The story of high mobility group protein B1 (HMGB1) in cancer is complicated and the function of HMGB1 in different cancers is uncertain. This review aims to retrieve literature regarding HMGB1 from English electronic resources, analyze and summarize the role of the HMGB1 signaling pathway in hepatocellular carcinoma (HCC), and provide useful information for carcinogenesis and progression of HCC. Results showed that HMGB1 could induce cell proliferation, differentiation, cell death, angiogenesis, metastasis, inflammation, and enhance immunofunction in in vitro and in vivo HCC models. HMGB1 and its downstream receptors RAGE, TLRs and TREM-1 may be potential anticancer targets. In conclusion, HMGB1 plays an important role in oncogenesis and represents a novel therapeutic target, which deserves further study.

Hyperuricemia (HUA) can lead to hyperuricemic nephropathy (HN) as a result of prolonged uric acid (UA) supersaturation, primarily characterized by excessive inflammation and oxidative stress. In clinical practice, the absence of specific drugs for HN treatment necessitates the use of urate-lowering drugs, despite their lack of reno-protective properties. Linarin, the principal pharmacological constituent of Chrysanthemum indicum L. (C. indicum L.), exhibits diverse bioactivities, including anti-inflammatory, antioxidant, and nephroprotective effects. However, there have been no reports on linarin's ability to mitigate HN, and the underlying mechanisms remain unexplored. This study aimed to investigate the mechanisms of linarin on ameliorating HN, with a particular emphasis on oxidative stress and inflammatory pathways. A HUA mouse model was developed using male ICR mice treated with hypoxanthine and potassium oxonate. Additionally, an adenosine-induced hyperuricemic cell model was established in NRK-52E cells. Following linarin treatment, serum UA levels and renal function parameters were assessed. The expression of proteins associated with UA production and excretion, oxidative stress, inflammation, and apoptosis was evaluated using western blot, immunohistochemical, and immunofluorescence analyses. Furthermore, Nrf2 knockout mice and Nrf2 inhibitor ML385 were utilized to investigate the mechanism of linarin on improving HN. Linarin significantly decreased the serum UA levels, inhibited XO activity and regulated UA transporter in the HUA mice. Moreover, linarin reversed the renal index, serum BUN and Cr levels, along with the expression levels of KIM-1, apoptosis-related molecules. Additionally, linarin obviously reduced the levels of TNF-α, IL-1β and IL-6, and alleviated renal inflammatory via suppressing the TLR4, p-NF-κB and p-IκBα levels. Furthermore, linarin was able to reverse the levels of SOD and MDA, and the expression of Nrf2, Keap1, NQO1, and HO-1 to mitigate oxidative stress both in vitro and in vivo. Inhibition of Nrf2 further confirmed that the renoprotective effect of linarin was linked to the activation of Nrf2. This study is the first to propose linarin as a potential natural compound for alleviating HN by modulating the Nrf2/Keap1 and TLR4/NF-κB signaling pathways, providing a promising strategy for HN.

Luteolin is a natural flavonoid, which exists in many plants, including onions, broccoli, carrots, peppers, celery, olive oil, and mint. Luteolin is a dietary flavonoid with potent uric acid‐lowering and antioxidant bioactivities. To date, the mechanism by which luteolin alleviates hyperuricemia nephropathy (HN) still needs to be better defined. This study aims to evaluate the therapeutic efficacy of luteolin in a preclinical mouse model and in vitro. Luteolin was administered in the HN mice induced by the combination of potassium oxonate and hypoxanthine to evaluate the potential renoprotective effects in vivo. The NRK‐52E cells were stimulated with adenosine for in vitro evaluation. Hematoxylin and eosin staining, biochemical analysis, immunoblotting, immunofluorescence, and immunohistochemistry were performed for the histopathologic and mechanistic investigations. The results suggest that luteolin attenuated tubular dilation and epithelial atrophy in the renal tissue of HN mice. Further, luteolin improved biochemical indicators concerning renal functions and oxidative stress in vivo. Mechanistically, luteolin reduced the renal expressions of KIM‐1 and caspase‐3. Luteolin activated renal SIRT1/6 cascade and its downstream Nrf2‐mediated antioxidant pathway. Furthermore, luteolin elevated the renal expressions of ATP‐binding cassette subfamily G isoform 2 protein (ABCG2) and organic anion/cation transporters. In addition, livers of luteolin‐treated HN mice exhibited robust inhibition of xanthine oxidase. Together, our study shows that luteolin alleviates renal injury in the HN mice by activating urate excretion and Nrf2/HO‐1/NQO1 antioxidant pathways and inhibiting liver xanthine oxidase activity. Thus, luteolin may be a potential agent for the treatment of HN.

Astragali Radix (A. Radix) is the dry root of the leguminous plants Astragalus membranaceus (Fisch) Beg. var. mongholicus (Beg) Hsiao, and Astragalus membranaceus (Fisch) Bge., being used as a medicinal and edible resource. AR is used in traditional Chinese medicine prescriptions to treat chronic nephritis. Calycosin (CA), the primary active compound derived from Astragali Radix, shows significant antifibrotic effects in multiple organs, but the anti-renal fibrosis effect of CA is rarely reported, and the associated mechanism of action is still need to be elucidated. The objective of this study was to investigate the protective effects of CA on the kidney against renal fibrosis and the underlying molecular mechanisms. Evaluation of the effects of CA on renal fibrosis using unilateral ureteral obstruction (UUO) mice and transforming growth factor β1 (TGF β1)-induced cell fibrosis. The mechanism of action supporting the investigated anti-renal fibrosis effects were studied by a series of biochemical experiments. Our research demonstrated that CA reduced kidney cell fibrosis in mice with UUO and in TGF-β1-stimulated NRK-52E cells. Additionally, CA mitigated renal fibrosis via toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) and had a synergistic effect with resatorvid (TAK-242). Our findings revealed an unobserved impact of CA in inhibiting neutrophil extracellular traps (NETs) formation in UUO mice and neutrophils activated by phorbol 12-myristate 13-acetate. Our findings revealed that calycosin reduces NETs production to alleviate renal fibrosis via TLR4 and NF-κB, supporting its potential as a strategy for treating renal fibrosis.

Platelet function and count display robust circadian oscillations with a period of approximately 24 hours, governed by the core molecular clock and modulated by environmental factors such as light, diet, and stress. This review elaborates on three key aspects. First, platelet surface markers peak around 8–9 AM, whereas platelet count, ATP release, and aggregability reach their maximum between 3–8 PM. Mechanistically, the nuclear receptor Rev-erbα drives the morning surge in platelet reactivity and thrombosis via the OPHN-1/RhoA/ERM signaling pathway. Second, through their circadian rhythm, platelets actively participate in the pathogenesis of cardiovascular diseases, neurological disorders, and metabolic diseases. Third, circadian-targeting drugs including tasimelteon, ramelteon, agomelatine, SR9009, VTP-43742, and PF-670462 offer novel therapeutic strategies for rhythm-related disorders. This review highlights the circadian regulation of platelets as an emerging therapeutic target in human diseases.