Jun Yu

Angiogenesis, an essential process controlling the formation of new blood vessels, has been recognized to play a pivotal role in the pathophysiology of various diseases. A major cause of pathological angiogenesis is dysregulated vascular endothelial cell proliferation, migration, and tube formation. Edgeworthia gardneri (Wall.) Meisn. (EG), a well-known traditional Tibetan medicine, exhibits diverse pharmacological properties and has been shown to exert an endothelium-protective effect. However, its role in regulating endothelial cell-mediated angiogenesis has yet to be determined. Herein, a 30% ethanolic extract of EG (EEEG) is prepared and characterized as a promising anti-angiogenic agent. EEEG significantly inhibits endothelial cell proliferation, migration, and capillary-like tube formation in vitro. Using a syngeneic mouse tumor model, we demonstrate that EEEG suppresses angiogenesis in vivo, as reflected by reductions in both CD31-positive microvessel density and the expression of pro-angiogenic biomarkers within tumors. This anti-angiogenic effect may impair tumor growth in EEEG-treated mice. Furthermore, our study shows that EEEG’s mode of action on endothelial cells may be attributed to the attenuation of PI3K/AKT, JNK, and ERK signaling pathways. Collectively, these findings highlight the anti-angiogenic effect of EEEG and provide novel insights into its potential application in managing angiogenesis-dependent diseases.

Nanomedicine harnesses the unique benefits of nanocarriers to markedly enhance drugs targeting tumors, which is becoming a promising approach to achieve precise and effective antitumor therapy. Extracellular vesicles (EVs), natural nanoscale entities, have garnered extensive attention due to their high biocompatibility and low immunogenicity. However, they often lack the specificity to identify and target lesion sites, leading to side effects when used systemically. Thus, modifying EVs to enhance their targeting ability is crucial. This review comprehensively elucidates the use of natural EVs in tumor treatment and functionalization strategies for EVs, including bioengineering modifications of parent cells, covalent and noncovalent modifications for the EV surface. The particular emphasis is placed on the precision delivery strategies of these functionalized EVs. According to the different delivery endpoints, they can be classified into tumor microenvironment delivery, intracellular delivery into tumor cells, and dual delivery to the tumor microenvironment and the tumor cell. Future perspectives focus on the essential aspects of constructing functionalized EVs and anticipate their evolving role in tumor-targeted therapies. Overall, this review offers a thorough analysis of recent advancements in functionalized EVs for antitumor therapy, providing valuable insights for their future development and precision biomedical applications.

Achieving a mature arteriovenous fistula (AVF) for hemodialysis remains a significant challenge, even for the most experienced vascular surgeons. Despite decades of research, ≈40% of new AVFs require salvage interventions or can never be used for dialysis. All clinical trials aimed at improving early AVF maturation have failed. This underscores the limitations of the existing biological model, which continues to frame stenosis through a reductionist lens centered on intimal hyperplasia, despite emerging evidence that this explanation is insufficient. This review seeks to redefine the biological framework of early AVF failure by adopting a human-centered perspective. In contrast to the prevailing paradigm, primarily built upon experimental data, our model is centered on human observational research and clinical trials. We then incorporate experimental data to provide mechanistic insights and contextualize or contrast the differences between human and animal biology. We unravel the biology of AVF maturation through 2 tightly connected phases: the acute biomechanical response, encompassing immediate structural and hemodynamic changes after AVF creation, and the subsequent vascular healing and remodeling processes that determine the long-term adaptation of the vein to supraphysiological circulation. By integrating these phases into a cohesive framework, this review advances a more comprehensive model of early AVF maturation failure, highlights therapeutic opportunities, and underscores that meaningful innovation in AVF biology remains both necessary and achievable.

The Apelinergic system (AS) is a crucial endocrine system that plays a vital role in renal physiology and disease. All components of the AS are expressed throughout the kidneys in both humans and rodents. A multitude of studies have consistently shown that the AS exerts a protective effect on the kidneys across a wide spectrum of renal pathologies, encompassing acute kidney injury, chronic kidney disease, diabetic nephropathy, hypertensive kidney injury, cardiorenal syndrome, and renal cell carcinoma. Considering its pivotal role, it shows immense potential as a viable therapeutic target for renal disorders. A deeper mechanistic understanding of the AS will accelerate the rational development of novel therapeutic agents for kidney diseases. In this review, we offer a concise overview of the physiological and pathological roles of the AS in the kidney. Our focus lies on its diuretic effect and its renoprotective action against kidney injury. Enhancing the levels of peripheral Apelin or ELABELA peptides to a certain degree could potentially serve as a promising pharmacological therapeutic strategy for kidney diseases.

Neutropenia is a common complication in oncology patients receiving chemotherapy, and rapid regeneration of functional neutrophils is critical for effective management. Bletilla striata polysaccharide (BSP) has shown therapeutic potential, but its mechanisms and molecular targets remain unclear. Here, we demonstrate that BSP accelerates the recovery of white blood cells, particularly neutrophils, in a chemotherapy-induced neutropenia (CIN) mouse model with cyclophosphamide (CY). The regenerated neutrophils retained phagocytic activity against bacteria, and BSP treatment significantly reduced mortality in the endotoxin-induced mouse death model. Furthermore, BSP enhanced the repopulation of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow and promoted cell-cycle entry, resulting in increased frequencies of long-term hematopoietic stem cells (LT-HSCs), multipotent progenitors 2 (MPP2), and MPP3/4 subsets. Both in vitro colony formation and in vivo competitive transplantation assays confirmed that BSP reshapes hematopoietic reconstitution and corrects aberrant myeloid differentiation. PCR array analysis of HSPCs indicated that this process is mediated by C/EBPε and its downstream genes (LTF, LCN2, and ELANE). Consistently, BSP failed to support myeloid reconstitution following C/EBPε knockdown in vitro. In a C/EBPε knockout mouse model, HSPCs repopulation and regeneration were impaired, and BSP failed to promote neutrophil recovery after CY challenge or the mobilization of MPP2 and MPP3/4 subsets. The regulatory effects of BSP on C/EBPε target genes were also abolished. In conclusion, our findings identify C/EBPε as a key mediator of BSP activity, driving HSPCs repopulation and restoring hematopoietic function. These results highlight BSP as a potential therapeutic strategy for chemotherapy-induced neutropenia.

High-viscosity rice soup is not only a popular food item but also a traditional Chinese medicinal remedy. The study employed ND-EESI-MS with untargeted metabolomics for the rapid detection of pollutants in rice soup without pretreatment.

Background: Atherosclerosis is a progressive arterial disease characterized by chronic inflammation and plaque formation in blood vessel walls. ELABELA, an endogenous ligand for the G protein‐coupled receptor APJ (apelin peptide jejunum, apelin receptor), has multiple pharmacological activities for protecting the cardiovascular system. This study aimed to determine the potential antiatherosclerotic effect of ELABELA and reveal the underlying mechanisms. Methods: We enrolled a cohort consisting of patients with and without atherosclerosis to determine the relationship between plasma ELABELA levels and atherosclerosis severity. The potential therapeutic action of ELA‐21 (ELABELA‐21) on atherosclerosis in high‐fat diet‐fed ApoE ^−/− mice was evaluated. Results: Plasma ELABELA levels were significantly reduced and negatively correlated with plasma MMP2 (matrix metallopeptidase 2) and MMP9 (matrix metallopeptidase 9) levels in patients with atherosclerosis and high‐fat diet‐induced atherosclerotic ApoE ^−/− mice. Plasma ELABELA levels exhibited a potential diagnostic value for patients with atherosclerosis. Applying ELA‐21 significantly decreased the atherosclerotic plaque area and inflammation in the aortas of the ApoE ^−/− mice. ELA‐21 administration modulated the balance between M1 and M2 macrophages in the abdominal cavity and aorta roots toward a more anti‐inflammatory status, accompanied by reduced MMP2, MMP9, and PRR ([pro]renin receptor), and enhanced macrophage APJ, ACE (angiotensin‐converting enzyme), and ACE2 (angiotensin‐converting enzyme 2) protein expression in plaques within aortic roots and decreased plasma soluble PRR levels. In vitro, ELA‐21 effectively suppressed oxidized low‐density lipoprotein‐induced foam cell formation and lipopolysaccharide/interferon‐γ‐induced M1 polarization in cultured macrophages. Interestingly, the anti‐inflammatory effect of ELA‐21 was further enhanced by APJ inhibitor ML221 [4‐oxo‐6‐((pyrimidin‐2‐ylthio)methyl)‐4H‐pyran‐3‐yl 4‐nitrobenzoate], accompanied by elevated ACE and ATP6AP2 (ATPase, H ⁺ ‐transporting, lysosomal accessory protein 2) and reduced ACE2 mRNA levels. Conclusions: Our data highlighted the diagnostic and therapeutic potential of ELABELA on atherosclerosis. ELA‐21 protects against atherosclerosis by inhibiting atherosclerotic plaque formation and promoting a more stable plaque phenotype, possibly via restoring the M1/M2 macrophage balance, enhancing macrophage ACE and ACE2 expression, and inhibiting the PRR system. ELABELA may be a novel diagnostic biomarker and candidate therapeutic target for atherosclerosis.