Monotropein alleviates acute pulmonary embolism in rats by inhibiting the NF-κB pathway.

OBJECTIVE: This study examines the therapeutic potential of monotropein (Mon) in a rat model of acute pulmonary embolism (APE), aiming to elucidate its mechanistic role and provide new insights for APE treatment. METHODS: Thirty Sprague Dawley (SD) rats were randomly assigned to five groups (n = 6 per group): sham, Mon (40 mg/kg), APE, APE + 20 mg/kg Mon, and APE + 40 mg/kg Mon. APE was induced via autologous thrombus infusion in all groups except sham and Mon-only groups. We assessed blood gas parameters, lung wet/dry weight (W/D) ratio, and oxidative stress markers. Additionally, excised lung tissues underwent evaluation for serum inflammatory factors via ELISA, apoptotic cells via TUNEL assay, and protein expression via Western blot. RESULTS: Compared to the sham group, APE-induced rats exhibited significantly elevated blood oxygen levels and increased pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-8. Mon treatment effectively mitigated these APE-induced changes, reducing blood oxygen concentration and downregulating IL-1ß and TNF-α levels. Furthermore, Mon demonstrated anti-apoptotic effects by decreasing cleaved caspase-3 and Bax protein levels while upregulating Bcl-2 expression. Mon also suppressed nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation levels of p65/RelA and IκBα proteins, while the total protein level of IκBα was increased with Mon treatment. CONCLUSION: Mon effectively ameliorated lung tissue injury in APE rats by inhibiting apoptosis, attenuating inflammatory responses, and alleviating oxidative stress. These beneficial effects appear to be mediated through modulation of the NF-κB pathway, suggesting Mon as a promising therapeutic candidate for APE treatment.

Herpud1 deficiency alleviates homocysteine-induced aortic valve calcification.

OBJECTIVES: To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD). BACKGROUND: The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited. METHODS: In vivo, we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice and used high methionine diet (HMD) to assess of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). In vitro, the role of Herpud1 in the Hcy-related osteogenic differentiation of AVICs was investigated by manipulating of Herpud1 expression. RESULTS: Herpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in HMD-fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis. CONCLUSIONS: These findings identify a previously unknown mechanism of Herpud1 upregulation in Hcy-related CAVD, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression. HIGHLIGHTS: • Herpud1 is upregulated in the leaflets of Hcy-treated mice and patients with CAVD. • In mice, global knockout of Herpud1 alleviates aortic valve calcification and Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of AVICs induced by Hcy. • 4-PBA suppressed Herpud1 expression to alleviate AVIC calcification in Hcy treated AVICs and to mitigate aortic valve calcification in mice.

Sevoflurane alleviates myocardial ischemia/reperfusion injury via actitation of heat shock protein-70 in patients undergoing double valve replacement surgery.

This study investigated the cardioprotective effect(s) of sevoflurane in rheumatic heart disease patients undergoing double valve replacement surgery (DVRS) under cardiopulmonary bypass (CPB) and its potential mechanisms (ChiCTR2100051220 on http://www.ChiCTR.org.cn). Forty-six patients were randomly assigned to undergo propofol or sevoflurane anesthesia during surgery. The levels of myocardial injury markers, inflammatory cytokines, heat shock protein-70 (HSP70), and superoxide dismutase (SOD) activity were measured from blood samples. Mean arterial pressure, cardiac index, and stroke volume index were significantly higher in the sevoflurane group than in the propofol group at the end of CPB. However, there were no significant differences in operative duration, length of CPB or aortic cross-clamp time, auto-resuscitation heart rate, drainage within 48 h after surgery, time to extubation, and recovery time after DVRS. The dose of inotropic agents (dopamine and noradrenaline) was significantly lower in the sevoflurane group than in the propofol group. Sevoflurane was associated with smaller increases in the levels of myocardial injury-associated markers (CK-MB and cardiac troponin I [cTnI]) and inflammatory cytokines (interleukin [IL]-6, IL-8, and tumor-necrosis factor-alpha [TNF-α]); however, there was a greater increase in HSP70 levels compared with propofol after surgery. Moreover, SOD activity after surgery was significantly higher in the sevoflurane group than in the propofol group. Increased HSP70 levels in the sevoflurane group were positively correlated with cTnI, IL-6, IL-8, and TNF-α levels, and negatively correlated with SOD activity. These results suggest a cardioprotective effect of sevoflurane during DVRS. Sevoflurane may reduce biomarkers of cardiac injury through its anti-inflammatory effects via upregulation of HSP70.

The clinical significance of preoperative serum triglyceride, high-density lipoprotein, and low-density lipoprotein levels in lung squamous cell carcinoma.

To evaluate the prognostic role of the preoperative plasma lipid profile, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with lung squamous cell carcinoma (LUSC) who underwent complete resection. Clinical data, including preoperative plasma profile levels, were retrospectively collected and reviewed in 300 patients with LUSC who underwent radical lung resection between 2016 and 2017. The overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method and the Cox proportional hazards regression model. TG ≤ 1.35, HDL-C ≤ 1.17, and LDL-C ≤ 2.32 were deemed as independent preoperative risk factors for OS, and HDL-C ≤ 1.17 was an independent preoperative risk factor for DFS. In the multivariate analyses involving OS and DFS, a decreased HDL-C level was significantly associated with worse OS (HR, 0.546; 95% CI, 0.380-0.784, P = 0.001) and DFS (HR, 0.644; 95% CI, 0.422-0.981, P = 0.041). Additionally, an increased TG (HR, 0.546; 95% CI, 0.366-0.814, P = 0.003) or LDL-C (HR, 0.652; 95% CI, 0.456-0.933, P = 0.019) level was significantly associated with better OS. In patients with LUSC, decreased levels of HDL-C may predict worse outcomes for both DFS and OS, while increased TG or LDL-C levels may predict better OS.

Expression of miR-590 in lung cancer and its correlation with prognosis.

The study aim was to evaluate the association of the expression of serum microribonucleic acid-590 (miR-590) with the risk of lung squamous cell carcinoma (LUSC), clinicopathological staging and prognosis. A total of 237 patients with LUSC and 100 healthy volunteers (control group) were included in the study. Total RNA was extracted from the peripheral blood serum of the subjects, and the expression level of miR-590 was detected by reverse transcription real-time quantitative polymerase chain reaction. The baseline clinicopathological information of LUSC patients was evaluated, and the patients were followed up with the median follow-up of 47 months. Compared with that in the control group, the expression level of serum miR-590 in LUSC patients was significantly decreased [0.532 (0.367- 0.821) vs. 1.63 (0.893-1.347), P<0.001]. The receiver operating characteristic (ROC) curve showed that the value of predicting LUSC risk using miR-590 was high, the area under curve (AUC) was 0.883, and 95% confidence interval (CI) was 0.829-0.934. In addition, the expression level of serum miR-590 was correlated with pathological staging (P=0.022), lymph node metastasis (P=0.012), distant metastasis (P<0.001) and tumor, node and metastasis (TNM) staging (P=0.044). The overall survival (OS) of patients in the serum miR-590 low expression group was significantly lower than that of the serum miR-590 high expression group (P=0.012), and the low expression of miR-590 was an independent risk factor for the prognosis of patients [hazard ratio (HR)=2.152, 95% CI=1.285-3.233, P=0.004]. The results suggested that the expression level of miR-590 can be used as a biomarker for the risk of disease, disease staging and prognosis of LUSC patients.

Association of serum cystatin C levels with mortality in patients with acute type A aortic dissection.

Increased serum cystatin C levels are related to the prognosis of cardiovascular diseases. This study aims to investigate the effect of admission serum cystatin C levels on short- and long-term mortality in patients with acute type A aortic dissection (ATAAD). From 2010 to 2014, 136 consecutive patients with ATAAD were enrolled and followed up. Clinical data and laboratory assays including were measured. During a median follow-up of 198.7 days, the short-term mortality (30-days) was 20.6%, whereas the long-term death rate was 10.2%. We identified that the expression of cystatin C and high-sensitivity C-reactive protein (hs-CRP) in the dying patients was higher than in the surviving patients (P < 0.01). Hs-CRP (HR = 1.41, 95% CI: 1.03-2.59, P = 0.037) was an independent risk factor of short-term death determined by univariate and multivariate Cox analyses. No impact of cystatin C was observed on the short-term mortality. For long-term mortality, cystatin C (HR = 1.49, 95% CI: 1.10-7.36, P = 0.013) was identified as an independent predictor at above the cut-off value ≥ 1.10 mg/L. ROC analysis showed the AUC values of cystatin C and hs-CRP were 0.772 (95% CI, 0.692-0.839) and 0.640 (95% CI, 0.574-0.739), respectively, in the prediction of long-term death. The combined AUC value of cystatin C and hs-CRP was 0.883 (95% CI, 0.826-0.935; P < 0.01). Taken together, high cystatin C levels (≥ 1.10 mg/L) on admission are independently associated with the long-term mortality in patients with ATAAD.