CRISPR/dCas9 for hepatic fibrosis therapy: implications and challenges.

Hepatic fibrosis is a pathological reaction of tissue damage and repair caused by various pathogenic factors acting on liver. At present, there is no effective anti-fibrotic specific therapy. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (dCas9) system is a new generation of gene editing technology. The CRISPR/dCas9 system provides a platform for studying site-specific transcriptional regulation, which has high efficiency in gene transcriptional activation for achieving robust. This system holds promise for hepatic fibrosis therapy via acting on liver fibrosis effector cells. However, there are some challenges associated with this novel technology, such as large structural variants at on-target, off-target sites, and targeted delivery efficiency. In this review, we present the potential implications and describe the challenges of CRISPR/dCas9 system that might be encountered in hepatic fibrosis therapy.

Bisphenol F suppresses insulin-stimulated glucose metabolism in adipocytes by inhibiting IRS-1/PI3K/AKT pathway.

Obesity is one of the risk factors of metabolic diseases. Decreased sensitivity to insulin or impairment of the insulin signaling pathway may affect the metabolism of adipose tissue. Bisphenol F (BPF) has been widely used in various products as a substitute for bisphenol A (BPA). BPA has been defined as "obesogen". However, knowledge about the correlation between BPF and obesity is very limited. This study was aimed to explore the effects of BPF on glucose metabolism and insulin sensitivity in mammalian tissues, using a mouse 3T3-L1 adipocyte line as the model. Differentiated 3T3-L1 adipocytes were treated with BPF at various concentrations for 24 h or 48 h, followed by the measurement of cell viability, lipid accumulation, expression levels of adipocytokines, glucose consumption, and impairment of the insulin signaling pathway. The results indicated that BPF had no effect on the size of 3T3-L1 adipocytes, but the expression of leptin, adiponectin and apelin was decreased, while that of chemerin and resistin was increased after 48 h of BPF treatment. Moreover, BPF inhibited the glucose consumption, the expression of GLUT4, and its translocation to the plasma membranes in 3T3-L1 adipocytes. Western blot analysis indicated that the activation of IRS-1/PI3K/AKT signaling pathway was inhibited by BPF, which resulted in reduced GLUT4 translocation. In conclusion, our data suggest that exposure of adipocytes to BPF may alter the expression of calorie metabolism-related adipokines and suppress insulin-stimulated glucose metabolism by impairing the insulin signaling (IRS-1/PI3K/AKT) pathway.

[Systematic review and Meta-analysis of efficacy and safety of Ningmitai Capsules in treatment of urinary tract infection].

This study aims to evaluate the effectiveness and safety of Ningmitai Capsules in the treatment of urinary tract infection.To be specific, articles on the treatment of urinary tract infection with Ningmitai Capsules were retrieved from China National Know-ledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, and Web of Science(from establishment to October 2021).Eligible randomized controlled trials(RCTs) were screened out, and ROB and RevMan 5.3 of Cochrane were employed for data integration and Meta-analysis.Finally, 17 articles were included, involving 1 972 cases, with 1 045 in the experimental group and 927 in the control group.The Meta-analysis results are as follows.Ningmitai Capsules combined with conventional antibiotics was superior to sensitive antibiotics alone in the treatment of acute pyelonephritis in aspects of clinical cure rate(RR=1.94, 95%CI[1.58, 2.37], P<0.000 01), reduction in the count of red blood cells in the urine(MD=-3.22, 95%CI[-3.23,-3.21], P<0.000 01), decrease in the count of white blood cells in the urine(MD=-2.34, 95%CI[-2.59,-2.10], P<0.000 01), and time for the disappearance of the symptoms(MD_(time for urinary tract irritation disappeared)=-2.19, 95%CI[-2.69,-1.68], P<0.000 01; MD_(time for waist aches disappeared)=-3.58, 95%CI[-4.20,-2.97], P<0.000 01; MD_(time for heating disappeared)=-0.57, 95%CI[-0.81,-0.33], P<0.000 01).The combination of either cephalosporin or quinolone with Ningmitai Capsules can improve clinical cure rate of acute pyelonephritis(RR_(combined with cephalosporin)=1.94, 95%CI[1.56, 2.42], P<0.000 01; RR_(combined with quinolone)=1.91, 95%CI[1.16, 3.15], P=0.01).The clinical cure rate(RR=1.91, 95%CI[1.47, 2.49], P<0.000 01) of diabetes complicated with urinary tract infection by Ningmitai Capsules was higher than that by quinolones.The clinical cure rate(RR=1.22, 95%CI[1.09, 1.37], P=0.000 5) of non-gonococcal urethritis by Ningmitai Capsules combined with conventional tetracycline and macrolide antibiotics was higher than that by conventional antibiotics.Ningmitai Capsules combined with conventional antibiotics/Ningmitai Capsules alone was superior to conventional antibiotics alone in the treatment of urinary tract infection in terms of the clinical cure rate(RR=1.35, 95%CI[1.17, 1.56], P<0.000 1) and incidence of adverse reactions(RR=0.32, 95%CI[0.15, 0.68], P=0.003), particularly the combination with quinolone antibiotics(RR=1.30, 95%CI[1.04, 1.61], P=0.02).The main adverse reactions were mild gastrointestinal discomfort, nausea, vomiting, and dry mouth.In summary, Ningmitai Capsules combined with conventional sensitive antibiotics/Ningmitai Capsules alone can improve the clinical cure rate of patients with urinary tract infection.Ningmitai Capsules combined with conventional sensitive antibiotics can significantly reduce the time for symptom disappearance of acute pyelonephritis and down-regulate the counts of red and white blood cells in the urine compared with antibiotics alone, and no serious adverse reactions have been found.However, in light of the low proportion of quality eligible articles, experiments with rigorous design, large sample size, and complete outcome in-dexes should be carried out in the future to verify the clinical efficacy and safety of Ningmitai Capsules in the treatment of urinary tract infection.

An Improved Scoring System Based on Platelet-Albumin-Bilirubin in Predicting Posthepatectomy Liver Failure Outcomes.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the major complications of liver resection that causes perioperative mortality. Accurate preoperative assessment of PHLF is of great significance to reduce the complication rate after hepatectomy and improve the survival rate. METHODS: A retrospective study of patients who received hepatectomy from January 2016 to October 2019 at Tang Du Hospital was performed. The area under the receiver operating characteristic (ROC) curve was used to compare the predictive effects of various scoring models on PHLF. RESULTS: The area under the ROC curve of platelet-albumin-bilirubin (PALBI) score, new platelet-albumin-bilirubin (I-PALBI) score, ALBI score, and MELD score was, respectively, 0.647, 0.772, 0.677, and 0.686 (p < 0.01). The I-PALBI score was significantly better than the other scores. CONCLUSIONS: I-PALBI score can be used as a predictive score of PHLF, and its prediction accuracy is better than other scoring systems.

Circular RNA: new star, new hope in cancer.

BACKGROUND: Circular RNAs are a new class of endogenous non-coding RNA that can function as crucial regulators of diverse cellular processes. The diverse types of circular RNAs with varying cytogenetics in cancer have also been reported. Circular RNAs can act as a microRNA sponge or through other mechanisms to regulate gene expression as either tumor inhibitors or accelerators, suggesting that circular RNAs can serve as newly developed biomarkers with clinic implications. Here, we summerized recent advances on circular RNAs in cancer and described a circular RNA network associated with tumorigenesis. The clinical implications of circular RNAs in cancer were also discussed in this paper. SHORT CONCLUSION: Growing evidence has revealed the crucial regulatory roles of circular RNAs in cancer and the elucidation of functional mechanisms involving circular RNAs would be helpful to construct a circRNA-miRNA-mRNA regulatory network. Moreover, circular RNAs can be easily detected due to their relative stability, widespread expression, and abundance in exosomes, blood and saliva; thus, circular RNAs have potential as new and ideal clinical biomarkers in cancer.

Magnetic compression anastomosis for enteroenterostomy under peritonitis conditions in dogs.

BACKGROUND: The risk of complications and mortality are high after enteroenterostomy in severe peritonitic conditions. Magnetic compression anastomosis (MCA) is a sutureless technique of high efficacy and safety. The purpose of this study was to compare the efficacy of MCA for enteroenterostomy with stapled and hand-sewn techniques under peritonitic conditions. METHODS: The peritonitic conditions were created by puncturing the colon with a circular blade in 27 mongrel dogs. Eight hours later, the peritoneal cavity was washed with warm, sterilized normal saline solution. The animals were then randomly divided into three groups and underwent colonic anastomosis with MCA, stapled, or hand-sewn techniques, respectively. Animals were euthanized at 1, 2, and 4 w after the operation; anastomoses were compared on the basis of gross appearance and histology. RESULTS: All magnetic devices formed patent anastomoses without a leak. However, one stapled anastomosis and three hand-sewn anastomoses resulted in leaks. The anastomosis time was significantly less in the MCA group than that of the other two groups (P < 0.05). All magnetic devices were expelled naturally. The pathologic observation showed that the healing of anastomoses for MCA was smoother than that of the other two groups. CONCLUSION: MCA is a feasible, safe, and effective alternative for enteroenterostomy under peritonitic conditions in the canine model.

[Treating influenza patients of wind-heat affecting Fei syndrome by jinhua qinggan granule: a double-blinded randomized control trial].

OBJECTIVE: To assess the effect and safety of Jinhua Qinggan Granule (JHG) in treating influenza patients of wind-heat affecting Fei syndrome (WHAFS). METHODS: Totally 136 influenza patients of WHAFS were randomized by stratification into 3 groups, the high dose JHG group (44 cases, 10 g each time), the low dose JHG group (45 cases, 5 g JHG + 5 g placebo each time), and the placebo control group (47 cases, 10 g placebo each time). All medication was administered three times daily for 5 days. The fever disappearance time, the fever disappearance rate, efficacy of TCM syndrome, the disappearance rate of main symptoms and physical signs of flu, the negative rate of virus nucleic acid in the pharyngeal secretion, and safety indicators were assessed. RESULTS: The median fever disappearance time was 32.8 h (95% CI: 22.5-41.0 h) in the high dose JHG group, 26.0 h (95% CI: 14.5-36.5 h) in the low dose JHG group, 39.5 h (95% CI: 29.0-46.0 h) in the placebo control group. There was statistical difference in the median fever disappearance time between the low dose JHG group and the placebo control group (P = 0.011). Three days after treatment, the markedly effective rate of TCM symptoms in the low dose JHG group was 66.7%, higher than that of the placebo control group (38.3%), and its effective rate was superior to that of the high dose JHG group (P = 0.043). Five days after treatment, the recovery rate of the low dose JHG group (42.2%) was higher than that of the high dose JHG group (25.0%, P = 0.026) and that of the placebo control group (14.9%, P = 0.002). The markedly effective rate of the low dose JHG group (86.7%) was higher than that of the placebo control group (55.3%, P = 0.001). Similar effects were obtained in the low dose JHG group and the high dose JHG group, but slightly poor in partial indicators of the high dose JHG group. There was no statistical difference in adverse reaction among these three groups (P > 0.05). CONCLUSIONS: JHG was effective and safe in treating influenza patients of WHAFS. Routinely low dose was the optimal dosage of JHG.

A rare case of concurrent intrahepatic splenosis and pancreatic adenocarcinoma following splenectomy.

We present an extremely rare case of intrahepatic splenosis (IHS). On admission and examination, the patient was diagnosed with hepatocellular carcinoma and postoperative injury or inflammatory lesions of the pancreas, based on image analysis. Postoperative histopathology showed that the lesions of the liver and diaphragm were of splenic origin, and the pancreatic lesion was identified as a moderately differentiated adenocarcinoma. The lesson of this case is that if there is a history of splenic rupture or splenectomy, even in the presence of hepatitis or cirrhosis, doctors should be alert to the possibility of IHS. Furthermore, splenectomy may affect the blood supply to the tail of the pancreas, so patients with a pancreatic tail mass following splenectomy need follow-up and biopsy, if necessary.

Establishment of a non-alcoholic fatty liver disease model by high fat diet in adult zebrafish.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in recent years, but the pathogenesis is not fully understood. Therefore, it is important to establish an effective animal model for studying NAFLD. METHODS: Adult zebrafish were fed a normal diet or a high-fat diet combined with egg yolk powder for 30 days. Body mass index (BMI) was measured to determine overall obesity. Serum lipids were measured using triglyceride (TG) and total cholesterol (TC) kits. Liver lipid deposition was detected by Oil Red O staining. Liver injury was assessed by measuring glutathione aminotransferase (AST) and glutamic acid aminotransferase (ALT) levels. Reactive oxygen species (ROS) and malondialdehyde (MDA) were used to evaluate oxidative damage. The level of inflammation was assessed by qRT-PCR for pro-inflammatory factors. H&E staining was used for pathological histology. Caspase-3 immunofluorescence measured apoptosis. Physiological disruption was assessed via RNA-seq analysis of genes at the transcriptional level and validated by qRT-PCR. RESULTS: The high-fat diet led to significant obesity in zebrafish, with elevated BMI, hepatic TC, and TG. Severe lipid deposition in the liver was observed by ORO and H&E staining, accompanied by massive steatosis and ballooning. Serum AST and ALT levels were elevated, and significant liver damage was observed. The antioxidant system in the body was severely imbalanced. Hepatocytes showed massive apoptosis. RNA-seq results indicated that several physiological processes, including endoplasmic reticulum stress, and glucolipid metabolism, were disrupted. CONCLUSION: Additional feeding of egg yolk powder to adult zebrafish for 30 consecutive days can mimic the pathology of human nonalcoholic fatty liver disease.

Role of MEG3 in Cellular Physiology of Atherosclerosis.

OBJECTIVE: To investigate the role of the lncRNA MEG3 (MEG3) in opposing the biochemical processes thought to be involved in the development of atherosclerosis (AS). METHODS: Thirty patients with AS and thirty healthy control subjects were enrolled in this study. The expression of MEG3, miR-200b-3p and ABCA1 was analyzed by RT-qPCR in the individuals and the macrophages-derived foam cells. Lipid accumulation was detected by oil red O staining. Cholesterol efflux was measured by ELISA assay in the foam cells. Expression of miR-200b-3p was identified by sequencing. Targeting relationships were determined by dual luciferase assay between MEG3 and miR-200b-3p, miR-200b-3p and ABCA1. RESULTS: In the patients with AS, MEG3 and ABCA1 expression were decreased and miR-200b-3p expression was upregulated. Foam cells transfected with an expression vector (pcDNA3.1) containing MEG3 (pcDNA3.1-MEG3) induced decrease of lipid accumulation and increase of cholesterol efflux compared to cells transfected with control plasmid alone. Foam cells transfected by pcDNA3.1-MEG3 also showed decreased miR-200b-3p and increased ABCA1 expression. Interestingly, co-expression of miR-200b-3p partially prevented these effects of MEG3 expression. CONCLUSION: Expression of MEG3 is downregulated in the patients with AS and foam cells. Overexpressed MEG3 may act as an anti-atherosclerotic factor by reducing lipid accumulation and accelerating cholesterol efflux through the miR-200b-3p/ABCA1 axis.

Exosome-Based Theranostics for Liver Diseases.

Exosomes are small extracellular vesicles that can be secreted by any type of cell, released into almost all biological fluids, and extracted from anybody fluid such as blood, urine, saliva, and amniotic fluid. The theranostic role of exosome in liver diseases has been widely studied in recent years. In this review, we briefly introduce the biological characteristics of exosomes and then focus on the theranostics of exosomes in liver diseases, specifically gene delivery associated with liver diseases.

The role of ncRNAs in neuroblastoma: mechanisms, biomarkers and therapeutic targets.

Neuroblastoma (NB) is a malignant tumor in young children that originates from the neural crest of the sympathetic nervous system. Generally, NB occurs in the adrenal glands, but it can also affect the nerve tissues of the neck, chest, abdomen, and pelvis. Understanding the pathophysiology of NB and developing novel therapeutic approaches are critical. Noncoding RNAs (ncRNAs) are associated with crucial aspects of pathology, metastasis and drug resistance in NB. Here, we summarized the pretranscriptional, transcriptional and posttranscriptional regulatory mechanisms of ncRNAs involved in NB, especially focusing on regulatory pathways. Furthermore, ncRNAs with the potential to serve as biomarkers for risk stratification, drug resistance and therapeutic targets are also discussed, highlighting the clinical application of ncRNAs in NB.

Targeted activation of HNF4α/HGF1/FOXA2 reverses hepatic fibrosis via exosome-mediated delivery of CRISPR/dCas9-SAM system.

Aim: Hepatic fibrosis is one of the most common conditions worldwide, and yet no effective antifibrotic therapy is available. This study aimed to reverse hepatic fibrosis via exosome-mediated delivery of the CRISPR/dCas9-SAM system. Materials & methods: The authors constructed a modified-exosome delivery system targeting hepatic stellate cells (HSCs), and constructed the CRISPR/dCas9-SAM system inducing HSCs convert into hepatocyte-like cells in vitro and in vivo. Results: RBP4-modified exosomes could efficiently load and deliver the CRISPR/dCas9 system to HSCs. The in vitro CRISPR/dCas9 system induced the conversion from HSCs to hepatocyte-like cells via targeted activation of HNF4α/HGF1/FOXA2 genes. Importantly, in vivo targeted delivery of this system significantly attenuated CCl4-induced hepatic fibrosis. Conclusion: Targeted activation of HNF4α/HGF1/FOXA2 reverses hepatic fibrosis via exosome-mediated delivery of the CRISPR/dCas9-SAM system, which provides a feasible antifibrotic strategy.

Explore the Effect of Asthma Regulating HIF-1 Pathway on Sperm Quality Based on Rat Model.

This study is to verify the effect of asthma on sperm quality and explore its potential underlying mechanism. We randomly categorized the Sprague-Dawley (SD) rats into control (Group C) and asthma model (Group M) groups. Rats in the asthma model group were induced allergic asthma by intraperitoneal injection of ovalbumin solution. We evaluated the sperm motility and sperm concentration. The expression of the Interleukin-6 (IL6), phosphorylation-signal transducer and activator of transcription 3 (p-Stat3), and hypoxia-inducible factor-1α (HIF-1α) proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. Compared with group C, sperm concentration and sperm motility in group M rats were significantly decreased (P < 0.05). Meanwhile, compared with group C, the expression levels of IL6, Stat3, and HIF-1α proteins and mRNAs in group M rats were significantly increased (P < 0.05). Asthma can regulate the HIF-1 signaling pathway, promoting the expression of IL6, Stat3, and HIF-1α protein and mRNAs, so as to promote sperm apoptosis and ultimately causing male infertility.

Application Value of a New Lung Ultrasound Scoring Method in Neonatal Respiratory Distress Syndrome Treatment.

The study was aimed at exploring the clinical value of a 14-zone lung ultrasound scoring (LUS) method in treating neonatal respiratory distress syndrome (NRDS) with pulmonary surfactant (PS) and determining the timing of mechanical ventilation (MV). In this study, 88 neonates with NRDS who received PS replacement therapy were selected. We applied a new 14-zone LUS method before and 12, 24, 48 and 72 h after PS treatment to explore the clinical value of assessing PS replacement therapy efficacy in NRDS. Additionally, 67 patients with NRDS under MV received LUS during extubation. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of LUS in the timing of extubation. LUS score was inversely associated with PS treatment. At 12 h after PS, only the 14-zone LUS method was significantly different (t = 4.08, p < 0.05) as compared with before PS, which was consistent with the change on chest x-ray (CXR); the other LUS methods did not differ (p > 0.05). The 14-zone LUS method exhibited better diagnostic performance for withdrawal time. A score of 41.0 points was used as the diagnostic threshold to predict the risk of withdrawal failure, with an area under the curve of 0.955, sensitivity of 92.4% and specificity of 93.8%. The new 14-zone LUS method improved scoring in the early efficacy of PS and had good diagnostic efficiency for timing the removal of MV in NRDS.

Mannose-binding lectin 1 haplotypes influence serum MBL-A concentration, complement activity, and milk production traits in Chinese Holstein cattle.

Mannose-binding lectin (MBL) is a member of the collectin protein family that binds a broad range of microorganisms and activates the lectin-complement pathway of innate immunity. MBL deficiency is associated with an increased risk for various infections and arises from five polymorphisms in the promoter and first exon of the MBL gene in humans. In this study, three novel single-nucleotide polymorphisms (SNPs) in the promoter region and two previously reported SNPs in exon 2 of the MBL1 gene were detected using PCR single-strand conformation polymorphism, restriction fragment length polymorphism, and DNA sequencing in 537 cattle from three Chinese breeds. Analysis of the genotypes and haplotypes was used to investigate the polymorphisms and their possible implications, especially their association with serum MBL-A levels, complement activity (CH50 and ACH50), and milk production traits was investigated. The g.2651G > A SNP in exon 2 affected the serum MBL-A concentrations and the serum CH50 values, whereas the g.-1330G > A SNP significantly affected CH50 and the somatic cell scores (SCSs). Statistical analysis revealed that cows with the ATGGC/ACAAC combined genotype and those with the AAGGT/ACGGT combined genotype exhibited the lowest and highest SCSs, respectively. Serum antibacterial activities were also conducted to verify the effect of the SNPs on resistance to mastitis pathogens. Results of real-time PCR showed that the liver of cows with clinical mastitis exhibited a higher MBL1 expression compared with healthy ones (P < 0.05). Findings of this study indicate that the MBL1 gene possibly contributes to bacterial infection resistance and can be used as a molecular marker of milk production traits to control mastitis.

Hepatic Stellate Cell: A Double-Edged Sword in the Liver.

Hepatic stellate cells (HSCs) are located in the space of Disse, between liver sinusoidal endothelia cells (LSECs) and hepatocytes. They have surprised and excited hepatologists for their biological characteristics. Under physiological quiescent conditions, HSCs are the major vitamin A-storing cells of the liver, playing crucial roles in the liver development, regeneration, and tissue homeostasis. Upon injury-induced activation, HSCs convert to a pro-fibrotic state, producing the excessive extracellular matrix (ECM) and promoting angiogenesis in the liver fibrogenesis. Activated HSCs significantly contribute to liver fibrosis progression and inactivated HSCs are key to liver fibrosis regression. In this review, we summarize the comprehensive understanding of HSCs features, including their roles in normal liver and liver fibrosis in hopes of advancing the development of emerging diagnosis and treatment for hepatic fibrosis.

Hepatic stellate cell reprogramming via exosome-mediated CRISPR/dCas9-VP64 delivery.

Hepatic stellate cells (HSCs) play a crucial role in the progression of liver fibrosis, which can be considered as the specific therapeutic target of anti-fibrotic treatment. Targeted induction of HSCs to hepatocytes via delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (dCas9) system holds promise for hepatic fibrosis treatment. Our study here revealed that CRISPR/dCas9-VP64 system encapsulated in AML12 cell-derived exosomes could efficiently and successfully be delivered into the HSCs. In turn, the CRISPR/dCas9-VP64 system loaded in the exosomes can be efficiently released into the HSCs. As a proof-of-concept study, gRNA against hepatocyte nuclear factor 4α (HNF4α) together with the delivery of CRISPR/dCas9-VP64 system induced the HSCs to hepatocyte-like phenotype. In conclusion, our study here revealed that CRISPR/dCas9-VP64 system encapsulated in AML12 cell-derived exosomes could be functional in HSCs, emerging as a gene therapy strategy for hepatic fibrosis.

N-Terminal 5-Mer Peptide Analog P165 of Amyloid Precursor Protein Repairs Skin Photodamage Induced by UVB through the Nrf2 Signaling Pathway.

BACKGROUND: Acute photodamage is an acute inflammatory reaction of the skin after ultraviolet (UV) irradiation. Many drugs have been successfully used for the treatment and prevention of photodamage. AIMS: To evaluate the molecular mechanism of N-terminal 5-mer peptide analog P165 of amyloid precursor protein in repairing photodamaged rat skin. MATERIALS AND METHODS: We establish a rat model of acute UVB photodamage. The ratskin was treated with or without 250, 500, and, 1000 µM P165. Histological analysis was performed by hematoxylin and eosin staining. Apoptotic cells were analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The kits were used to measure the levels of protein carbonyl (PC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH). Western blotting was used to measure Nrf2. RESULTS: P165 repaired UVB-induced cutaneous erythema and edema, and reduced apoptosis of skin cells. The levels of PC, MDA, and 8-OHdG in 250 and 500 µM P165 groups were all lower than those in the solvent group. Activities of SOD, CAT, and GPx, and the level of GSH in P165 groups were higher than those in the solvent group. Nrf2 expression in the solvent group was higher than that in the negative group, whereas in the 500 µM P165 group was higher than in the solvent group. CONCLUSIONS: Our findings suggest that P165 repairs the rat skin with acute photodamage by reducing oxidative stress. These activities may be mediated by promoting the Nrf2 signaling pathway. Thus, P165 may be a promising agent for the treatment of acute photodamage, which may be used in cosmetics and postsun repair.

LncRNAs serve as novel biomarkers for diagnosis and prognosis of childhood ALL.

BACKGROUND: Although some studies have demonstrated that lncRNAs are dysregulated in hematopoietic malignancies and may regulate the progression of leukemia, the detailed mechanism underlying tumorigenesis is still unclear. This study aimed to investigate lncRNAs that are differentially expressed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) and their potential roles in the progression of childhood ALL. METHODS: Microarrays were used to detect differentially expressed lncRNAs and mRNAs. Several aberrantly expressed lncRNAs were validated by qRT-PCR. Leukemia-free survival was analyzed using the Kaplan-Meier method with a log-rank test. The co-expression correlations of lncRNAs and mRNAs were determined by Spearman's correlation coefficient. CCK-8 assays and flow cytometry were performed to measure cell proliferation and apoptosis. RESULTS: We revealed that many lncRNAs were abnormally expressed in B-ALL and T-ALL. LncRNA/mRNA co-expression and the gene locus network showed that dysregulated lncRNAs are involved in diverse cellular processes. We also assessed the diagnostic value of the differentially expressed lncRNAs and confirmed the optimal combination of TCONS_00026679, uc002ubt.1, ENST00000411904, and ENST00000547644 with an area under the curve of 0.9686 [95 % CI: 0.9369-1.000, P < 0.001], with 90.7 % sensitivity and 92.19 % specificity, at a cut-off point of -0.5700 to distinguish childhood B-ALL patients from T-ALL patients, implying that these specific lncRNAs may have potential to detect subsets of childhood ALL. Notably, we found that the 8-year leukemia-free survival of patients with high TCONS_00026679 (p = 0.0081), ENST00000522339 (p = 0.0484), ENST00000499583 (p = 0.0381), ENST00000457217 (p = 0.0464), and ENST00000451368 (p = 0.0298) expression levels was significantly higher than that of patients with low expression levels of these lncRNAs, while patients with high uc002ubt.1 (p = 0.0499) and ENST00000547644 (p = 0.0451) expression levels exhibited markedly shorter 8-year leukemia-free survival. In addition, some lncRNAs were found to play different roles in cell proliferation and apoptosis in T-ALL and B-ALL. CONCLUSIONS: Dysregulated lncRNAs involved in different regulatory mechanisms underlying the progression of childhood T-ALL and B-ALL might serve as novel biomarkers to distinguish ALL subsets and indicate poor outcomes.