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Purpose: Treatment of triple-negative breast cancer (TNBC) remains challenging. Intermittent fasting (IF) has emerged as a promising approach to improve metabolic health of various metabolic disorders. Clinical studies indicate IF is essential for TNBC progression. However, the molecular mechanisms underlying metabolic remodeling in regulating IF and TNBC progression are still unclear. Methods: In this study, we utilized a robust mouse model of TNBC and exposed subjects to a high-fat diet (HFD) with IF to explore its impact on the metabolic reprogramming linked to cancer progression. To identify crucial serum metabolites and signaling events, we utilized targeted metabolomics and RNA sequencing (RNA-seq). Furthermore, we conducted immunoblotting, real-time quantitative polymerase chain reaction (RT-qPCR), cell migration assays, lentivirus-mediated Mmp9 overexpression, and Mmp9 inhibitor experiments to elucidate the role of decanoylcarnitine/Mmp9 in TNBC cell migration. Results: Our observations indicate that IF exerts notable inhibitory effects on both the proliferation and cancer metastasis. Utilizing targeted metabolomics and RNA-seq, we initially identified pivotal serum metabolites and signaling events in the progression of TNBC. Among the 349 serum metabolites identified, decanoylcarnitine was picked out to inhibit TNBC cell proliferation and migration. RNA-seq analysis of TNBC cells treated with decanoylcarnitine revealed its suppressive effects on extracellular matrix-related protein components, with a notable reduction observed in Mmp9. Further investigations confirmed that decanoylcarnitine could inhibit Mmp9 expression in TNBC cells, primary tumors, lung, and liver metastasis tissues. Mmp9 overexpression abolished the inhibitory effect of decanoylcarnitine on cell migration. Conclusion: This study pioneers the exploration of IF intervention and the role of decanoylcarnitine/Mmp9 in the progression of TNBC in obese mice, enhancing our comprehension of the potential roles of various dietary patterns in the process of cancer treatment.

Abstract At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand‐1 (PD‐L1) expression. Incredibly, intracellular PD‐L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD‐L1function still limits the effectiveness of radio‐immunotherapy. Therefore, better PD‐L1 regulation strategies are still urgently needed to better sensitize radio‐immunotherapy. Hence, for this purpose, TPP‐LND is synthesized by linking mitochondrial‐targeted triphenylphosphine cations (TPP+) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, TPP‐LND is wrapped with liposomes to form TPP‐LND@Lip nanoparticles. By doing this, TPP‐LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD‐L1 via enhancing the adenosine 5′‐monophosphate‐activated protein kinase activation. As expected, these well‐designed economical TPP‐LND@Lip nanoparticles are more effective than conventional anti‐PD‐L1 antibodies to some extent.

BackgroundRadiation proctitis is a common complication after radiotherapy for cervical cancer. Unlike simple radiation damage to other organs, radiation proctitis is a complex disease closely related to the microbiota. However, analysis of the gut microbiota is time-consuming and expensive. This study aims to mine rectal information using radiomics and incorporate it into a nomogram model for cheap and fast prediction of severe radiation proctitis prediction in postoperative cervical cancer patients.MethodsThe severity of the patient’s radiation proctitis was graded according to the RTOG/EORTC criteria. The toxicity grade of radiation proctitis over or equal to grade 2 was set as the model’s target. A total of 178 patients with cervical cancer were divided into a training set (n = 124) and a validation set (n = 54). Multivariate logistic regression was used to build the radiomic and non-raidomic models.ResultsThe radiomics model [AUC=0.6855(0.5174-0.8535)] showed better performance and more net benefit in the validation set than the non-radiomic model [AUC=0.6641(0.4904-0.8378)]. In particular, we applied SHapley Additive exPlanation (SHAP) method for the first time to a radiomics-based logistic regression model to further interpret the radiomic features from case-based and feature-based perspectives. The integrated radiomic model enables the first accurate quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients, addressing the limitations of the current qualitative assessment of the plan through dose-volume parameters only.ConclusionWe successfully developed and validated an integrated radiomic model containing rectal information. SHAP analysis of the model suggests that radiomic features have a supporting role in the quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients.

ABSTRACT Context • Ischemic heart disease is a common disease in older surgical patients. The current treatments for myocardial ischemia mainly restore blood flow to an extent, but reperfusion inevitably causes reperfusion injury. Single-point acupuncture and moxibustion can strengthen the body’s resistance and eliminate pathogenic factors, but medical practitioners haven’t considered matching acupoints in treatments for myocardial ischemia. Objective • The study intended to examine the effects of electroacupuncture using the Biao and Ben acupoints on the structure and function of myocardial mitochondria, the changes in the expression of related proteins, and the intraoperative circulation of rats with myocardial ischemia and to provide a theoretical basis for the clinical use of the Biao-Ben acupoints. Design • The research team performed an animal study. Setting • The study took place in Lanzhou Maternal and Child Health Hospital. Animals • The animals were 84 male Sprague-Dawley (SD) rats, weighing 160-220 g. Intervention • The research team divided the rats into seven groups, with 12 rats in each group. The study evaluated two types of interventions: (1) zinc chloride (ZnCl2) and (2) electroacupuncture. The team used two versions of each type of intervention, for four groups in total: (1) a low dose of ZnCl2, the low-dose ZnCl2 group; (2) a high dose of ZnCl2, the high-dose ZnCl2 group; (3) electroacupuncture using a single acupoint, the Neiguan point, for the Neiguan group; and (4) electroacupuncture using three acupoints, the Neiguan point and the Biao and Ben points, for the Biao-Ben group. The study included three control groups—the control group, a positive control group; the sham group, a ZnCl2 control group; and the model group, a negative control group. The team collectively called five of the groups the operation group, which included all four intervention groups and the model group, in which the team induced ischemic heart disease. Outcome Measures • The research team measured: (1) the relative changes in the mitochondrial ultrastructure of the rat cardiomyocytes for each group using a laser confocal, fluorescent indicator assay to detect the concentration of calcium(2+) [Ca2+] in the cytoplasm of cardiomyocytes; (2) the content of adenosine triphosphate (ATP) in myocardial tissue using ATP-detection technology; (3) mitochondrial activity using the fluorescent probe method; and (4) the protein levels of P2X purinoceptor 7 (P2X7) and mitochondria-related oxidative stress factors on the myocardial cell membrane using Western blot technology. The team monitored the physiology of the rats in each group. Results • Compared with the model group, the two ZnCl2 groups and the two electroacupuncture groups showed: (1) a significantly improved mitochondrial structure and function of the ischemic cardiomyocytes, (2) a significant increase in the mitochondrial activity, (3) a significant increase in the permeability of the membrane and thus an increase the concentration of Ca2+ in the cytoplasm, (4) a significant increase in the content of ATP inside and outside the myocardium, (5) at the same time, a significant reduction in the protein levels of the P2X7 receptors on the myocardial cell membrane and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and manganese superoxide dismutase (MnSOD) in mitochondria, and (6) a significant reduction in the protein levels of nitric oxide (NO) and cytochrome C (CytC). Conclusions • The Biao and Ben electroacupuncture can improve the structure and function of mitochondria in the myocardial cells of rats with myocardial ischemia, reduce the expression levels of the P2X7 receptor, NO, and CytC proteins, increase the expression levels of PGC-1α and MnSOD, and improve the intraoperative circulation, thus having a positive effect on myocardial ischemia. [ABSTRACT FROM AUTHOR]