Non-alcoholic fatty liver disease (NAFLD) is the primary chronic liver disease worldwide, mainly manifested by hepatic steatosis. Hepatic lipids may be derived from dietary intake, plasma free fatty acid (FFA) uptake, or hepatic de novo lipogenesis (DNL). Currently, cellular and animal models of hepatocellular steatosis are widely used to study the pathogenesis of NAFLD and to investigate therapeutic agents. However, whether there are differences between the in vivo and in vitro models of the mechanisms that cause lipid accumulation has not been reported. We used OA/PA-induced NCTC 1469 cells and high-fat-diet-fed C57BL/6J mice to simulate a hepatocyte steatosis model of NAFLD and to detect indicators related to FFA uptake and DNL. In addition, when serological indicators were analysed in the mouse model, it was found that serum FASN levels decreased. The results revealed that, in the cellular model, indicators related to DNL were decreased, FASN enzyme activity was unchanged, and indicators related to FFA uptake were increased, including the high expression of CD36; while, in the animal model, indicators related to both FFA uptake and de novo synthesis were increased, including the high expression of CD36 and the increased protein levels of FASN with enhanced enzyme activity. In addition, after an analysis of the serological indicators in the mouse model, it was found that the serum levels of FASN were reduced. In conclusion, the OA/PA-induced cellular model can be used to study the mechanism of FFA uptake, whereas the high-fat-diet-induced mouse model can be used to study the mechanism of FFA uptake and DNL. Combined treatment with CD36 and FASN may be more effective against NAFLD. FASN in the serum can be used as one of the indicators for the clinical diagnosis of NAFLD.

Uncarboxylated osteocalcin (GluOC), a small-molecule protein specifically synthesized and secreted by osteoblasts, is important in the regulation of energy metabolism. In our previous study, GluOC was shown to be effective in ameliorating dyslipidemia and hepatic steatosis in KKAy mice. However, the underlying mechanism of GluOC action on hepatocytes has not been well validated. In this study, oleic acid/palmitic acid (OA/PA)-induced HepG2 and NCTC 1469 cells were used as non-alcoholic fatty liver disease (NAFLD) cell models, and triacylglycerol (TG) levels were measured by oil red O staining, Nile Red staining, and ELISA. The fatty acid synthesis-related protein expression was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. The results show that GluOC reduced triglyceride levels, and decreased the expression of sterol regulatory element-binding protein-1c (SREBP-1c) and stearyl-coenzyme A desaturase 1 (SCD1). si-SCD1 mimicked the lipid accumulation-reducing effect of GluOC, while overexpression of SCD1 attenuated the effect of GluOC. In addition, GluOC activated AMP-activated protein kinase (AMPK) phosphorylation to affect lipid metabolism in hepatocytes. Overall, the results of this study suggest that GluOC decreases SCD1 by activating AMPK to alleviate hepatocyte lipid accumulation, which provides a new target for improving NAFLD in further research.

This study aims to determine the effect of polysaccharides extracted from Enteromorpha intestinalis (EI) on the intestinal function of Sprague Dawley (SD) rats. The polysaccharides were extracted from the green alga using water and alkaline solution, where these extracts were named WPEI and APEI, respectively. The dried powder of EI was labeled as DPEI. Proximate compositions, minerals, and amino acids of the DPEI, WPEI, and APEI were determined. The growth-promoting effect of the polysaccharides on selected intestinal microflora was determined based on the plate count method. In contrast, the in vivo effect of DPEI and its polysaccharides on the intestinal function of the SD rats was determined. These rats were fed with 1% WPEI, APEI, and DPEI. The result showed that APEI had lower total sugars and total proteins content than the WPEI. WPEI did not contain arabinose. The WPEI and APEI also had a better ability to promote microbial growth than the DPEI. The in vivo study showed that WPEI improved intestinal peristalsis and other intestinal functions compared with the other rat groups. The average final body weight of the experimental rats treated with DPEI was also lower than the other groups. The pH value of the feces of all treated rats was lower than the control rats, and the moisture content of the fecal samples of these experimental groups was higher than the control group. Also, the intestinal activated carbon propulsion of the WPEI, APEI, and DPEI fed rats increased. Among the short-chain fatty acids content determined in the fecal samples, the propionic acid content of the WPEI group was significantly highest. Therefore, WPEI had the best effect in improving intestinal digestion.

Triple-negative breast cancer (TNBC) is an exceptionally aggressive malignancy with poor prognosis. Patients often have elevated mortality and recurrence rates, along with a pronounced risk of distant metastasis. Our earlier research highlighted the role of uncarboxylated osteocalcin (GluOC) in fueling TNBC cell proliferation and metastasis; however the molecular underpinnings of its impact on cancer invasion and migration remain enigmatic. In this study, we identified miR-143-3p as a significantly downregulated miRNA following GluOC treatment in TNBC cells. Notably, increased miR-143-3p has been linked to more favorable clinical outcomes in patients with TNBC. miR-143-3p expression has been shown to target and repress the expression of SP7. Furthermore, our findings indicate that GluOC modulates the miR-143-3p/PI3K/Akt signaling pathway, which in turn fosters the invasive and migratory capabilities of TNBC cells. In a xenograft animal model, we observed that the administration of GluOC led to a marked enhancement in tumor growth. Conversely, the delivery of miR-143-3p agomir was associated with a notable reduction in tumor growth. Notably, concurrent administration of miR-143-3p agomir and GluOC partially abrogated the tumorigenic effects induced by GluOC alone. Furthermore, GluOC downregulated the expression of miR-143-3p. Our study findings indicate that GluOC plays a role in the invasion and migration of TNBC cells by regulating the miR-143-3p/SP7 and miR-143-3p/PI3K/Akt axes. These insights suggest that GluOC and miR-143-3p are integral to the invasive and migratory processes of TNBC cells and may serve as promising targets for therapeutic interventions in TNBC.

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder associated with impaired lipid metabolism and oxidative stress. As a natural antioxidant and dithiol compound, α-lipoic acid (ALA) may play a beneficial role in modulating hepatic metabolism. This study investigates the potential mechanisms through which ALA may alleviate NAFLD. Methods: To construct an NAFLD model, NCTC 1469 cells were exposed to oleic acid and palmitic acid (OA/PA) and glucose for 24 h. RT-qPCR, Western blotting, and siRNA analyses were used to examine the effects and mechanisms of ALA. In vivo, C57BL/6J mice were fed a high-fat diet for 11 weeks and treated with ALA (200 mg/kg/day, intragastrical) for 4 weeks to evaluate its impact on NAFLD. Results: In NCTC 1469 cells exposed to OA/PA and glucose, ALA markedly reduced lipid accumulation by activating TFEB, which in turn promoted fatty acid β-oxidation and chaperone-mediated autophagy (CMA). Furthermore, ALA activated NRF2-dependent CMA and mitigated oxidative stress. Inhibition of AMPK or silencing of TFEB/NRF2 abolished these effects, indicating the key role of the AMPK–TFEB/NRF2 axis. In HFD-fed mice, ALA alleviated hepatic steatosis, serum lipid abnormalities, and liver injury, consistent with its activation of CMA and β-oxidation and reduction in oxidative stress via this pathway. Conclusions: ALA synchronously activates CMA, β-oxidation, and antioxidant responses via a unified AMPK pathway to reduce lipid accumulation and oxidative stress, providing a mechanistically integrated therapeutic strategy for NAFLD.

Introduction:: We explored the relationship between secondary degeneration of white matter (WM) tracts and motor outcomes after left basal ganglia infarction and investigated alterations in the diffusion indices of WM tracts in distal areas. Methods:: Clinical neurological evaluations were accomplished using the Fugl–Meyer scale (FMS). Then, the fractional anisotropy (FA) of the bilateral superior corona radiata (SCR), cerebral peduncle (CP), corticospinal tracts (CST), and corpus callosum (CC) were measured in all patients and control subjects. Results:: Regional-based analysis revealed decreased FA values in the ipsilesional SCR, CP, and CST of the patients, compared to the control subjects at 5- time points. The relative FA (rFA) values of the SCR, CP, and CST decreased progressively with time, the lowest values recorded at 90 days before increasing slightly at 180 days after stroke. Compared to the contralateral areas, the FA values of the ipsilesional SCR and CST areas were significantly decreased (P=0.023), while those of the CP decreased at 180 days (P=0.008). Compared with the values at 7 days, the rFA values of the ipsilesional SCR and CP areas were significantly reduced at 14, 30, and 90 days, while those in the CST area were significantly reduced at 14, 90, and 180 days. The CP rFA value at 7 days correlated positively with the FM scores at 180 days (r=0.469, P=0.037). Conclusion:: This study provides an objective, comprehensive, and automated protocol for detecting secondary degeneration of WM, which is important in understanding rehabilitation mechanisms after stroke.