The First Affiliated Hospital of Nanyang Medical College

The kidney is essential for lactate metabolism. Under normal conditions, the renal cortex mainly absorbs and metabolizes lactate, with minimal amounts excreted in urine. This process is part of a glucose-lactate recycling system between the cortex and medulla. In conditions such as acute kidney injury (AKI) and diabetic kidney disease (DKD), the kidney's ability to metabolize lactate is impaired, leading to lactate accumulation and exacerbated renal dysfunction. Novel post-translational modifications, such as lactylation, are critical in kidney disease pathophysiology by modulating gene transcription, protein function, and cellular metabolism. Lactylation is involved in inflammatory responses and tumor promotion in AKI, mitochondrial dysfunction in DKD, and tumor progression in clear cell renal cell carcinoma (ccRCC). The lactate-lactylation axis is central to the Warburg effect in ccRCC, where tumor cells preferentially rely on glycolysis rather than oxidative phosphorylation. Understanding the mechanisms of lactate metabolism and lactylation in kidney diseases may offer new therapeutic strategies. This review examines the role of lactate esters, especially lactylation, in kidney diseases, with a focus on their regulatory mechanisms and potential as therapeutic targets.

Angiogenesis is a complex physiological process. In recent years, the immune regulation of angiogenesis has received increasing attention, and innate immune cells, which are centred on macrophages, are thought to play important roles in vascular neogenesis and development. Various innate immune cells can act on the vasculature through a variety of mechanisms, with commonalities as well as differences and synergistic effects, which are crucial for the progression of vascular lesions. In recent years, monotherapy with antiangiogenic drugs has encountered therapeutic bottlenecks because of the short-term effect of 'vascular normalization'. The combination treatment of antiangiogenic therapy and immunotherapy breaks the traditional treatment pattern. While it has a remarkable curative effect and survival benefits, it also faces many challenges. This review focuses on innate immune cells and mainly introduces the regulatory mechanisms of monocytes, macrophages, natural killer (NK) cells, dendritic cells (DCs) and neutrophils in vascular lesions. The purpose of this paper was to elucidate the underlying mechanisms of angiogenesis and development and the current research status of innate immune cells in regulating vascular lesions in different states. This review provides a theoretical basis for addressing aberrant angiogenesis in disease processes or finding new antiangiogenic immune targets in inflammation and tumor.

Zein and its complexes have been considered as promising carriers for encapsulating and delivering various biological active ingredients, however, there still have some issues about Zein-based drug delivery systems should be considered, including poor colloidal stability, low drug encapsulation efficiency as well as rapid initial drug release, and uncontrollable release. In this work, we reported for the first time that hyperbranched polymers (HPG) functionalized Zein with terminal alkyne (Zein-HPG-PA) can be used for loading anticancer agent curcumin (CUR) via a facile phenol-yne click reaction. The resultant product (Zein-HPG-PA@CUR) displays high drug loading capacity, small particle size and excellent water dispersibility. More importantly, almost no CUR was released from Zein-HPG-PA@CUR under pH 7.4 and the cargo will be gradually released under acidic environment. As compared with free CUR, Zein-HPG-PA@CUR shows considerable cytotoxicity towards MDA-MB-231 cells under dark environment, while the cytotoxicity was significantly enhanced upon light-irradiation, implying great potential of Zein-HPG-PA@CUR for cancer treatment. Considered the above aspects, we believe that this work should be of significant impact on the biomedical applications of Zein, especially for fabrication of Zein-based responsive drug delivery systems.