Effect of sodium aescinate on methyl parathion-induced myocardial injury in rats

Purpose: To explore the effects and mechanism of sodium aescinate (SA) on methyl parathion (MP)-induced myocardial injury.Methods: Rats were divided into following groups: In Control group, rats were administered 0.9 % NaCl by intraperitoneal injection. In MP group, rats were administered 20 mg/kg MP by intraperitoneal injection. In MP + SA group, rats were administered 20 mg/kg MP in combination with SA at a concentration of 0.5, 1.0, or 1.5 mg/kg by intraperitoneal injection. Histological changes were assessed by H&E staining. Serum levels of cardiac troponin T (CTnT) and atrial natriuretie peptide (ANP) were measured by automatic biochemical analyzer and real-time polymerase chain reaction (RT-PCR), respectively. The levels of malondiadehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH - Px), and glutathione (GSH) in heart tissue was detected by spectrophotometry. The apoptosis of myocardial cells was measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The level of apoptosis-related proteins was assessed by western blot.Results: Superoxide dismutase attenuated MP-induced myocardial injury, and decreased the levels of ANP and cTnT in serum (p < 0.01). Superoxide dismutase attenuated the MP-induced decrease in GSH, GSH-px, and SOD expression (p < 0.05) but increased MDA level (p < 0.01). Moreover, SA inhibited the apoptosis of myocardial cells and regulation of apoptosis-related protein expression (e.g., Bax, Bcl-2, and caspase 3).Conclusion: These results demonstrate that SA attenuates MP-induced myocardial injury by regulating oxidative stress and apoptosis.Keywords: Sodium Aescinate, Methyl Parathion, Acute Organophosphorus Pesticide Poisoning, Myocardial Injur

Inhibition of Stimulator of Interferon Genes Protects Against Myocardial Ischemia-Reperfusion Injury in Diabetic Mice

Background: Although the past decade has witnessed substantial scientific progress with the advent of cardioprotective pharmacological agents, most have failed to protect against myocardial ischemia/reperfusion (I/R) injury in diabetic hearts. This study was aimed at investigating the role of stimulator of interferon genes (STING) in I/R injury in diabetic mice and further exploring the underlying mechanisms. Methods: Type 2 diabetic mice were subjected to I/R or sham operation to investigate the role of STING. STING knockout mice were subjected to 30 minutes of ischemia followed by reperfusion for 24 hours. Finally, myocardial injury, cardiac function, and inflammation levels were assessed. Results: STING pathway activation was observed in diabetic I/R hearts, as evidenced by increased p-TBK and p-IRF3 expression. STING knockout significantly decreased the ischemic area and improved cardiac function after I/R in diabetic mice. STING knockout also elicited cardio-protective effects by decreasing serum cardiac troponin T and lactate dehydrogenase levels, thus diminishing the inflammatory response in the heart after I/R in diabetic mice. In vitro , STING inhibition decreased the expression of hypoxia-re-oxygenation-induced inflammatory cytokines. Conclusions: Targeting STING inhibits inflammation and prevents I/R injury in diabetic mice. Thus, STING may be a potential novel therapeutic target against myocardial I/R injury in diabetes

Revisiting the potential of regulated cell death in glioma treatment: a focus on autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis, immunogenic cell death, and the crosstalk between them

Gliomas are primary tumors that originate in the central nervous system. The conventional treatment options for gliomas typically encompass surgical resection and temozolomide (TMZ) chemotherapy. However, despite aggressive interventions, the median survival for glioma patients is merely about 14.6 months. Consequently, there is an urgent necessity to explore innovative therapeutic strategies for treating glioma. The foundational study of regulated cell death (RCD) can be traced back to Karl Vogt’s seminal observations of cellular demise in toads, which were documented in 1842. In the past decade, the Nomenclature Committee on Cell Death (NCCD) has systematically classified and delineated various forms and mechanisms of cell death, synthesizing morphological, biochemical, and functional characteristics. Cell death primarily manifests in two forms: accidental cell death (ACD), which is caused by external factors such as physical, chemical, or mechanical disruptions; and RCD, a gene-directed intrinsic process that coordinates an orderly cellular demise in response to both physiological and pathological cues. Advancements in our understanding of RCD have shed light on the manipulation of cell death modulation - either through induction or suppression - as a potentially groundbreaking approach in oncology, holding significant promise. However, obstacles persist at the interface of research and clinical application, with significant impediments encountered in translating to therapeutic modalities. It is increasingly apparent that an integrative examination of the molecular underpinnings of cell death is imperative for advancing the field, particularly within the framework of inter-pathway functional synergy. In this review, we provide an overview of various forms of RCD, including autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis and immunogenic cell death. We summarize the latest advancements in understanding the molecular mechanisms that regulate RCD in glioma and explore the interconnections between different cell death processes. By comprehending these connections and developing targeted strategies, we have the potential to enhance glioma therapy through manipulation of RCD

Risk factors, management, and future fertility of empty follicle syndrome: a retrospective study with real-world data

BackgroundEmpty follicle syndrome (EFS) is a challenging clinical problem. This study aims to identify the risk factors for EFS, to present pregnancy outcomes in both EFS cycle as well as subsequent cycles, and to summarize an effective rescue protocol to improve outcomes.MethodsA retrospective analysis between 2016 and 2020 was conducted at our center. Stricter criteria were applied to diagnose EFS. Logistic regression analysis was used to identify the risk factors for EFS. Further analyses were performed within the EFS cycle to present pregnancy outcomes and to find optimal rescue protocols. Long-term follow-up was conducted until live birth was achieved, covering at least two complete oocyte retrieval cycles.ResultsAmong 14,066 patients, 54 (0.38%) were identified as EFS. Patients with polycystic ovary syndrome (PCOS) had a significantly higher risk of developing EFS than non-PCOS ones (aOR = 2.67; 95% CI, 1.47 to 4.83). Within EFS patients, delaying the second oocyte retrieval by 3–6 h significantly improved the rates of obtaining oocyte (97.4% versus 58.3%, P = 0.002), getting embryo available for transfer (92.3% versus 33.3%, P < 0.001), and pregnancy (48.7% versus 8.3%, P = 0.017) compared to other delayed retrieval times. Overall, 31.5% (17/54) and 46.7% (7/15) EFS patients achieved live birth in the EFS cycle and the future cycle, respectively.ConclusionsPCOS is an independent risk factor for EFS, indicating that longer exposure time to human chorionic gonadotropin (hCG) may be necessary. Delaying the second oocyte retrieval by 3–6 h is an effective rescue protocol for EFS patients to achieve optimal outcomes. EFS in a single cycle does not necessarily indicate future fertility decline, but repeated EFS may result in poor outcomes

Chest pain in a patient with transthyretin cardiac amyloidosis: A case report

Key Clinical Message Patients with transthyretin cardiac amyloidosis (ATTR‐CM) commonly present with dyspnea, fatigue, and edema. In our case, the main presentation was exertional angina, which was atypical in patients with ATTR‐CM and should be paid more attention to. Abstract A 54‐year‐old woman was admitted with a complaint of exertional chest pain, and she had a history of hypertension. The results of the electrocardiogram and echocardiography revealed the clues of cardiac amyloidosis, and the patient was finally diagnosed with transthyretin cardiac amyloidosis, then she received tafamidis, and the symptoms improved significantly

Hyperkalemia mimicking de Winter T waves: A case report

Abstract “De Winter” electrocardiogram pattern is considered an equivalent risk to ST‐elevation myocardial infarction and usually indicates occlusion of the left anterior descending artery, which needs emergent revascularization treatment. However, some conditions can mimic “de Winter” electrocardiogram pattern and may cause misdiagnosis. Here, we reported a case of hyperkalemia presented with “de Winter‐like” electrocardiogram pattern. This study aimed to increase physicians' awareness about the impact of electrolyte disorder on electrocardiographic changes

An Updated Meta-Analysis of Treatment in Patients with Heart Failure Complicated Ventricular Functional Mitral Regurgitation

Backgrounds: Ventricular functional mitral regurgitation (FMR) is a common morbidity in patients with heart failure (HF). In addition to guideline-directed medical therapy, mitral valve (MV) repair or replacement has become an option for such patients. However, the impact of different treatments on cardiac remodeling, function, and clinical outcomes remains unclear. Methods: We systematically searched PubMed, EMBASE, Medline, Clinical Trials.gov, and the Cochrane Central Register of Controlled Trials with search terms related to mitral regurgitation, mitral valve repair, surgical mitral valve replacement, mitral annuloplasty device, and MitraClip. The outcomes were left ventricular ejection fraction (LVEF), left ventricular (LV) remodeling, all-cause mortality, cardiovascular death, and HF hospitalization. Sensitivity analysis was performed by removing high-bias risk studies. The analysis was done by Review Manager 5.4 Analyzer and MedCalc Statistical Software version 19.2.6. Results: This meta-analysis included 10 studies with a total of 2533 patients (567 with transcatheter MitraClip, 823 with surgical MV repair, 651 with surgical MV replacement, and 492 with medical therapy). Our meta-analysis revealed that surgical MV repair had significant improvement in LVEF compared to the surgical MV replacement (mean differences (MD) 2.32, [95% CI 0.39, 4.25]), while transcatheter MitraClip treatment was associated with LVEF reduction (MD –4.82, [95% CI –7.29, –2.34]). In terms of LV remodeling, transcatheter MitraClip treatment was associated with improvement in left ventricular end-diastolic volume (MD –10.36, [95% CI –18.74, –1.99]). Furthermore, compared to surgical MV replacement, surgical MV repair was not associated with a reduction of all-cause mortality (risk ratio (RR) 0.83, [95% CI 0.61, 1.13]) and cardiovascular death (RR 0.95, [95% CI 0.56, 1.62]), while transcatheter MitraClip was associated with reduced risk of all-cause mortality (RR 0.87, [95% CI 0.78, 0.98]). Conclusions: Surgical MV repair was associated with significant improvement in LVEF but had no significant effect on all-cause mortality compared to surgical MV replacement. Transcatheter MitraClip was associated with better long-term survival than the non-MitraClip group, thus, transcatheter MitraClip could be considered an alternative treatment in patients with HF-complicated ventricular FMR