Fang Fang

Background: Radioresistance remains a significant obstacle in lung cancer radiotherapy, necessitating novel strategies to enhance therapeutic efficacy. This study investigated the radiosensitizing potential of a soybean lecithin–gallic acid complex (SL–GAC) in non-small cell lung cancer (NSCLC) cells and explored its underlying ferroptosis-related mechanisms. SL–GAC was synthesized to improve the bioavailability of gallic acid (GA), a polyphenol with anticancer properties. Methods: NSCLC cell lines (A549 and H1299) and normal bronchial epithelial cells (BEAS-2B) were treated with SL–GAC, ionizing radiation (IR), or their combination. Through a series of in vitro experiments, including cell viability assays, scratch healing assays, flow cytometry, and Western blot analysis, we comprehensively evaluated the effects of SL-GAC on NSCLC cell proliferation, migration, oxidative stress, and ferroptosis induction. Results: SL–GAC combined with IR synergistically suppressed NSCLC cell proliferation and migration, exacerbated oxidative stress via elevated ROS and malondialdehyde levels, and induced mitochondrial dysfunction marked by reduced membrane potential and structural damage, whereas no significant ROS elevation was observed in BEAS-2B cells. Mechanistically, the combination triggered ferroptosis in NSCLC cells, evidenced by iron accumulation and downregulation of Nrf2, SLC7A11, and GPX4, alongside upregulated ACSL4. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, reversed these effects and restored radiosensitivity. Conclusions: Our findings demonstrate that SL–GAC enhances NSCLC radiosensitivity by promoting ferroptosis via the Nrf2/SLC7A11/GPX4 axis, highlighting its potential as a natural radiosensitizer for clinical translation.

Background The Energy-Adjusted Dietary Inflammatory Index (E-DII) is related to both body mass index (BMI) and hyperuricemia. However, the association among BMI, hyperuricemia and DII is yet to be fully elucidated. The purpose of this study is to explore the role of BMI in the relationship between E-DII and hyperuricemia in the American population. Methods A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016, with a sample size of 10,571 participants. The study used a weighted logistic regression model and a generalized additive model (GAM) to explore the associations among BMI, hyperuricemia and E-DII. Furthermore, mediation analysis was utilized to illustrate the mediating relationships among these variables. Results The results of the study indicated that a higher E-DII was related to an increased risk of hyperuricemia. The association between E-DII and hyperuricemia was partially mediated by BMI. Conclusions E-DII is associated with hyperuricemia. BMI mediates the relationship between E-DII and hyperuricemia among Americans, which provides crucial information for the prevention of hyperuricemia.

Cervical cancer causes malignant tumors in females and threatens the physical and mental health of women. Current research shows that persistent infection of high-risk HPV is the main cause of cervical cancer. However, not all cervical cancer is caused by HPV infection, which may also be related to other factors, such as nutritional status and lifestyle. This study focuses on the effect of alcohol consumption on the methylation status of cervical cancer from the perspective of methyl donors. We established a mouse tumor-bearing model with cervical cancer SiHa cells, and at the same time, we cultured SiHa cells in vitro. Different concentrations of ethanol were administered to the model mice and SiHa cells. Then, we detected the levels of the methyl-donor folate and methionine and their metabolite homocysteine levels in mice serum, tumor tissues, and SiHa cells. Furthermore, we determined the expression of the members of the DNA methyltransferase family (DNMT1, DNMT3a, and DNMT3b) in tumor tissue by immunohistochemistry. qRT-PCR and Western blotting analysis were used to detect the mRNA and protein levels of members of the DNA methyltransferase family in cervical cancer SiHa cells. Our results show that the levels of the methyl donor (folate and methionine) decreased with the increase of ethanol concentration (p < 0.05), and the homocysteine level increased significantly (p < 0.05). In SiHa cells, the mRNA and protein levels of the DNMT family members and their receptors were significantly higher than those in the control group (p < 0.05). Collectively, these results suggest that ethanol could influence DNMT expression by inducing methyl donor consumption, thereby causing cervical cancer cells to exhibit genome-wide hypomethylation.

Colorectal cancer (CRC) is one of the most common cancers, with a high mortality rate, and is a major burden on human health worldwide. Gut microbiota regulate human immunity and metabolism through producing numerous metabolites, which act as signaling molecules and substrates for metabolic reactions in various biological processes. The importance of host-gut microbiota interactions in immunometabolic mechanisms in CRC is increasingly recognized, and interest in modulating the microbiota to improve patient’s response to therapy has been raising. However, the specific mechanisms by which gut microbiota interact with immunotherapy and radiotherapy remain incongruent. Here we review recent advances and discuss the feasibility of gut microbiota as a regulatory target to enhance the immunogenicity of CRC, improve the radiosensitivity of colorectal tumor cells and ameliorate complications such as radiotoxicity. Currently, great breakthroughs in the treatment of non-small cell lung cancer and others have been achieved by radioimmunotherapy, but radioimmunotherapy alone has not been effective in CRC patients. By summarizing the recent preclinical and clinical evidence and considering regulatory roles played by microflora in the gut, such as anti-tumor immunity, we discuss the potential of targeting gut microbiota to enhance the efficacy of radioimmunotherapy in CRC and expect this review can provide references and fresh ideas for the clinical application of this novel strategy.

Background: The dietary inflammatory index (DII) is thought to be related to many healthy events. However, the association between the DII and sarcopenia remains unclear. Methods: The meta-analysis was conducted to evaluate the effects of the DII on the risk of sarcopenia utilizing available studies. Up to September 2022, Cochrane, PubMed, Web of Science, Medline, and EMBASE databases were searched to evaluate the relationships between the DII and sarcopenia. A random‒effects model was used to calculate the effect size and 95% confidence intervals (CIs). Result: Eleven studies with 19,954 participants were included in our meta-analysis. The results indicated that a high DII increased the risk of sarcopenia (OR = 1.16, 95%CI [1.06, 1.27], p < 0.05). The result of the dose–response analysis showed that the risk of sarcopenia increased by 1.22 times for each 1-point increase in the DII score (OR = 1.22, 95%CI [1.12, 1.33], p < 0.05). Conclusion: The meta-analysis demonstrated that the DII is associated with sarcopenia. Considering some limitations in this study, more studies are needed to verify this relationship.

Cancer is the second most common cause of death among humans in the world, and the threat that it presents to human health is becoming more and more serious. The mechanisms of cancer development have not yet been fully elucidated, and new therapies are changing with each passing day. Evidence from the literature has validated the finding that the composition and modification of gut microbiota play an important role in the development of many different types of cancer. The results also demonstrate that there is a bidirectional interaction between the gut microbiota and radiotherapy treatments for cancer. In a nutshell, the modifications of the gut microbiota caused by radiotherapy have an effect on tumor radiosensitivity and, as a result, affect the efficacy of radiotherapy and show a certain radiation toxicity, which leads to numerous side effects. What is of new research significance is that the “gut-organ axis” formed by the gut microbiota may be one of the most interesting potential mechanisms, although the relevant research is still very limited. In this review, we combine new insights into the relationship between the gut microbiota, cancer, and radiotherapy. Based on our current comprehensive understanding of this relationship, we give an overview of the new cancer treatments based on the gut microbiota.

Background: The triglyceride glucose (TyG) index, which is a new surrogate indicator of insulin resistance (IR), is thought to be associated with many diseases, such as cardiovascular disease, but its relationship with cerebrovascular disease is still controversial. Methods: The PubMed, EMBASE, Cochrane Library, Web of Science and Medline databases were searched until March 2022 to evaluate the association between the TyG index and cerebrovascular disease risk. A random‒effects model was used to calculate the effect estimates and 95% confidence intervals (CIs). Results: A total of 19 cohort studies and 10 case‒control/cross‒sectional studies were included in our study, which included 11,944,688 participants. Compared with a low TyG index, a higher TyG index increased the risk of cerebrovascular disease (RR/HR = 1.22, 95% CI [1.14, 1.30], P< 0.001; OR = 1.15, 95% CI [1.07, 1.23], P< 0.001). Furthermore, the results of the dose-response analysis of the cohort study demonstrated that the risk of cerebrovascular disease increased by 1.19 times per 1 mg/dl increment of the TyG index (relative risk = 1.19, 95% CI [1.13,1.25], P< 0.001). Conclusion: TyG index is related to cerebrovascular disease. More data and basic research are needed to confirm the association.

Alcoholic liver disease (ALD) is associated with significant morbidity and mortality globally. In this study, the soybean lecithin–gallic acid complex was synthesized, and its physicochemical properties were evaluated, which confirmed the complex formation. Compared with the free state of the drug, gallic acid exhibited significantly different physicochemical properties after it was complexed with soybean lecithin. To clarify the binding mode between two monomers, computational investigation was performed. From the computational data, we deduced the structure of the compound and predicted that it has a high affinity for human phosphatidylcholine transfer protein and exhibits strong pharmacological activities in vivo. The complex not only effectively ameliorated liver fibrosis, lipid peroxidation, and oxidative stress, but also reduced liver iron overload in a mouse ALD model induced by alcohol (p < 0.05). Additionally, it regulated iron metabolism by inhibiting TfR1 expression (p < 0.05) and promoting hepcidin expression (p < 0.05). These results suggest that the soybean lecithin–gallic acid complex ameliorates hepatic damage and iron overload induced by alcohol and exert hepatoprotective effects.