Trimethylamine-N-oxide (TMAO), a phospholipid metabolite, can modulate cholesterol synthesis and promote vascular inflammation and endothelial dysfunction, thereby increasing the risk of atherosclerosis (AS). Previously, it was found that naringin reduced damage to human umbilical vein endothelial cells (HUVECs) triggered by oxidized low-density lipoprotein. This article continues to explore the role and mechanism of naringin in protecting HUVECs from TMAO-induced damage. After the construction of TMAO-induced AS model in HUVECs, inflammation, oxidative stress, and endothelial function were examined by real-time quantitative polymerase chain reaction, Western blotting, nitric oxide (NO), reactive oxygen species (ROS), superoxide dismutase, and malondialdehyde (MDA) kits. Results showed that naringin pretreatment inhibited endothelial inflammation and oxidative stress, promoted NO release, and inhibited the degradation of Zona occludens-2, occludin, and vascular endothelial-cadherin, thereby restoring the functional and structural integrity of the endothelium. Furthermore, the addition of mitogen-activated protein kinase (MAPK) agonist demonstrated that the therapeutic effect of naringin was achieved through inactivating TMAO-stimulated MAPK signaling in HUVECs.

Cancer cachexia is a fatal syndrome associated with muscle regeneration disability. Tumor factors induce the apoptosis of myoblasts to impair the regeneration of skeletal muscle. Cancer cachectic myoblast apoptosis is associated with mitochondria injury. It has been reported that activated mitochondrial calpain caused mitochondria injury in mouse cardiomyocytes and pulmonary smooth muscle. We wondered if mitochondrial calpains exist in skeletal myoblast and their potential role in myoblast apoptosis of cancer cachexia. We used a transwell to build a novel myoblast-carcinoma cell coculture model to simulate the cancer cachexia environment in vitro. Calpain inhibitors, calpastatin (CAST) and calpeptin (CAPT), were used during coculture. We found for the first time that two calpains (calpain-1 and calpain-2) and CAST were present in the mitochondria of myoblast. The activation of mitochondrial calpain decreased mitochondrial complex I activity, promoted mitochondrial permeability transition pore opening, and impaired mitochondrial membrane potential in myoblast during coculture, which induced myoblasts apoptosis. CAST and CAPT protected myoblasts from apoptosis by inhibiting mitochondrial calpain activity, which may attenuate or even reverse cancer cachectic muscle atrophy by improving muscle regeneration ability. Our study provides a new perspective for understanding the mechanism of cancer cachexia, and will further contribute to treat cancer cachexia by focusing on the mitochondrial calpain activity.

Bone marrow mesenchymal stem cells (BM-MSCs), with the properties of self-renewal and pluripotency, can migrate to the tumor sites and exert complex effects on tumor progression and communications by releasing exosomes. However, to our knowledge, only a few studies have reported the effects of BM-MSCs exosomes on breast cancer cells development. Here, utilizing exosomes isolated from in vitro BM-MSCs, we systematically investigated this issue in a breast cancer cell line. In this study, we found that BM-MSCs exosomes are actively incorporated by breast cancer cell MDA-MB-231 cells and subsequently promote MDA-MB-231 cells proliferation and migration. Mechanistically, we further found Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) which are Hippo signaling components were involved in this promoting progress. Consistently, YAP and TAZ knockdown could significantly reverse breast cancer cells proliferation and migration improved by BM-MSCs exosomes. Taken together, our findings demonstrated a new mechanism through which BM-MSCs-derived exosomes may contribute to breast cancer cells proliferation and migration, which might provide an evidence for novel drug discovery based on exosomes and Hippo signaling.

Cardiopulmonary bypass (CPB) depletes endogenous Vitamin C and generates oxidative stress in cardiac surgery. This study aimed to clarify whether Vitamin C supplementation reduces oxidant production and improves erythrocyte deformability in cardiac surgery with CPB. In a randomized and controlled design, 30 eligible patients undergoing cardiac surgery with hypothermic CPB were equally assigned to the Vitamin C group and control group. Subjects of the Vitamin C group and control group received an intravenous infusion of Vitamin C 20 mg·kg^–1 and a placebo during rewarming period of CPB, respectively. We measured the plasma level of reactive oxygen species (ROS) and phosphorylation levels of non-muscle myosin IIA (NMIIA) in erythrocyte membrane, as an index of erythrocyte deformability, before and after CPB. Vitamin C supplementation attenuated the surge in plasma ROS after CPB, mean 1.661 ± standard deviation 0.801 folds in the Vitamin C group and 2.743 ± 1.802 in the control group. The tyrosine phosphorylation level of NMIIA after CPB was upregulated in the Vitamin C group compared to the control group, 2.159 ± 0.887 folds and 1.384 ± 0.445 (P = 0.0237). In addition, the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and focal adhesion kinase (FAK) in erythrocytes was concurrently enhanced in the Vitamin C group after CPB. The phosphorylation level of endothelial nitric oxide synthase in erythrocytes was significantly increased in the Vitamin C group (1.734 ± 0.371 folds) compared to control group (1.102 ± 0.249; P = 0.0061). Patients receiving Vitamin C had lower intraoperative blood loss and higher systemic vascular resistance after CPB compared to controls. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability via VASP/FAK signaling pathway in erythrocytes during CPB.

This study aimed to investigate the effects of triiodothyronine (T₃)- or dopamine (Dp)-supplemented diets on oxygen consumption by Na⁺, K⁺-ATPase activity in broiler chicks. Five groups, each with twenty-four 6-day-old chicks, randomly received one of the five dietary treatments: (1) Basal diet (commercial broiler rations with 23.0% crude protein and 3,133 kcal metabolizable energy/kg) or CON, (2) basal diet plus 0.7 μmol Dp/kg diet or Dp0.7, (3) basal diet plus 2.4 μmol Dp/kg diet or Dp2.4, (4) basal diet plus 1.9 μmol T₃/kg diet or T1.9, and (5) basal diet plus 3.8 μmol T₃/kg diet or T3.8 from 6 to 14 days of age. There were four replicates per treatment and 120 birds in total. At 14 days of age, three chicks from each replicate of each treatment were pooled into a flock and fed commercial broiler diets until 7 weeks of age. Compared to CON group, birds fed with T3-supplemented diets had lower thyroid, abdominal fat pad, gizzard and pancreas weight, and heavier heart weight adjusted for fasted body weight. Chicks with T1.9 had lower ileal densities at 14 day old compared with those in Dp groups or CON. Chicks with T3.8 exhibited greater duodenal and jejunal O₂ consumptions as well as ouabain-sensitive O₂ consumptions of jejunum and small intestine (duodenum, jejunum, and ileum) by 46.5%, 58.3%, 40.6%, and 26.4% increases, than those in CON. Partial correlation analysis revealed that the weight and length of the small intestine were negatively correlated with body weight gain. Oxygen consumption in the various small intestinal segments was negatively correlated with their respective densities (mg/mm²). In conclusion, a greater oxygen requirement for maintaining ouabain-sensitive respiration (Na⁺-K⁺-ATPase) in the intestine limits energy availability to support gastrointestinal tract growth and, thereby, may result in lower body weight gain.

Hepatocellular carcinoma is a common malignant tumor with high recurrence rate. Long non-coding RNA (lncRNA) ZNF561 antisense RNA 1 (ZNF561-AS1) functions as an oncogenic lncRNA to promote the tumorigenesis of colorectal cancer. The role of ZNF561-AS1 in hepatocellular carcinoma remains unknown. ZNF561-AS1 was elevated in hepatocellular carcinoma tissues and cells. Silence of ZNF561-AS1 reduced cell viability and inhibited the proliferation of hepatocellular carcinoma. The angiogenesis of hepatocellular carcinoma was also suppressed by loss of ZNF561-AS1 with a decrease of angiopoietin 2, fibroblast growth factor 1, and vascular endothelial growth factor. ZNF561-AS1 bind to miR-302a-3p, and decreased expression of miR-302a-3p in hepatocellular carcinoma. Moreover, miR-302a-3p reduced platelet-derived growth factor-D (PDGFD) in hepatocellular carcinoma, and inhibition of miR-302a-3p attenuated ZNF561-AS1 silence-induced decrease of PDGFD. In conclusion, silence of ZNF561-AS1 might inhibit cell proliferation and angiogenesis of hepatocellular carcinoma through downregulation of miR-302a-3p-mediated PDGFD.

Lung squamous cell carcinoma (SCC) is considered the frequent subtype of non-small cell lung cancer (NSCLC) and results in high mortality worldwide every year. Forkhead box S1 (FOXS1) is correlated to multiple cancers, but the role and the mechanism of FOXS1 in lung SCC are unclear. This study revealed that FOXS1 was low expressed in the lung SCC tissues by utilizing UALCAN and TIMER databases. Western blotting analysis was introduced to estimate the FOXS1 expression in the lung SCC cells. Functionally, overexpression of FOXS1 dramatically inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition in the lung SCC cells. However, knockdown of FOXS1 exerted diverse effects on lung SCC cell progression. Moreover, FOXS1 overexpression suppressed tumor growth in nude mice remarkably. Furthermore, FOXS1 overexpression reduced the activity of Wnt/β-catenin signal, while FOXS1 silence reversed the roles notably. In conclusion, our present study proved that FOXS1 inhibited lung SCC development in vitro and in vivo might by modulating Wnt/β-catenin signaling pathway.