Analysis of influencing factors and construction of prediction model for postoperative nausea and vomiting in patients undergoing laparoscopic sleeve gastrectomy: a single-center retrospective cohort study.

BACKGROUND: With the increasing number of bariatric surgeries, the high incidence of postoperative nausea and vomiting (PONV) associated with this surgery has also gradually attracted attention. Among the common bariatric surgery methods, patients undergoing sleeve gastrectomy (SG) have the highest incidence of nausea and vomiting. The mechanism of occurrence of PONV is very complex. This study aims to explore the influencing factors of PONV in patients undergoing laparoscopic sleeve gastrectomy (LSG) and construct a nomogram prediction model based on these factors. METHODS: With the approval of the Ethics Committee, the electronic medical records of patients who underwent LSG from July 2022 to May 2023 were collected retrospectively. RESULTS: A total of 114 patients with complete medical records who underwent LSG from July 2022 to May 2023 were included in this study. Among them, 46 patients developed PONV, resulting in a PONV incidence rate of 40.4%. Multivariate logistic regression analysis revealed that female gender, the use of inhalation anesthesia, and operation time ≥ 120 min were risk factors for PONV in LSG. Additionally, the use of more than two kinds of antiemetic drugs was identified as a protective factor. Based on these factors, a nomogram model was constructed. CONCLUSION: PONV in patients undergoing LSG is related to gender, type of anesthesia, duration of surgery, and combination therapy with antiemetic drugs. The nomogram prediction model constructed in this study demonstrates high accuracy and discrimination in predicting the occurrence of PONV in patients undergoing LSG.

The longitudinal relationship between self-compassion and cancer patients' unmet supportive care needs.

OBJECTIVES: Unmet supportive care needs are associated with psychological symptoms such as depression and anxiety. However, so far, few studies have explored the protective psychological factors of unmet needs. Therefore, this study intends to explore the protective effect of self-compassion on unmet needs of Chinese cancer patients and to examine the predictive role of self-compassion on these needs during treatment. METHODS: A longitudinal study was performed at Shaanxi Provincial Cancer Hospital in Xi'an, China. A total of 153 heterogeneous cancer patients were assessed after the first diagnosis (T1), at the beginning (T2) and end (T3) of medical treatment. Hierarchical linear regression analyses were used to examine the research questions. RESULTS: Cross-sectional regression analyses showed that self-compassion at T1 was significantly related to psychological needs at T1. Negative self-compassion at T1 was significantly related to total unmet needs, psychological needs, health system, and information and sexual needs. Longitudinal regression analyses showed that self-compassion at T1 significantly predicted total unmet needs; health system and information (HSI) needs at T2, psychological needs at T3, and negative self-compassion at T1 significantly predicted total unmet needs, HSI needs, physical needs, and patient care needs at T2 when controlling for unmet needs at T1. Positive self-compassion was not a predictor of unmet needs. CONCLUSIONS: Self-compassion can be a protective factor of unmet needs in cancer patients. Future intervention studies should focus on improving the overall level of self-compassion and reducing the level of negative self-compassion in cancer patients to reduce patients' unmet needs.

Sex-related differences in SIRT3-mediated mitochondrial dynamics in renal ischemia/reperfusion injury.

The prevalence of renal ischemia/reperfusion injury (IRI) in premenopausal women is considerably lower than that in age-matched men. This suggests that sex-related differences in mitochondrial function and homeostasis may contribute to sexual dimorphism in renal injury, though the mechanism remains unclear. Mouse model of unilateral left renal IRI with contralateral kidney enucleation, Ovariectomy in female mice, and a human embryonic kidney (HEK) cell model of hypoxia-reoxygenation were used to study how estrogen affects the sexual dimorphism of renal IRI through SIRT3 in vitro and in vivo, respectively. Here, we demonstrate differential expression of renal SIRT3 may induce sexual dimorphism in IRI using the renal IRI model. Higher SIRT3 level in female mice was associated with E2-induced protection of renal tubular epithelium, reduced mitochondrial reactive oxygen species (ROS), and IRI resistance. In hypoxia-reoxygenated HEK cells, SIRT3 knockdown increased oxidative stress, shifted the interconnected mitochondrial network toward fission, exacerbated hypoxia/reoxygenation-induced endoplasmic reticulum stress (ERS), and abolished the protective effects of E2 on IRI. Mechanistically, the SIRT3 level is E2-dependent and that E2 increases the SIRT3 protein level via estrogen receptor. SIRT3 targeted an i-AAA protease, yeast mitochondrial AAA metalloprotease (YME1L1), and hydrolyzed long optic atrophy 1 (L-OPA) to short-OPA1 (S-OPA1) by deacetylating YME1L1, regulating mitochondrial dynamics toward fusion to reduce oxidative stress and ERS. These findings explored the mechanism by how estrogen alleviates renal IRI and providing a basis for potential therapeutic interventions targeting SIRT3.

Prolyl isomerase Pin1 sculpts the immune microenvironment of colorectal cancer.

Pin1, a peptide prolyl cis-trans isomerase, is overexpressed and/or overactivated in many human malignancies. However, whether Pin1 regulates the immunosuppressive TME has not been well defined. In this study, we detected the effect of Pin1 on immune cells and immune checkpoint PD-L1 in the TME of CRC and explored the anti-tumor efficacy of Pin1 inhibitor ATRA combined with PD-1 antibody. We found that Pin1 facilitated the immunosuppressive TME by raising the proportion of myeloid-derived suppressor cells (MDSCs) and declining the percentage of CD8+ T cells and CD4+ T cells. Pin1 restrained PD-L1 protein expression in CRC cells and the effect was tempered by endoplasmic reticulum (ER) stress inducers. Mechanically, Pin1 overexpression decreased the stability of PD-L1 and promoted its degradation by mitigating ER stress. Silencing or inhibiting Pin1 promoted PD-L1 protein expression by inducing ER stress. Hence, Pin1 inhibitor ATRA enhanced the anti-tumor efficacy of PD-1 antibody in the CRC allograft by upregulating PD-L1. Our results reveal the critical and pleiotropic effects of Pin1 on managing the immune cells and immune checkpoint PD-L1 in the TME of CRC, providing a new promising candidate for combination with immunotherapy.

Theoretical insights into the enantiodivergence induced by chiral phosphoric acid catalysis with a Lewis acid for the synthesis of N-N axially chiral atropisomers.

A detailed theoretical mechanistic investigation on chiral phosphoric acid (CPA)-catalyzed Paal-Knorr reactions, in the presence and absence of a Lewis acid, for the synthesis of N-N axially chiral atropisomers is described herein. Density functional theory (DFT) studies elucidate that in the absence of a Lewis acid, CPA catalyzes both the initial cyclization and the subsequent dehydroxylation processes, ambiguously identified as the rate-determining step in the reactions. Conversely, when a Lewis acid participates in the reaction, it facilitates the second dehydroxylation process with a significantly lower energy barrier, thereby reversing the rate-determining step to the initial cyclization step. It is noteworthy that in the case of N-aminoindoles, both the S-configurational transition state TS1 in the cyclization step and TS2 in the dehydroxylation process are favourable. In contrast, for the synthesis of a bispyrrole, the R-configurational TS1 and the S-configurational TS2 are dominant. Therefore, the enantiodivergence observed is essentially induced by the reversed rate-determining steps in the absence or presence of a Lewis acid in the case of a bispyrrole. Furthermore, the non-covalent interaction (NCI) and atoms-in-molecules (AIM) analysis of the TS structures reveal that the non-covalent interactions play a pivotal role in determining the enantiodivergence observed in these reactions.

Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro.

BACKGROUND: Bladder urothelial carcinoma (BLCA) is the most common genitourinary cancer and the prognosis of patients is often poor. However, studies of basement membrane-related genes (BM-related genes) in BLCA are less reported. Therefore, we established a BM-related genes signature to explore their functional and prognostic value in BLCA. METHODS: In this study, a BM-related genes signature was constructed by LASSO-Cox regression analysis, and then a series of bioinformatics methods was used to assess the accuracy and validity of the signature. We constructed a nomogram for clinical application and also screened for possible therapeutic drugs. To investigate the functions and pathways affected by BM-related genes in BLCA, we performed functional enrichment analyses. In addition, we analyzed the immune cell infiltration landscape and immune checkpoint-related genes in the high and low-risk groups. Finally, we confirmed the prognostic value of BM-related genes in BLCA in vitro. RESULTS: Combining multiple bioinformatics approaches, we identified a seven-gene signature. The accuracy and validity of this signature in predicting BLCA patients were confirmed by the test cohort. In addition, the risk score was strongly correlated with prognosis, immune checkpoint genes, drug sensitivity, and immune cell infiltration landscape. The risk score is an independent prognostic factor for BLCA patients. Further experiments revealed that all seven signature genes were differentially expressed between BLCA cell lines and normal bladder cells. Finally, overexpression of LAMA2 inhibited the migration and invasion ability of BLCA cell lines. CONCLUSIONS: In summary, the BM-related genes signature was able to predict the prognosis of BLCA patients accurately, indicating that the BM-related genes possess great clinical value in the diagnosis and treatment of BLCA. Moreover, LAMA2 could be a potential therapeutic target, which provides new insights into the application of the BM-related genes in BLCA patients.

Identification of disulfidptosis related subtypes, characterization of tumor microenvironment infiltration, and development of DRG prognostic prediction model in RCC, in which MSH3 is a key gene during disulfidptosis.

Disulfidptosis is a newly discovered mode of cell death induced by disulfide stress. However, the prognostic value of disulfidptosis-related genes (DRGs) in renal cell carcinoma (RCC) remains to be further elucidated. In this study, consistent cluster analysis was used to classify 571 RCC samples into three DRG-related subtypes based on changes in DRGs expression. Through univariate regression analysis and LASSO-Cox regression analysis of differentially expressed genes (DEGs) among three subtypes, we constructed and validated a DRG risk score to predict the prognosis of patients with RCC, while also identifying three gene subtypes. Analysis of DRG risk score, clinical characteristics, tumor microenvironment (TME), somatic cell mutations, and immunotherapy sensitivity revealed significant correlations between them. A series of studies have shown that MSH3 can be a potential biomarker of RCC, and its low expression is associated with poor prognosis in patients with RCC. Last but not least, overexpression of MSH3 promotes cell death in two RCC cell lines under glucose starvation conditions, indicating that MSH3 is a key gene in the process of cell disulfidptosis. In summary, we identify potential mechanism of RCC progression through DRGs -related tumor microenvironment remodeling. In addition, this study has successfully established a new disulfidptosis-related genes prediction model and discovered a key gene MSH3. They may be new prognostic biomarkers for RCC patients, provide new insights for the treatment of RCC patients, and may inspire new methods for the diagnosis and treatment of RCC patients.

Crosstalk between KIF1C and PRKAR1A in left atrial myxoma.

Cardiac myxoma (CM) is the most common benign cardiac tumor, and most CMs are left atrial myxomas (LAMs). Six variations of KIF1C, c.899 A > T, c.772 T > G, c.352 A > T, c.2895 C > T, c.3049 G > A, and c.*442_*443dup in left atrial myxoma tissues are identified by whole-exome sequencing (WES) and Sanger sequencing. RNA-seq and function experiments show the reduction of the expression of KIF1C and PRKAR1A caused by rare variations of KIF1C. KIF1C is observed to be located in the nucleus, bind to the promoter region of PRKAR1A, and regulate its transcription. Reduction of KIF1C decreases PRKAR1A expression and activates the PKA, which causes an increase in ERK1/2 phosphorylation and SRC-mediated STAT3 activation, a reduction of CDH1, TP53, CDKN1A, and BAX, and eventually promotes tumor formation both in vitro and in vivo. The results suggest that inhibition of KIF1C promotes the pathogenesis of LAM through positive feedback formed by the crosstalk between KIF1C and PRKAR1A.

GOLM1 Promotes Epithelial-Mesenchymal Transition by Activating TGFß1/Smad2 Signaling in Prostate Cancer.

Background: Prostate cancer (PC) is one of the most commonly diagnosed cancer in men worldwide. Epithelial-mesenchymal transition (EMT) is considered to play a crucial role in the development of the metastatic castration-resistant prostate cancer, which causes the majority of the death cases in PC. Golgi membrane protein 1 (GOLM1) is highly expressed in PC and has been identified as a driver factor for EMT in various cancers. However, its biological functions and underlying mechanisms remain ambiguous in PC. Method: GOLM1 expression level of PC was detected by Western blot and immunohistochemistry analyses. To investigate GOLM1 functions in cancer cells, we overexpressed and knocked down GOLM1 in different prostate cancer cell lines. Transwell assay and wound healing assay were used to determine the role of GOLM1 in cell EMT, such as migration and invasion abilities. TGF-ß1/Smad2 signaling pathway downstream of GOLM1 was detected by Western blot and Transwell assay. Result: GOLM1 expression is up-regulated in PC and correlated with a worse prognosis. GOLM1 promotes the abilities of migration and invasion in PC cell lines (DU145 and LNCaP). Furthermore, TGF-ß1/Smad2 signaling is positively regulated by GOLM1 to facilitate EMT in PC, whereas this role can be restored by TGF-ß1 after GOLM1 knockdown or be abrogated by p-Smad inhibitor SB431542. Conclusion: GOLM1 is significantly upregulated in PC and acts as a critical oncogene by promoting PC cell EMT process by activating TGF-ß1/Smad2 signaling pathway. Therefore, GOLM1 has the potential to be a biomarker for PC diagnosis and to predict the prognosis of PC patients. It is of great significance to seek effective and specific inhibitor of GOLM1 for PC treatment as well.

The role of histone methylation in renal cell cancer: an update.

Renal cell carcinoma accounts for 2-3% of all cancers. It is difficult to diagnose early. Recently, genome-wide studies have identified that histone methylation was one of the functional classes that is most frequently dysregulated in renal cell cancer. Mutation or mis-regulation of histone methylation, methyltransferases, demethylases are associated with gene expression and tumor progression in renal cell cancer. Herein, we summarize histone methylations, demethylases and their alterations and mechanisms in renal cell cancer.

Development and validation of a deep-learning based assistance system for enhancing laparoscopic control level.

BACKGROUND AND AIMS: Inter-operator variations in the level of intraoperative laparoscope control by surgeons influence surgical outcomes. We aimed to construct a laparoscopic surgery quantification system (LSQS) for real-time evaluation of the surgeon's laparoscope control to improve intraoperative manipulation of the laparoscope. METHODS: Using 1888 images from 80 laparoscopic videos for training, the U-Net, PSPNet, LinkNet, and DeepLabv3+ models were used to segment surgical instruments. The percentage of the instruments in central area was defined as the new indicator and the threshold was determined from 20 laparoscopic videos. The differences between expert and non-expert laparoscopic operators before and after LSQS were compared. RESULTS: Among the three segmentation models (U-Net, PSPNet, and LinkNet), the PSPNet model had the highest index (precision 0.9135; F1 score 0.9058; mIoU 0.8280). The validation experiment showed that LSQS could help non-expert users to more easily achieve expert-level control of the laparoscope. CONCLUSIONS: Deep-learning technology successfully fed back real-time intraoperative information on level of laparoscope control and may facilitate better visualisation of the surgical field.

Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer.

Energy stress is an unfavorable condition that tumor cells are often exposed to. Ferroptosis is considered an emerging target for tumor therapy. However, the role of ferroptosis in energy stress in renal cancer is currently unknown. In this study, we found that glucose deprivation significantly enhanced GPX4-dependent ferroptosis through AMPK activation. Further, AMPK activation suppressed GPX4 expression at the transcriptional level through the upregulation of P53 expression. Additionally, the inactivation of JAK2/STAT3 transcriptionally promoted P53 expression, thereby promoting AMPK-mediated GPX4-dependent ferroptosis. In conclusion, energy stress promotes AMPK-mediated GPX4-dependent erastin-induced ferroptosis in renal cancer through the JAK2/STAT3/P53 signaling axis.

MITD1 Deficiency Suppresses Clear Cell Renal Cell Carcinoma Growth and Migration by Inducing Ferroptosis through the TAZ/SLC7A11 Pathway.

Clear cell renal cell carcinoma (ccRCC), the major histopathological subtype of renal cancer, is sensitive to ferroptosis. MIT-domain containing protein 1 (MITD1) has been reported to play an important role in hepatocellular carcinoma, while it remains unclear whether MITD1 is involved in ccRCC. Based on available data in The Cancer Genome Atlas, we found the expression of MITD1 increased through bioinformatics analysis and high MITD1 expression suggests a poor prognosis. And we validated that MITD1 expressed significantly in ccRCC through Western blot analysis. Then, we further compared the proliferation and migration capacity of ccRCC before and after MITD1 knockdown and further explored the effect of MITD1 knockdown on ferroptosis. The results indicated that MITD1 knockdown inhibited ccRCC cell proliferation and migration and induced ferroptosis in ccRCC. Furthermore, we found and analyzed the key molecule TAZ which was involved in ferroptosis caused by MITD1 knockdown. Subsequent overexpression experiments demonstrated that MITD1 knockdown induced ferroptosis and suppressed tumor growth and migration through the TAZ/SLC7A11 pathway. In summary, our study revealed the role of MITD1 in the ferroptosis of ccRCC and provided a novel target for ccRCC treatment.

A prognosis model for clear cell renal cell carcinoma based on four necroptosis-related genes.

Necroptosis is a type of caspase-independent cell death, and it plays a critical role in regulating the development of cancer. To date, little is known about the role of necroptosis-related genes (NRGs) in clear cell renal cell carcinoma (ccRCC). In this study, we downloaded data regarding the expression of NRGs and overall survival (OS) from The Cancer Genome Atlas (TCGA) database and constructed a risk model to determine the prognostic features of necroptosis using COX regression analysis. Patients with ccRCC were divided into low-risk and high-risk groups based on their risk scores. Thereafter, Kaplan-Meier curves were used to evaluate OS, and receiver operating characteristic (ROC) curves were used to determine the accuracy of prediction. Stratified analyses were performed according to different clinical variables. Furthermore, we assessed the correlation between clinical variables and risk scores; the NRGs with differential expression were mainly enriched in positive regulation of intracellular transport and platinum resistance pathways. We constructed prognostic signatures for OS based on four NRGs and showed that the survival time was significantly longer in the low-risk groups than in the high-risk groups (p < 0.001). The area of the ROC curve for OS was 0.717, indicating excellent predictive accuracy of the established model. Therefore, a predictive model based on NRGs was constructed, which can predict the prognosis of patients and provides insights into the biological mechanisms underlying necroptosis in patients with ccRCC.

Prognostic Pathways Guide Drug Indications in Pan-Cancers.

Pathway-level analysis is a powerful approach enabling the interpretation of post-genomic data at a higher level than that of individual molecules. Molecular-targeted therapy focusing on cascade signaling pathways has become a new paradigm in anticancer therapy, instead of a single protein. However, the approaches to narrowing down the long list of biological pathways are limited. Here, we proposed a strategy for in silico Drug Prescription on biological pathways across pan-Cancers (CDP), by connecting drugs to candidate pathways. Applying on a list of 120 traditional Chinese medicines (TCM), we especially identified the "TCM-pathways-cancers" triplet and constructed it into a heterogeneous network across pan-cancers. Applying them into TCMs, the computational prescribing methods deepened the understanding of the efficacy of TCM at the molecular level. Further applying them into Western medicines, CDP could promote drug reposition avoiding time-consuming developments of new drugs.

GMrepo: a database of curated and consistently annotated human gut metagenomes.

GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purpose is to facilitate the reusability and accessibility of the rapidly growing human metagenomic data. This is achieved by consistently annotating the microbial contents of collected samples using state-of-art toolsets and by manual curation of the meta-data of the corresponding human hosts. GMrepo organizes the collected samples according to their associated phenotypes and includes all possible related meta-data such as age, sex, country, body-mass-index (BMI) and recent antibiotics usage. To make relevant information easier to access, GMrepo is equipped with a graphical query builder, enabling users to make customized, complex and biologically relevant queries. For example, to find (1) samples from healthy individuals of 18 to 25 years old with BMIs between 18.5 and 24.9, or (2) projects that are related to colorectal neoplasms, with each containing >100 samples and both patients and healthy controls. Precomputed species/genus relative abundances, prevalence within and across phenotypes, and pairwise co-occurrence information are all available at the website and accessible through programmable interfaces. So far, GMrepo contains 58 903 human gut samples/runs (including 17 618 metagenomes and 41 285 amplicons) from 253 projects concerning 92 phenotypes. GMrepo is freely available at: https://gmrepo.humangut.info.

Picroside II attenuates ischemia/reperfusion testicular injury by alleviating oxidative stress and apoptosis through reducing nitric oxide synthesis

Abstract Purpose: To investigate the effect of Picroside II on testicular ischemia and reperfusion (l/R) injury and the underlying mechanism. Methods: Sprague-Dawley rats were randomly divided into 4 groups: sham operated group (Sham), Sham with Picroside II treatment group (Sham+ Pic II), l/R group (l/R) and l/R with Picroside II treatment group (I/R+ Pic II). l/R model was established by rotating the left testis 720° in a clock-wise direction for 4 hours. The histopathologic and spermatogenetic evaluation was performed. The apoptosis changes and the levels of HO-1 (heme oxygenase-1), MPO (myeloperoxidase), NOX (NADPH oxidase), SOD (superoxide dismutase), XO (xanthine oxidase) and NOS (nitric oxide synthase) were measured. Results: The seminiferous tubules were damaged in l/R rats, but Picroside II alleviated the changes induced by l/R. The increased level of apoptosis was decreased by Picroside II (P=0.01, 9.05±0.35 vs. 4.85±0.25). The activities of HO-1, MPO, NOX, XO and MDA content were increased and the SOD activity was decreased in l/R (P<0.05) and could be reversed by Picroside II (P=0.03, 405.5±7.5 vs. 304±17U/mgprot; P=0.02, 0.99±0.05 vs. 0.52±0.04 mgprot; P=0.01, 260+7 vs. 189±2 mgprot; P=0.04, 10.95+0.55 vs. 8.75+0.35 U/mgprot; P=0.045, 6.8+0.7 vs. 3.75+0.35 mgprot; P=0.04, 44.5+3.5 vs. 57.5+3.5 mgprot). Western blot showed that the expression of iNOS, nNOS and eNOS were increased in l/R (P<0.05); however, they were decreased after Picroside II treatment (P<0.05). Conclusion: Picroside II attenuated testicular I/R injury in rats mainly through suppressing apoptosis and oxidative stress through reduction of nitric oxide synthesis.

Stabilization of P/CAF, as a ubiquitin ligase toward MDM2, suppresses mitotic cell death through p53-p21 activation in HCT116 cells with SIRT2 suppression.

We previously reported that the suppression of SIRT2, an NAD + -dependent protein deacetylases, induces p53 accumulation via degradation of p300 and the subsequent MDM2 degradation, eventually leading to apoptosis in HeLa cells. The present study identified a novel pathway of p53 accumulation by SIRT2 suppression in HCT116(p53+/+) cells in which SIRT2 suppression led to escape from mitotic cell death caused by spindle assembly checkpoint activation induced by microtubule inhibitors such as nocodazole but not apoptosis or G1 or G2 arrest. We found that SIRT2 interacts with P/CAF, a histone acetyltransferase, which also acts as a ubiquitin ligase against MDM2. SIRT2 suppression led to an increase of P/CAF acetylation and its stabilization followed by a decrease in MDM2 and activation of the p53-p21 pathway. Depression of mitotic cell death in HCT116(p53+/+) cells with SIRT2 suppression was released by suppression of P/CAF or p21. Thus, the P/CAF-MDM2-p53-p21 axis enables the escape from mitotic cell death and confers resistance to nocodazole in HCT116(p53+/+) cells with SIRT2 suppression. As SIRT2 has attracted attention as a potential target for cancer therapeutics for p53 regulation, the present study provides a molecular basis for the efficacy of SIRT2 for future cancer therapy based on p53 regulation. These findings also suggest an undesirable function of the SIRT2 suppression associated with activation of the p53-p21 pathway in the suppression of mitotic cell death caused by spindle assembly checkpoint activation.

Effects of ethanol on the anticancer function of doxorubicin in JJ012 cells.

AIM: Chondrosarcoma is difficult to treat because of resistance to conventional chemotherapy and radiotherapy. This study evaluated the effects of ethanol in combination with doxorubicin in chondrosarcoma cells. MATERIALS & METHODS: JJ012, was treated with doxorubicin alone or in combination with ethanol. Effects on cellular proliferation, migration, invasion, apoptosis, and the cell cycle were evaluated. RESULTS: Treatment of JJ012 cells with 100 mM ethanol and doxorubicin resulted in reduced cell growth, invasion, and migration. In addition, doxorubicin uptake into the nucleus was enhanced and p53 mRNA expression was upregulated in JJ012 cells. CONCLUSION: Ethanol combined with doxorubicin increased doxorubicin uptake in the nucleus and enhanced the effects of doxorubicin in JJ012 cells.

SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic fatty liver Mice.

Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is a member of cell death-inducing DFF45-like effector (CIDE) protein. The initial function of CIDE is the promotion of cell death and DNA fragmentation in mammalian cells. Cidea was recently reported to play critical roles in the development of hepatic steatosis. The purpose of present study is to determine the effect of chronic alcohol intake on Cidea expression in the livers of mice with alcoholic fatty liver disease. Cidea expression was significantly increased in the liver of alcohol-induced fatty liver mice. While, knockdown of Cidea caused lipid droplets numbers reduction. Next, we detected the activity of ALDH2 reduction and the concentration of serum acetaldehyde accumulation in our alcohol-induced fatty liver mice. Cidea expression was elevated in AML12 cells exposed to 100uM acetaldehyde. Interestingly, Dual-luciferase reporter gene assay showed that 100 uM acetaldehyde led to the activation of Cidea reporter gene plasmid which containing SRE element. What's more, the knockdown of SREBP1c suppressed acetaldehyde-induced Cidea expression. Overall, our findings suggest that Cidea is highly associated with alcoholic fatty liver disease and Cidea expression is specifically induced by acetaldehyde, and this up-regulation is most likely mediated by SREBP1c.