ARRB1 downregulates acetaminophen-induced hepatoxicity through binding to p-eIF2α to inhibit ER stress signaling.

Acetaminophen (APAP) stands as the predominant contributor to drug-induced liver injury (DILI), and limited options are available. ß-Arrestin1 (ARRB1) is involved in numerous liver diseases. However, the role of ARRB1 in APAP-induced liver injury remained uncertain. Wild-type (WT) and ARRB1 knockout (KO) mice were injected with APAP and sacrificed at the indicated times. The histological changes, inflammation, endoplasmic reticulum (ER) stress, and apoptosis were then evaluated. Hepatic cell lines AML-12 and primary hepatocytes were used for in vitro analyses. Systemic ARRB1-KO mice were susceptible to APAP-induced hepatotoxicity, as indicated by larger areas of centrilobular necrosis area and higher levels of ALT, AST, and inflammation level. Moreover, ARRB1-KO mice exhibited increased ER stress (indicated by phosphorylated α subunit of eukaryotic initiation factor 2 (p-eIF2α)-activating transcription factor 4 (ATF4)-CCAAT-enhancer-binding protein homologous protein (CHOP)) and apoptosis (indicated by cleaved caspase 3). Further rescue experiments demonstrated that the induction of apoptosis was partially mediated by ER stress. Overexpression of ARRB1 alleviated APAP-induced ER stress and apoptosis. Moreover, co-IP analysis revealed that ARRB1 directly bound to p-eIF2α and eIF2α. ARRB1 protected against APAP-induced hepatoxicity through targeting ER stress and apoptosis. ARRB1 is a prospective target for treating APAP-induced DILI.

Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 - 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 - 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 - 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 - 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 - 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 - 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS.

The mediating role of children's intergenerational support in association between grandparenting and cognitive function among middle-aged and older Chinese: findings from the CHARLS cohort study.

OBJECTIVES: With the world's population increasing in age, there has been a significant rise in the prevalence of cognitive impairment and dementia among individuals. This study aims to investigate the association between grandparenting and cognitive function among middle-aged and older Chinese using data from 2011 to 2018 China Health and Retirement Longitudinal Study (CHARLS). Additionally, the study seeks to explore the potential mediating effect of intergenerational support from children on this relationship, using data from the CHARLS 2011 database. METHODS: 5254 participants were recruited at the baseline survey in CHARLS 2011. Subsequently, a follow-up survey was conducted over 8 years, from CHARLS 2011 to 2018, with 1472 individuals completing the follow-up survey. The CHARLS included surveys on grandparenting and cognitive assessments. Grandparenting was categorized as yes and no. The assessment of cognitive function involved the evaluation of episodic memory and mental intactness. The present study used cross-sectional and longitudinal analyses to examine the relationship between grandparenting and cognitive function. The bootstrap method assessed the mediating effect of children's intergenerational support. RESULTS: The results of both cross-sectional and longitudinal studies indicated a positive association between grandparenting and cognitive function in middle-aged and older Chinese (B = 0.138, p < 0.05; B = 0.218, p < 0.05). Children's emotional and economic support played intermediary roles between grandparenting and cognitive function. CONCLUSION: The results emphasized the significance of policymakers considering the consequences of intergenerational care and family support when formulating and executing social service policies targeted at the middle-aged and older population in China.

Development and validation of a novel mitophagy-related gene prognostic signature for glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most malignant tumors in brain with high morbidity and mortality. Mitophagy plays a significant role in carcinogenesis, metastasis, and invasion. In our study, we aim to construct a mitophagy-related risk model to predict prognosis in GBM. METHODS: RNA-seq data combined with clinical information were downloaded from TCGA. The 4-gene risk model and nomograph was then constructed and validated in external cohort. Evaluation of immune infiltration, functional enrichment and tumor microenvironment (TME) were then performed. RESULT: A mitophagy-related risk model was established and patients in TCGA and CGGA were classified into low-risk and high-risk groups. In both cohorts, patients in low-risk group had improved survival, while high-risk group had poor prognosis. Also, the risk model was identified as an independent factor for predicting overall survival via Cox regression. Furthermore, a prognostic nomogram including mitophagy signatures was established with excellent predictive performance. In addition, the risk model was closely associated with regulation of immune infiltration as well as TME. CONCLUSION: In conclusion, our study constructed a mitophagy-related risk model, which can be utilized for the clinical prognostic prediction in GBM.

The Role of the lncRNA-LRCF in Propofol-Induced Oligodendrocyte Damage in Neonatal Mouse.

In this study, LRCF, a long noncoding RNA (lncRNA) related to cognitive function, which was first discovered and named by our group, was shown to be involved in the propofol-induced proliferation and apoptosis of oligodendrocytes (OLGs). Our systematic study showed that LRCF expression differs in OLGs of mice of different ages. We found that neonatal mice with a high level of LRCF typically showed greater propofol-induced injury of OLGs. Mechanistic research has shown that LRCF can block the HIF-1α/miR138-5p/Caspase-3 pathway by binding to miR138-5p to form a microRNA (miRNA) sponge and result in cell damage through HIF-1α/Caspase-3 pathway in propofol induced OLGs. This may be the intrinsic reason why neonatal animals with high levels of LRCF tend to develop learning disability and neuro-degeneration more frequently than adults' after exposure to general anesthesia. When LRCF is highly expressed, HIF-1α directly regulates the transcription of the Caspase-3 gene by binding to the transcription factor binding site (TFBS) in its promoter, which induces OLGs apoptosis. LRCF is crucial for the mutual activation of the HIF-1α/miR138-5p/Caspase-3 OLGs survival pathway and the HIF-1α/Caspase-3 OLGs damage pathway. This study is the first to report that up-regulation of HIF-1α in OLGs treated with Propofol can promote apoptosis through HIF-1α/caspase-3 pathway and resist apoptosis through HIF-1α/miR-138-5p/caspase-3 pathway. The effect of HIF-1α on Caspase-3 expression depends on LRCF expression, which provides important theoretical support for gene therapy targeting LRCF. The further significance of this study is points to an involvement of the genetic background with high LRCF expression may serve as an important marker for identifying patients with a high risk of OLGs injury by Propofol. Thus, caution should be taken when administrating propofol in these patients, especially pediatric patients with high level of LRCF.

The Protective Effect of Rosavin from Rhodiola rosea on Radiation-Induced Intestinal Injury.

Bioactive constituents from Rhodiola rosea L. (RRL) exhibit multiple pharmacological effects on diverse diseases. However, whether they are suitable for the treatment of radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate their roles and mechanisms in the RIII rat model. The radioprotective effects of the four bioactive constituents of RRL (salidroside, herbacetin, rosavin and arbutin) were evaluated by the cell viability of irradiated IEC-6 cells. Intestinal tissues were collected for histological analysis, localized inflammation and oxidative stress assessments. Our work showed that salidroside, rosavin and arbutin improved the cell viability of the irradiated IEC-6 cells, with the highest improvement in 12.5 µM rosavin group. The rosavin treatment significantly improved survival rate and intestinal damage in irradiated rats by modulating the inflammatory response and oxidative stress. Our work indicated that rosavin may be the optimal constituent of RRL for RIII treatment, providing an attractive candidate for radioprotection.

[Efficacy and safety of Xiyanping injection combined with azithromycin in treating mycoplasma pneumonia of children: Meta-analysis].

To systemically evaluate the safety and efficacy of Xiyanping injection combined with azithromycin in the treatment of mycoplasmal pneumonia in children. PubMed, Wanfang Data, CNKI, VIP and CBM were used to search for the clinical randomized controlled trials on Xiyanping injection combined with azithromycin in the treatment of mycoplasmal pneumonia in children from database establishment to July, 2017. The papers were screened according to the established inclusion and exclusion criteria, and then the quality of the included studies was evaluated to extract valid data for Meta-analysis by using Revman 5.3 software. A total of 31 clinical randomized controlled trials were included, involving 2 881 patients. Meta-analysis showed that as compared with azithromycin alone, the combination of azithromycin with azithromycin had obvious advantages in the total effective rate（OR=5.42,95%CI[3.98,7.38],P<0.000 01）, fever clearance time（MD=-1.29,95%CI[-1.51,-1.08],P<0.000 01）, cough disappearance time （MD=-1.72,95%CI[-1.99,-1.46],P<0.000 01）, lung wet rales disappearance time（MD=-1.51,95%CI[-1.88,-1.14],P<0.000 01）, chest X-ray recovery time（MD=-2.72,95%CI[-3.82,-1.63],P<0.000 01）, shortening the hospital stay（MD=-1.88,95%CI[-2.26,-1.50],P<0.000 01）, reducing the incidence of adverse reactions（MD=0.51,95%CI[0.33,0.79],P=0.002）, and other aspects, with statistically significant difference. Based on the existing evidences, Xiyanping injection combined with azithromycin in the treatment of mycoplasmal pneumonia in children can significantly improve the overall clinical efficiency, shorten the hospital stay and reduce the incidence of adverse reactions. However, the clinical trials of existing small randomized controlled trials have low quality of methodology and require a large sample of high quality clinical trials for further validation.

Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles.

Rationale: The therapeutic benefits of bilirubin in the treatment of ulcerative colitis (UC) are considerable, whereas the underlying mechanism of bilirubin on UC remains unclear remains unexplored. In addition, the weak hydrophilicity and toxicity have limited its translational applications. Methods: We have developed a colon dual-targeting nanoparticle, for orally delivering bilirubin through hydrogel encapsulation of hyaluronic acid (HA)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGABilirubin). Confocal microscopy and in vivo imaging were used to evaluate the uptake and the targeted property of HA-PLGABilirubin in UC. Immunohistochemistry, immunofluorescence, and transcriptomic analyses were applied to examine the therapeutic effect and potential mechanism of HA-PLGABilirubin in UC. Results: Our results indicated that HA-PLGAbilirubin can significantly enhance the release of bilirubin at simulated intestinal pH and demonstrate higher cellular uptake in inflammatory macrophages. Moreover, in vivo biodistribution studies revealed high uptake and retention of HA-PLGAbilirubin in inflamed colon tissue of UC mouse model, resulting in effective recovery of intestinal morphology and barrier function. Importantly, HA-PLGAbilirubin exerted potent therapeutic efficacy against ulcerative colitis through modulating the intestinal epithelial/stem cells regeneration, and the improvement of angiogenesis and inflammation. Furthermore, genome-wide RNA-seq analysis revealed transcriptional reprogramming of immune response genes in colon tissue upon HA-PLGAbilirubin treatment in UC mouse model. Conclusion: Overall, our work provides an efficient colon targeted drug delivery system to potentiate the treatment of ulcerative colitis via modulating intestinal epithelium regeneration and immune response in ulcerative colitis.

Association Between the Serum Copper Levels and Environmental Tobacco Exposure on the Risk of Overweight and Obesity in Children: a Study Based on the National Health and Nutrition Examination Survey.

This study was to assess the individual effects of serum copper levels and environmental tobacco exposure and their joint effects on the risk of overweight and obesity among children and adolescents of 6 to 19 year olds. We analyzed cross-sectional data from 1849 children and adolescents participating in the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2016. Environmental tobacco exposure was determined by cotinine levels. The serum copper level was divided into < median group and ≥ median groups according to the median of 109.81 µg/dL. The outcome was overweight/obese in children and adolescents. Weighted multinomial multivariate logistic regression models were used to assess the association of serum copper and cotinine levels, with the risk of overweight/obesity, and the joint effects on the risk of overweight and obesity among children and adolescents. The subgroup analyses based on age, gender, and household smoking status were conducted. Among 1849 children and adolescents, 332 children and adolescents had overweight BMI, and 450 children and adolescents had obese BMI. Higher serum copper levels were associated with the risk of obesity in children and adolescents (odds ratio (OR) 2.96, 95% confidence interval (CI) 1.39-6.31, P = 0.006). A positive association between increasing levels of cotinine levels and the risk of overweight (OR 1.83, 95% CI 1.16-2.87, P = 0.010) and obesity (OR 2.56, 95% CI 1.03-6.40, P = 0.044) in children and adolescents was observed. A remarkable association was found between higher serum copper in combination with higher cotinine levels and the risk of overweight (OR 3.23, 95% CI 1.19-8.83, P = 0.023) and obesity (OR 8.76, 95% CI 2.14-35.87, P = 0.003) in children and adolescents. The subgroup analyses revealed positive associations between high serum copper levels in combination with high cotinine levels and overweight and obesity in children and adolescents aged ≥ 12 years, of female sex, and without smoking family members. There may exist a joint effect of serum copper levels and environmental tobacco exposure on overweight/obesity among children and adolescents. These findings offer an insight that early weight control and reduction of tobacco exposure and the detection of serum copper levels may be important in reducing the risk of obesity in children.

Hepatitis B virus X protein induces ALDH2 ubiquitin-dependent degradation to enhance alcoholic steatohepatitis.

Background: Excessive alcohol intake with hepatitis B virus (HBV) infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease. Hepatitis B virus X protein (HBx) plays a crucial role in disease pathogenesis, while its specific role in alcoholic liver disease (ALD) progression has not yet been elucidated. Here, we studied the role of HBx on the development of ALD. Methods: HBx-transgenic (HBx-Tg) mice and their wild-type littermates were exposed to chronic plus binge alcohol feeding. Primary hepatocytes, cell lines, and human samples were used to investigate the interaction between HBx and acetaldehyde dehydrogenase 2 (ALDH2). Lipid profiles in mouse livers and cells were assessed by using liquid chromatography-mass spectrometry. Results: We identified that HBx significantly aggravated alcohol-induced steatohepatitis, oxidative stress, and lipid peroxidation in mice. In addition, HBx induced worse lipid profiles with high lysophospholipids generation in alcoholic steatohepatitis, as shown by using lipidomic analysis. Importantly, serum and liver acetaldehyde were markedly higher in alcohol-fed HBx-Tg mice. Acetaldehyde induced lysophospholipids generation through oxidative stress in hepatocytes. Mechanistically, HBx directly bound to mitochondrial ALDH2 to induce its ubiquitin-proteasome degradation, resulting in acetaldehyde accumulation. More importantly, we also identified that patients with HBV infection reduced ALDH2 protein levels in the liver. Conclusions: Our study demonstrated that HBx-induced ubiquitin-dependent degradation of mitochondrial ALDH2 aggravates alcoholic steatohepatitis.

Identification of shared fatty acid metabolism related signatures in dilated cardiomyopathy and myocardial infarction.

Aim: It is to be elucidated the risk-predictive role of differentially expressed fatty acid metabolism related genes (DE-FRGs) in dilated cardiomyopathy (DCM) and myocardial infarction. Materials & methods: Four gene enrichment analyses defined DE-FRGs' biological functions and pathways. Three strategies were applied to identify risk biomarkers and construct a nomogram. The 4-DE-FRG correlation with immune cell infiltration, drugs, and ceRNA was explored. Results: DE-FRGs were enriched in lipid metabolism. A risk nomogram was established by ACSL1, ALDH2, CYP27A1 and PPARA, demonstrating a good ability for DCM and myocardial infarction prediction. PPARA was positively correlated with adaptive immunocytes. Thirty-five drugs are candidate therapeutic targets. Conclusion: A nomogram and new biological targets for early diagnosis and treatment of DCM and myocardial infarction were provided.

Dilated cardiomyopathy (DCM) and myocardial infarction (MI) are two common types of heart disease. This study investigated the fatty acid metabolism related genes to predict the risk of DCM or MI. Four of them (ACSL1, ALDH2, CYP27A1 and PPARA) were effective in predicting disease risk. Additionally, PPARA was found to be associated with immune cell infiltration, and 35 drugs emerged as potential therapeutic targets for these diseases. This study may provide insights into the early diagnosis and treatment of DCM and MI.

Rho GTPase signaling in rheumatic diseases.

Rho guanosine triphosphatase (GTPases), as molecular switches, have been identified to be dysregulated and involved in the pathogenesis of various rheumatic diseases, mainly including rheumatoid arthritis, osteoarthritis, systemic sclerosis, and systemic lupus erythematosus. Downstream pathways involving multiple types of cells, such as fibroblasts, chondrocytes, synoviocytes, and immunocytes are mediated by activated Rho GTPases to promote pathogenesis. Targeted therapy via inhibitors of Rho GTPases has been implicated in the treatment of rheumatic diseases, demonstrating promising effects. In this review, the effects of Rho GTPases in the pathogenesis of rheumatic diseases are summarized, and the Rho GTPase-mediated pathways are elucidated. Therapeutic strategies using Rho GTPase inhibitors in rheumatic diseases are also discussed to provide insights for further exploration of targeted therapy in preclinical studies and clinical practice. Future directions on studies of Rho GTPases in rheumatic diseases based on current understandings are provided.

A Case Report of Imatinib-induced Acute Heart Failure and Literature Review.

Patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GISTs) or acute lymphoblastic leukemia (ALL) are appropriate candidates for medical treatment using imatinib. Here, we report a case of imatinib-induced acute heart failure in a patient with ALL and retrospectively analyse the adverse reactions of imatinib. The patient was a 45-year man with Ph+ and bcr-abl positive (bcr-abl+) ALL. He was treated with imatinib approximately four months ago. At that time, he had no risk factors for cardiac disease, and his heart function was normal. Then, four months after starting imatinib, he manifested signs of acute heart failure. A retrospective analysis of the adverse reactions in 100 cases of leukemia patients, who took imatinib in the past three years, indicated a rare incidence of congestive heart failure among those patients. Our experience in treating the patient suggests that brain natriuretic peptide levels and cardiac doppler examinations should be monitored closely in these patients. Key Words: Imatinib, Acute lymphoid leukemia, Acute heart failure.

Current therapy option for necrotizing enterocolitis: Practicalities and challenge.

Necrotizing enterocolitis (NEC) is one of the most prevalent neonatal gastrointestinal disorders. Despite ongoing breakthroughs in its treatment and prevention, the incidence and mortality associated with NEC remain high. New therapeutic approaches, such as breast milk composition administration, stem cell therapy, immunotherapy, and fecal microbiota transplantation (FMT) have recently evolved the prevention and the treatment of NEC. This study investigated the most recent advances in NEC therapeutic approaches and discussed their applicability to bring new insight to NEC treatment.

Development and validation of a novel ubiquitination-related gene prognostic signature based on tumor microenvironment for colon cancer.

Background: Colon cancer (CC) is one of the most common cancers with high morbidity globally. Ubiquitination is involved in the characterization of multiple biological processes, and some ubiquitinated enzymes are associated with the prognosis of CC. However, the prognostic model associated with ubiquitination-related genes (URGs) for CC is unavailable. Methods: Gene expression data, somatic mutations, transcriptome profiles, microsatellite instability status (MSI) status, and clinical information for CC were obtained from The Cancer Genome Atlas (TCGA) dataset. Seven URGs were used for establishing a prognostic prediction model, which was constructed and validated in GSE17538. Besides, genomic variance analysis (GSVA) was used to explore further the differences in biological pathway activation status between the high-risk and low-risk groups. Finally, the single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithm analysis were used to characterize the cellular infiltration in the microenvironment. Results: A seven-URG prognostic signature was established, based on which patients in the training and test groups could be divided into high-risk and low-risk groups. The results demonstrated that the model has a solid ability to predict the prognosis of CC patients. Conclusions: We established a prognostic prediction model for CC based on ubiquitination. Then we analyzed the genetic characteristics associated with ubiquitination and the tumor microenvironment (TME) cell infiltration in CC. These results are worthy of exploring new clinical treatment strategies for CC.

Stem cells and exosomes: promising candidates for necrotizing enterocolitis therapy.

Necrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.

Effect of baduanjin on the fall and balance function in middle-aged and elderly people: A protocol for systematic review and meta-analysis.

BACKGROUND: The risk of fall seriously affects the health and quality of life of the middle-aged and elderly people, especially the injury and disability caused by fall of the middle-aged and elderly people, which imposes a huge burden on family and social medical care. Baduanjin exercise may be an effective intervention to enhance the muscle strength and stability of lower limbs, improve the balance ability and gait of middle-aged and elderly people, reduce the incidence of falls, improve the quality of life, and promote the health of middle-aged and elderly people. The aim of this study is to summarize evidence and systematically review the efficacy and safety of Baduanjin on the fall and balance function in middle-aged and elderly people. METHODS: We conducted a systematic search of English and Chinese RCTs in the following 8 electronic databases: PubMed, EMBASE, Web of Science, The Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database, from their respective dates of inception to July 2021. Other resources will be searched if necessary. The primary outcome is the fall rate in middle-aged and elderly people and the secondary outcomes include the Single-Leg Standing (SLS) Test, Berg Balance Scale (BBS), Timed Up and Go (TUG) Test. The study selection, data extraction, risk of bias, data synthesis and analysis, reporting biases, and the quality of evidence will be independently conducted by 2 reviewers who use the EndNote X9 software, Cochrane handbook assessment tool, RevMan 5.3 software, a funnel plot and GRADE system. RESULTS: This study will evaluate the effect of Baduanjin on falls and balance function of middle-aged and elderly people from multiple outcome evaluation indicators such as fall rate, and provide high-quality evidence. CONCLUSION: This study will provide evidence for whether Baduanjin has an effect on falls and balance function in middle-aged and elderly people. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review, since it does not infringe on personal interests. The results will be submitted to peer-review journals or disseminated at scientific conferences.

Development and Validation of a Novel Mitophagy-Related Gene Prognostic Signature for Hepatocellular Carcinoma Based on Immunoscore Classification of Tumor.

Emerging evidence suggested that mitophagy may play an important role in the progression of hepatocellular carcinoma (HCC), whereas the association between mitophagy-related genes and HCC patients' prognosis remains unknown. In this study, we aimed to investigate the potential prognostic values of mitophagy-related genes (MRGs) on HCC patients at the genetic level. According to median immunoscore, we categorized HCC patients from TCGA cohort into two immune score groups, while 39 differential expression MRGs were identified. By using univariate analysis, we screened out 18 survival-associated MRGs, and then, the least absolute shrinkage and selection operator (LASSO) analysis was applied to construct a prognosis model that consisted of 9 MRGs (ATG7, ATG9A, BNIP3L, GABARAPL1, HTRA2, MAP1LC3B2, TFE3, TIGAR, and TOMM70). In our prognostic model, overall survival in the high and low-risk groups was significantly different (P < 0.001), and the respective areas under the curve (AUC) of our prognostic model were 0.686 for 3-year survival in the TCGA cohort and 0.776 for 3-year survival in the ICGC cohort. Moreover, we identified the risk score as the independent factor for predicting the HCC patients' prognosis by using single and multifactor analyses, and a nomogram was also constructed for future clinical application. Further functional analyses showed that the immune status between two risk groups was significantly different. Our findings may provide a novel mitophagy-related gene signature, and these will be better used for prognostic prediction in HCC, thus improving patient outcome.

Targeted extracellular vesicle delivery systems employing superparamagnetic iron oxide nanoparticles.

In the past decade, the study of extracellular vesicles (EVs), especially exosomes (50-150 nm) have attracted growing interest in numerous areas of cancer and tissue regeneration due to their unique biological features. A low isolation yield and insufficient targeting abilities limit their therapeutic applicability. Recently, superparamagnetic iron oxide nanoparticles (SPIONs) with magnetic navigation have been exploited to enhance the targeting ability of EVs. To construct targeted EV delivery systems engineered by SPIONs, several groups have pioneered the use of different techniques, such as electroporation, natural incubation, and cell extrusion, to directly internalize SPIONs into EVs. Furthermore, some endogenous ligands, such as transferrins, antibodies, aptamers, and streptavidin, were shown to enable modification of SPIONs, which increases binding with EVs. In this review, we summarized recent advances in targeted EV delivery systems engineered by SPIONs and focused on the key methodological approaches and the current applications of magnetic EVs. This report aims to address the existing challenges and provide comprehensive insights into targeted EV delivery systems. STATEMENT OF SIGNIFICANCE: Targeted extracellular vesicle (EV) delivery systems engineered by superparamagnetic iron oxide nanoparticles (SPIONs) have attracted wide attention and research interest in recent years. Such strategies employ external magnet fields to manipulate SPION-functionalized EVs remotely, aiming to enhance their accumulation and penetration in vivo. Although iron oxide nanoparticle laden EVs are interesting, they are controversial at present, hampering the progress in their clinical application. A thorough integration of these studies is needed for an advanced insight and rational design of targeted EV delivery systems. In this review, we summarize the latest advances in the design strategies of targeted EV delivery systems engineered by SPIONs with a focus on their key methodological approaches, current applications, limitation and future perspectives, which may facilitate the development of natural theranostic nanoplatforms.

Association between cardiovascular risk factors and colorectal cancer: A systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Emerging data have suggested colorectal cancer (CRC) often coexists with cardiovascular diseases, but whether cardiovascular risk factors play a role in CRC remains unclear. We performed a systematic review and meta-analysis to better illustrate the associations between cardiovascular risk factors and CRC. METHODS: We searched EMBASE, MEDLINE and Web of Science databases from inception up to June 14, 2020. Prospective cohort studies were included if they evaluated the association between at least one of cardiovascular risk factors and CRC incidence, containing sufficient data to obtain relative risk (RR) and 95% confidence interval (CI). We performed separate meta-analyses for each cardiovascular risk factor using random-effect model. PROSPERO registration number: CRD42020175537. FINDINGS: Data from 84 studies, reporting 52, 348, 827 individuals and 384, 973 incident cases were included in the analysis. Overall, the risk of CRC was 1.31(95% CI, 1.21-1.42) for obesity, 1.14 (95% CI, 1.09-1.20) for per 5 kg/m2 increase in body mass index, 1.18 (95% CI, 1.14-1.23) for former smoker, 1.20 (95% CI, 1.11-1.30) for current smoker, 1.25 (95% CI, 1.16-1.35) for diabetes, 1.07 (95% CI, 1.02-1.12) for hypertension. The summary RRs of CRC for the highest versus lowest quartiles of total cholesterol, triglyceride, low-density lipoprotein were 1.12 (95% CI, 1.03-1.22), 1.18 (95% CI, 1.04-1.35), 0.85 (95% CI, 0.62-1.17) respectively and the pooled RR for the lowest versus highest quartile of high-density lipoprotein was 1.14 (95% CI, 1.02-1.28). INTERPRETATION: Unfavorable cardiovascular risk factors are associated with increased risk of CRC, which may provide novel insight into the screening strategies of CRC in patient with these risk factors.