Ketone bodies promote epididymal white adipose expansion to alleviate liver steatosis in response to a ketogenic diet.

Liver can sense the nutrient status and send signals to other organs to regulate overall metabolic homoeostasis. Herein, we demonstrate that ketone bodies act as signals released from the liver that specifically determine the distribution of excess lipid in epididymal white adipose tissue (eWAT) when exposed to a ketogenic diet (KD). An acute KD can immediately result in excess lipid deposition in the liver. Subsequently, the liver sends the ketone body ß-hydroxybutyrate (BHB) to regulate white adipose expansion, including adipogenesis and lipogenesis, to alleviate hepatic lipid accumulation. When ketone bodies are depleted by deleting 3-hydroxy-3-methylglutaryl-CoA synthase 2 gene in the liver, the enhanced lipid deposition in eWAT but not in inguinal white adipose tissue is preferentially blocked, while lipid accumulation in liver is not alleviated. Mechanistically, ketone body BHB can significantly decrease lysine acetylation of peroxisome proliferator-activated receptor gamma in eWAT, causing enhanced activity of peroxisome proliferator-activated receptor gamma, the key adipogenic transcription factor. These observations suggest that the liver senses metabolic stress first and sends a corresponding signal, that is, ketone body BHB, to specifically promote eWAT expansion to adapt to metabolic challenges.

Repetitive transcranial magnetic stimulation can improve the fixation of eyes rather than the fixation preference in children with autism spectrum disorder.

Background: Transcranial magnetic stimulation (TMS) has been introduced into the intervention of autism spectrum disorders (ASD) as a possible new therapeutic option for modifying pathological neuroplasticity. However, the stimulating protocols of rTMS for ASD have not been approved unanimously, which affects the clinical popularization and application of rTMS. In addition, there is little research on the improvement of social processing of autistic children by rTMS. Methods: We explored the clinical efficacy of rTMS and improvement of face processing with the protocol of left high-frequency and right low-frequency on bilateral dorsolateral prefrontal cortex (DLPFC), with a sample of 45 ASD participants aged 2-18. Results: Our results showed that both the score on the Childhood Autism Rating Scale (CARS) and the fixations on the eyes of the human faces improved by two-session rTMS intervention, except for the percentage of eyes fixation. The mediation analysis indicated the item of "Adaptation to Change" of CARS mediated dominantly the improvement of eye-gaze behavior of ASD participants by rTMS. Conclusion: Our study revealed the mechanism of rTMS in improving the eye-gaze behavior of the autism population, deepened the understanding of the function of rTMS in treating autistic social disorders, and provided a reference for combined treatment for ASD.

Exercise is the dominant factor affecting the development of teenagers' eyesight-Based on the Bayesian model averaging.

Objective: The model uncertainty may result in inconsistency about the environmental factors of myopia among students, and the Bayesian model average (BMA) is an effective way to eliminate it. We aimed to explore the influencing factors of myopia in primary and middle school students by BMA. Methods: The data came from the 2021 National Surveillance of Common Diseases and Health Influencing Factors of students. By stratified random cluster sampling, the physical and mental health status of students in Tianjin and the factors affecting their physical health, such as diet, exercise, mental stress, school bullying, sleep time, and internet use, were investigated. The sample consisted of 8,457 primary school students, 8,191 junior middle school students, and 5,901 senior middle school students. Besides the physical examination, we used computer optometry (non-ciliary paralysis) to screen myopia. And we used BMA to select the risk factors through the BMS package in R. Results: The exercise was the only factor that affected the eyesight of junior and senior middle schoolers by BMA, with the posterior probability of 0.9736 and 0.9762, but not for the primary students. And we failed to select variables that affected eyesight in grades 4-6 of primary school. Conclusion: The exercise was a strong influencing factor for the eyesight of students in Tianjin's junior and senior middle schools.

The balance of protein farnesylation and geranylgeranylation during the progression of nonalcoholic fatty liver disease.

Protein prenylation is an essential posttranslational modification and includes protein farnesylation and geranylgeranylation using farnesyl diphosphate or geranylgeranyl diphosphate as substrates, respectively. Geranylgeranyl diphosphate synthase is a branch point enzyme in the mevalonate pathway that affects the ratio of farnesyl diphosphate to geranylgeranyl diphosphate. Abnormal geranylgeranyl diphosphate synthase expression and activity can therefore disrupt the balance of farnesylation and geranylgeranylation and alter the ratio between farnesylated and geranylgeranylated proteins. This change is associated with the progression of nonalcoholic fatty liver disease (NAFLD), a condition characterized by hepatic fat overload. Of note, differential accumulation of farnesylated and geranylgeranylated proteins has been associated with differential stages of NAFLD and NAFLD-associated liver fibrosis. In this review, we summarize key aspects of protein prenylation as well as advances that have uncovered the regulation of associated metabolic patterns and signaling pathways, such as Ras GTPase signaling, involved in NAFLD progression. Additionally, we discuss unique opportunities for targeting prenylation in NAFLD/hepatocellular carcinoma with agents such as statins and bisphosphonates to improve clinical outcomes.

G Protein-Coupled Receptor 30 Mediates the Anticancer Effects Induced by Eicosapentaenoic Acid in Ovarian Cancer Cells.

PURPOSE: While numerous epidemiological studies have indicated that omega-3 polyunsaturated fatty acids have anticancer properties in various cancers, the effects and mechanisms of eicosapentaenoic acid (EPA) in ovarian cancer cell growth are poorly understood. MATERIALS AND METHODS: ES2 ovarian clear cell carcinoma cells and SKOV3 adenocarcinoma cells were treated with palmitic acid or EPA, followed by flow cytometry and cell counting to measure apoptosis and proliferation, respectively. A modified protein lipid overlay assay was used to further verify whether EPA was a ligand of G protein-coupled receptor 30 (GPR30) in ES2 cells. The levels of apoptosis-related genes, phosphorylated AKT, and phosphorylated ERK1/2 were detected to explore the underlying mechanism. Finally, inhibitory effect of EPA on tumor growth via GPR30 was determined in vitro and in vivo. RESULTS: EPA suppressed ES2 ovarian clear cell carcinoma cells growth via GPR30, a novel EPA receptor, by inducing apoptosis. As a ligand of GPR30, EPA activated the GPR30-cAMP- protein kinase A signaling pathway. When GPR30 was suppressed by siRNA or its inhibitor G15, the antiproliferative action of EPA was impaired. Furthermore, EPA inhibited tumor growth by blocking the activation of AKT and ERK. In the mouse xenograft model, EPA decreased tumor volume and weight through GPR30 by blocking tumor cell proliferation. CONCLUSION: These results confirm that EPA is a tumor suppressor in human ovarian clear cell carcinoma cells and functions through a novel fatty acid receptor, GPR30, indicating a mechanistic linkage between omega-3 fatty acids and cancers.

Liver governs adipose remodelling via extracellular vesicles in response to lipid overload.

Lipid overload results in lipid redistribution among metabolic organs such as liver, adipose, and muscle; therefore, the interplay between liver and other organs is important to maintain lipid homeostasis. Here, we show that liver responds to lipid overload first and sends hepatocyte-derived extracellular vesicles (EVs) targeting adipocytes to regulate adipogenesis and lipogenesis. Geranylgeranyl diphosphate synthase (Ggpps) expression in liver is enhanced by lipid overload and regulates EV secretion through Rab27A geranylgeranylation. Consistently, liver-specific Ggpps deficient mice have reduced fat adipose deposition. The levels of several EV-derived miRNAs in the plasma of non-alcoholic fatty liver disease (NAFLD) patients are positively correlated with body mass index (BMI), and these miRNAs enhance adipocyte lipid accumulation. Thus, we highlight an inter-organ mechanism whereby the liver senses different metabolic states and sends corresponding signals to remodel adipose tissue to adapt to metabolic changes in response to lipid overload.

Decreased serum complement component 4 levels in patients with schizophrenia.

Dysregulation of the immune system in mental disease, particularly complement component 4 (C4), which may be associated with schizophrenia, has been repeatedly observed. This study investigated the association between the level of serum component 4 and schizophrenia. Data were derived from a case-control association study of 40 unrelated adult patients with schizophrenia and 40 matched healthy controls. The component 4 level in serum was measured for comparative analysis by a component 4 enzyme-linked immunosorbent assay kit. Our findings suggest that the serum component 4 level is lower in patients with schizophrenia than in the controls, and the results apply to both males and females. Our results will lay an important foundation for establishing diagnostic methods and provide feasible and reliable evidence for the clinical treatment of schizophrenia.

Anti-inflammatory activity of cecropin-A2 from Musca domestica.

This study aimed to investigate the anti-inflammatory activity of Musca domestica cecropin-A2 (Mdc-A2) toward Staphylococcus aureus (S. aureus) to learn more about their immunological functions. RAW264.7 cells were transfected with recombinant lentiviruses introduce pLEX-Mdc-A2into the RAW264.7 cell line (RAW-Mdc-A2). The RAW264.7 cell line with empty pLEX (RAW-pLEX) was produced in the same manner as a negative control. Real-time quantitative reverse transcription PCR (RT-PCR) was performed to analyze the mRNA expression of TNF-a, IL-1ß, NFκB-1 and NFκB-2 in S. aureus-stimulated RAW-Mdc-A2 cells and RAW-pLEX cells in untreated cells and cells treated for 3 h, 6 h, 12 h and 24 h. RT-PCR was performed to analyze the mRNA expression of TNF-a, NFκB-1 and NFκB-2 stimulated by Lipoteichoic acid (LTA). Production of TNF-a was detected by enzyme-linked immunosorbent assay (ELISA). Colony counts were used to calculate the number of CFU per mL of cell culture supernatants. The results showed that compared to RAW-pLEX cells, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by S. aureus significantly down-regulated the mRNA expression of TNF-a transcript variant 1 (TNF-a-tv-1) at 6 h and 12 h and the mRNA expression of TNF-a transcript variant 2 (TNF-a-tv-2) at 3 h, 6 h and 12 h. Compared to RAW-pLEX cells, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by S. aureus significantly down-regulated the mRNA expression of IL-1ß-T at 3 h, 6 h and 12 h as well as the mRNA expression of IL-1ß at 3 h and 6 h. The expression and production of TNF-a and bacterial burden of cell culture supernatants were significantly down-regulated in RAW-Mdc-A2 cells stimulated by S. aureus, and the expression and production of TNF-a were significantly down-regulated in RAW-Mdc-A2 cells stimulated by LTA. Compared to RAW-pLEX cells, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by S. aureus significantly down-regulated the mRNA expression of NFκB-1 at 3 h, 6 h and 12 h as well as the mRNA expression of NFκB-2 at 6 h. Additionally, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by LTA significantly down-regulated the mRNA expression of NFκB-1. In conclusion, Mdc-A2 possesses potent anti-inflammatory activity and potent antimicrobial activity. Additionally, Mdc-A2 may interact with LTA and execute strong anti-inflammatory activity by blocking the activation of NF-κB signaling pathways.

[Correlation of Speciated Mercury with Carbonaceous Components in Atmospheric PM2.5 in Shengsi Region].

PM2.5 samples of four seasons were collected from Nov. 2014 to Aug. 2015 at the site of Shengsi island in Zhoushan islands. Mercury (Hg) and speciated mercury concentrations in PM2.5 samples were measured by Atomic Fluorescence Spectrometry (AFS-9130, China) after digestion with CEM Mars Xpress (PyNN Corporation, USA). The concentrations of organic carbon (OC) and elemental carbon (EC) in PM2.5 samples were determined by thermal/optical carbon analyzer (DRI, USA). The results showed that the daily concentrations of PM2.5-bounded mercury (PBM) ranged from 0.02 to 1.25 ng·m-3. Moreover, the mass content of PBM was (12.46±18.79) µg·g-1, which was higher than those in continental cities. ANOVA analysis result suggested that the highest average mass concentrations of PBM occurred in fall, sequentially followed by spring, winter and summer. Higher concentrations of PBM were in fall and spring, which might be related to biomass burning. In addition, RPM took the highest fraction of 53.1% in PBM, followed by HPM (27.3%) and EPM (19.7%), which might be resulted from the complicated composition of marine aerosols. The strong correlations among OC, EC and PBM indicated that carbonaceous composition may affect the transport of Hg in the atmosphere. The ratio of OC/EC represents atmospheric photo-oxidation capacity, so the positive correlation between OC/EC ratio and HPM indicated that HPM was resulted from atmospheric gas-particle transformation. The negative correlation between Char-EC/soot-EC and mercury species indicated that the atmospheric particle-bounded mercury might come mainly from the input of external mercury sources.

Combined transjugular intrahepatic portosystemic shunt and other interventions for hepatocellular carcinoma with portal hypertension.

AIM: To evaluate combination transjugular intrahepatic portosystemic shunt (TIPS) and other interventions for hepatocellular carcinoma (HCC) and portal hypertension. METHODS: Two hundred and sixty-one patients with HCC and portal hypertension underwent TIPS combined with other interventional treatments (transarterial chemoembolization/transarterial embolization, radiofrequency ablation, hepatic arterio-portal fistulas embolization, and splenic artery embolization) from January 1997 to January 2010 at Beijing Shijitan Hospital. Two hundred and nine patients (121 male and 88 female, aged 25-69 years, mean 48.3 ± 12.5 years) with complete clinical data were recruited. We evaluated the safety of the procedure (procedure-related death and serious complications), change of portal vein pressure before and after TIPS, symptom relief [e.g., ascites, hydrothorax, esophageal gastric-fundus variceal bleeding (EGVB)], cumulative rates of survival, and distributary channel restenosis. The characteristics of the patients surviving ≥ 5 and < 5 years were also analyzed. RESULTS: The portosystemic pressure was decreased from 29.0 ± 4.1 mmHg before TIPS to 18.1 ± 2.9 mmHg after TIPS (t = 69.32, P < 0.05). Portosystemic pressure was decreased and portal hypertension symptoms were ameliorated. During the 5 year follow-up, the total recurrence rate of resistant ascites or hydrothorax was 7.2% (15/209); 36.8% (77/209) for EGVB; and 39.2% (82/209) for hepatic encephalopathy. The cumulative rates of distributary channel restenosis at 1, 2, 3, 4, and 5 years were 17.2% (36/209), 29.7% (62/209), 36.8% (77/209), 45.5% (95/209) and 58.4% (122/209), respectively. No procedure-related deaths and serious complications (e.g., abdominal bleeding, hepatic failure, and distant metastasis) occurred. Moreover, Child-Pugh score, portal vein tumor thrombosis, lesion diameter, hepatic arterio-portal fistulas, HCC diagnosed before or after TIPS, stent type, hepatic encephalopathy, and type of other interventional treatments were related to 5 year survival after comparing patient characteristics. CONCLUSION: TIPS combined with other interventional treatments seems to be safe and efficacious in patients with HCC and portal hypertension.

Transjugular intrahepatic portosystemic shunt for severe jaundice in patients with acute Budd-Chiari syndrome.

AIM: To evaluate the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) for severe jaundice secondary to acute Budd-Chiari syndrome (BCS). METHODS: From February 2009 to March 2013, 37 patients with severe jaundice secondary to acute BCS were treated. Sixteen patients without hepatic venule, hepatic veins (HV) obstruction underwent percutaneous angioplasty of the inferior vena cava (IVC) and/or HVs. Twenty-one patients with HV occlusion underwent TIPS. Serum bilirubin, liver function, demographic data and operative data of the two groups of patients were analyzed. RESULTS: Twenty-one patients underwent TIPS and the technical success rate was 100%, with no technical complications. Sixteen patients underwent recanalization of the IVC and/or HVs and the technical success rate was 100%. The mean procedure time for TIPS was 84.0±12.11 min and angioplasty was 44.11±5.12 min (P<0.01). The mean portosystemic pressure in the TIPS group decreased significantly from 40.50±4.32 to 16.05±3.50 mmHg (P<0.01). The mean portosystemic pressure gradient decreased significantly from 33.60±2.62 to 7.30±2.21 mmHg (P<0.01). At 8 wk after the procedures, in the TIPS group, total bilirubin (TBIL) decreased significantly from 266.24±122.03 before surgery to 40.11±3.52 µmol/L (P<0.01) and direct bilirubin (DBIL) decreased significantly from 194.22±69.82 µmol/L to 29.82±3.10 µmol/L (P<0.01). In the angioplasty group, bilirubin returned to the normal range, with TBIL decreased significantly from 258.22±72.71 µmol/L to 13.33±3.54 µmol/L (P<0.01) and DBIL from 175.08±39.27 to 4.03±1.74 µmol/L (P<0.01). Liver function improved faster than TBIL. After 2 wk, in the TIPS group, alanine aminotransferase (ALT) decreased significantly from 50.33±40.61 U/L to 28.67±7.02 U/L (P<0.01) and aspartate aminotransferase (AST) from 49.46±34.33 U/L to 26.89±8.68 U/L (P<0.01). In the angioplasty group, ALT decreased significantly from 51.56±27.90 to 14.22±2.59 µmol/L (P<0.01) and AST from 60.66±39.89 µmol/L to 8.18±1.89 µmol/L (P<0.01). After mean follow-up of 12.6 mo, there was no recurrence of jaundice in either group. CONCLUSION: Severe jaundice is not a contraindication for TIPS in patients with acute BCS and TIPS is appropriate for severe jaundice due to BCS.