Frigid Zone Medicine

Seasonal variation in dietary intake and its association with obesity-related chronic diseases in northeast China

Cheng Wang, Zican Li, Dongwei Guan, Hongxin Fu, Rennan Feng

2024, 4(3): 129-136. doi: 10.1515/fzm-2024-0014

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Abstract:
Objective The objective of this study was to assess seasonal changes in dietary and nutrient intake of residents (18-75 years old) in Northeast China during summer and winter, and to explore the associations between fatty acids, phytosterols, and the prevalence of obesity-related chronic diseases, particularly obesity, hyperlipidemia, and NAFLD. Methods A total of 4773 participants from the Internet-based Dietary Questionnaire for Chinese (IDQC) were included in this study. Dietary intake information was collected using a validated food frequency questionnaire. Student's t-test or Mann-Whitney U-test was used to analyze continuous variables, while Chi-squared tests were used to compare categorical variables. Multivariable logistic regression was employed to assess the relationship between fatty acids, phytosterols, and obesity-related chronic diseases. Results The mean consumption of legumes, vegetables, fruits, nuts, dairy products, fish, condiments, energy, protein, fat, and carbohydrate differed significantly between summer and winter (P < 0.05). Significant inverse associations were found between both fatty acids and phytosterols and obesity-related chronic diseases in multivariate adjusted models. Summer polyunsaturated fatty acid (PUFA) intake was negatively associated with the prevalence of hyperlipidemia (Q4, OR, 0.515; 95%CI, 0.283-0.921; P < 0.05) and non-alcoholic fatty liver disease (NAFLD) (Q4, OR, 0.331; 95%CI, 0.176-0.599; P < 0.001). Phytosterols intake was negatively associated with the prevalence of obesity (Q4, OR, 0.603; 95%CI, 0.414-0.873; P < 0.05), hyperlipidemia (Q4, OR, 0.420; 95%CI, 0.233-0.731; P < 0.001), and NAFLD (Q4, OR, 0.206; 95%CI, 0.111-0.360; P < 0.001) during the summer. Conclusions Higher PUFA intake was associated with a lower prevalence of obesity, hyperlipidemia, and NAFLD. Phytosterol intake was inversely associated with the prevalence of hyperlipidemia and NAFLD. These findings suggest that the associations between PUFA and phytosterols and the prevalence of obesity-related chronic diseases may be influenced by seasonal differences in food intake.

Circulating CCRR serves as potential novel biomarker for predicting acute myocardial infarction

Lina Xuan, Huishan Luo, Shu Wang, Guangze Wang, Xingmei Yang, Jun Chen, Jianjun Guo, Xiaomeng Duan, Xiufang Li, Hua Yang, Shengjie Wang, Hailong Zhang, Qingqing Zhang, Shulei Liu, Yongtao She, Kai Kang, Lihua Sun

2024, 4(3): 137-151. doi: 10.1515/fzm-2024-0015

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Abstract:
Objective Cold regions exhibit a high prevalence of cardiovascular disease, particularly acute myocardial infarction (AMI), which is one of the leading causes of death associated with cardiovascular conditions. Cardiovascular disease is closely linked to the abnormal expression of long non-coding RNA (lncRNA). This study investigates whether circulating levels of lncRNA cardiac conduction regulatory RNA (CCRR) could serve as a biomarker for AMI. Materials and methods We measured circulating CCRR from whole blood samples collected from 68 AMI patients and 69 non-AMI subjects. An AMI model was established using C57BL/6 mice. Quantitative reverse transcription PCR (qRT-PCR) was used to assess CCRR expression. Exosomes were isolated from cardiomyocytes, and their characteristics were evaluated using electron microscope and nanoparticle tracking analysis. The exosome inhibitor GW4869 was employed to examine the effect of exosomal CCRR on cardiac function using echocardiography. Protein expression was detected using Western blot and immunofluorescence staining. Results The circulating level of CCRR was significantly higher in AMI patients (1.93 ± 0.13) than in nonAMI subjects (1.00 ± 0.05, P < 0.001). The area under the ROC curve (AUC) of circulating CCRR was 0.821. Similar changes in circulating CCRR levels were consistently observed in an AMI mouse model. Exosomal CCRR derived from hypoxia-induced cardiomyocytes and cardiac tissue after AMI were increased, a change that was reversed by GW4869. Additionally, CCRR-overexpressing exosomes improved cardiac function in AMI. Conclusion Circulating lncRNA CCRR is a potential predictor of AMI. Exosomal CCRR plays a role in the communication between the heart and other organs through circulation.

Clinical study of a new nutritional index for predicting long-term prognosis in patients with coronary atherosclerotic heart disease following percutaneous coronary intervention

Xinqiu Chu, Yuewen Yuan, Jiya Chen, Yanwei Yu, Yang Li

2024, 4(3): 152-159. doi: 10.1515/fzm-2024-0016

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Abstract:
Background and Objective Some patients continue to experience major adverse cardiovascular and cerebrovascular events (MACCE) after percutaneous coronary intervention (PCI) in frigid places. Indexes of inflammation and nutrition alone were shown to predict outcomes in patients with PCI. However, the clinical predictive value of mixed indicators is unclear. This study aimed to assess the predictive value of the albumin/neutrophil/lymphocyte ratio (NLR) on the long-term prognosis of patients with coronary heart disease (CHD) following percutaneous coronary intervention (PCI). Methods A total of 608 post-PCI CHD patients were categorized into low- and high-index groups based on the optimal cut-off values for albumin and NLR. The primary outcome was a composite endpoint comprising all-cause mortality and major adverse cerebrovascular events. The secondary outcome was the comparison of the predictive efficiency of the new nutritional index, albumin/NLR, with that of albumin or NLR alone. Results Over the five-year follow-up period, 45 patients experienced the composite endpoint. The incidence of endpoint events was significantly higher in the low-index group (12%) compared to the high-index group (4.9%). Receiver operating characteristic (ROC) curve analysis revealed that the albumin/NLR index had a larger area under the curve (AUC: 0.655) than albumin (AUC: 0.621) or NLR (AUC: 0.646), indicating superior predictive efficiency. The prognostic nutritional index had an AUC of 0.644, further supporting the enhanced predictive value of the albumin/NLR index over individual nutritional and inflammatory markers. Conclusion The albumin/neutrophil/lymphocyte ratio is independently associated with the long-term prognosis of CHD patients post-PCI and demonstrates superior predictive efficiency compared to individual nutritional and inflammatory markers.

Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways

Wen Li, Jia Wang, Yilian Yang, Chunlei Duan, Bing Shao, Mingxiu Zhang, Jiapan Wang, Peifeng Li, Ye Yuan, Yan Zhang, Hongyu Ji, Xingda Li, Zhimin Du

2024, 4(3): 160-176. doi: 10.1515/fzm-2024-0017

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Abstract:
Background and objective In northern China's cold regions, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) exceeds 50%, significantly higher than the national and global rates. MASLD is an important risk factor for cardiovascular and cerebrovascular diseases, including coronary heart disease, stroke, and tumors, with no specific therapeutic drugs currently available. The ethanol extract of cassia seed (CSEE) has shown promise in lowering blood lipids and improving hepatic steatosis, but its mechanism in treating MASLD remains underexplored. This study aims to investigate the therapeutic effects and mechanisms of CSEE. Methods MASLD models were established in male Wistar rats and golden hamsters using a high fat diet (HFD). CSEE (10, 50, 250 mg/kg) was administered via gavage for six weeks. Serum levels of total cholesterol (TC), triglyceride (TG), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as liver TC and TG, were measured using biochemical kits. Histopathological changes in the liver were evaluated using Oil Red O staining, Hematoxylin-eosin (H&E) staining, and transmission electron microscopy (TEM). HepG2 cell viability was assessed using the cell counting kit-8 (CCK8) and Calcein-AM/PI staining. Network pharmacology was used to analyze drug-disease targets, and western blotting was used to confirm these predictions. Results CSEE treatment significantly reduced serum levels of TC, TG, LDL-C, ALT, and AST, and improved liver weight, liver index, and hepatic lipid deposition in rats and golden hamsters. In addition, CSEE alleviated free fatty acid (FFA)-induced lipid deposition in HepG2 cells. Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK, p-ACC, PPARα, CPT1A, PI3K P110 and p-AKT, while decreasing the protein levels of SREBP1, FASN, C/EBPα, and PPARγ, thus improving hepatic lipid metabolism and reducing lipid deposition. The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro. Conclusion CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK, PPARα, and PI3K/AKT signaling pathways.

LCN2 aggravates diabetic cataracts by promoting ferroptosis in lens epithelial cells

Jiayue Zhang, Liyao Sun, Xiaohan Yu, Chen Yang, Qi An, Chaoqun Wei, Hongyan Ge

2024, 4(3): 177-192. doi: 10.1515/fzm-2024-0018

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Abstract:
Background Cataracts are the leading cause of reversible blindness worldwide. Diabetic cataract (DC), a prevalent complication of diabetes mellitus, is characterized by its high occurrence, rapid progression, and severe impact. The prevalence of diabetes varies greatly between the northern and southern regions, with higher rates observed among northern residents. DC-induced lens opacity is mainly attributed to oxidative stress. However, it remains unclear whether ferroptosis, a form of regulated cell death, occurs in crystalline epithelial cells during the pathogenesis, which may represent a novel mechanism contributing to DC. Methods Transmission electron microscopy, quantitative assays for iron levels and reactive oxygen species (ROS), real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, immunofluorescence, and immunohistochemistry were used to detect ferroptosis. Gene editing techniques were utilized to study the regulatory relationships among lipocalin 2 (LCN2), glutathione peroxidase 4 (GPX4), and ferritin heavy chain (FTH). Local knockdown of the LCN2 gene in B-3 cells and the eyes of Sprague Dawley (SD) rats was performed to verify and further explore the role and regulatory mechanisms of LCN2 in DC-associated ferroptosis. Results An in vitro model using high glucose levels and an in vivo model with streptozotocin-induced diabetes in SD rats were successfully established. Ferroptosis was observed in both in vitro and in vivo experiments. LCN2 protein was normally expressed in human and rat lens epithelial cells, but its expression significantly increased during ferroptosis. The ferroptosis inhibitor, ferrostatin-1 (Fer-1) effectively inhibited ferroptosis and reduced LCN2 protein expression. Notably, local knockdown of LCN2 via gene editing protected lens epithelial cells from ferroptosis in vitro and slowed the progression of DC in SD rats in vivo. Conclusion Our findings underscore the significant role of ferroptosis in the pathogenesis of DC, suggesting that selectively targeting LCN2 activation and enhancing ferroptosis resistance may offer a novel therapeutic approach for treating DC.

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