Bovine-derived α-lactalbumin exhibits cardiovascular protection against aging by ameliorating the inflammatory process in mice.

Cardiovascular aging is the most important factor leading to cardiovascular disease (CVD), and the incidence and severity of cardiovascular events increase with age. Cardiovascular disease is one of the leading causes of death in the aging population. Therefore, it is extremely urgent to develop and explore effective drugs or bioactive molecules to prevent cardiovascular aging and related diseases. In the current work, the effect of bovine α-lactalbumin (α-lactalbumin is one of the major bioactive protein molecules in milk) on cardiovascular aging was investigated in vitro and in vivo. First, a cellular model of cardiovascular aging was established using H2O2-induced in vitro cellular models. It was found that α-lactalbumin could alleviate cardiovascular senescence by assessing Sa-ß-gal and senescence-related markers (such as p16/p21/p53) in in vitro cellular models. Bovine α-lactalbumin attenuated aging-related inflammation and oxidative stress. Furthermore, aged mice were used as an in vivo cardiovascular aging model. We explored the effect of α-lactalbumin on cardiovascular aging and found that cardiovascular aging was significantly attenuated by evaluating Sa-ß-gal staining and aging-related marker molecules. Mechanistically, we found that α-lactalbumin may alleviate cardiovascular aging by regulating the expression of Sirt1 (Sirtuin 1). In summary, in the current work, we systematically explored the potential biological activity of α-lactalbumin against cardiovascular aging and found that α-lactalbumin has good anti-aging potential in vitro and in vivo, suggesting that α-lactalbumin could be used as an antiaging functional food in the future.

The association between severe or death COVID-19 and solid organ transplantation: A systematic review and meta-analysis.

BACKGROUND: The effect of solid organ transplantation (SOT) on the severity and mortality of coronavirus disease 2019 (COVID-19) remained controversial. There is still no consensus on whether solid organ transplantation (SOT) recipients with COVID-19 are at greater risk of developing severe or fatal COVID-19. Therefore, we conducted a systematic review and meta-analysis to investigate the association between SOT, severe COVID-19 illness, and mortality. METHODS: A systemically comprehensive search in Pubmed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure was performed for relevant studies and articles. Consequently, we pooled the odds ratio (OR) from individual studies and performed heterogeneity, quality assessment and subgroup/sensitivity analysis. RESULTS: A total number of 15 articles with 265,839 participants were included in this study. Among the total number of participants, 1485 were SOT recipients. The meta-analysis results showed that transplant patients with COVID-19 were remarkably associated with a higher risk of intensive care unit admission than non-transplant patients (OR = 1.57, 95%CI: 1.07 to 2.31, P = 0.02). On the other hand, there were no statistically significant differences between SOT recipients and non-SOT recipients in mechanical ventilation need (OR = 1.55, 95%CI: 0.98 to 2.44, P = 0.06). In addition, we found that SOT recipients with COVID-19 had 1.40-fold increased odds of mortality than non-SOT recipients (OR = 1.40, 95%CI: 1.10 to 1.79, P = 0.007). Moreover, pooled analysis of adjusted results revealed that SOT recipients had a greater risk of mortality compared with non-SOT patients (HR = 1.54, 95%CI: 1.03 to 2.32, P = 0.037). LIMITATIONS: The main limitations in our study are attributed to the relatively small sample size, short follow-up period, and the fact that most of the studies included were retrospective in design. CONCLUSIONS: The results of this study indicate that SOT recipients with COVID-19 had a more significant risk of COVID-19 severity and mortality than the general population.

Exosomes derived from MSC pre-treated with oridonin alleviates myocardial IR injury by suppressing apoptosis via regulating autophagy activation.

This study aimed to investigate the molecular mechanisms underlying the role of bone marrow mesenchymal stem cells (BMMSCs)-derived exosomes in ischaemia/reperfusion (IR)-induced damage, and the role of oridonin in the treatment of IR. Exosomes were isolated from BMMSCs. Western blot analysis was done to examine the expression of proteins including CD63, CD8, apoptotic-linked gene product 2 interacting protein X (AliX), Beclin-1, ATG13, B-cell lymphoma-2 (Bcl-2), apoptotic peptidase activating factor 1 (Apaf1) and Bcl2-associated X (Bax) in different treatment groups. Accordingly, the expression of CD63, CD81 and AliX was higher in BMMSCs-EXOs and IR + BMMSCs-EXOs + ORI groups compared with that in the BMMSCs group. And BMMSCs-derived exosomes inhibited the progression of IR-induced myocardial damage, while this protective effect was boosted by the pre-treatment with oridonin. Moreover, Beclin-1, ATG13 and Bcl-2 were significantly down-regulated while Apaf1 and Bax were significantly up-regulated in IR rats. And the presence of BMMSCs-derived exosomes partly alleviated IR-induced dysregulation of these proteins, while the oridonin pre-treatment boosted the effect of these BMMSCs-derived exosomes. The inhibited proliferation and promoted apoptosis of H9c2 cells induced by hypoxia/reperfusion (HR) were mitigated by the administration of BMMSCs-derived exosomes. Meanwhile, HR also induced down-regulation of Beclin-1, ATG13 and Bcl-2 expression and up-regulation of Apaf1 and Bax, which were mitigated by the administration of BMMSCs-derived exosomes. And oridonin pre-treatment boosted the effect of BMMSCs-derived exosomes. In conclusion, our results validated that BMMSCs-derived exosomes suppressed the IR-induced damages by participating in the autophagy process, while the pre-treatment with oridonin could boost the protective effect of BMMSCs-derived exosomes.

The expression and prognostic value of ischemia modified albumin (IMA), red blood cell distribution width (RDW), and lipoprotein (LP) in patients with diabetes mellitus complicated with coronary heart disease.

BACKGROUND: This study explored the levels and prognostic value of ischemia modified albumin (IMA), red blood cell distribution width (RDW), and lipoprotein (LP) in patients with diabetes melltus (DM) complicated withcoronary heart disease (CHD). METHODS: A total of 95 patients with DM who were diagnosed and treatedfrom January 2018 to January 2019 were retrospectively analyzed. All included patients underwent percutaneous coronary intervention (PCI). Patients with DM complicated with CHDwere designated group A (n=61) and patients without CHD complications were designated group B (n=34). During the same period, 45 patients without DM who underwent physical examination in our hospital were included as a control group.The levels of IMA, LP, and RDW in the 3 groups of patients were compared. The study examined the occurrence of cardiovascular events after PCI treatment in patients with DM complicated with CHD, and the related risk factors were assessed using multivariate logistic regression analysis. Furthermore, the receiver operating characteristic (ROC) curve was used to analyze the value of IMA, LP, and RDW in predicting cardiovascular events in DM patients complicated with CHD. RESULTS: The levels of IMA, LP, and RDW werehigher in groups A and B compared to the control group (P<0.05). In patients who experienced a cardiovascular event, the levels of IMA, LP, and RDW were higher than those observed in patients who did not experience a cardiovascular event (P<0.05). The area under the ROC curve of IMA, LP, RDW, and the combination of the three factors for the prediction of cardiovascular events were 0.910, 0.774, 0.846, and 0.995, respectively. The combined detection of the 3 factors showed the best predictive value.Patients with abnormal values in blood lipids, blood creatinine, IMA, LP, and RDW had a significantly poorer prognosis in terms of adverse cardiovascular events (P<0.05). The unconditional multivariate logistic regression model showed that abnormal levels of blood creatinine, IMA, LP, and RDW were independent risk factors for cardiovascular events in patients with DM complicated with CHD after PCI treatment (P<0.05). CONCLUSIONS: The levels of IMA, RDW, and LP wereincreased in patients with DM complicated with CHD. Furthermore, abnormal levels of IMA, LP, and RDW are independent risk factors that affect cardiovascular events in these patients following PCI treatment. The combined detection of all three indicators may be an effective means to predict the prognosis of these patients.

Associated factors of orthostatic hypotension in the elderly essential hypertension patients and relationship between orthostatic hypotension and early renal damage.

BACKGROUND: This study sought to explore the related factors of orthostatic hypotension (OH) in elderly patients with essential hypertension, and analyze the relationship between early renal damage and OH in elderly hypertensive patients. METHODS: The demographic and clinical data of 511 elderly patients with essential hypertension (EH) were collected from September 2017 to September 2018.These patients were divided into group with OH and group without OH. The data were compared between the two groups to analyze correlations between OH and early renal damage indicators [urine microalbumin (mAlb) >30 mg/L]. RESULTS: In the study, 118 were in the OH+ group, and 393 were in the OH-group. The proportion of patients with coronary heart disease, atherosclerosis, grade 3 hypertension, persistent rapid atrial fibrillation, left ventricular diastolic dysfunction, and left ventricular hypertrophy in OH+ group was significantly higher than in OH- group (P<0.05). Further, logistic regression analysis showed that coronary heart disease, carotid atherosclerosis, and grade 3 hypertension are independent associated factors for OH in elderly EH patients. In the 511 patients, 249 had urine mAlb >30 mg/L, and 262 had urine mAlb ≤30 mg/L. The 24-hour systolic blood pressure (SBP)-coefficient of variation (CV), the 24-hour diastolic blood pressure (DBP)-coefficient of variation (CV), the drop difference of both SBP and DBP from supine to standing position in 3-minute were higher in patients with urine mAlb >30 mg/L than in patients with urine mAlb ≤30 mg/L (P<0.05). The urine mAlb of patients with OH was higher than that of patients without OH, and the urine mAlb of patients with elevated blood pressure variability (BPV) was also higher than that in patients with normal BPV (P<0.05). Further groupings revealed that patients with both OH and elevated BPV had the highest urine mAlb levels (P<0.05). CONCLUSIONS: Coronary heart disease, atherosclerosis, and grade 3 hypertension are independent associated factors of OH in elderly EH patients. In elderly hypertensive patients with both OH and elevated BPV, the urine mAlb is much higher than that in patients with OH or elevated BPV alone. OH is associated with early renal damage.

Etomidate alleviates cardiac dysfunction, fibrosis and oxidative stress in rats with myocardial ischemic reperfusion injury.

BACKGROUND: Etomidate has been shown to reduce ischemia/reperfusion (I/R) injury in several tissues. Here we aimed to investigate the protective effects of etomidate on I/R injury in Sprague-Dawley (SD) rats. METHODS: Thirty rats were randomly divided into 5 groups and pretreated with saline or 0.5/1/2 mg/kg etomidate. I/R injury was induced in all groups except the sham control group. After administration with saline or 0.5/1/2 mg/kg etomidate daily for another 27 days, rats were sacrificed and the effects of etomidate were analyzed. RESULTS: Treatment with etomidate dose dependently improved echocardiography indexes, ameliorated myocardial histological alterations and reduced serum creatine kinase isoenzyme (CK-MB), myoglobin (Mb) and troponin I (cTnl) levels. Fibrosis markers transforming growth factor beta (TGF-ß), alpha-smooth muscle actin (α-SMA) and fibronectin was decreased with etomidate treatment. Etomidate also decreased oxidative stress and inflammation in rats, indicated by increased superoxide dismutase (SOD) and glutathione (GSH), and reduced malondialdehyde (MDA) in myocardial tissues, as well as decreased inducible NO synthase (iNOS) and increased interleukin (IL)-10 in both serum and myocardial tissues. CONCLUSIONS: Altogether, we showed that etomidate alleviated I/R injury in rats through reduced cardiac dysfunction, fibrosis and oxidative stress. These results supported the protective role of etomidate to myocardial I/R injury.

Galanthamine improves myocardial ischemia-reperfusion-induced cardiac dysfunction, endoplasmic reticulum stress-related apoptosis, and myocardial fibrosis by suppressing AMPK/Nrf2 pathway in rats.

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is an important cause of myocardial infarction and heart failure after cardiovascular surgery. Galanthamine (Gal) is an important Amaryllidaceae alkaloid with anti-acetylcholinesterase and anti-inflammatory activity. The purpose of this study was to investigate the role of Gal in myocardial I/R injury. METHODS: In this study, an animal model of myocardial I/R injury was constructed, and the rats were divided into five groups (n=10): the sham, I/R model, I/R + Gal (1 mg/kg), I/R + Gal (3 mg/kg), and I/R + Aspirin (20 mg/kg) groups. The expression of related proteins was detected by Western blotting and Immunohistochemistry, and Histological lesion was detected by HE staining. RESULTS: Results showed that Gal improves I/R-induced cardiac dysfunction in rats. Moreover, Gal inhibits I/R-induced endoplasmic reticulum stress (ERS)-related apoptosis by suppressing the expression of CHOP, Cleaved caspase 12, and caspase 3, and promoting the expression of CADD34 and BiP in rats. Furthermore, Gal mitigates I/R-induced myocardial fibrosis through restraining the expression of α-SMA and Collagen I in rats. Mechanically, Gal promoted the expression of AMPKα1, Nrf2 and HO-1. However, AMPK inhibitor Compound C exhibited the opposite effects. Collectively, this finding suggests that Gal improves I/R-induced cardiac dysfunction, ERS-related apoptosis, and myocardial fibrosis by activating AMPK/Nrf2 pathway in myocardial I/R rats. CONCLUSIONS: Given this evidence, Gal may be a potential therapeutic drug for the treatment of I/R injury.