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Rheum officinale Baill. Treats zebrafish embryo thrombosis by regulating NOS3 expression in the arginine biosynthesis pathway

Phytomedicine. 2022 Feb 5;99:153967. doi: 10.1016/j.phymed.2022.153967. Online ahead of print.

ABSTRACT

BACKGROUND: Rheum officinale Baill. (ROB), as one of the traditional Chinese medicines for promoting blood circulation and removing blood stasis, has a wide range of pharmacological effects, such as cardiovascular protection, and has become a common drug in the clinical care of thrombosis.

OBJECTIVE: Although there are some pharmacological studies on ROB in the treatment of thrombotic diseases, the mechanism and material basis are still unclear. Based on the arginine biosynthesis signalling pathway, this research explored the target proteins and metabolites related to the intervention of ROB in thrombosis and expounded on the antithrombotic mechanism of ROB from the comprehensive perspectives of target prediction, intermediate metabolites and potential metabolic pathways.

METHODS: In this research, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology was used to qualitatively detect the chemical compounds of ROB, and the antithrombotic activity of ROB was evaluated by establishing a zebrafish model. The target function was predicted by network pharmacology, and differential metabolites were screened by metabolomics and multivariate statistical analysis methods. Correlation analysis of network pharmacology and metabolomics screening results was conducted to identify the potential pathway of ROB intervention in thrombosis, and the prediction results were further verified.

RESULTS: ROB significantly reduced the reactive oxygen species (ROS) staining intensity in zebrafish induced by phenylhydrazine (PHZ) and improved the inhibition rate of thrombosis. By constructing the “herb-disease-component-target” network, it was concluded that the active ingredients of ROB in treating thrombosis involved emodin, aloe-emodin and physcion, and the key targets included nitric oxide synthase 2 (NOS2) and nitric oxide synthase 3 (NOS3). A total of 341 differential metabolites in zebrafish with thrombosis were screened by partial least squares discriminant analysis (PLS-DA). The results of reverse transcription-polymerase chain reaction (RT-PCR) experiments and targeted metabolomics verification showed that ROB was mainly involved in improving thrombosis by upregulating the expression of NOS3 mRNA and regulating the levels of arginine, glutamate and glutamine in the arginine biosynthesis pathway.

CONCLUSIONS: ROB improved thrombosis by regulating the expression of NOS3 mRNA and the contents of arginine, glutamate and glutamine in the arginine biosynthesis signalling pathway.

PMID:35182903 | DOI:10.1016/j.phymed.2022.153967

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Patellofemoral contact forces after ACL reconstruction: A longitudinal study

J Biomech. 2022 Feb 10;134:110993. doi: 10.1016/j.jbiomech.2022.110993. Online ahead of print.

ABSTRACT

Osteoarthritis (OA) development after ACL reconstruction (ACLR) is common. Patellofemoral OA after ACLR is as prevalent as tibiofemoral OA; however, few have explored the mechanisms leading to disease development in this compartment. Biomechanical alterations may be one mechanism responsible for post-traumatic knee OA. Patellofemoral contact forces during dynamic tasks, such as running and single leg hops, have been assessed at return to sport and later time points. The results of these studies, however, contradict each other, are only cross-sectional in nature, and are limited to specific points in time within the movement pattern. The purpose of this study was to assess patellofemoral contact forces 3, 6, and 24 months after ACLR during level walking over the entirety of the movement pattern. Patellofemoral contact forces were calculated after determination of muscle forces from a validated, subject-specific, EMG-driven neuromusculoskeletal model. Statistical parametric mapping was used to compare patellofemoral contact forces between limbs and across time points. Patellofemoral underloading of the involved limb (vs. uninvolved) was present at 3 months (p < 0.001 from 7 to 30% of stance) and 6 months (p = 0.001 from 11 to 23% of stance and p = 0.025 from 27 to 32%) after ACLR but was resolved by 24 months. Both limbs’ load increased from 3 to 6 months. The involved limb displayed relatively consistent loads from 6 months onward, while the uninvolved limb’s decreased back down towards their 3-month values. Overall, these results suggest that early patellofemoral underloading exists after ACLR and may be leading to patellofemoral OA development.

PMID:35182902 | DOI:10.1016/j.jbiomech.2022.110993

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Effectiveness of progressive muscle relaxation technique on anxiety caused by Covid-19 in pregnant women: A randomized clinical trial

Neuropsychopharmacol Rep. 2022 Feb 18. doi: 10.1002/npr2.12241. Online ahead of print.

ABSTRACT

AIM: To determine the effectiveness of the progressive muscle relaxation (PMR) technique on anxiety caused by Covid-19 in pregnant women under the auspices of comprehensive health service centers in the nineteenth district of Tehran University of Medical Sciences.

METHOD: This study is a randomized clinical trial. A total of 126 pregnant women were randomly allocated to the intervention group (N = 63) and control group (N = 63). All participants completed demographic questionnaires and the Corona Disease Anxiety Scale electronically. The intervention was held in six sessions through Sky Room (three times a week). It consisted of training and practicing the PMR. The intervention group was re-evaluated with the related questionnaires immediately after the intervention and 2 weeks later, and the control group 2 and 4 weeks after the baseline.

RESULTS: There was a significant difference between the control and intervention groups at the baseline (P = .05). Nevertheless, analysis of variance test results showed that the difference between the intervention and control groups was found to be significantly different statistically; (22.92 ± 6.07) for intervention versus (28.13 ± 6.93) for control, with the second follow up (P = .01).

CONCLUSIONS: Progressive muscle relaxation is used as a useful intervention to reduce anxiety in pregnant women during coronavirus pandemics educated and recommended with more emphasis and sensitivity in pregnancy care by healthcare providers.

PMID:35182048 | DOI:10.1002/npr2.12241

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‘Escalibur’ – a practical pipeline for the de novo-analysis of nucleotide variation in non-model eukaryotes

Mol Ecol Resour. 2022 Feb 18. doi: 10.1111/1755-0998.13600. Online ahead of print.

ABSTRACT

The revolution in genomics has enabled large-scale population genetic investigations of a wide range of organisms, but there has been a relatively limited focus on improving analytical pipelines. To efficiently analyse large data sets, highly integrated and automated software pipelines, which are easy to use, efficient, reliable, reproducible and run in multiple computational environments, are required. A number of software workflows have been developed to handle and process such data sets for population genetic analyses, but effective, specialised pipelines for genetic and statistical analyses of non-model organisms are lacking. For most species, resources for variomes (sets of genetic variations found in populations of species) are not available, and/or genome assemblies are often incomplete and fragmented, complicating the selection of the most suitable reference genome when multiple assemblies are available. Additionally, often biological samples used contain extraneous DNA from sources other than the species under investigation (e.g., microbial contamination), which needs to be removed prior to genetic analyses. For these reasons, we established a new pipeline, called Escalibur, which includes functionalities, such as data trimming and mapping; selection of a suitable reference genome; removal of contaminating read data; recalibration of base calls; and variant-calling. Escalibur uses a proven GATK variant caller and workflow description language (WDL), and is, therefore, a highly efficient and scalable pipeline for the genome-wide identification of nucleotide variation in eukaryotes. This pipeline is available at https://gitlab.unimelb.edu.au/bioscience/escalibur (v0.3-beta) and is essentially applicable to any prokaryote or eukaryote.

PMID:35182034 | DOI:10.1111/1755-0998.13600

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Development and validation of a nomogram for predicting the prognosis in cancer patients with sepsis

Cancer Med. 2022 Feb 18. doi: 10.1002/cam4.4618. Online ahead of print.

ABSTRACT

BACKGROUND: To develop a multiparameter-based, easy-to-use nomogram and to predict the prognosis of cancer patients with sepsis in the intensive care unit (ICU).

METHODS: Clinical data on cancer patients with sepsis who met the definition of sepsis 3.0 admitted to the ICU from January 2016 to October 2021 were collected. All patients were randomly entered into the development cohort or validation cohort according to the ratio of 7:3. Patients in the development cohort were divided into the survivors and the nonsurvivors according to the outcome of 28 days in ICU. The independent risk factors of mortality due to sepsis were screened out from the two groups (the survivors and the nonsurvivors) in the development cohort through multivariate logistic regression analysis. A nomogram was established with these independent risk factors, and the calibration plot was subsequently evaluated. Finally, the predictive power of the nomogram was verified in the validation cohort.

RESULTS: A total of 317 cancer patients with sepsis who met the requirements were enrolled in this study, of which 229 entered into the development cohort and 88 entered into the validation cohort. The 28-day mortality rates of the two cohorts were 17.5% and 20.5%, respectively. The neutrophil-to-lymphocyte ratio (NLR) on day 3 (d3), brain natriuretic peptide (BNP) d3, fluid accumulation at 72 hours (h), and Sequential Organ Failure Assessment (SOFA) score were independent risk factors for the 28-day mortality between the survivors and the nonsurvivors in the development cohort. A nomogram was established on the above variables. The calibration plots fit well with the nomogram and had good statistical consistency in predicting the 28-day mortality of sepsis (the C value was 0.938 and 0.968 in the two cohorts, respectively). With a nomogram score of 83.8 points, the diagnostic accuracy was 90.8% vs 92.0%, the sensitivity was 72.5% vs 77.7%, the specificity was 94.7% vs 95.7%, the positive predictive value was 72.3% vs 82.4%, and the negative predictive value was 94.2% vs 94.4% for predicting the 28-day mortality in the development cohort and the validation cohort, respectively.

CONCLUSION: This easy-to-use nomogram based on NLR d3, BNP d3, and fluid accumulation at 72 h and SOFA score provides an accurate 28-day prognosis prediction for cancer patients with sepsis admitted to the ICU.

PMID:35182022 | DOI:10.1002/cam4.4618

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Efficacy and Safety of 5% Glycolic Acid-based Gel Essence in the Treatment of Mild to Moderate Acne

J Cosmet Dermatol. 2022 Feb 18. doi: 10.1111/jocd.14865. Online ahead of print.

ABSTRACT

The efficacy and safety of commercial low-concentration glycolic acid products on acne were evaluated by recruiting volunteers accompanying mild to moderate acne of different ages and genders, which is a clinical practice for acne. We recruited a total of 30 volunteers according to the inclusion criteria, conducting clinical evaluation and skin physiological index testing, VISIA skin analysis, distributing products, and informing the trial method. Clinical testing and assessment will be carried out in weeks 0, 1, 2, and 4. 27 acne volunteers finished the entire trial. After 4 weeks of using low-concentration glycolic acid products, most subjects experienced significant improvement in their skin lesions and the GAGS score. At the same time, the VISIA test showed that the subjects had an obvious amelioration in facial porphyrins, which was statistically significant, and there was a slight improvement in residual spots and erythema. The skin physiological indexes showed that the skin hydration value increased from 236.2 ± 98.05 to 278.2 ± 90.26 after 14 days. At the end of the test, the skin hydration value dropped to 234.6 ± 81.88. Regarding the melanin and erythema, the value decreased in the 4th week significantly. Repeated use of 5% low-concentration glycolic acid improves the appearance and chromaticity of the treatment site. It increases the brightness L* and reduces the redness a*. This study shows that low concentrations of glycolic acids have a good effect on the treatment of mild to moderate acne. It may pay the way to carry out further large-scale clinical research.

PMID:35182003 | DOI:10.1111/jocd.14865

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CD86 occupancy in belatacept-treated kidney transplant patients is not associated with clinical and infectious outcomes

Am J Transplant. 2022 Feb 18. doi: 10.1111/ajt.17005. Online ahead of print.

ABSTRACT

The CD86 occupancy assay has been developed to measure the number of CD86 molecules unbound to belatacept, but its association with clinical outcomes has not been assessed yet. All kidney transplant patients switched to belatacept in our centre between 2016 and 2018 were included. Blood samples were collected before each infusion for one year to assess CD86 occupancy by CD86 antibody cytometry staining on the surface of CD14+ monocytes. Results were expressed as the median fluorescence intensity (MFI) value of CD86 staining. At each infusion, the MFIDay of infusion /MFIDay0 ratio was calculated. Forty-one patients were consecutively included. After the every-two-weeks infusions period, CD86 MFI ratio dropped from 1.00 to 0.73 [0.57-0.98], p=0.07. However, this ratio progressively increased to 0.78 [0.53-1.13] at one year, which was not statistically different from pre-switch ratio, p=0.4. Over the first year, the MFI ratio coefficient of variation was 31.58% [23.75-38.31]. MFI ratio was not different between patients with or without opportunistic infections: 0.73 [0.60-0.88] versus 0.80 [0.71-1.00], p=0.2, or between patients with or without EBV DNAemia, p=0.2. Despite previous in-vitro results, the CD86 occupancy assay suffers from a high intra-individual variability and does not appear to be relevant to clinical outcomes.

PMID:35181996 | DOI:10.1111/ajt.17005

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Nur77 Prevents Osteoporosis by Inhibiting the NF-κB Signalling Pathway and Osteoclast Differentiation

J Cell Mol Med. 2022 Feb 19. doi: 10.1111/jcmm.17238. Online ahead of print.

ABSTRACT

Inflammation is a major risk factor for osteoporosis, and reducing inflammatory levels is important for the prevention of osteoporosis. Although nuclear receptor 77 (Nur77) protects against inflammation in a variety of diseases, its role in osteoporosis is unknown. Therefore, the main purpose of this study was to investigate the osteoprotective and anti-inflammatory effects of Nur77. The microCT and haematoxylin and eosin staining results indicated that knockout of Nur77 accelerated femoral bone loss in mice. The enzyme-linked immunosorbent assay (ELISA) results showed that knockout of Nur77 increased the serum levels of hsCRP and IL-6. The expression levels of NF-κB, IL-6, TNF-α and osteoclastogenesis factors (TRAP, NFATC1, Car2, Ctsk) in the femurs of Nur77 knockout mice were increased significantly. Furthermore, in vitro, shNur77 promoted the differentiation of RAW264.7 cells into osteoclasts by activating NF-κB, which was confirmed by PDTC treatment. Mechanistically, Nur77 inhibited osteoclast differentiation by inducing IκB-α and suppressing IKK-β. In RAW264.7 cells, overexpression of Nur77 alleviated inflammation induced by siIκB-α, while siIKK-β alleviated inflammation induced by shNur77. Consistent with the in vivo studies, we found that compared with control group, older adults with high serum hsCRP levels were more likely to suffer from osteoporosis (OR = 1.76, p < 0.001). Our data suggest that Nur77 suppresses osteoclast differentiation by inhibiting the NF-κB signalling pathway, strongly supporting the notion that Nur77 has the potential to prevent and treat osteoporosis.

PMID:35181992 | DOI:10.1111/jcmm.17238

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Efficacy and adverse reactions of fractional CO2 laser for atrophic acne scars and related clinical factors: a retrospective study on 121 patients

J Cosmet Dermatol. 2022 Feb 18. doi: 10.1111/jocd.14868. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was performed to analyze the efficacy, adverse reactions of fractional CO2 laser for atrophic acne scars, and related clinical factors.

METHODS: The clinical data of 121 patients with atrophic acne scars treated with ultra-pulsed fractional CO2 laser in the Cosmetic Dermatology from August 2014 to March 2020 were retrospectively analyzed. The efficacy and adverse reactions of atrophic acne scar after fractional CO2 laser therapy were statistically analyzed. The clinical factors related to efficacy and adverse reactions after the first therapy session were analyzed by multivariate logistic regression.

RESULTS: A total of 121 patients received 206 sessions of fractional CO2 laser therapy, with an average of 1.7 sessions. Moderate to excellent improvement rate reached 50.4% after the first session. Multivariate logistic regression analysis indicated that rolling scars responded better to fractional CO2 laser treatment than icepick scars (OR = 7.3, 95% CI [1.2, 43.4], P = 0.029), and scar improvement was more significant in the high-energy laser group than in the low-energy laser group (OR = 10.9, 95% CI [1.1, 106.8], P = 0.041). The main adverse reactions after fractional laser surgery were pigmentation, skin sensitivity, persistent erythema and acneiform eruption. Multivariate logistic analysis revealed that the longer the scar duration, the higher incidence of postoperative adverse reactions (OR = 1.3, 95% CI [1.1, 1.5], P = 0.008). Compared with icepick scars, rolling scars (OR = 10.4, 95% CI [2.3, 47.7], P = 0.003) and boxcar scars (OR = 12.0, 95% CI [3.3, 44.0], P < 0.001) had higher risk of developing adverse reactions. The incidence of postoperative adverse reactions was also higher in the combined mode group (DeepFX mode + ActiveFX mode) than in the single mode group (OR = 7.8, 95% CI [2.4, 25.5], P < 0.001).

CONCLUSION: Fractional CO2 laser was effective in the treatment of atrophic acne scars, without serious adverse reactions. Scar type and laser energy were independent clinical factors affecting its efficacy. Scar course, scar type and fractional laser mode were independent clinical factors affecting its adverse reactions.

PMID:35181995 | DOI:10.1111/jocd.14868

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The influence of a major pre-clinical program restructure on undergraduate student fixed prosthodontics clinical unit completions

Eur J Dent Educ. 2022 Feb 18. doi: 10.1111/eje.12791. Online ahead of print.

ABSTRACT

INTRODUCTION: Research is limited in measuring the effectiveness of pre-clinical programs in preparing students for fixed prosthodontics clinical practice. The aim of this retrospectively study was to assess the influence of a major pre-clinical program restructure on undergraduate student fixed prosthodontics clinical unit completions.

MATERIALS AND METHODS: The fixed prosthodontics treatment registers from 2011 to 2020 were reviewed and units completed per student (UCS) and units completed per student per session (UCSS) were calculated in the years before (2011-2013) and after (2014-2020) a major pre-clinical program restructure (PR). Data was summarised in Microsoft Excel software (version 2016) and Student’s t-test and paired t-tests were performed to determine the significance of difference in UCS and UCSS in the years before and after the PR.

RESULTS: There was a significant difference in the UCS (p < .05) and UCSS (p < .01) in the years before and after the PR. The average UCS in the years before the PR was 2.20 units compared with 3.86 units after the PR, an increase of 75% per student. The average UCSS in the years before the PR was 0.15 units compared with 0.28 units after the PR, an increase of 87% per session.

CONCLUSION: The fixed prosthodontics pre-clinical program restructure resulted in statistically significantly increased student clinical unit completions.

PMID:35181974 | DOI:10.1111/eje.12791