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BackgroundPituitary tumors (PTs) are common benign intracranial tumors. Investigating the metabolites in serum and cerebrospinal fluid in PTs is essential to understanding the underlying biological mechanisms and identifying new biomarkers and therapeutic strategies.MethodsWe used the GWAS dataset of PTs from the FinnGen database, a dataset of 486 plasma metabolites from the GWAS catalog database, and a dataset of 338 cerebrospinal fluid (CSF) metabolites from the WADRC and WRAP study collections. An inverse variance weighting (IVW) approach was utilized as the mainly method to investigate causality between metabolites and PTs, supplemented by four complementary methods to strengthen our findings. Additionally, we utilized several sensitivity methods to guarantee the robustness of our findings.ResultsThe study identified 17 plasma metabolites and 10 CSF metabolites related to PTs. Among these, 11 metabolites indicated a significant positive causality with PTs, while 16 displayed a remarkable negative causality. Particularly, plasma levels of 3-dehydrocarnitine (OR = 2.73, 95% CI = 1.55–4.83, P = 0.001) and acetylcarnitine (OR = 0.35, 95% CI = 0.19–0.63, P = 0.001) were found to be significant exposure factors for PTs. Multiple sensitivity analyses confirm the robustness of the results. The study found no evidence of a reverse causality between PTs and the plasma levels of 3-dehydrocarnitine and acetylcarnitine.ConclusionsThe present study identified 27 metabolites associated with the incidence of PTs, among which 3-dehydrocarnitine and acetylcarnitine are the most noteworthy.

BackgroundEarlier researches have demonstrated that ischemic stroke, metabolic factors, and associated medications may influence the risk of epilepsy. Nevertheless, the causality between these elements and epilepsy remains inconclusive. This study aims to examine whether ischemic stroke, metabolic factors, and related medications affect the overall risk of epilepsy.MethodsWe used single nucleotide polymorphisms associated with ischemic stroke, hypothyroidism, hypertension, blood glucose levels, high cholesterol, serum 25-Hydroxyvitamin D levels, testosterone, HMG CoA reductase inhibitors, and beta-blocking agents as instrumental variables in a Mendelian randomization technique to investigate causality with epilepsy. Multiple sensitivity methods were performed to evaluate pleiotropy and heterogeneity.ResultsThe IVW analysis revealed positive associations between ischemic stroke (OR = 1.29; p = 0.020), hypothyroidism (OR = 1.05; p = 0.048), high blood pressure (OR = 1.10; p = 0.028), high cholesterol (OR = 1.10; p = 0.024), HMG CoA reductase inhibitors (OR = 1.19; p = 0.003), beta-blocking agents (OR = 1.20; p = 0.006), and the risk of epilepsy. Conversely, blood glucose levels (OR = 0.79; p = 0.009), serum 25-Hydroxyvitamin D levels (OR = 0.75; p = 0.020), and testosterone (OR = 0.62; p = 0.019) exhibited negative associations with the risk of epilepsy. Sensitivity analyses confirmed the robustness of these findings (p > 0.05).ConclusionOur research suggests that ischemic stroke, hypothyroidism, high blood pressure, high cholesterol, HMG CoA reductase inhibitors, and beta-blockers may increase the risk of epilepsy, whereas serum 25-Hydroxyvitamin D levels and blood glucose levels may reduce the risk.

Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment.

BackgroundWhile osteoimmunology interactions between the immune and skeletal systems are known to play an important role in osteoblast development, differentiation and bone metabolism related disease like osteoporosis, such interactions in either bone microenvironment or peripheral circulation in vivo at the single-cell resolution have not yet been characterized.MethodsWe explored the osteoimmunology communications between immune cells and osteoblastic lineage cells (OBCs) by performing CellphoneDB and CellChat analyses with single-cell RNA sequencing (scRNA-seq) data from human femoral head. We also explored the osteoimmunology effects of immune cells in peripheral circulation on skeletal phenotypes. We used a scRNA-seq dataset of peripheral blood monocytes (PBMs) to perform deconvolution analysis. Then weighted gene co-expression network analysis (WGCNA) was used to identify monocyte subtype-specific subnetworks. We next used cell-specific network (CSN) and the least absolute shrinkage and selection operator (LASSO) to analyze the correlation of a gene subnetwork identified by WGCNA with bone mineral density (BMD).ResultsWe constructed immune cell and OBC communication networks and further identified L-R genes, such as JAG1 and NOTCH1/2, with ossification related functions. We also found a Mono4 related subnetwork that may relate to BMD variation in both older males and postmenopausal female subjects.ConclusionsThis is the first study to identify numerous ligand-receptor pairs that likely mediate signals between immune cells and osteoblastic lineage cells. This establishes a foundation to reveal advanced and in-depth osteoimmunology interactions to better understand the relationship between local bone microenvironment and immune cells in peripheral blood and the impact on bone phenotypes.

ObjectiveAchieving negative resection margin is critical but challenging in breast-conserving surgery. Fluorescence-guided surgery allows the surgeon to visualize the tumor bed in real-time and to facilitate complete resection. We envisioned that intraoperative real-time fluorescence imaging with a human serum albumin decorated indocyanine green probe could enable complete surgical removal of breast cancer in a mouse model.MethodsWe prepared the probe by conjugating indocyanine green (ICG) with human serum albumin (HSA). In vitro uptake of the HSA-ICG probe was compared between human breast cancer cell line MDA-MB-231 and normal breast epithelial cell line MCF 10A. In vivo probe selectivity for tumors was examined in nude mice bearing MDA-MB-231-luc xenografts and the FVB/N-Tg (MMTV-PyMT) 634Mul/J mice model with spontaneous breast cancer. A positive-margin resection mice model bearing MDA-MB-231-luc xenograft was established and the performance of the probe in assisting surgical resection of residual lesions was examined.ResultsA significantly stronger fluorescence intensity was detected in MDA-MB-231 cells than MCF 10A cells incubated with HSA-ICG. In vivo fluorescence imaging showed that HSA-ICG had an obvious accumulation at tumor site at 24 h with tumor-to-normal tissue ratio of 8.19 ± 1.30. The same was true in the transgenic mice model. The fluorescence intensity of cancer tissues was higher than that of non-cancer tissues (58.53 ± 18.15 vs 32.88 ± 11.34). During the surgical scenarios, the residual tumors on the surgical bed were invisible with the naked eye, but were detected and resected with negative margin under HSA-ICG guidance in all the mice (8/8). Recurrence rate among mice that underwent resection with HSA-ICG (0/8) was significantly lower than the rates among mice with ICG (4/8), as well as the control group under white light (7/7).ConclusionsThis study suggests that real-time in vivo visualization of breast cancer with an HSA-ICG fluorescent probe facilitates complete surgical resection of breast cancer in a mouse xenograft model.