functional prediction and metabolic pathway statistics, seven metabolic pathways were obtained consistent with gut microbiota sequencing, and the NOD-like receptor signaling pathway may be its potential molecular mechanism. These results help to understand the mechanism of Huangqin decoction on DE and provide the theoretical basis for further study of Huangqin decoction.
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Optimized Protocol for the Isolation of Extracellular Vesicles from the Parasitic Worm Schistosoma mansoni with Improved Purity, Concentration, and Yield

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In the past decade, the interest in helminth-derived extracellular vesicles (EVs) increased owing to their role in pathogen-host communication. However, the availability of EVs from these parasitic worms is often limited due to the restricted occurrence and culturing possibilities of these organisms. Schistosoma mansoni is one of several helminths that have been shown to release EVs affecting the immune response of their host. Further investigation of mechanisms underlying these EV-induced effects warrants separation of EVs from other components of the helminth excretory/secretory products. However, isolation of high-purity EVs often come to the expense of reduced EV yield. We therefore aimed to develop an optimized protocol for isolation of EVs from S. mansoni schistosomula and adult worms with respect to purity, concentration, and yield. We tested the use of small (1.7 ml) iodixanol density gradients and demonstrated that this enabled western blot-based analysis of the EV marker protein tetraspanin-2 (TSP-2) in gradient fractions without additional concentration steps. Moreover, the concentration and yield of EVs obtained with small iodixanol gradients were higher compared to medium-sized (4.3 ml) or conventional large-sized (12 ml) gradients. Additionally, we provide evidence that iodixanol is preferred over sucrose as medium for the small density gradients, because EVs in iodixanol gradients reached equilibrium much faster (2 hours) and iodixanol but not sucrose was suitable for purification of schistosomula EVs. Finally, we demonstrate that the small iodixanol gradients were able to separate adult worm EVs from non-EV contaminants such as the blood digestion product hemozoin. Our optimized small iodixanol density gradient allows to simultaneously separate and con centrate EVs while reducing handling time and EV loss and can be applied for EVs from helminths and other limited EV sources.
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Τετάρτη 6 Απριλίου 2022

Single-cell transcriptomics reveals cell type diversity of human prostate

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Publication date: Available online 6 April 2022

Source: Journal of Genetics and Genomics

Author(s): Yang Chen, Peng Zhang, Jinling Liao, Jiwen Cheng, Qin Zhang, Tianyu Li, Haiying Zhang, Yonghua Jiang, Fangxing Zhang, Yanyu Zeng, Linjian Mo, Haibiao Yan, Deyun Liu, Qinyun Zhang, Chunlin Zou, Gong-Hong Wei, Zengnan Mo

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Differences in oral anticoagulant prescriptions between specialists and non-specialists in patients with cardioembolic stroke caused by non-valvular atrial fibrillation

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Abstract

Atrial fibrillation (AF) is a common disease encountered in daily practice; however, few patients with AF received oral anticoagulant (OAC) therapy. This study focused on differences in OAC prescriptions and influencing factors between specialists (neurological and cardiovascular) and non-specialists. A retrospective comparative analysis was conducted on 480 patients with acute cardioembolic stroke caused by non-valvular AF who were admitted to our hospital between January 1, 2015, and December 31, 2020. All patients had visited our hospital or other hospitals for their underlying diseases. Overall, 232 (specialist group SG) and 248 patients (non-specialist group NSG) were examined by specialists and non-specialists, respectively. The NSG had a significantly lower percentage of OAC prescriptions on admission than the SG (P < 0.01), even after propensity score matching. Factors influencing OAC prescription in the SG were age, hypertension, paroxy smal AF, dementia, CHADS2 score, and antiplatelet drug use, while those in the NSG were a history of cerebral infarction, paroxysmal AF, dementia, and antiplatelet drug use [SG: age, odds ratio (OR) 0.919, 95% confidence interval (CI) 0.865–0.976; hypertension, OR 0.266, 95% CI 0.099–0.713; paroxysmal AF, OR 0.189, 95% CI 0.055–0.658; dementia, OR 0.253, 95% CI 0.085–0.758; CHADS2 score, OR 2.833, 95% CI 1.682–4.942; and antiplatelet drug use, OR 0.072, 95% CI 0.025–0.206; NSG: cerebral infarction, OR 5.940, 95% CI 1.581–22.309; paroxysmal AF, OR 0.077, 95% CI 0.010–0.623; dementia, OR 0.077, 95% CI 0.014–0.438; and antiplatelet drug use, OR 0.024, 95% CI 0.004–0.152]. In conclusion, the OAC prescription rate was higher in patients with non-valvular AF whose family physicians were specialists at the time of cerebral infarction onset. In addition, in the SG, advanced age and hypertension were associated with not prescribing OAC, whereas a hig her CHADS2 score was associated with the prescription of OACs. In the NSG, a history of cerebral infarction was associated with the prescription of OACs. Further, paroxysmal AF, antiplatelet drug use, and dementia were associated with non-OAC therapy in both the groups.

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Peritoneal Tuberculosis Mimicking Peritoneal Carcinomatosis on 68Ga-FAPI-04 and 18F-FDG PET/CT

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imageWe report a case of tuberculosis peritonitis in a 26-year-old woman who presented with abdominal pain, fatigue, and weight loss for the last 4 months. Abdominal US and CT demonstrated intra-abdominal massive ascites, misty mesentery, and diffuse peritoneal thickening. In addition, 3 nodular lesions were detected in the right lung. 18F-FDG PET/CT showed hypermetabolism in lung nodules, mesenteric area, peritoneal thickening, and ascites. 68Ga-FAPI-04 (fibroblast activation protein–specific inhibitor) PET/CT imaging was also performed; high uptakes were detected in the same regions of 18F-FDG PET/CT. Tuberculosis diagnosis was made after histopathological examination of wedge resection of the right lung.
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A multi-pollutant approach to estimating causal effects of air pollution mixtures on overall mortality in a large, prospective cohort.

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Background: Several studies have confirmed associations between air pollution and overall mortality, but it is unclear to what extent these associations reflect causal relationships. Moreover, few studies to our knowledge have accounted for complex mixtures of air pollution. In this paper, we evaluate causal effects of a mixture of air pollutants on overall mortality in a large, prospective cohort of Dutch individuals. Methods: We evaluated 86,882 individuals from the LIFEWORK study, assessing overall mortality between 2013-2017 through national registry linkage. We predicted outdoor concentration of five air pollutants (PM2.5, PM10, NO2, PM2.5 absorbance, oxidative potential) with land-use regression. We used logistic regression and mixture modeling (weighted quantile sum and boosted regression tree models) to identify potential confounders, assess pollutants relevance in the mixture–outcome association, and investigate interactions and non-linearities. Based on these results, we built a multivariate generalized propensity score model to estimate causal effects of pollutant mixtures. Results: Regression model results were influenced by multicollinearity. Weighted quantile sum and boosted regression tree models indicated that all components contributed to a positive linear association with the outcome, with PM2.5 being the most relevant contributor. In the multivariate propensity score model, PM2.5 (OR=1.18, 95% CI:1.08,1.29) and PM10 (OR=1.02, 95% CI:0.91,1.14) were associated with increased odds of mortality per interquartile range increase. Conclusion: Using novel methods for causal inference and mixture modeling in a large prospective cohort, this study strengthened the causal interpretation of air pollution effects on overall mortality, emphasizing the primary role of PM2.5 within the pollutant mixture. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Comparison of cervical and ocular vestibular-evoked myogenic potential responses between tone burst versus chirp stimulation

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Abstract

Purpose

To compare the effectiveness of chirp and tone burst stimuli in oVEMP and cVEMP testing for healthy adults

Methods

This study was conducted in 56 healthy volunteers (112 ears). Ocular and cervical VEMP (oVEMP, cVEMP) tests were performed for each participant using tone burst and chirp stimuli. VEMP response rates, latency of each peak (p1–n1, n1–p1), peak to peak amplitude (p1–n1 amplitude and n1–p1 amplitude), and rectified amplitudes were measured and compared between these two different stimuli.

Results

VEMP response rates with chirp stimuli are higher than the tone burst stimuli for both cVEMP and oVEMP tests (The difference was statistically significant for oVEMP, p = 0.001). Chirp stimuli have higher p1n1 amplitude and rectified amplitude and shorter p1and n1 latency then tone burst stimuli for cVEMP (p = 0.015, p = 0.007, p < 0.001, p < 0.001, respectively). Chirp stimuli also have higher n1p1 amplitude and shorter n1and p1 latency then tone burst stimuli for oVEMP (p = 0.006, p < 0.001, p < 0.001, respectively).

Conclusion

The present findings show that the chirp stimulus triggers earlier VEMP responses with higher amplitudes than the tone burst stimulus during cVEMP and oVEMP testing. VEMP response rate with chirp stimulus is also higher than the tone burst. Therefore chirp stimulus can be used in VEMP testing as effectively as, if not more than, tone burst stimulus in clinical practice.

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Conventional approaches versus laser CO2 surgery in stapes surgery: a multicentre retrospective study

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Abstract

Purpose

To analyze and compare surgical and audiological outcomes of conventional approaches versus laser CO2 surgery in stapes surgery.

Methods

333 patients who underwent stapes surgery were enrolled in the study; the patient population was divided into three groups: group 1: 170 patients treated with conventional stapedotomy with manual microdrill (average age 49.13 years); group 2: 119 patients treated with conventional stapedotomy with electrical microdrill (average age 51.06 years); group 3: 44 patients (average age 50.4 years) who underwent CO2 laser stapedotomy. Intra-operative, postoperative outcomes and audiological results were investigated.

Results

The average surgical time of laser CO2 surgery was longer than for other surgical procedures. No statistical differences emerged in post-operative abnormal taste sensation. There was also no difference in postoperative dizziness. Air-bone gap (ABG) went down from 29.7 ± 10 dB (group 1) and 27.32 ± 9.20 (group 2) to 10 ± 6.9 dB (group 1) and 10.7 ± 6.03 dB (group 2). In group 3 the preoperative ABG was lowered from 28.3 ± 10.1 to 11.8 ± 10.9, with a statistical difference in auditory recovery (p = 0.0001); The group of patients treated with laser CO2 showed a percentage of patients with an ABG closure of between 0 and 10 dB higher than in the group treated with manual microdrills (77.2% vs. 60%, respectively; p = 0.03).

Conclusion

Overall surgical results of CO2 laser and conventional stapedotomy are comparable without any significant difference; however, the group treated with CO2 laser appears to have a percentage of patients with an ABG closure 0–10 dB higher than the group treated using the conventional technique.

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Endolymphatic sac tumor: single-institution series of seven cases with updated review of literature

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Abstract

Background

Endolymphatic sac tumour (ELST) is a rare low-grade locally aggressive neoplasm arising from the endolymphatic duct or sac. It presents mostly with vestibulo-cochlear symptoms either sporadically or as part of von Hippel–Lindau (VHL) syndrome. Micro-neurosurgical excision remains the cornerstone of therapy with the role of radiotherapy (RT) being controversial. This is a clinico-pathological analysis of consecutive ELST patients presenting to a single-institution in India.

Methods

Neuropathology database of a tertiary-care comprehensive cancer centre was searched electronically to identify consecutive patients with histopathological diagnosis of ELST registered at the institute over last one decade. Data regarding demographic profile, clinical presentation, histopathological features, treatment details and outcomes were retrieved from electronic medical records for this retrospective analysis.

Results

Electronic search identified seven unique patients with biopsy-proven ELST registered at the institute between 2009 and 2020. Median age of the study cohort was 39 years (range 24–65 years) with strong male predilection (5:2 ratio) and left-sided preponderance (71%). Most common presenting symptoms were hearing loss (86%) and earache (71%) on affected side followed by headache (43%). All patients underwent maximal safe resection at initial diagnosis and were followed-up closely with periodic surveillance imaging. Two patients underwent salvage RT using high-precision conformal techniques at recurrence/progression.

Conclusion

ELST is a rare low-grade locally aggressive neoplasm that arises generally as part of VHL syndrome or sometimes sporadically. Gross total resection provides the best chance of cure with RT being reserved for unresectable disease, large residue, medical inoperability, or as salvage therapy for recurrent/progressive tumor.

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