Cancer cells frequently display fundamentally altered cellular metabolism, which provides the biochemical foundation and directly contributes to tumorigenicity and malignancy. Rewiring of metabolic programmes, such as aerobic glycolysis and increased glutamine metabolism, are crucial for cancer cells to shed from a primary tumor, overcome the nutrient and energy deficit, and eventually survive and form metastases. However, the role of lipid metabolism that confers the aggressive properties of malignant cancers remains obscure. The present review is focused on key enzymes in lipid metabolism associated with metastatic disease pathogenesis. We also address the function of an important membrane structure-lipid raft in mediating tumor aggressive progression. We enumerate and integrate these recent findings into our current understanding of lipid metabolic reprogramming in cancer metastasis accompanied by new and exciting therapeutic implications.

Cancer cells frequently adapt fundamentally altered metabolism to support tumorigenicity and malignancy. Epigenetic and metabolic networks are closely interactive, in which DNA methyltransferases (DNMTs) play important roles. Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (EBV-LMP1) is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis because it can trigger multiple cell signaling pathways that promote cell transformation, proliferation, immune escape, invasiveness, epigenetic modification, and metabolic reprogramming. Our current findings reveal for the first time that LMP1 not only upregulates DNMT1 expression and activity, but also promotes its mitochondrial translocation. This induces epigenetic silencing of pten and activation of AKT signaling as well as hypermethylation of the mtDNA D-loop region and downregulation of oxidative phosphorylation (OXPHOS) complexes, consequently, leading to metabolic reprogramming in NPC. Furthermore, we demonstrate that grifolin, a natural farnesyl phenolic compound originated from higher fungi, is able to attenuate glycolytic flux and recover mitochondrial OXPHOS function by inhibiting DNMT1 expression and activity as well as its mitochondrial retention in NPC cells. Therefore, our work establishes a mechanistic connection between epigenetics and metabolism in EBV-positive NPC and provides further evidence for pathological classification based on CpG island methylator phenotype (CIMP) in EBV-associated malignancies. In addition, grifolin might be a promising lead compound in the intervention of high-CIMP tumor types. The availability of this natural product could hamper tumor cell metabolic reprogramming by targeting DNMT1.

Metastasis is the most malignant stage of cancer. Lipid metabolic abnormalities are now increasingly recognized as characteristics of cancer cells. The accumulation of certain lipid species, such as signaling lipids, due to the avidity of lipid metabolism may be a causal factor of tumor malignant progression and metastatic behavior. In this review, we first describe signaling lipids implicated in cancer migration, invasion and metastasis. Next, we summarize the regulatory signaling hubs of lipid anabolic and catabolic metabolism. We then address lipid-rich circulating tumor cells (CTCs) and the lipid composition of exosomes budded off from tumor cells. We also present advances in targeting the regulatory hubs of lipid metabolism and signaling lipids in cancer therapy. Given the complexity of metabolic disorders in cancer, the development of significant portfolios of approaches to target signaling lipids by the integration of multiple chemical modulations, as well as molecular imaging modalities, should offer promising strategies for cancer therapy.

HIV protease inhibitor (PI) ritonavir (RTV) may cause vascular injury through oxidative stress. Our purpose in this study was to determine whether equol, a soy isoflavone, could prevent RTV-induced endothelial dysfunction in porcine pulmonary arteries and in human pulmonary artery endothelial cells (HPAEC). Fresh porcine pulmonary artery rings were treated with 15 micromol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 micromol/L for 24 h. A control was set with no amount of equol or RTV administered. Based on myograph tension analysis, RTV significantly reduced endothelium-dependent relaxation in response to bradykinin in the artery rings compared with untreated vessels, whereas the antioxidant equol effectively reversed the RTV effect in a concentration-dependent manner. RTV also reduced the contraction of artery rings in response to thromboxane A(2) analogue U46619 and this reduction was blocked by equol. In addition, RTV treatment significantly reduced endothelial nitric oxide synthase (eNOS) expression in both porcine pulmonary arteries and HPAEC, whereas equol effectively blocked RTV-induced eNOS downregulation. Furthermore, RTV significantly increased superoxide anion production, whereas equol reversed this effect of RTV in porcine pulmonary arteries. Thus, the antioxidant equol effectively protects vascular function from the detrimental effects of HIV PI RTV in both porcine pulmonary arteries and HPAEC via a reduction in the vasomotor dysfunction, eNOS downregulation, and oxidative stress induced by RTV. These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications.

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This study is to evaluate the efficacy and safety of vaginoscopic incision of oblique vaginal septum in adolescents with Obstructed hemi-vagina and ipsilateral renal agenesis (OHVIRA) syndrome. It is about Fourteen adolescents with OHVIRA syndrome managed by vaginoscopic incision of the oblique vaginal septum using a “No-touch” technique over an 8-year period. In all fourteen adolescents with OHVIRA the oblique vaginal septum was incised successfully without any intraoperative complications. Postoperative pain was unremarkable and each patient’s symptoms resolved postoperatively. The 3-month postoperative follow up office vaginoscopy revealed that the vaginal septum had not reformed nor was any vaginal stenosis noted. Vaginoscopic incision of the oblique vaginal septum using a “No-Touch” technique is a safe, minimally invasive, and effective approach for treating OHVIRA syndrome in adolescents with hematocolpos. This technique may be utilized to minimize disruption to the undeveloped vaginal wall and postoperative pain while providing excellent surgical visualization throughout the procedure.

MVT is associated with significant mortality. Prompt diagnostic evaluation with computed tomography may reduce potential treatment delay. Underlying malignancy, advanced age, and prolonged symptom duration are predictive of poor outcome.

Metabolic disorders can lead to a scarcity or excess of certain metabolites such as glucose, lipids, proteins, purines, and metal ions, which provide the biochemical foundation and directly contribute to the etiology of metabolic diseases. Nonalcoholic fatty liver disease, obesity, and cancer are common metabolic disorders closely associated with abnormal lipid metabolism. In this review, we first describe the regulatory machinery of lipid metabolism and its deregulation in metabolic diseases. Next, we enumerate and integrate the mechanism of action of some natural compounds, including terpenoids and flavonoids, to ameliorate the development of metabolic diseases by targeting lipid metabolism. Medicinal natural products have an established history of use in health care and therapy. Natural compounds might provide a good source of potential therapeutic agents for treating or preventing metabolic diseases with lipid metabolic abnormalities.