Conectar
by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao
A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.To find potential biomarkers based on miRNA and their potential targets in splenic monocytes in burn-injured mice. Male Balb/c mice were subjected to sham or scalding injury of 15% total body surface area. Spenic CD11b+ monocytes were purified with magnetic beads. The monocytes were cultured in the presence of lipopolysaccharide. The proliferation of monocytes was detected by MTT assay, and the cytokines in the supernatant were examined by enzyme linked immunosorbent assay. The purified monocytes were also under total RNA extraction. The differential monocytic miRNAs expression between the sham and burn-injured mice was analysed by miRNA microarray. The activity of monocytes was comparable between the two groups (p > 0.05). However, monocytes from burn-injured mice secreted higher levels of tumour necrosis factor (TNF)-α and transforming growth factor-β, but lower level of monocyte chemoattratctant protein-1. A total of 54 miRNAs were differentially expressed in monocytes from burn relative to sham-injured mice (fold >3). Further quantitative reverse transcription polymerase chain reaction confirmed that the expression of miR-146a was significantly down-regulated, while miR-3091-6p was up-regulated after burn injury. Using the combination of Miranda and TargetScan softwares, we found that mir-146a may regulate 180 potential target genes including TNF receptor related factor 6 (TRAF6), interleukin-1 receptor related kinase 1 (IRAK1) and CD28. Mir-3091-6p may regulate 39 potential targets, including SOCS7 (cytokine signal transduction inhibitor 7) and ARRB2 (arrestin, β 2). The miRNAs expressed by monocytes after burn injury may be involved in the regulation of innate immune response in burn injury.
The incidence of squamous cell carcinoma (SCC) is on the rise, making it a significant global health concern. Environmental risk factors are crucial to the development of SCC. This study sought to examine comprehensively the impact of these factors on the onset of SCC. We conducted a cross-sectional study involving 480 participants at Beijing tertiary care hospital. Utilizing structured questionnaires, data on demographics, environmental exposures, medical history and clinical characteristics were collected. The cohort was composed of 272 men (56.67%) and 208 women (43.33%). The majority (44.38%) were between ages of 41 and 60, and Type III skin predominated (34.79%). Most of the participants belonged to the middle socioeconomic class (60.83%). ‘Vegetarian’ dietary habits (46.67%) were prevalent, as was the ‘Sedentary’ lifestyle (49.79%). Regarding environmental exposures, moderate sun exposure of 3 to 5 h per day (54.58%) and UV protective eyewear (30.83%) were prevalent. The majority (69.58%) of respondents indicated ‘Never’ exposure to carcinogens. A variety of wound characteristics were observed, with ‘non-smokers’ (64.17%) dominating. Most SCC lesions were located on the extremities (40.21%), lasted less than 6 months (44.38%) and measured 1–3 cm (39.79%). The majority (54.58%) did not have a history of cutaneous injuries. Our research uncovered substantial relationships between SCC and numerous environmental variables, gender, Fitzpatrick skin type, occupation, duration of sun exposure, exposure to carcinogens, dietary practices, history of skin wounds, wound location, duration, size and depth were significantly associated with the onset of SCC. These results highlighted the complexity of SCC aetiology and need for individualized prevention and treatment strategies.
by Shengjuan Lu, Lin Zeng, Guojun Mo, Danqing Lei, Yuanhong Li, Guodi Ou, Hailian Wu, Jie Sun, Chao Rong, Sha He, Dani Zhong, Qing Ke, Qingmei Zhang, Xiaohong Tan, Hong Cen, Xiaoxun Xie, Chengcheng Liao
We investigated the functional mechanism of long non-coding small nucleolar host gene 17 (SNHG17) in diffuse large B-cell lymphoma (DLBCL). lncRNAs related to the prognosis of patients with DLBCL were screened to analyze long non-coding small nucleolar host gene 17 (SNHG17) expression in DLBCL and normal tissues, and a nomogram established for predicting DLBCL prognosis. SNHG17 expression in B-cell lymphoma cells was detected using qPCR. The effects of SNHG17 with/without doxorubicin on the proliferation and apoptosis of DoHH2 and Daudi were detected. The effects of combined SNHG17 and doxorubicin were analyzed. The regulatory function of SNHG17 in DLBCL was investigated using a mouse tumor xenotransplantation model. RNA sequencing was used to analyze the signaling pathways involved in SNHG17 knockdown in B-cell lymphoma cell lines. The target relationships among SNHG17, microRNA, and downstream mRNA biomolecules were detected. A higher SNHG17 level predicted a lower survival rate. SNHG17 was highly expressed in DLBCL patient tissues and cell lines. We established a prognostic model containing SNHG17 expression, which could effectively predict the overall survival rate of DLBCL patients. SNHG17 knockdown inhibited the proliferation and induced the apoptosis of B-cell lymphoma cells, and the combination of SNHG17 and doxorubicin had a synergistic effect. SNHG17, miR-34a-5p, and ZESTE gene enhancer homolog 2 (EZH2) had common hypothetical binding sites, and the luciferase reporter assay verified that miR-34a-5p was the direct target of SNHG17, and EZH2 was the direct target of miR-34a-5p. The carcinogenic function of SNHG17 in the proliferation and apoptosis of DLBCL cells was partially reversed by a miR-34a-5p inhibitor. SNHG17 increases EZH2 levels by inhibiting miR-34a-5p. Our findings indicate SNHG17 as critical for promoting DLBCL progression by regulating the EZH2 signaling pathway and sponging miR-34a-5p. These findings provide a new prognostic marker and therapeutic target for the prognosis and treatment of DLBCL.by Yong Zhou, Chao Sun, Yingxu Ma, Yunyin Huang, Keke Wu, Shengyuan Huang, Qiuzhen Lin, Jiayi Zhu, Zuodong Ning, Ningyuan Liu, Tao Tu, Qiming Liu
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the clinic. Aging plays an essential role in the occurrence and development of AF. Herein, we aimed to identify the aging-related genes associated with AF using bioinformatics analysis. Transcriptome profiles of AF were obtained from the GEO database. Differential expression analysis was performed to identify AF-specific aging-related genes. GO and KEGG enrichment analyses were performed. Subsequently, the LASSO, SVM-RFE, and MCC algorithms were applied to screen aging-related genes. The mRNA expression of the screened genes was validated in the left atrial samples of aged rapid atrial pacing-induced AF canine models and their counterparts. The ROC curves of them were drawn to evaluate their diagnostic potential. Moreover, CIBERSORT was used to estimate immune infiltration. A correlation analysis between screened aging-related genes and infiltrating immune cells was performed. A total of 24 aging-related genes were identified, which were found to be mainly involved in the FoxO signaling pathway, PI3K-Akt signaling pathway, longevity regulating pathway, and peroxisome according to functional enrichment analysis. LASSO, SVM-RFE, and MCC algorithms identified three genes (HSPA9, SOD2, TXN). Furthermore, the expression levels of HSPA9 and SOD2 were validated in aged rapid atrial pacing-induced AF canine models. HSPA9 and SOD2 could be potential diagnostic biomarkers for AF, as evidenced by the ROC curves. Immune infiltration and correlation analysis revealed that HSPA9 and SOD2 were related to immune cell infiltrates. Collectively, these findings provide novel insights into the potential aging-related genes associated with AF. HSPA9 and SOD2 may play a significant role in the occurrence and development of AF.The study aims to evaluate the clinical application of posterior tibial artery or peroneal artery perforator flap in the treatment of plate exposure after ankle fracture fixation. A posterior tibial artery or peroneal artery perforator flap was used on 16 patients with plate exposure after ankle fracture fixation in our hospital between July 2018 and July 2021. The time required to harvest the flap, the amount of intraoperative blood loss, the duration of postoperative drainage tube placement, the outcome of the flap and the healing observed at the donor site are reported. The sizes of the flaps were 2.5–7.0 cm × 5.0–18.0 cm and averaged 4.0 cm × 12.0 cm. The time required to harvest the posterior tibial artery or peroneal artery perforator flap ranged from 35 to 55 min and averaged 45 min. The amount of intraoperative blood loss ranged from 20 to 50 mL and averaged 35 mL. The duration of postoperative drainage tube placement ranged from 3 to 5 days and averaged 4 days. A total of 15 flaps survived and one flap had partial necrosis and survived after conservative treatment. All donor area defects were directly sewed and stitched without complications. There are multiple advantages of the posterior tibial artery or peroneal artery perforator flap, including simple preparation technique, reliable repair of the defects and without the need for performing microvascular anastomosis. It can be safely used in curing plate exposure after ankle fracture fixation and worth popularizing in grassroots hospitals.
A meta-analysis research was implemented to appraise the perineal wound complications (PWCs) after vertical rectus abdominis myocutaneous (VRAM) flap and mesh closure (MC) following abdominoperineal surgery (AS) and pelvic exenteration (PE) of anal and rectal cancers. Inclusive literature research till April 2023 was done and 2008 interconnected researches were revised. Of the 20 picked researches, enclosed 2972 AS and PE of anal and rectal cancers persons were in the utilized researchers' starting point, 1216 of them were utilizing VRAM flap, and 1756 were primary closure (PC). Odds ratio (OR) and 95% confidence intervals (CIs) were utilized to appraise the consequence of VRAM flap in treating AS and PE of anal and rectal cancers by the dichotomous approach and a fixed or random model. VRAM flap had significantly lower PWCs (OR, 0.64; 95% CI, 0.42–0.98, p < 0.001), and major PWCs (OR, 0.50; 95% CI, 0.32–0.80, p = 0.004) compared to PC in AS and PE of anal and rectal cancers persons. However, VRAM flap and PC had no significant difference in minor PWCs (OR, 1; 95% CI, 0.54–1.85, p = 1.00) in AS and PE of anal and rectal cancer persons. VRAM flap had significantly lower PWCs, and major PWCs, however, no significant difference was found in minor PWCs compared to PC in AS and PE of anal and rectal cancers persons. However, caution needs to be taken when interacting with its values since there was a low sample size of most of the chosen research found for the comparisons in the meta-analysis.
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