The relationship between proportions of carbohydrate and fat intake and hyperglycemia risk in Chinese adults.

OBJECTIVE: To address the relationship between the proportions of carbohydrates and fat and hyperglycemia in the Chinese population. DESIGN: A cross-section research involving data from the China Health and Nutrition Survey in 2009, and nutritional status and health indicators were mainly focused. SETTING: China. PARTICIPANTS: 8197 Chinese individuals aged over 16 years, including 1345 subjects had a low carbohydrate and high fat diet (LCHF), 3951 individuals had a medium proportion of carbohydrate and fat (MPCF) diet, 2660 participants had a high carbohydrate and low fat (HCLF) diet and 241 people had the very high carbohydrate and low fat (VHCLF) diet. RESULTS: Subjects with the HCLF diet were significantly associated with an increased risk of hyperglycemia (OR:1.142, 95%CI:1.022-1.276) when compared with the individuals with the MPCF diet. Meanwhile, people with a VHCLF diet had a higher risk of hyperglycemia (OR:1.829, 95%CI:1.377-2.429). In contrast, the association between participants with an LCHF diet and hyperglycemia was not significant (OR:1.082, 95%CI:0.942-1.243) with adjusting a series of confounding factors. Furthermore, people with a VHCLF diet were significantly associated with a higher risk of hyperglycemia in the major energy levels and social characteristics subgroup. CONCLUSION: We found the HCLF and VHCLF diets were significantly associated with a high risk of hyperglycemia. And, the association between LCHF diets and the risk of hyperglycemia was not significant.

Construction of a ferroptosis and hypoxia-related gene signature in cervical cancer to assess tumour immune microenvironment and predict prognosis.

BACKGROUND: This study aimed to investigate the potential role of ferroptosis/hypoxia-related genes in cervical cancer to improve early management and treatment of cervical cancer. METHODS: All data were downloaded from public databases. Ferroptosis/hypoxia-related genes associated with cervical cancer prognosis were selected to construct a risk score model. The relationship between risk score and clinical features, immune microenvironment and prognosis were analysed. RESULTS: Risk score model was constructed based on eight signature genes. Drug prediction analysis showed that bevacizumab and cisplatin were related to vascular endothelial growth factor A. Risk score, as an independent prognostic factor of cervical cancer, had a good survival prediction effect. The two groups differed significantly in degree of immune cell infiltration, gene expression, tumour mutation burden and somatic variation. CONCLUSIONS: We developed a novel prognostic gene signature combining ferroptosis/hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer.

Ferroptosis, hypoxia and immune regulation play important roles in cervical cancer progression. In this study, we developed a novel prognostic signature combining ferroptosis and hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer patients. The risk score established by ferroptosis and hypoxia-related gene as an independent prognostic factor of cervical cancer has a good survival prediction effect. High and low risk groups showed significant differences in TIME, prognosis, biological metabolic pathway and tumour mutation burden. In addition, we found drugs associated with signature genes. In short, this study has laid a theoretical foundation for exploring the related molecular mechanisms and prognosis of cervical cancer. It also contributes to the exploration of clinical management and treatment.

Depressive symptom trajectories and new-onset arthritis in a middle-aged and elderly Chinese population.

OBJECTIVE: Previous studies reported that depression was associated with a high risk of arthritis. However, the effect of different long-term depressive symptom trajectory patterns on the risk of arthritis has not been evaluated. Our study aimed to explore the association between depressive symptom trajectories and the risk of arthritis. METHODS: A total of 5583 participants from the China Health and Retirement Longitudinal Study from 2011 to 2018 were included in this analysis. Group-based trajectory modeling was used to identify depressive symptom trajectories, and a multivariable competitive Cox regression model was used to examine the association of depressive symptom trajectories with arthritis during follow-up. RESULTS: Five depressive symptom trajectories were identified in our research: stable-high, decreasing, increasing, stable-moderate and stable-low. Compared with participants in the stable-low trajectory group, those in the stable-moderate, increasing, decreasing and stable-high trajectory groups had a higher cumulative risk of arthritis, with HRs (95% CIs) for arthritis of 1.64 (1.30, 2.07), 1.86 (1.30, 2.66), 1.99 (1.41, 2.80) and 2.19 (1.38, 3.48), respectively. Participants with the stable-high symptoms trajectory had the highest cumulative risk of arthritis. There was still a high risk of arthritis, although the depression state was reduced and remained at a level that is generally considered reasonable. CONCLUSIONS: The higher depressive symptoms trajectories were significantly associated with the increased risk of arthritis, and the long-term depressive symptoms trajectories may be a strong predictor of having arthritis.

Melatonin protects against nonylphenol caused pancreatic ß-cells damage through MDM2-P53-P21 axis.

Nonylphenol (NP) is an endocrine disrupting chemical, which widely exists in environment and can result in multiple system dysfunction. Pancreas as one of the most important organs is sensitive to NP, while the detail toxic effect is still less studied. Previously, we unveiled nonylphenol causes pancreatic damage in rats, herein, we further explore the potential mechanism and seek protection strategy in vitro. Insulinoma (INS-1) cells exposed to NP were observed to suffer oxidative stress and mitochondrial dysfunction, as reflected by the abnormal levels of reactive oxygen species, malonic dialdehyde, superoxide dismutase, Ca2+, and mitochondrial membrane potential. Melatonin (MT) was found to alleviate NP-induced mitochondrial dysfunction and oxidative stress, further inhibit apoptosis and restore pancreas function. Mechanically, MT induced the MDM2-P53-P21 signaling, which upregulated the Nrf2 signaling pathway. In summary, our study clarified NP-induced INS-1 cells mitochondrial dysfunction and oxidative stress, which could be ameliorated by MT through MDM2-P53-P21 axis.

Self-rated health, socioeconomic status and all-cause mortality in Chinese middle-aged and elderly adults.

Our study aims to investigate the association between SRH and all-cause mortality, and to investigate whether the SRH-mortality association varies across different socioeconomic status (SES) groups among middle-aged and older Chinese adults. We used data from China Health and Retirement Longitudinal Study (CHARLS), including 11,762 participants for the final analysis. Cox proportional hazards regression was conducted to investigate the association between SRH status and subsequent mortality. There were 724 death events occurred. The results were shown that fair/poor SRH participants tend to die than better SRH peers (HR 1.46, 95% CI 1.12-1.91). The association only occurred in those with rural residency (HR 1.46, 95% CI 1.05-2.04), those who were literate (HR 1.65, 95% CI 1.17-2.33), those with above-average household income (HR 1.95, 95% CI 1.15-3.29) and those working in agriculture and below (HR 1.38, 95% CI 1.02-1.88). In conclusion, worse SRH may be a predictor of all-cause mortality among middle-aged and elderly Chinese, especially in people with rural residency, literacy, above-average household income and working in agriculture and below.

Association between visceral adipose index and risk of hypertension in a middle-aged and elderly Chinese population.

BACKGROUND AND AIMS: Visceral adipose index (VAI) had been widely used to predict the risks of several diseases. However, few studies have clarified the association between VAI and the risk of hypertension in Chinese population. Thus, we investigate the association between VAI and the increased risk of hypertension in a nationwide cohort of middle-aged and elderly adults in China. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study from 2011 to 2015. A total of 5200 Chinese participants aged 45 years and older were included. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of hypertension, with the lowest quartile of VAI score group as the reference. During the 4-years follow-up, 979 cases of hypertension were recorded. Compared with those in the lowest VAI score group, the participants with the highest quartile of VAI score were at a higher risk level of hypertension (HR: 1.454; 95% CI 1.204 to 1.755), especially subjects living in the urban area (2.142, 1.522 to 3.014). Furthermore, VAI can improve the ability of both BMI and WC in predicting the risk of hypertension by 12.72% (95% CI: 5.78%-19.67%) and 10.12% (95% CI: 3.17%-17.07%), respectively. CONCLUSION: In summary, VAI was positively associated with an increased risk of hypertension among a middle-aged and elderly Chinese population; VAI score can improve the ability of BMI and WC in predicting risk of hypertension.

Integrin α1 promotes tumorigenicity and progressive capacity of colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of death globally. Integrin α1 (ITGA1) belongs to integrin family and involves in regulating cell adhesion, invasion, proliferation and tumorigenicity, its expression is up-regulated in various cancers, including CRC. However, the molecular understanding and clinical relevance of ITGA1 in the development and progression of CRC remain unclear. In the present study, we detected ITGA1 in 50 CRC tissues and adjacent non-cancerous tissues, sera from 100 CRC patients and 50 healthy subjects, and four CRC cell lines using immunohistochemistry staining, enzyme-linked immunosorbent assay and Western blotting. We found that the ITGA1 protein was significantly higher in human CRC tissues and cell lines than both paired non-tumor tissues and normal cells, respectively. In addition, the serum concentration of ITGA1 was also higher in CRC patients compared to the healthy subjects (p<0.01) and was significantly associated with metastatic TNM stages (p<0.0001) and circulating carbohydrate antigen 199 (CA199) (p<0.022). Furthermore, down-regulation of ITGA1 with transfecting LV-shITGA1 inhibited the progressive capacity of cell migration and invasion in CRC SW480 cell line and the tumorgenicity in nude mice. In functional studies, ITGA1 knockdown also inhibited Ras/ERK signaling pathway by decreasing the expression of Ras, p-Erk1/2 and c-Myc in SW480. Contrastly, when evelated expression of ITGA1 in NCM460 coincided with the increased expression of Ras, p-Erk1/2 and c-Myc. Taken together, our findings suggest that ITGA1 is an oncogene with a capability to promote CRC cell migration, invasion and tumorigenicity by activating the Ras/Erk signaling, implying that it may be a novel target for the diagnosis and treatment of CRC, and warrants further investigation.

Amentoflavone Affects Epileptogenesis and Exerts Neuroprotective Effects by Inhibiting NLRP3 Inflammasome.

Brain inflammation is one of the main causes of epileptogenesis, a chronic process triggered by various insults, including genetic or acquired factors that enhance susceptibility to seizures. Amentoflavone, a naturally occurring biflavonoid compound that has anti-inflammatory effects, exerts neuroprotective effects against nervous system diseases. In the present study, we aimed to investigate the effects of amentoflavone on epilepsy in vivo and in vitro and elucidate the underlying mechanism. The chronic epilepsy model and BV2 microglial cellular inflammation model were established by pentylenetetrazole (PTZ) kindling or lipopolysaccharide (LPS) stimulation. Cognitive dysfunction was tested by Morris water maze while hippocampal neuronal apoptosis was evaluated by immunofluorescence staining. The levels of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome complexes and inflammatory cytokines were determined using quantitative real-time polymerase chain reaction, Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. Amentoflavone reduced seizure susceptibility, minimized PTZ-induced cognitive dysfunction, and blocked the apoptosis of hippocampal neurons in PTZ-induced kindling mice. Amentoflavone also inhibited the activation of the NLRP3 inflammasome and decreased the levels of inflammatory cytokines in the hippocampus of PTZ-induced kindling mice. Additionally, amentoflavone could alleviate the LPS-induced inflammatory response by inhibiting the NLRP3 inflammasome in LPS-induced BV2 microglial cells. Our results indicated that amentoflavone affects epileptogenesis and exerts neuroprotective effects by inhibiting the NLRP3 inflammasome and, thus, mediating the inflammatory process in PTZ-induced kindling mice and LPS-induced BV2 microglial cells. Therefore, amentoflavone may be a potential treatment option for epilepsy.

Disparate roles of CXCR3A and CXCR3B in regulating progressive properties of colorectal cancer cells.

Human C-X-C Motif Chemokine Receptor 3A (CXCR3A) and CXCR3B are two splice variants of CXCR3 that is involved in a variety of progressive processes of cancer cells, including proliferation, migration, invasion, and tumorigenicity. However, the molecular mechanisms of CXCR3 in colorectal cancer (CRC) remain incomplete understood. In the present study, a significantly up-regulated CXCR3 protein was firstly observed in CRC tissues and cell lines in comparison with the paired non-tumor tissues and normal intestinal epithelial cells, which was positively associated with CRC TNM stages. In contrast, CXCR3B was down-regulated in CRC tumor tissues compared with that in the corresponding paired paracancerous tissues, and negatively correlated with the TNM stages of cancer. Of interest, the overexpression of CXCR3A enhanced the progressive capacity of cell proliferation, migration, invasion in CRC LOVO and HCT116 cells in vitro, and the tumorigenicity in nude mice in vivo. Conversely, the overexpression of CXCR3B exhibited an opposite phenotype of CXCR3A, with an ability to inhibit the progressive properties in CRC cell lines in vitro and tumorigenesis in vivo. In addition, immunoblotting analysis further demonstrated that an increased expression of CXCR3A inhibited the expression of CXCR3B in CRC cells and NCM460 normal colon epithelial cells; vice verse, an overexpression of CXCR3B suppressed the expression of CXCR3A in these cells. These data imply that an interaction between the CXCR3A and CXCR3B may play an important regulatory role in tumorigenicity of CRC, which warrants for further investigation.