Pachymic acid (PA) inhibits ferroptosis of cardiomyocytes via activation of the AMPK in mice with ischemia/reperfusion-induced myocardial injury.

Pachymic acid (PA) is a lanostane-type triterpenoid with various pharmacological effects. However, little is known about the effect of PA on myocardial infarction (MI) induced by ischemia/reperfusion (I/R). In this study, we aimed to investigate the protective effect of PA and its underlying mechanism. A cellular MI model was established by oxygen-glucose deprivation and reperfusion (OGD/R) treatment in HL-1 cardiomyocytes, and we found that OGD/R treatment decreased cell viability and glutathione peroxide (GSH-Px) activity, increased Fe2+ concentration and lactate dehydrogenase (LDH) activity, promoted malondialdehyde (MDA) and reactive oxygen species (ROS) production, and inhibited the expression of ferroptosis marker proteins SLC7A11 and GPX4 in a time-dependent manner. OGD/R-induced HL-1 cells were pretreated with different concentrations of PA (0, 20, 40, 60 µg/mL) for 24 h, and toxicological experiments showed that 150 µg/mL PA decreased cell viability, while low concentrations of PA had no toxic effect on cells. 20 µg/mL PA reversed the inhibitory effect of OGD/R on cell viability, reduced MDA and ROS production, and Fe2+ accumulation, increased GSH-Px activity and the expression of SLC7A11 and GPX4, and decreased LDH activity, especially at 60 µg/mL PA. Meanwhile, PA promoted the phosphorylation of IRS-1, AKT, and AMPK proteins in a dose-dependent manner. AICAR, an AMPK activator, inhibited ferroptosis, while STO-609, an AMPK inhibitor, largely abolished the effect of PA on OGD/R-induced ferroptosis of HL-1 cells. In addition, PA inhibited ferroptosis and myocardial I/R injury in wild-type mice and AMPK knockout (AMPK-/- ) mice. Collectively, PA inhibited ferroptosis of cardiomyocytes through activating of the AMPK pathway, thereby alleviating myocardial I/R injury in mice.

Transcutaneous electrical nerve stimulation over acupoint for chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Background: Transcutaneous electrical nerve stimulation over an acupoint (acu-TENS), a new technique applied in pulmonary rehabilitation programs, has been gradually used in the management of chronic obstructive pulmonary disease (COPD). However, the effects of acu-TENS have not been fully evaluated. Therefore, this review was conducted to assess the effects of acu-TENS on COPD. Methods: A total of seven electronic databases were searched from their inception to September 2021 for randomized controlled trials of acu-TENS for COPD. Two investigators independently performed data extraction and methodological quality assessment. Heterogeneity was examined by Cochrane χ2 and I 2 tests. The source of heterogeneity was investigated by subgroup analysis or sensitivity analysis. Results: In our review, ten studies between 2008 and 2021 were included. The aggregated results indicated that acu-TENS showed positive effects in forced expiratory volume in 1 s (FEV1) [MD = 0.13 L, 95% CI (0.11-0.16), P < 0.00001], FEV1% predicted [MD = 5.92%, 95% CI (3.43-8.41), P < 0.00001], 6-min walk distance (6MWD) [MD = 14.68m, 95% CI (6.92-22.44), P = 0.0002], dyspnea visual analog scale (DVAS) [MD = -7.58, 95%CI (-14.33 to -0.84), P = 0.03], modified Borg scale (MBS) [MD = -0.46, 95% CI (-0.86 to -0.06), P = 0.03], and COPD assessment test (CAT) [MD = -4.25, 95% CI (-5.24 to -3.27), P < 0.00001]. Although six studies reported adverse effects, only one patient had shoulder pain after acu-TENS. Conclusion: Acu-TENS seems to be effective in improving pulmonary function and health status in patients with COPD, with little effect on exercise capacity and dyspnea. However, this result should be interpreted with caution, and high-quality RCTs were needed for further verification.

NLRP3 Inflammasome Activation: A Therapeutic Target for Cerebral Ischemia-Reperfusion Injury.

Millions of patients are suffering from ischemic stroke, it is urgent to figure out the pathogenesis of cerebral ischemia-reperfusion (I/R) injury in order to find an effective cure. After I/R injury, pro-inflammatory cytokines especially interleukin-1ß (IL-1ß) upregulates in ischemic brain cells, such as microglia and neuron. To ameliorate the inflammation after cerebral I/R injury, nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome is well-investigated. NLRP3 inflammasomes are complicated protein complexes that are activated by endogenous and exogenous danger signals to participate in the inflammatory response. The assembly and activation of the NLRP3 inflammasome lead to the caspase-1-dependent release of pro-inflammatory cytokines, such as interleukin (IL)-1ß and IL-18. Furthermore, pyroptosis is a pro-inflammatory cell death that occurs in a dependent manner on NLRP3 inflammasomes after cerebral I/R injury. In this review, we summarized the assembly and activation of NLRP3 inflammasome; moreover, we also concluded the pivotal role of NLRP3 inflammasome and inhibitors, targeting the NLRP3 inflammasome in cerebral I/R injury.

Efficacy and safety of warm needle acupuncture in knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic disease, which is also recognized as a common disease affecting the elderly. However, the application of Western medicine is limited in clinical because of its obvious adverse reactions. Warm needle acupuncture (WNA) has a long history in the treatment of KOA and is widely used in Chinese. Here we will submit a protocol to evaluate the efficacy and safety of WNA in the treatment of KOA. METHODS: We will search 5 English databases (PubMed, MEDLINE, Embase, Cochrane Library, Web of Science), 4 Chinese databases [China National Knowledge Infrastructure (CNKI), China Biology Medicine, Chinese Science and Technology Journal Database (VIP), and Wanfang database] and grey literature for randomized controlled trials of WNA in the treatment of KOA. The primary outcome measure is Western Ontario and McMaster Universities Arthritis Index (WOMAC), and the secondary outcome will include degree of knee flexion and adverse events caused by WNA, such as dizziness, nausea, abdominal pain, arrhythmia, etc. The selection of the literatures will be conducted by endnote X7 software, and we will use Review Manger V.5.3 software to conduct the meta-analysis. RESULTS: This study will provide reliable evidence for WNA in the treatment of KAO. CONCLUSION: The conclusion of this study will testify the efficacy and safety of WNA in the treatment of KAO. REGISTRATION: OSF Preregistration. 2020, October 11; osf.io/bu5qw.