Phenolic acids from Prunella vulgaris alleviate cardiac remodeling following myocardial infarction partially by suppressing NLRP3 activation.

Acute myocardial infarction (MI) is one of the leading causes of mortality around the world. Prunella vulgaris (Xia-Ku-Cao in Chinese) is used in traditional Chinese medicine practice for the treatment of cardiovascular diseases. However, its active ingredients and mechanisms of action on cardiac remodeling following MI remain unknown. In this study, we investigated the cardioprotective effect of P. vulgaris on MI rat models. MI rats were treated with aqueous extract of P. vulgaris or phenolic acids from P. vulgaris, including caffeic acid, ursolic acid or rosmarinic acid, 1 day after surgery and continued for the following 28 days. Then the cardioprotective effect, such as cardiac function, inflammatory status, and fibrosis areas were evaluated. RNA-sequencing (RNA-seq) analysis, real-time polymerase chain reaction (PCR), western blotting, and ELISA were used to explore the underlying mechanism. In addition, ultra-high performance liquid chromatography/mass spectrometer analysis was used to identify the chemicals from P. vulgaris. THP-1NLRP3-GFP cells were used to confirm the inhibitory effect of P. vulgaris and phenolic acids on the expression and activity of NLRP3. We found that P. vulgaris significantly improved cardiac function and reduced infarct size. Meanwhile, P. vulgaris protected cardiomyocyte against apoptosis, evidenced by increasing the expression of anti-apoptosis protein Bcl-2 in the heart and decreasing lactate dehydrogenase (LDH) levels in serum. Results from RNA-seq revealed that the therapeutic effect of P. vulgaris might relate to NLRP3-mediated inflammatory response. Results from real-time PCR and western blotting confirmed that P. vulgaris suppressed NLRP3 expression in MI heart. We also found that P. vulgaris suppressed NLRP3 expression and the secretion of HMGB1, IL-1ß, and IL-18 in THP-1NLRP3-GFP cells. Further studies indicated that the active components of P. vulgaris were three phenolic acids, those were caffeic acid, ursolic acid, and rosmarinic acid. These phenolic acids inhibited LPS-induced NLRP3 expression and activity in THP-1 cells, and improved cardiac function, suppressed inflammatory aggregation and fibrosis in MI rat models. In conclusion, our study demonstrated that P. vulgaris and phenolic acids from P. vulgaris, including caffeic acid, ursolic acid, and rosmarinic acid, could improve cardiac function and protect cardiomyocytes from ischemia injury during MI. The mechanism was partially related to inhibiting NLRP3 activation.

Discovery of Salidroside as a Novel Non-Coding RNA Modulator to Delay Cellular Senescence and Promote BK-Dependent Apoptosis in Cerebrovascular Smooth Muscle Cells of Simulated Microgravity Rats.

Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts' health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague-Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K+ channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights.

Liver Injury in Patients with COVID-19: A Retrospective Study.

Objectives: The objective of this study is to explore the incidence, characteristics, risk factors, and prognosis of liver injury in patients with COVID-19. Methods: We collected clinical data of 384 cases of COVID-19 and retrospectively analyzed the incidence, characteristics, and risk factors of liver injury of the patients. In addition, we followed the patient two months after discharge. Results: A total of 23.7% of the patients with COVID-19 had liver injury, with higher serum AST (P < 0.001), ALT (P < 0.001), ALP (P = 0.004), GGT (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P = 0.025) and direct bilirubin (P < 0.001) than the control group. The median serum AST and ALT of COVID-19 patients with liver injury were mildly elevated. Risk factors of liver injury in COVID-19 patients were age (P = 0.001), history of liver diseases (P = 0.002), alcoholic abuse (P = 0.036), body mass index (P = 0.037), severity of COVID-19 (P < 0.001), C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), Qing-Fei-Pai-Du-Tang treatment (P = 0.032), mechanical ventilation (P < 0.001), and ICU admission (P < 0.001). Most of the patients (92.3%) with liver injury were treated with hepatoprotective drugs. 95.6% of the patients returned to normal liver function tests at 2 months after discharge. Conclusions: Liver injury was commen in COVID-19 patients with risk factors, most of them have mild elevations in transaminases, and conservative treatment has a good short-term prognosis.

Curcumin Alleviates the Side Effects of Cisplatin on Gastric Emptying of Mice by Inhibiting the Signal Changes of Acetylcholine and Interstitial Cells of Cajal.

Cisplatin is a widely used anticancer drug that has adverse effects on gastrointestinal function. Curcumin is a natural polyphenol extracted from the rhizome of turmeric that has a wide range of biological activities. The present study investigated the effects of cisplatin on gastric emptying in mice and examined whether these can be inhibited by curcumin. We found that pretreatment with curcumin (200 mg/kg/day) for 10-30 days partly inhibited the decreases in gastric emptying rate and body weight induced by cisplatin. Furthermore, cisplatin reduced acetylcholine (ACh) concentration and the messenger RNA (mRNA) level of ACh receptor (AChR) as well as acetylcholinesterase activity in the stomach of mice; caused ultrastructural damage to interstitial cells of Cajal (ICC); and altered the expression of c-kit/stem cell factor and the gap junction protein connexin 43 in ICC. Curcumin pretreatment inhibited the effects of cisplatin on ACh indicators and ICC. These results demonstrate that curcumin can protect against cisplatin-induced gastric emptying disorder and thus has therapeutic potential for alleviating this condition in cancer patients receiving cisplatin chemotherapy.

[Nutrient balance and mechanism of biological degradation of oil].

This paper studied the nutrient balance and mechanism for enhancing the bioremediation of petroleum contaminated soils by the bio-slurry method. Oil degrading strains isolated and screened from Liaohe oil field was used. The results show that the suitable weight ratio of N and P element in the nutrient is 5.67:1, which is similar to their proportion in the microbial cells. It was found that the degradation of oil was significantly enhanced by adding nutriment and about 30% oil was decreased in the 14,000 mg/kg-15,000 mg/kg samples during 16 days. Using (NH4)2SO4, NH4NO3, NaNO3, CO(NH2)2 as the nitrogen source respectively, it shows that the inorganic nitrogen is better than the organic one, and the nitrogen in nitrate is more effective than that in ammonia. Adding nutrient salt can change the system's pH and promote the growing of the microbes.

Sixty-one cases of angina pectoris due to coronary heart disease treated by external use of the paste of nitrum and realgar powder on zhiyang (GV 9).

In order to inquire into the therapeutic effects of Xiao Shi Xiong Huang San (the Nitrum and Realgar Powder), one of the Dunhuang Prescription, on angina pectoris due to coronary heart disease (APCHD), the authors have treated 61 cases of APCHD by externally applying paste of the powder on Zhiyang (GV 9), with another 30 cases of APCHD treated with the nitroglycerin paste on Zhiyang as the controls. The results showed that the total effective rate was 82% and markedly effective rate 31.2% in the treatment group (the Paste of Nitrum and Realgar Powder), and the total effective rate was 46.6% and markedly effective rate 23.2% in the control group (the nitroglycerin paste). The difference in therapeutic effects between the two groups was very significant (P<0.01), indicating that the therapeutic effect of the former was significantly superior to that of the latter.