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Interferon Gamma Inducible Protein 16 (IFI16) belongs to the HIN-200 protein family and is pivotal in immunological responses. Serving as a DNA sensor, IFI16 identifies viral and aberrant DNA, triggering immune and inflammatory responses. It is implicated in diverse cellular death mechanisms, such as pyroptosis, apoptosis, and necroptosis. Notably, these processes are integral to the emergent concept of PANoptosis, which encompasses cellular demise and inflammatory pathways. Current research implies a significant regulatory role for IFI16 in PANoptosis, particularly regarding cardiac pathologies. This review delves into the complex interplay between IFI16 and PANoptosis in heart diseases, including atherosclerosis, myocardial infarction, heart failure, and diabetic cardiomyopathy. It synthesizes evidence of IFI16's impact on PANoptosis, with the intention of providing novel insights for therapeutic strategies targeting heart diseases.
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Background: Tanshinone IIA (TIIA) is the major lipid-soluble active ingredient of the traditional Chinese medicine Salvia miltiorrhiza, which slows down atherosclerosis (AS). However, it remains unclear whether TIIA has the potential to enhance macrophage efferocytosis and thereby improve atherosclerosis. Objective: The focus of this examination was to determine if TIIA could reduce lipid accumulation and treat AS by enhancing efferocytosis. Methods: Firstly, we conducted in vivo experiments using LDLR knockout (LDLR-/-) mice for a period of 24 weeks, using histopathological staining, immunofluorescence and Western blot experiments to validate from the efficacy and mechanism parts, respectively; in addition, we utilized cells to validate our study again in vitro. The specific experimental design scheme is as follows: In vivo, Western diet-fed LDLR-/- mice for 12 weeks were constructed as an AS model, and normal diet-fed LDLR-/- mice were taken as a blank control group. The TIIA group and positive control group (atorvastatin, ATO) were intervened for 12 weeks by intraperitoneal injection (15 mg/kg/d) and gavage (1.3 mg/kg/d), respectively. In vitro, RAW264.7 cells were cultured with ox-LDL (50 ug/mL) or ox-LDL (50 ug/mL) + TIIA (20 uM/L or 40 uM/L). Pathological changes in aortic plaques and foam cell formation in RAW264.7 cells were evaluated using Masson and Oil Red O staining, respectively. Biochemical methods were used to detect lipid levels in mice. The immunofluorescence assay was performed to detect apoptotic cells and efferocytosis-related signal expression at the plaques. RT-qPCR and Western blot were carried out to observe the trend change of efferocytosis-related molecules in both mouse aorta and RAW264.7 cells. We also used the neutral red assay to assess RAW264.7 cells' phagocytic capacity. Results: Compared with the model group, TIIA decreased serum TC, TG, and LDL-C levels (p < 0.01), reduced the relative lumen area of murine aortic lipid-rich plaques (p < 0.01), enhanced the stability of murine aortic plaques (p < 0.01), reduced ox-LDL-induced lipid build-up in RAW264.7 cells (p < 0.01), and upregulated efferocytosis-related molecules expression and enhance the efferocytosis rate of ox-LDL-induced RAW264.7 cells. Conclusion: TIIA might reduce lipid accumulation by enhancing the efferocytosis of macrophages and thus treat AS.
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Cancer represents one of the leading causes of mortality worldwide. Conventional clinical treatments include radiation therapy, chemotherapy, immunotherapy, and targeted therapy. However, these treatments have inherent limitations, such as multidrug resistance and the induction of short- and long-term multiple organ damage, ultimately leading to a significant decrease in cancer survivors' quality of life and life expectancy. Paeonol, a nature active compound derived from the root bark of the medicinal plant Paeonia suffruticosa, exhibits various pharmacological activities. Extensive research has demonstrated that paeonol exhibits substantial anticancer effects in various cancer, both in vitro and in vivo. Its underlying mechanisms involve the induction of apoptosis, the inhibition of cell proliferation, invasion and migration, angiogenesis, cell cycle arrest, autophagy, regulating tumor immunity and enhanced radiosensitivity, as well as the modulation of multiple signaling pathways, such as the PI3K/AKT and NF-κB signaling pathways. Additionally, paeonol can prevent adverse effects on the heart, liver, and kidneys induced by anticancer therapy. Despite numerous studies exploring paeonol's therapeutic potential in cancer, no specific reviews have been conducted. Therefore, this review provides a systematic summary and analysis of paeonol's anticancer effects, prevention of side effects, and the underlying mechanisms involved. This review aims to establish a theoretical basis for the adjunctive strategy of paeonol in cancer treatment, ultimately improving the survival rate and enhancing the quality of life for cancer patients.
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To systematically evaluate the clinical efficacy and safety of Xinmailong Injection in the treatment of heart failure after acute myocardial infarction. Seven Chinese and English databases, namely CNKI, VIP, Wanfang, SinoMed and PubMed, EMbase, Cochrane Library, were retrieved from the establishment of the database to March 2020. Randomized controlled trials for Xinmailong Injection in the treatment of heart failure after acute myocardial infarction were screened out. Cochrane collaboration network bias risk assessment tool was used to evaluate the literature quality of the studies included, and RevMan 5.3 software was used for Meta-analysis. A total of 926 relevant literatures were retrieved, and 12 studies were finally included, involving 972 patients, including 486 patients in the treatment group and 486 patients in the control group. The quality of the literatures included was generally low. The results of Meta-analysis showed that Xinmailong Injection combined with Western medicine could decrease the levels of BNP(SMD=-5.90, 95%CI[-8.45,-3.36], P<0.000 01) and NT-proBNP(SMD=-2.28, 95%CI[-3.13,-1.43], P<0.000 01) and decrease the levels of cTnI(SMD=-2.91, 95%CI[-4.21,-1.60], P<0.000 1), increase LVEF(MD=4.67, 95%CI[4.19, 5.16], P<0.000 01), increased 6 MWT(MD=73.90, 95%CI[67.51, 80.28], P<0.000 01], decreased LVEDD(MD=-5.46, 95%CI[-9.66,-1.25], P=0.01), reduce the level of serum inflammatory factor(hs-CRP, CRP, IL-6). In terms of safety, less adverse reactions occurred in the study, with no impact on the treatment. The results showed that clinical use of Xinmailong Injection combined with Western medicine in the treatment of heart failure after acute myocardial infarction can further alleviate clinical symptoms and relevant indexes, with less adverse reactions. However, due to the limitations in quantity and quality of the clinical studies included, the positive results can only be used as a hint and reference for clinical diagnosis and treatment, and more high-quality studies are needed to further confirm its efficacy.