Promote lipolysis in white adipocytes by magnetic hyperthermia therapy with Fe3O4microsphere-doped hydrogel.

Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4microsphere-doped composite hydrogel (Fe3O4microspheres @chitosan/ß-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol-gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytesin vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

Early childhood SARS experience leads to long-lasting impacts on adulthood mental health in China.

The association between pandemic experience and immediate mental health risks, such as depression, is well-documented, yet the long-term effects remain unclear. This study examines the impact of early childhood exposure to the 2003 SARS pandemic on adulthood mental health after 17 years in China, using data from the 2020 China Family Panel Studies (CFPS). The analysis included 6289 participants, aged 3 to 30 years during the SARS outbreak, with an average age of 35.3 years at the time of survey. Adulthood mental health was assessed using Center for Epidemiologic Studies Depression Scale (CESD) and an indicator of clinical depression. The severity of local SARS outbreaks was assessed by cumulative cases per 10,000 population. Results show that each additional case per 10,000 population was linked to a 1.617-fold (95% confidence interval (CI): 1.425-1.836) increase in odds of depression after 17 years for younger children (aged 3-12 years in 2003) relative to older cohorts (aged 13-30). This risk was higher in children from rural areas (adjusted odds ratio (aOR) 3.64; 95% CI 2.92-4.55), with poor physical health (1.98; 1.59-2.48), and from low-income families (2.87; 2.03-4.05). The childhood pandemic experience elevated the probability of developing depression-prone personality traits, which contributes to the enduring impact of childhood pandemic experiences on adulthood mental health. These findings highlight the long-lasting psychological impact of early-childhood pandemic exposure, underscoring the need for targeted interventions to mitigate its effects on the younger generation and emphasizing the importance of monitoring long-term mental health and personality development in children post-pandemics, particularly in light of COVID-19.

Liver transplantation for advanced-stage primary hepatic yolk sac tumor: A case report and literature review.

RATIONALE: Primary hepatic yolk sac tumors (YSTs) are rare in adults. Liver resection is an acknowledged treatment modality for primary hepatic YST. Liver transplantation may offer a possible cure for unresectable cases. PATIENT CONCERNS: We present a case of a 31-year-old woman with an abdominal mass who had abnormally elevated alpha-fetoprotein (AFP) levels (31,132 ng/mL; normal: 0-7 ng/mL). Contrast-enhanced computed tomography (CT) revealed large tumors located in both lobes of the liver, with arterial enhancement and venous washout. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT indicated increased 18F-FDG uptake (maximum standardized uptake value, 24.4) in the liver tumors and left middle intra-abdominal nodule. DIAGNOSES: The diagnosis was primary hepatic YST with metastasis to the greater omentum. INTERVENTIONS: The patient underwent orthotopic liver transplantation and intra-abdominal nodule resection after transarterial chemoembolization (TACE) as a bridge. Intraoperatively, an intra-abdominal nodule was confirmed in the greater omentum. Histopathological examination of the liver tumors revealed Schiller-Duval bodies. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib was administered, followed by four cycles of chemotherapy with bleomycin, etoposide, and cisplatin based on the next-generation sequencing results. OUTCOMES: The AFP level decreased to within the normal range. No evidence of tumor collapse was observed during the 34-month follow-up period. LESSONS: This case suggests that multimodal therapy dominated by liver transplantation, including preoperative TACE, postoperative adjuvant chemotherapy, and TRK inhibitors, is an effective treatment modality for unresectable primary hepatic YST.

The oncogenic role of NF1 in gallbladder cancer through regulation of YAP1 stability by direct interaction with YAP1.

BACKGROUND: Gallbladder cancer (GBC) is the most prevalent and invasive biliary tract malignancy. As a GTPase-activating protein, Neurofibromin 1 (NF1) is a tumor suppressor that negatively regulates the RAS signaling pathway, and its abnormality leads to neurofibromatosis type 1 (NF-1) disease. However, the role of NF1 playing in GBC and the underlying molecular mechanism has not been defined yet. METHODS: A combination of NOZ and EH-GB1 cell lines as well as nude mice, were utilized in this study. mRNA expression and protein levels of NF1 and YAP1 were evaluated by quantitative real-time PCR (qRT-PCR), western blot (WB), and immunohistochemistry (IHC). In vitro and in vivo assays were performed to explore the biological effects of NF1 in NOZ and EH-GB1 cells via siRNA or lv-shRNA mediated knockdown. Direct interaction between NF1 and YAP1 was detected by confocal microscopy and co-immunoprecipitation (Co-IP), and further confirmed by GST pull-down assay and isothermal titration calorimetry assay (ITC). The stability of proteins was measured by western blot (WB) in the presence of cycloheximide. RESULTS: This study showed that a higher level of NF1 and YAP1 was found in GBC samples than in normal tissues and associated with worse prognoses. The NF1 knockdown impaired the proliferation and migration of NOZ in vivo and in vitro by downregulating YAP1 expression. Moreover, NF1 co-localized with YAP1 in NOZ and EH-GB1 cells, and the WW domains of YAP1 specifically recognized the PPQY motif of NF1. The structural modeling also indicated the hydrophobic interactions between YAP1 and NF1. On the other hand, YAP1 knockdown also impaired the proliferation of NOZ in vitro, phenocopying the effects of NF1 knockdown. Overexpression of YAP1 can partially rescue the impaired proliferation in NF1 stably knockdown cells. In mechanism, NF1 interacted with YAP1 and increased the stability of YAP1 by preventing ubiquitination. CONCLUSIONS: Our findings discovered a novel oncogenic function of NF1 by directly interacting with YAP1 protein and stabilizing YAP1 to protect it from proteasome degradation in NOZ cells. NF1 may serve as a potential therapeutic target in GBC.

NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-ß/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer.

Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-ß/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR-Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-ß, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-ß/Smad3 pathway.

LncRNAs as epigenetic regulators of epithelial to mesenchymal transition in pancreatic cancer.

Pancreatic cancer is the leading cause of cancer-related mortality because of tumor metastasis. Activation of the epithelial-to-mesenchymal transition (EMT) pathway has been confirmed to be an important driver of pancreatic cancer progression from initiation to metastasis. Long noncoding RNAs (lncRNAs) have been reported to exert essential physiological functions in pancreatic cancer progression by regulating the EMT program. In this review, we have summarized the role of EMT-related lncRNAs in human pancreatic cancer and the potential molecular mechanisms by which lncRNAs can be vital epigenetic regulators of epithelial to mesenchymal transition. Specifically, EMT-activating transcription factors (EMT-TFs) regulate EMT via TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT pathways. In addition, the interaction between lncRNAs and HIF-1α and m6A RNA methylation also have an impact on tumor metastasis and EMT in pancreatic cancer. This review will provide insights into lncRNAs as promising biomarkers for tumor metastasis and potential therapeutic strategies for pancreatic cancer.

Nomogram based on prognostic nutrition index and Chest CT imaging signs predicts lymph node metastasis in NSCLC patients.

OBJECTIVE: To establish and validate a model capable of predicting lymph node metastasis (LNM) of non-small cell lung cancer (NSCLC) patients. METHODS: Preoperative clinical and CT imaging data on patients with NSCLC undergoing surgery were retrospectively analyzed. A model was developed using a training cohort of 290 patients. The univariate analysis followed by dichotomous logistic regression was performed to estimate different risk factors of lymph node metastasis, and a nomogram was constructed. Using another testing cohort of 120 patients, the performance of the nomogram was validated using several evaluation methods and indices and evaluated including via the area under the curve (AUC), calibration curve, Hosmer-Lemeshow test and decision curve analysis (DCA). RESULTS: CT-based imaging signs were important independent risk factors for lymph node metastasis in NSCLC patients. The possible risk factors also included four other independent risk factors through dichotomous logistic regression, i.e., age, SIRI, PNI and CEA, which were filtered and included in the nomogram. Nomogram yields AUC values of 0.828 [95% confidence interval (CI): 0.778-0.877] in the training cohort and 0.816 (95% CI: 0.737-0.895) in the validation cohort, respectively. The calibration curves showed high agreement in both the training and validation cohorts. At the threshold probability of 0-0.8, the nomogram increases the net outcomes compared to the treat-none and treat-all lines in the decision curve. CONCLUSIONS: The nomogram based on the PNI and CT images signs holds promise as a novel and accurate tool for predicting the LNM in NSCLC patients and guiding intraoperative lymph node dissection.

Non-contrast CT-based radiomic signature for screening thoracic aortic dissections: a multicenter study.

OBJECTIVE: To develop a non-contrast CT-based radiomic signature to effectively screen for thoracic aortic dissections (ADs). METHODS: We retrospectively enrolled 378 patients who underwent non-contrast chest CT scans along with CT angiography or MRI from 4 medical centers. The training and validation sets were from 3 centers, while the external test set was from a 4th center. Radiomic features were extracted from non-contrast CT images. The radiomic signature was created on the basis of selected features by a logistic regression algorithm. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were conducted to assess the predictive ability of radiomic signature. RESULTS: The radiomic signature demonstrated AUCs of 0.91 (95% confidence interval [CI], 0.86-0.95) in the training set, 0.92 (95% CI, 0.86-0.98) in the validation set, and 0.90 (95% CI, 0.82-0.98) in the external test set. The predicted diagnosis was in good agreement with the probability of thoracic AD. In the external test group, the diagnostic accuracy, sensitivity, specificity, PPV, and NPV were 90.5%, 85.7%, 91.7%, 70.6%, and 96.5%, respectively. CONCLUSIONS: A radiomic signature based on non-contrast CT images can effectively predict thoracic ADs. This method may serve as a potential screening tool for thoracic ADs. KEY POINTS: • The non-contrast CT-based radiomic signature can effectively predict the thoracic aortic dissections. • This radiomic signature shows better predictive performance compared to the current clinical model. • This prediction method may be a potential tool for screening thoracic aortic dissections.

Prognostic implication of NQO1 overexpression in hepatocellular carcinoma.

To explore the role of NQO1 overexpression for prognostic implication in hepatocellular carcinoma (HCC), NQO1 mRNA levels were detected in HCC fresh tissue samples of HCC and nontumor tissues, respectively. One hundred fifty-six cases of HCC meeting strict follow-up criteria were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological features of HCC were evaluated using χ2 tests, survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient 5-year survival was analyzed using Cox proportional hazards analysis. In results, the levels of NQO1 mRNA were significantly up-regulated in 14 fresh tissue samples of HCC. Immunohistochemical analysis showed that the NQO1 expression and overexpression rates were significantly higher in HCC samples compared with either adjacent nontumor tissues or normal liver tissues. NQO1 overexpression correlated to tumor size, venous infiltration and late pTNM stage of HCC. NQO1 overexpression was also related to low disease-free survival and 5-year survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with NQO1 overexpression were significantly lower than those of patients without NQO1 expression. Further analysis using a Cox proportional hazards regression model revealed that NQO1 expression emerged as a significant independent hazard factor for the 5-year survival rate of patients with HCC. Therefore, NQO1 plays an important role in the progression of HCC. NQO1 may potentially be used as an independent biomarker for prognostic evaluation of HCC.

The role of DEK protein in hepatocellular carcinoma for progression and prognosis.

OBJECTIVE: The study aim was to explore the role of DEK in tumor progression and prognostic of hepatocellular carcinoma (HCC). METHODOLOGY: DEK protein in 178 samples of HCC was evaluated by immunohistochemical method. Additionally, the correlation between DEK expression and the clinicopathological features was evaluated by x(2) test or Fisher's exact test, the survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also by the Cox analysis. RESULTS: DEK protein expression was noted in 86 cases of HCC, and 61 cases of normal liver tissues. DEK positive rate were closely correlated with the tumor size, grade, AJCC stage and survival rate (P<0.05, respectively). HCC with large tumor, lower grade, and late-stage, concomitant with DEK expression, had the lowest 5-years survival rate than HCC with above factors but without DEK expression (P<0.01, respectively). DEK expression emerged as significant independent hazard factors for survival in HCC (P<0.01). CONCLUSIONS: DEK could promote aggressiveness of cancer behavior, and hence poor prognosis of the HCC. It might be an independent poor prognostic factor and can serve as a useful new therapeutic biomarker.

Insulin-like growth factor-II mRNA-binding protein 3 predicts a poor prognosis for colorectal adenocarcinoma.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) has been recently identified as a marker of aggressive behavior in several types of tumors. The aim of the present study was to detect the expression of the IMP3 protein in colorectal adenocarcinoma (CRA) and to identify a correlation with the clinicopathological features of the disease. IMP3 was evaluated in 186 samples of CRA using immunohistochemical methods. The correlation between IMP3 expression and the clinicopathological features of colorectal cancer was evaluated by the χ2 and Fisher's exact tests. Survival rates were calculated using the Kaplan-Meier method and the correlation between IMP3 protein expression and the prognosis of patients with CRA was analyzed using Cox analysis. Of the 186 adjacent normal mucosa (ANM) cases, the 22 that exhibited dysplasia demonstrated weak IMP3 expression and the 164 without dysplasia showed no expression. Of the 186 CRA cases, immunohistochemical staining for IMP3 was observed in 143 cases (76.9%). A comparison of IMP3 expression between the CRA and ANM samples revealed stronger immunohistochemical reactivity in the CRA tissues (P<0.01). High IMP3 expression was associated with differentiation, lymphoid metastasis, TNM stage, Ki-67 labeling index and a poor patient outcome (P<0.05). In the multivariate analysis, IMP3 emerged as an independent predictor of survival. The present study demonstrated that IMP3 is able to promote the aggressiveness of cancer behavior, resulting in a poor prognosis for patients with CRA. Consequently, IMP3 may be regarded as a novel proliferation and prognostic indicator for patients with CRA.

Association between ezrin protein expression and the prognosis of colorectal adenocarcinoma.

Ezrin is involved in maintaining cell structure and cell motility. Expression levels of the ezrin gene correlate with numerous human malignancies. The aim of this study was to explore the role of ezrin in tumor progression and the prognostic evaluation of colorectal adenocarcinoma (CRA). The levels of ezrin protein in 186 CRA samples were evaluated using immunohistochemistry. Furthermore, the correlation between the expression of ezrin and the clinicopathological features of CRA was evaluated with the χ2 and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method, and the correlation between prognostic factors and patient survival was calculated by Cox analysis. Ezrin protein expression demonstrated an immunohistochemical cytoplasmic staining pattern in CRA. The difference between the positive rate of ezrin expression in CRA (38.7%, 72/186) and the adjacent normal mucosal tissues was deemed to be statistically significant (91.9%, 171/186; P=0.000). The positive rate of ezrin expression in cases with a large tumor, serosal invasion, lymph node (LN) metastasis, high LN ratio (LNR) and at a late tumor stage was significantly lower than in cases without these factors (P=0.044, P=0.032, P=0.002, P=0.011 and P=0.000, respectively). The 5-year survival rate of CRA without ezrin expression was lower than CRA with expression (P=0.000). Furthermore, analysis by Kaplan-Meier demonstrated that CRA cases with poor differentiation, serosal invasion and at a late tumor stage combined with no ezrin expression had a lower survival rate than cases that had these factors plus ezrin expression (P=0.000, respectively). Additionally, the non-expression of ezrin emerged as a significant independent prognostic factor in CRA prognosis (HR, 0.562; 95% CI, 0.404-0.783; P=0.001), in addition to the LNR (HR, 0.589; 95% CI, 0.369-0.939; P=0.026) and tumor stage (HR, 0.655; 95% CI, 0.487-0.880; P=0.005). This study demonstrated that ezrin may be useful to identify at-risk patients who may benefit from a more aggressive adjuvant therapy following tumor resection. Ezrin may serve as a useful therapeutic biomarker.

Systematic functional comparative analysis of four single-stranded DNA-binding proteins and their affection on viral RNA metabolism.

The accumulation of single-stranded DNA-binding (SSB) proteins is essential for organisms and has various applications. However, no study has simultaneously and systematically compared the characteristics of SSB proteins. In addition, SSB proteins may bind RNA and play an unknown biological role in RNA metabolism. Here, we expressed a novel species of SSB protein derived from Thermococcus kodakarensis KOD1 (KOD), as well as SSB proteins from Thermus thermophilus (TTH), Escherichia coli, and Sulfolobus Solfataricus P2 (SSOB), abbreviated kod, tth, bl21, and ssob, respectively. These SSB proteins could bind ssDNA and viral RNA. bl21 resisted heat treatment for more than 9 h, Ssob and kod could withstand 95°C for 10 h and retain its ssDNA- and RNA-binding ability. Four SSB proteins promoted the specificity of the DNA polymerase in PCR-based 5- and 9-kb genome fragment amplification. kod also increased the amplification of a 13-kb PCR product, and SSB protein-bound RNA resisted Benzonase digestion. The SSB proteins could also enter the host cell bound to RNA, which resulted in modulation of viral RNA metabolism, particularly ssob and bl21.

The correlation between insulin-like growth factor II mRNA binding protein 3 expression in hepatocellular carcinoma and prognosis.

BACKGROUND/AIMS: The study aims to explore the expression of IMP3 in HCC and the correlation between its expression and prognosis. METHODOLOGY: We collected several clinical and pathological files including 92 cases of HCC and 58 cases of adjacent liver tissues. Expression of IMP3 in these tissues was detected by immunohistochemistry, while compared with clinicopathological characteristics and expression of Ki-67. A χ2 test was used to analyze the relationship between expression of IMP3 and clinicοpathologic factors. The Kaplan-Meier survival curve was used to calculate survival rate. A Cox analysis was used to evaluate the relationship between index and patients' lifetime. RESULTS: The positive rate of IMP3 in HCC tissues was significantly higher than that in adjacent tissues. The expression of IMP3 was related to the histological differentiation of HCC, metastasis, the stage of ACJJ, the expression of Ki-67 and survival. The ACJJ stage, metastases and the expression of IMP3 were independent factors for the HCC patients' survival. CONCLUSIONS: IMP3, which is associated with tumor formation, invasion, tumor cell proliferation and so on, may become the target for inhabiting cell proliferation and the biomarker for predicting prognosis.