UCHL1 aggravates skin fibrosis through an IGF-1-induced Akt/mTOR/HIF-1α pathway in keloid.

Keloid is a heterogeneous disease featured by the excessive production of extracellular matrix. It is a great challenge for both clinicians and patients regarding the exaggerated and uncontrolled outgrowth and the therapeutic resistance of the disease. In this study, we verified that UCHL1 was drastically upregulated in keloid fibroblasts. UCHL1 had no effects on cell proliferation and migration, but instead promoted collagen I and α-SMA expression that was inhibited by silencing UCHL1 gene and by adding in LDN-57444, a pharmacological inhibitor for UCHL1 activity as well. The pathological process was mediated by IGF-1 promoted Akt/mTOR/HIF-1α signaling pathway because inhibition of any of them could reduce the expression of collagen I and α-SMA driven by UCHL1 in fibroblasts. Also, we found that UCHL1 expression in keloid fibroblasts was promoted by M2 macrophages via TGF-ß1. These findings extend our understanding of the pathogenesis of keloid and provide potential therapeutic targets for the disease.

Improving oral hygiene for better cognitive health: Interrelationships of oral hygiene habits, oral health status, and cognitive function in older adults.

OBJECTIVES: To explore the interrelationships between oral hygiene habits, oral health status and cognitive function in older adults. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 371 participants (age 76.79 [7.99] years) were enrolled from June 2020 to November 2021 in an aged care facility. METHODS: Cognitive function was screened using the mini-mental state examination (MMSE) with adjusted cut-off points for age and education. Periodontal status (Biofilm-Gingival Interface index based on periodontal probing depth and bleeding on probing), dental status (plaque, calculus, and caries), and tooth loss were assessed through full-mouth examination. Oral hygiene habits were based on self- or informant-reporting. RESULTS: Poor periodontal status was an associated factor for MCI (OR = 2.89, 95% CI = 1.20-6.95), while multiple tooth loss (OR = 4.90, 95% CI = 1.06 ~ 22.59), brushing teeth less than once a day (OR = 2.88, 95% CI = 1.12 ~ 7.45) and delayed dental visits (OR = 2.45, 95% CI = 1.05 ~ 5.68) were associated factors for cognitive impairment. An indirect effect of brushing teeth ≥2 daily on MMSE score through periodontal status was observed only in older adults without cognitive impairment (Bootstrap-corrected B = 0.17, 95%CI = 0.03 ~ 0.36, SE = 0.08, ß = 0.08). CONCLUSIONS AND IMPLICATIONS: Adequate toothbrushing might prevent cognitive decline indirectly by improving periodontal health only in older adults without cognitive impairment. Multiple tooth loss, infrequent toothbrushing, and delayed dental visits were associated factors for cognitive impairment. Nursing professionals and health care policymakers should advocate for the improvement of basic oral hygiene in older adults, and provide regular professional oral hygiene care for older adults with cognitive impairment. PATIENT OR PUBLIC CONTRIBUTION: The information on oral health habits of this study was based on an interview with the participants or their caregivers during the study period.

Assessing health-related quality of life in Chinese children and adolescents with cancer: validation of the DISABKIDS chronic generic module (DCGM-37).

BACKGROUND: With increasing cancer incidence and decreasing cancer mortality, there is a growing need for a valid and culturally adapted tool to measure health-related quality of life in children with cancer. This study validated the DISABKIDS Chronic Generic Module (DCGM-37) in Chinese children and adolescents with cancer. METHODS: The DCGM-37 was translated and adapted for use in China following the guidelines from its copyright holders. In total, 140 children and adolescents with cancer and their guardians were included in this cross-sectional study. Internal consistency and test-retest reliability were evaluated. Convergent validity was examined using Pearson correlation between the DCGM-37 and the PedsQL 4.0 Generic Core Scale. Dimensionality was clarified using exploratory factor analysis. Discriminant validity was evaluated by comparing DCGM-37 scores by sex, age, family income, and clinical characteristics. RESULTS: Internal consistency (Cronbach's alpha 0.91) and test-retest reliability were good (intraclass correlation coefficient 0.87, 95% confidence interval 0.73-0.94). Strong correlations between the DCGM-37 and the PedsQL 4.0 (r = 0.83) suggest good convergent validity. Six factors explained 51.94% of the total variance. Children with leukemia scored higher than those with sarcoma in all subscales (effect size ranged from 0.39 to 0.83), especially the "social exclusion" subscales (effect size 0.83). Small to moderate differences (effect size ranged from 0.38 to 0.58) were observed by sex, age, and family income. Neither floor nor ceiling effects were observed. CONCLUSION: The DCGM-37 is reliable and valid for measuring health-related quality of life in Chinese children and adolescents with cancer.

A reference peptide database for proteome quantification based on experimental mass spectrum response curves.

Motivation: Mass spectrometry (MS) based quantification of proteins/peptides has become a powerful tool in biological research with high sensitivity and throughput. The accuracy of quantification, however, has been problematic as not all peptides are suitable for quantification. Several methods and tools have been developed to identify peptides that response well in mass spectrometry and they are mainly based on predictive models, and rarely consider the linearity of the response curve, limiting the accuracy and applicability of the methods. An alternative solution is to select empirically superior peptides that offer satisfactory MS response intensity and linearity in a wide dynamic range of peptide concentration. Results: We constructed a reference database for proteome quantification based on experimental mass spectrum response curves. The intensity and dynamic range of over 2 647 773 transitions from 121 318 peptides were obtained from a set of dilution experiments, covering 11 040 gene products. These transitions and peptides were evaluated and presented in a database named SCRIPT-MAP. We showed that the best-responder (BR) peptide approach for quantification based on SCRIPT-MAP database is robust, repeatable and accurate in proteome-scale protein quantification. This study provides a reference database as well as a peptides/transitions selection method for quantitative proteomics. Availability and implementation: SCRIPT-MAP database is available at http://www.firmiana.org/responders/. Supplementary information: Supplementary data are available at Bioinformatics online.

Multidimensional Proteomics Reveals a Role of UHRF2 in the Regulation of Epithelial-Mesenchymal Transition (EMT).

UHRF1 is best known for its positive role in the maintenance of DNMT1-mediated DNA methylation and is implicated in a variety of tumor processes. In this paper, we provided evidence to demonstrate a role of UHRF2 in cell motility and invasion through the regulation of the epithelial-mesenchymal transition (EMT) process by acting as a transcriptional co-regulator of the EMT-transcription factors (TFs). We ectopically expressed UHRF2 in gastric cancer cell lines and performed multidimensional proteomics analyses. Proteome profiling analysis suggested a role of UHRF2 in repression of cell-cell adhesion; analysis of proteome-wide TF DNA binding activities revealed the up-regulation of many EMT-TFs in UHRF2-overexpressing cells. These data suggest that UHRF2 is a regulator of cell motility and the EMT program. Indeed, cell invasion experiments demonstrated that silencing of UHRF2 in aggressive cells impaired their abilities of migration and invasion in vitro Further ChIP-seq identified UHRF2 genomic binding motifs that coincide with several TF binding motifs including EMT-TFs, and the binding of UHRF2 to CDH1 promoter was validated by ChIP-qPCR. Moreover, the interactome analysis with IP-MS uncovered the interaction of UHRF2 with TFs including TCF7L2 and several protein complexes that regulate chromatin remodeling and histone modifications, suggesting that UHRF2 is a transcription co-regulator for TFs such as TCF7L2 to regulate the EMT process. Taken together, our study identified a role of UHRF2 in EMT and tumor metastasis and demonstrated an effective approach to obtain clues of UHRF2 function without prior knowledge through combining evidence from multidimensional proteomics analyses.

Differential proteomics profiling identifies LDPs and biological functions in high-fat diet-induced fatty livers.

Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets (LDs) enclosed in a monolayer of phospholipids and associated proteins [LD proteins (LDPs)]. Growing evidence has demonstrated that LDPs play important roles in the pathogenesis of liver diseases. However, the composition of liver LDPs and the role of their alterations in hepatosteatosis are not well-understood. In this study, we performed liver proteome and LD sub-proteome profiling to identify enriched proteins in LDs as LDPs, and quantified their changes in a high-fat diet (HFD)-induced fatty liver model. Among 5,000 quantified liver proteins, 101 were enriched by greater than 10-fold in the LD sub-proteome and were classified as LDPs. Differential profiling of LDPs in HFD-induced fatty liver provided a list of candidate LDPs for functional investigation. We tested the function of an upregulated LDP, S100a10, in vivo with adenovirus-mediated gene silencing and found, unexpectedly, that knockdown of S100a10 accelerated progression of HFD-induced liver steatosis. The S100A10 interactome revealed a connection between S100A10 and lipid transporting proteins, suggesting that S100A10 regulates the development and formation of LDs by transporting and trafficking. This study identified LD-enriched sub-proteome in homeostatic as well as HFD-induced fatty livers, providing a rich resource for the LDP research field.

Assessing limb apraxia after ischemic stroke: validation of the Chinese version of the diagnostic instrument for limb apraxia-short version (DILA-S) classic subtests.

OBJECTIVE: This study aimed to translate and validate the Chinese version of the Diagnostic Instrument for Limb Apraxia-Short Version (DILA-S) classic subtests in Chinese patients after ischemic stroke. METHODS: The DILA-S was translated and adapted for use in Mandarin-speaking Chinese patients. Internal consistency, test-retest reliability, dimensionality, convergent validity, divergent validity, and concurrent validity were tested. RESULTS: A total of 112 ischemic stroke patients were included. The internal consistency (Cronbach's alpha 0.85 ~ 0.92) and test-retest reliability (ICC 0.88 ~ 0.93) were found satisfactory. Exploratory factor analysis obtained two factors for the imitation subtests and the execution scale of the pantomime of tool use. Convergent validity was supported by strong correlations (ρ > 0.7) between the scores of the DILA-S subtests and the LOTCA motor praxis subscale. Divergent validity was acceptable for weak to moderate correlations (ρ ranged from -0.25~ -0.41) between the scores of the DILA-S subtests and the NIHSS. Concurrent validity was supported by strong correlations (ρ > 0.7) between the scores of the DILA-S subtests and the MoCA, as well as strong correlations (ρ > 0.6 < 0.7) between the scores of the DILA-S subtests and the BI. CONCLUSION: The Chinese version of the DILA-S classic subtests demonstrated satisfactory psychometric properties for assessing limb apraxia in Chinese patients after ischemic stroke.

The efficacy and safety of acupoint catgut embedding therapy for depression: a protocol for systematic review and meta-analysis.

Background: Depression is a common public health problem, characterized by persistent low mood, lack of pleasure and exhaustion. Conventional treatments such as antidepressants and psychotherapy have some limitations, including variable efficacy, adverse side effects and high costs. Acupoint catgut embedding (ACE) therapy, as a subtype of acupuncture, has gained increasing clinical application due to its long-term effects, higher patient compliance, and cost-effectiveness. This study aims to conduct a meta-analysis to evaluate the efficacy and safety of ACE for depression. Methods: Electronic searches will be conducted in 12 databases (both in English and Chinese databases), encompassing from inception to April 2022, without language restrictions. Randomized controlled trials (RCTs) that involve ACE for treating depression will be included. The primary outcome measures will include the response rate, Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), and Traditional Chinese Medicine Symptom Scale (TCMSSS). The secondary outcome measure will include Quality of Life scale score (QoL) and the incidence of adverse events. Results will be presented as risk ratios for dichotomous data and mean differences for continuous data. Two reviewers will independently conduct study selection, data extraction, and quality assessment. The methodological quality of eligible studies will be evaluated according to the criteria specified by the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Meta-analysis will be performed by RevMan 5.3 software. Discussion: Due to the limitations, a safer, high-efficacy and non-pharmacological intervention with minimal side effects is required for treating depression. ACE has the advantages of longer-lasting effects, improved patient compliance, and reduced treatment costs. This protocol represents a meta-analysis and systematic review, aiming to present the current evidence regarding the efficacy and safety of ACE for depression. It seeks to provide clinicians with a theoretical basis and valuable references for complementary and alternative medicine therapies in their treatment approaches. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, Identifier CRD42022325966.

Translation and linguistic validation of the DISABKIDS chronic generic module into simplified Chinese (DCGM-37) for use among children with cancer.

PURPOSE: To develop a simplified Chinese version of the DISABKIDS chronic generic module-37 (DCGM-37), and to test the translated measures in children with cancer by employing a cognitive interviewing technique. DESIGN AND METHODS: The English version of DCGM-37 was translated forward and backward into simplified Chinese by bilingual translators, following the guidelines from its copyright holders, which also involved a cultural adaptation component. Twelve Chinese children aged 8-18 years and eight parents were cognitively interviewed. RESULTS: The findings support the relevance, comprehensibility, and efficacy of the Chinese version. Consideration was given, and improvements were made, to the language, cultural concerns, and content, which improved functionality and increased validation. The patients/caregivers understood the instructions, questions, and answer choices. Some revisions, however, were made to address patient/caregiver feedback obtained through cognitive interviews. Conceptually and semantically, the simplified Chinese version of the DCGM-37 version was identical to the original. Conclusions The simplified Chinese version of the DCGM-37 was semantically and conceptually equivalent to the English version. Chinese children aged 8 to 18 years were able to comprehend this instrument. CONCLUSIONS: The simplified Chinese version of the DCGM-37 was semantically and conceptually equivalent to the English version. Chinese children aged 8 to 18 years were able to comprehend this instrument and express their experiences and feelings about their life. PRACTICE IMPLICATIONS: The simplified Chinese version of the DCGM-37 was translated, and cross-cultural adaptation and validation were performed. Chinese children found the tool easy to use and were able to express their experiences and feelings about their health-related quality of life.