Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

The etiology of melasma is complicated. Although there are many treatment methods for melasma at present, no definite or satisfactory efficacy has been achieved. In recent years, good therapeutic outcomes have been achieved in the treatment of melasma with intense pulsed light. This review summarizes the progress in the treatment of melasma with intense pulsed light alone or in combination with various lasers, external drugs and systemic drugs in recent years.

Propranolol is a non-selective β-adrenoceptor blocker. Various studies have confirmed that it is safe and effective for the treatment of infantile hemangioma. The mechanism of action mainly includes: (1) pericyte-mediated hemodynamic changes and subsequent effects; (2) inhibiting proliferation of hemangioma-derived endothelial cells and stem cells by blocking cell cycle progression, inducing apoptosis of hemangioma-derived endothelial cells and differentiation of hemangioma-derived stem cells into adipocytes; (3) inhibiting the recruitment of endothelial progenitor cells; (4) reducing levels of pro-angiogenic factors, such as vascular endothelial growth factor, matrix metalloproteinase, etc.