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Aims Extracellular vesicles, especially exosomes, have emerged as key mediators of intercellular communication with the potential to improve cardiac function as part of cell-based therapies. We previously demonstrated that the cardioprotective factor, macrophage migration inhibitory factor (MIF), had an optimizing effect on mesenchymal stem cells (MSCs). The aim of this study was to determine the protective function of exosomes derived from MIF-pretreated MSCs in cardiomyocytes and to explore the underlying mechanisms. Methods and results Exosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosome MIF ), and delivered to cardiomyocytes subjected to H 2 O 2 in vitro. Regulatory long non-coding RNAs (lncRNAs) activated by MIF pretreatment were explored using genomics approaches. Exosome MIF protected cardiomyocytes from H 2 O 2 -induced apoptosis. Mechanistically, we identified lncRNA-NEAT1 as a mediator of exosome MIF by regulating the expression of miR-142-3p and activating Forkhead class O1 (FOXO1). The cardioprotective effects of exosome MIF were consistently abrogated by depletion of lncRNA-NEAT1, by overexpression of miR-142-3p, or by FOXO1 silencing. Furthermore, exosome MIF inhibited H 2 O 2 -induced apoptosis through modulating oxidative stress. Conclusions Exosomes obtained from MIF-pretreated MSCs have a protective effect on cardiomyocytes. The lncRNA-NEAT1 functions as an anti-apoptotic molecule via competitive endogenous RNA activity towards miR-142-3p. LncRNA-NEAT1/miR-142-3p/FOXO1 at least partially mediates the cardioprotective roles of exosome MIF in protecting cardiomyocytes from apoptosis.

Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including anti-proliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

Cancer immunotherapy has become a well-established treatment option for some cancers; however, its use is hampered by its cardiovascular adverse effects. Immune checkpoint inhibitors (ICIs)-related cardiac toxicity took place in kinds of different forms, such as myocarditis, acute coronary syndrome, and pericardial disease, with high mortality rates. This study aimed to investigate the roles of programmed death-1 (PD-1) inhibitor, one of widespread used ICIs, in the development of murine cardiac injury. PD-1 inhibitor is known to transduce immunoregulatory signals that modulate macrophages polarization to attack tumor cells. Hence, this study explored whether the cardiovascular adverse effects of PD-1 inhibitor were related to macrophage polarization. MicroRNA-34a (miR-34a), which appears to regulate the polarization of cultured macrophages to induce inflammation, is examined in cardiac injury and macrophage polarization induced by the PD-1 inhibitor. As a target of miR-34a, Krüppel-like factor 4 (KLF4) acted as an anti-inflammation effector to take cardiac protective effect. Further, it investigated whether modulating the miR-34a/KLF4-signaling pathway could influence macrophage polarization. The PD-1 inhibitor markedly induced M1 phenotype macrophage polarization with impaired cardiac function, whereas miR-34a inhibitor transfection treatment reversed M1 polarization and cardiac injury in vivo. In vitro, PD-1 inhibitor-induced M1 polarization was accompanied by an increase in the expression of miR-34a but a decrease in the expression of KLF4. TargetScan and luciferase assay showed that miR-34a targeted the KLF4 3′-untranslated region. Either miR-34a inhibition or KLF4 overexpression could abolish M1 polarization induced by the PD-1 inhibitor. The findings strongly suggested that the PD-1 inhibitor exerted its effect in promoting M1 polarization and cardiac injury by modulating the miR-34a/KLF4-signaling pathway and inducing myocardial inflammation. These findings might help us to understand the pathogenesis of cardiac injury during immunotherapy, and provide new targets in ameliorating cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.

Standardized guidelines for optimal tunnel length in tunneled peripherally inserted central catheters (PICCs) are lacking. The objective of this study was to evaluate the real-world impact of tunnel length on clinical outcomes. This retrospective cohort study included 207 cancer patients who received tunneled PICCs, categorized into a control group (tunnel length > 4 cm, n = 134) and an observation group (tunnel length ≤ 4 cm, n = 73). Propensity score matching (PSM) was used to address baseline heterogeneity. Cox regression analyses were used to assess the risk of complication during a 120-day follow-up. Compared to the control group (tunnel length > 4 cm), the observation group (tunnel length ≤ 4 cm) had a significantly higher adjusted overall complication risk (HR = 2.92, 95% CI: 1.07-7.94, P = 0.036) and unplanned catheter removal rate (4.4% vs. 0.0%, P = 0.027), confirming the safety of longer tunnels despite comparable comfort levels between groups. After PSM, Cox regression analysis showed results consistent with those from the unmatched cohort. Subgroup analyses revealed a reduced risk of complications with longer tunnels in patients with BMI ≤ 25 kg/m² (HR = 0.29, 95% CI: 0.11-0.82), without hypertension (HR = 0.36, 95% CI: 0.13-1.00), without diabetes (HR = 0.38, 95% CI: 0.15-0.97), and with solid tumors (HR = 0.31, 95% CI: 0.11-0.85). The results show that tunnel lengths > 4 cm reduce overall complications and prolong catheter retention, supporting the implementation of standardized protocols while advocating for personalized adjustments based on BMI, comorbidities, and cancer type.

Radiotherapy is one of the main treatment modalities for advanced hepatocellular carcinoma (HCC). Ferroptosis has been shown to promote the radiosensitivity of HCC cells, but it remains unclear whether epigenetic regulations function in this process. In this study, we found that the overexpression of METTL3 was associated with poor prognosis. Knockdown of METTL3 promoted radiosensitivity of HCC by inducing ferroptosis. Mechanistically, METTL3 targeted adenine (+1795) on the SLC7A11 mRNA, and the m 6 A reader IGF2BP2 promoted SLC7A11 mRNA stability by recognizing and binding to the m 6 A site. Additionally, METTL3 decreased the ubiquitination of SLC7A11 protein through the m 6 A/YTHDF2/SOCS2 axis. Furthermore, in vivo studies showed that HCC models with low METTL3/IGF2BP2 expression have higher radiosensitivity. In conclusion, our study suggests that METTL3 regulates the stability of SLC7A11 mRNA in an m 6 A/IGF2BP2-dependent manner and the ubiquitination of SLC7A11 protein through the m 6 A/YTHDF2/SOCS2 pathway, both of which require the m 6 A methyltransferase activity of METTL3. METTL3 or IGF2BP2 may be promising targets for radiotherapy of HCC. Highlights METTL3 contributed to the resistance to radiation by regulating the expression of SLC7A11 in HCC cells. METTL3 maintained the mRNA stability of SLC7A11 in an m 6 A/IGF2BP2-dependent manner, via the binding of IGF2BP2 with the m6A site (+1795) of SLC7A11 mRNA. METTL3 decreased the ubiquitination of SLC7A11 protein through the m 6 A/YTHDF2/SOCS2 axis. Knockdown of METTL3/IGF2BP2 improved the radiosensitivity of HCC.

BackgroundImmune checkpoint inhibitors (ICIs) have been an important therapeutic advancement in the field of cancer medicine. Recent reports provided greater insights into the cardiovascular adverse events, which prohibited the use of ICIs. Cardiovascular adverse events occur in different forms, such as myocarditis and cardiomyopathy, myocardial fibrosis, heart failure and pericardial disease. Cardiac aging overlapped with the occurrence of some cardiac diseases. Exosomes mediate cell–cell cross talk in cardiac diseases by transferring a variety of biomolecules, including microRNAs (miRs). miR-34a-5p is a well-known miR associated with the cardiac senescence. This study aimed to investigate whether cardiovascular adverse effects of the programmed cell death 1 (PD-1) inhibitor, a widely used ICI, were related to exosomal-transferred miR-34a-5p in cardiac senescence in a mouse model.Methods and resultsThe upregulation of miR-34a-5p in cardiomyocytes induced by exosomes derived from PD-1 inhibitor–treated macrophages, accompanied by cardiac senescence, caused cardiac injury in mouse hearts. miR-34a-5p was identified as an exosomal transfer RNA to induce cardiac senescence–related injury. Inhibiting miR-34a-5p in macrophages attenuated the exosomePD-1 inhibitor-induced pro-senescent effect in cardiomyocytes. TargetScan and luciferase assay showed that miR-34a-5p targeted the serine/threonine-protein phosphatase 1 regulatory subunit 10 (PNUTS) 3′-untranslated region.ConclusionsExosomes derived from PD-1 inhibitor–treated macrophages exerted a pro-senescent effect by modulating the miR-34a-5p/PNUTS signaling pathway. The findings might supply new targets to ameliorate cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.

Malate dehydrogenase 1 (MDH1), an NAD(H)-dependent isoenzyme, is a key component of the malate-aspartate shuttle (MAS). A significant association has been observed between MDH1 expression and various characteristics of the tumor microenvironment across different cancer types. This study provides comprehensive pan-cancer analyses exploring the expression patterns, clinical and pathological correlations, genetic alterations, immunogenomic profiles, single-cell dynamics, alternative splicing signatures, and pharmacological sensitivities related to MDH1. Drug sensitivity profiling and molecular docking techniques have been employed to identify potential anti-cancer compounds targeting MDH1. Experiments have also been conducted to investigate the biological function of MDH1 in lung adenocarcinoma (LUAD) and to confirm the interaction between MDH1 and macrophages using immunofluorescence assays. MDH1 expression levels are elevated across a wide range of malignancies, and overexpression of MDH1 was consistently linked to poor prognosis in multiple cancer subtypes. Moreover, MDH1 expression shows complex correlations with various immune cell populations, particularly macrophages, and cohort analysis of both bulk and pan-cancer single-cell immunotherapy data suggest that MDH1 could serve as a predictive marker for immunotherapy responses. Moreover, knockdown of MDH1 suppresses macrophage invasion. To investigate the role of MDH1 in LUAD cells, a potential inhibitor of MDH1 was identified, BI-2536, and has been confirmed to impact MDH1 activity and impede the growth of LUAD cells. Our findings indicate that MDH1 may serve as a potential prognostic marker and a promising target for cancer immunotherapy.

Coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly around the globe. By the establishment of an integrative system combining both traditional Chinese medicine (TCM) and western medicine, China has achieved good clinical efficacy in the prevention and control of the pandemic. The advantages of TCM in the treatment of COVID-19 include effective relief of symptoms, retarding the development from mild and moderate to severe, improvement of cure rate, reducing death rates, and promotion of rehabilitation. Besides, according to the different severity levels of individual cases, the National Health Commission of the People’s Republic of China issued treatment guidelines that provide corresponding prescriptions for patients. From the perspective of TCM, this review aims to analyze the role of a variety of TCM prescriptions in the treatment of COVID-19, focusing on the analysis of the “Three TCM prescriptions and three medicines” recommended by the Chinese authorities during the pandemic. We expect that this review will provide insights into the prevention and treatment of COVID-19 with TCM.

Background A family history of colorectal cancer among first-degree relatives is recognized as one of the most significant and prevalent risk factors for colorectal cancer in China. Colonoscopy remains the most crucial screening method, as early colonoscopy screening can effectively reduce the risk of advanced colorectal cancer. However, the factors influencing the decision-making behavior of first-degree relatives regarding colonoscopy screening have predominantly been examined through quantitative studies, while mixed-methods research remains scarce. This study aimed to evaluate the decision-making behaviors of first-degree relatives of patients with colorectal cancer and to identify the factors influencing these behaviors. Methods An explanatory sequential design was adopted within a mixed-methods framework. For the quantitative phase, convenience sampling was used to select 272 first-degree relatives of colorectal cancer patients who were treated at a tertiary hospital’s gastrointestinal surgery department in Wuhan, China from March to December 2023, for a questionnaire survey. For the qualitative component, a maximum variation purposive sampling method, guided by the Protection Motivation Theory, was employed to select 16 participants from the initial survey group for semi-structured interviews. Results Our findings revealed that participants had a high health belief score. Key factors influencing their decision to undergo colonoscopy screening included marital status, average monthly household income, medical payment method, and perceived severity. The qualitative study identified six core themes: perceived susceptibility, perceived severity, internal and external rewards, response efficacy, response costs, and self-efficacy. Conclusion Medical staff should focus on first-degree relatives of colorectal cancer who are unmarried or widowed, have lower family income, have lower reimbursement rate of medical insurance, and lack of disease severity perception. Through establishing social support system, issuing subsidies for colonoscopy screening, increasing reimbursement rate of medical insurance, emphasizing the severity of colorectal cancer, to enhance their health belief level and promote colonoscopy screening decision-making behavior. Trial registration Not applicable.

Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.