Correction: Innovative wound management: creating dynamic Alg-Mg/SF hydrogels for controlled Mg2+ release in wound healing.

[This corrects the article DOI: 10.1039/D4RA00793J.].

The role of PKM2 in cancer progression and its structural and biological basis.

Pyruvate kinase M2 (PKM2), a subtype of pyruvate kinase (PK), has been shown to play an important role in the development of cancer. It regulates the last step of glycolytic pathway. PKM2 has both pyruvate kinase and protein kinase activity, and the conversion of these two functions of PKM2 depends on the mutual change of dimer and tetramer. The dimerization of PKM2 can promote the proliferation and growth of tumor cells, so inhibiting the dimerization of PKM2 is essential to curing cancer. The aggregation of PKM2 is regulated by both endogenous and exogenous cofactors as well as post-translational modification (PTM). Although there are many studies on the different aggregation of PKM2 in the process of tumor development, there are few summaries in recent years. In this review, we first introduce the role of PKM2 in various biological processes of tumor growth. Then, we summarize the aggregation regulation mechanism of PKM2 by various endogenous cofactors such as Fructose-1, 6-diphosphate (FBP), various amino acids, and post-translational modification (PTMs). Finally, the related inhibitors and agonists of PKM2 are summarized to provide reference for regulating PKM2 aggregation in the treatment of cancer in the future.

Naringenin protects myocardial ischemia/reperfusion injury by regulating miR-24-3p to inhibit cell death-inducing p53 target 1 expression.

Myocardial ischemia/reperfusion (I/R) causes serious threats to human life. Naringenin, a polyphenolic compound naturally occurring in citrus fruit, has cardioprotective effects against myocardial I/R injury. Besides, miR-24-3p is also reported to have cardioprotective effects. We intended to explore whether the cardioprotective effects of naringenin relate to miR-24-3p and its underlying mechanism. In this study, we used an in vivo rat myocardial I/R model and an in vitro cardiomyocyte H9c2 hypoxia/reoxygenation (H/R) model. Myocardial injury was detected by hematoxylin-eosin staining and ELISA for creatine kinase (CK), malondialdehyde (MDA), and lactate dehydrogenase (LDH). miR-24-3p and cell death inducing p53 target 1 (Cdip1) mRNA expressions were examined by RT-PCR. We find that naringenin pretreatment significantly relieves myocardial I/R injury, reduces LDH, CD, and MDA levels, and increases miR-24-3p expression. Furthermore, miR-24-3p alleviates myocardial I/R injury partially through regulating Cdip1. Moreover, naringenin protects myocardial I/R injury partially by regulating miR-24-3p to inhibit Cdip1 expression. In conclusion, our data suggest naringenin protects myocardial I/R injury partially through miR-24-3p/Cdip1 axis.

Dietary copper requirement of broilers fed a corn-soybean meal diet during 22-42 d of age.

This research was to assess the dietary copper (Cu) requirement of broiler chickens fed a practical corn-soybean meal diet during 22-42 d of age. A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages (6 broilers per cage) per treatment. Broilers were fed a Cu-unsupplemented corn-soybean meal basal diet (control, containing 7.36 mg Cu/kg) or the basal diet added with 3, 6, 9, 12, or 15 mg Cu/kg from CuSO4·5H2O for 21 d. Quadratic, asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu requirements. The results revealed that the contents of Cu in serum and liver, mRNA expression levels of Cu- and zinc-containing superoxide dismutase (CuZnSOD) in liver and monoamine oxidase b (MAO B) in heart, as well as protein expression level of CuZnSOD in liver were affected (P < 0.05) by supplemental Cu levels, and the above indices varied linearly and quadratically (P < 0.05) with increasing Cu levels. Dietary Cu requirements assessed according to the best fitted broken-line models (P < 0.05) of the above indexes were 10.45-13.81 mg/kg. It was concluded that mRNA expression levels of CuZnSOD in liver and MAO B in heart, as well as liver CuZnSOD protein expression level were new specific sensitive biomarkers for estimating dietary Cu requirements, and the dietary Cu requirement was recommended to be 14 mg/kg to support Cu metabolic needs related to key Cu-containing enzymes in broilers fed the corn-soybean meal diet during 22-42 d of age, which was higher than the dietary Cu requirement (8 mg/kg) for broilers at the corresponding stage suggested by the Chinese Feeding Standard of Chicken.

The chemical characteristics of different sodium iron ethylenediaminetetraacetate sources and their relative bioavailabilities for broilers fed with a conventional corn-soybean meal diet.

BACKGROUND: Our previous studies demonstrated that divalent organic iron (Fe) proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation (Qf) values displayed higher Fe bioavailabilities for broilers. Sodium iron ethylenediaminetetraacetate (NaFeEDTA) is a trivalent organic Fe source with the strongest chelating ligand EDTA. However, the bioavailability of Fe when administered as NaFeEDTA in broilers and other agricultural animals remains untested. Herein, the chemical characteristics of 12 NaFeEDTA products were determined. Of these, one feed grade NaFeEDTA (Qf = 2.07 × 108), one food grade NaFeEDTA (Qf = 3.31 × 108), and one Fe proteinate with an extremely strong chelation strength (Fe-Prot ES, Qf value = 8,590) were selected. Their bioavailabilities relative to Fe sulfate (FeSO4·7H2O) for broilers fed with a conventional corn-soybean meal diet were evaluated during d 1 to 21 by investigating the effects of the above Fe sources and added Fe levels on the growth performance, hematological indices, Fe contents, activities and gene expressions of Fe-containing enzymes in various tissues of broilers. RESULTS: NaFeEDTA sources varied greatly in their chemical characteristics. Plasma Fe concentration (PI), transferrin saturation (TS), liver Fe content, succinate dehydrogenase (SDH) activities in liver, heart, and kidney, catalase (CAT) activity in liver, and SDH mRNA expressions in liver and kidney increased linearly (P < 0.05) with increasing levels of Fe supplementation. However, differences among Fe sources were detected (P < 0.05) only for PI, liver Fe content, CAT activity in liver, SDH activities in heart and kidney, and SDH mRNA expressions in liver and kidney. Based on slope ratios from multiple linear regressions of the above indices on daily dietary analyzed Fe intake, the average bioavailabilities of Fe-Prot ES, feed grade NaFeEDTA, and food grade NaFeEDTA relative to the inorganic FeSO4·7H2O (100%) for broilers were 139%, 155%, and 166%, respectively. CONCLUSIONS: The bioavailabilities of organic Fe sources relative to FeSO4·7H2O were closely related to their Qf values, and NaFeEDTA sources with higher Qf values showed higher Fe bioavailabilities for broilers fed with a conventional corn-soybean meal diet.

The rapid antidepressant effect of acupuncture on two animal models of depression by inhibiting M1-Ach receptors regulates synaptic plasticity in the prefrontal cortex.

BACKGROUND: It is unclear whether acupuncture has a rapid antidepressant effect and what is the main mechanism. METHODS: In this study, forced swimming stress test (FST) in mice were divided into five groups: control group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Chronic unpredictable mild stress (CUMS) model rats were divided into six groups: naïve (non-CUMS) group, CUMS group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Twenty-four hours after the end of treatment, FST was conducted in mice and rats. The expression of M1-AchR, AMPA receptors (GluR1 and GluR2), BDNF, mTOR, p-mTOR, synapsin I, and PSD95 in the prefrontal cortex was determined by western blot. The spine density of neurons in the prefrontal cortex was detected by golgi staining. RESULTS: The results showed that acupuncture reduced the immobility time of FST in two depression models. Acupuncture inhibited the expression of M1-AchR and promoted the expression of GluR1, GluR2, BDNF, p-mTOR, synapsin I, PSD95, and increased the density of neuron dendritic spine in the prefrontal cortex. CONCLUSIONS: The rapid antidepressant effect of acupuncture may be activating the "glutamate tide" - AMPA receptor activation - BDNF release - mTORC1 pathway activation through inhibiting the expression of M1-AchR in the prefrontal cortex, thereby increasing the expression of synaptic proteins and regulating synaptic plasticity.

Pregnane X receptor as a therapeutic target for cholestatic liver injury.

Cholestatic liver injury (CLI) is caused by toxic bile acids (BAs) accumulation in the liver and can lead to inflammation and liver fibrosis. The mechanisms underlying CLI development remain unclear, and this disease has no effective cure. However, regulating BA synthesis and homeostasis represents a promising therapeutic strategy for CLI treatment. Pregnane X receptor (PXR) plays an essential role in the metabolism of endobiotics and xenobiotics via the transcription of metabolic enzymes and transporters, which can ultimately modulate BA homeostasis and exert anticholestatic effects. Furthermore, recent studies have demonstrated that PXR exhibits antifibrotic and anti-inflammatory properties, providing novel insights into treating CLI. Meanwhile, several drugs have been identified as PXR agonists that improve CLI. Nevertheless, the precise role of PXR in CLI still needs to be fully understood. This review summarizes how PXR improves CLI by ameliorating cholestasis, inhibiting inflammation, and reducing fibrosis and discusses the progress of promising PXR agonists for treating CLI.

Hydrophilic chitosan/graphene oxide composite sponge for rapid hemostasis and non-rebleeding removal.

Hydrophilic hemostatic sponge plays an important role in trauma bleeding control because of its robust coagulant functions. However, its strong tissue adhesion can easily result in wound tear and rebleeding during removing the sponge. Herein, the design of a hydrophilic anti-adhesive chitosan/graphene oxide composite sponge (CSAG) that possesses stable mechanical strength, rapid liquid absorption and strong intrinsic/extrinsic coagulation stimulations, is reported. For one thing, CSAG exhibits outstanding hemostatic performance, which significantly outperforms two commercial hemostats in two in vivo serious bleeding models. For another, CSAG shows low tissue adhesion; its peeling force is approximately 79.3 % lower than the commercial gauze. Moreover, in the peeling process, CSAG triggers partial detachment of the blood scab, because of the exist of bubbles or cavities at the interface, allowing the CSAG to be easily and safely peeled off from the wound without rebleeding. This study opens new avenues in constructing anti-adhesive trauma hemostatic materials.

Acupuncture inhibits autophagy and repairs synapses by activating the mTOR pathway in Parkinson's disease depression model rats.

Acupuncture is a good treatment for depression in Parkinson's disease (DPD), so the possible mechanism of acupuncture in the treatment of DPD was explored in this study. Firstly, observing the behavioral changes of the DPD rat model, the regulation of monoamine neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT) in the midbrain, the change of α-synuclein (α-syn) in the striatum, the efficacy of acupuncture in the treatment of DPD was discussed. Secondly, autophagy inhibitors and activators were selected to judge the effect of acupuncture on autophagy in the DPD rat model. Finally, an mTOR inhibitor was used to observe the effect of acupuncture on the mTOR pathway in the DPD rat model. The results showed that acupuncture could improve the motor and depressive symptoms of DPD model rats, increase the content of DA and 5-HT, and decrease the content of ɑ-syn in the striatum. Acupuncture inhibited the expression of autophagy in the striatum of DPD model rats. At the same time, acupuncture upregulates p-mTOR expression, inhibits autophagy, and promotes synaptic protein expression. Therefore, we concluded that acupuncture might improve the behavior of DPD model rats by activating the mTOR pathway, inhibiting autophagy from removing α-syn and repairing synapses.

The organic zinc with moderate chelation strength enhances the expression of related transporters in the jejunum and ileum of broilers.

Our previous study demonstrated that the zinc (Zn) proteinate with moderate chelation strength (Zn-Prot M) enhanced the Zn absorption in the small intestine partially via increasing the expression of some Zn and amino acid transporters in the duodenum of broilers. However, it remains unknown whether the Zn-Prot M could also regulate the expression of related transporters in the jejunum and ileum of broilers in the above enhancement of Zn absorption. The present study was conducted to investigate the effect of the Zn-Prot M on the expression of related transporters in the jejunum and ileum of broilers compared to the Zn sulfate (ZnS). Zinc-deficient broilers (13-d-old) were fed with the Zn-unsupplemented basal diets (control) or the basal diets supplemented with 60 mg Zn/kg as ZnS or Zn-Prot M for 26 d. The results showed that in the jejunum, compared to the control, supplementation of the organic or inorganic Zn increased (P < 0.05) mRNA and protein expression of b0,+-type amino acid transporter (rBAT), Zn transporter 10 (ZnT10), and peptide-transporter 1 (PepT1) mRNA expression and Zn transporter 7 (ZnT7) protein expression on d 28, while y+L-type amino transporter 2 (y+LAT2) mRNA and protein expression, and protein expression of ZnT7 and ZnT10 on 28 d and zrt-irt-like protein 3 (ZIP3) and zrt-irt-like protein 5 (ZIP5) on d 39 were higher (P < 0.05) for Zn-Prot M than for ZnS. In the ileum, Zn addition regardless of Zn source up-regulated (P < 0.05) mRNA expression of Zn transporter 9 (ZnT9) and ZIP3, ZIP5, and y+LAT2 protein expression on d 28, and PepT1 mRNA and protein expression, ZIP3 and y+LAT2 mRNA expression and ZnT10 protein expression on d 39. Furthermore, Zn transporter 4 (ZnT4) and ZnT9 mRNA expression and Zn transporter 1 (ZnT1) protein expression on d 28, and y+LAT2 mRNA expression and ZnT10 and PepT1 protein expression on d 39 were higher (P < 0.05) for Zn-Prot M than for ZnS. It was concluded that the Zn-Prot M enhanced the expression of the ZnT1, ZnT4, ZnT9, ZnT10, ZIP3, ZIP5, y+LAT2, and PepT1 in the jejunum or ileum of broilers compared to the ZnS.

An optimal dietary sodium chloride supplemental level of broiler chicks fed a corn-soybean meal diet from 1 to 21 days of age.

Sodium chloride (NaCl) is usually added to diets to meet the Na and Cl requirements of broilers in the Chinese poultry industry, but the optimal dietary NaCl supplemental level was not well-established. The present study was conducted to estimate the optimal dietary NaCl supplemental level of broilers fed a corn-soybean meal diet from 1 to 21 days of age. A total of 490, 1-day-old Arbor Acres male broilers were fed a NaCl-unsupplemented corn-soybean meal basal diet (control) and the basal diet supplemented with 0.10, 0.20, 0.30, 0.40, 0.50 or 0.60% NaCl for 21 days. Regression analysis was conducted to evaluate the optimal dietary NaCl level using the best fitted broken-line or asymptotic models. As dietary supplemental NaCl levels increased, average daily gain (ADG), average daily feed intake (ADFI), blood partial pressure of CO2, total CO2, base excess and anion gap, blood concentrations of HCO3, Na and Cl, serum Na concentration, jejunal villus height (VH) and tibia ash content increased linearly and quadratically (P < 0.05), while feed/gain ratio, relative weights of heart, liver and kidney, blood K concentration, serum concentrations of K, uric acid and glucose, and osmotic pressure decreased linearly and quadratically (P < 0.05). The estimates of optimal dietary NaCl levels were 0.20-0.22% based on the best fitted broken-line or asymptotic models (P < 0.0001) of ADG, ADFI and feed/gain ratio, and 0.08-0.24% based on the best fitted broken-line or asymptotic models (P < 0.0001) of blood gas indices, serum parameters, jejunal VH, tibia ash content and organ indices. These results suggested that the optimal dietary NaCl supplemental level would be 0.24% for broilers fed the corn-soybean meal diet from 1 to 21 days of age, which is lower than the current dietary NaCl supplemental level (0.30%) in the Chinese broiler production.

Graphene oxide reinforced hemostasis of gelatin sponge in noncompressible hemorrhage via synergistic effects.

Effective hemostasis for noncompressible bleeding has been a key challenge because of the deep, narrow, and irregular wounds. Swellable gelatin is an available hemostatic material but is limited by weak mechanical strength and slow liquid absorption. Herein, the design of a gelatin and graphene oxide (GO) composite sponge (GP-GO) that possesses stable cross-linked networks and excellent absorbability, is reported. The GP-GOs are constructed via the thermal radical polymerization technique, using methacrylate gelatin (Gel-MA) and poly(ethylene glycol) diacrylate (PEGDA) as the crosslinker, while GO is uniformly fixed in the network via the curing reaction to further strengthen the stability. The optimized GP-GO5 with GO addition (5 wt%) exhibits high porosity (> 90%), distinguished liquid absorption rate (106 ms), rapidly responsive swelling (422% expansion within 10 s), and stable mechanical properties. The addition of GO effectively reinforces coagulation stimulation of GP-GOs though the stimulation of platelets and the enrichment effect at the interface, significantly reducing the blood coagulation index (BCI) (< 17.5%). Hemostatic mechanism study indicated the liquid absorbability of GP-GOs is the critical foundation to trigger the subsequent physical expansion, blood cells enrichment, and coagulation stimulations. Besides, GP-GO5 exhibits excellent biosafety assessed by hemolysis and cytotoxicity. Under the synergistic effects, the biocompatible GP-GO5 showed excellent hemostatic properties in the hemostasis of severe bleeding and noncompressible wounds compared with a pure gelatin sponge (GP) and the commercial hemostatic agent Celox™. This study demonstrated a promising candidate for practical application of noncompressible wound hemostasis.

Organic zinc with moderate chelation strength enhances zinc absorption in the small intestine and expression of related transporters in the duodenum of broilers.

Our previous study demonstrated that the absorption of zinc (Zn) from the organic Zn proteinate with moderate chelation strength was significantly higher than that of Zn from the inorganic Zn sulfate in the in situ ligated duodenal segment of broilers, but the underlying mechanisms are unknown. The present study aimed to determine the effect of organic Zn with moderate chelation strength and inorganic Zn on the Zn absorption in the small intestine and the expression of related transporters in the duodenum of broilers. The Zn-deficient broilers (13 days old) were fed with the Zn-unsupplemented basal diets (control) containing 25.72 and 25.64 mg Zn/kg by analysis or the basal diets supplemented with 60 mg Zn/kg as the Zn sulfate or the Zn proteinate with moderate chelation strength (Zn-Prot M) for 26 days. The results showed that the plasma Zn contents from the hepatic portal vein of broilers at 28 days and 39 days of age were increased (p < 0.05) by Zn addition and greater (p < 0.05) in the Zn-Prot M than in the Zn sulfate. On d 28, Zn addition upregulated (p < 0.05) mRNA expression of zinc transporter 1 (ZnT1), Zrt-irt-like protein 5 (ZIP5), y + L-type amino transporter 2 (y + LAT2) and b0,+-type amino acid transporter (rBAT), zinc transporter 4 (ZnT4) protein expression, and zinc transporter 9 (ZnT9) mRNA and protein expression in the duodenum. Moreover, ZnT9 mRNA expression, ZnT4, ZIP5, and rBAT protein expression, zinc transporter 7 (ZnT7), and y + LAT2 mRNA and protein expression in the duodenum of broilers on 28 days were higher (p < 0.05) in the Zn-Prot M than in the Zn sulfate. On d 39, supplemental Zn increased (p < 0.05) peptide-transporter 1 (PepT1) mRNA expression and y + LAT2 protein expression, while the mRNA expression of ZnT7 and Zrt-irt-like protein 3 (ZIP3) were higher (p < 0.05) for the Zn-Prot M than for the Zn sulfate in the duodenum. It was concluded that the Zn-Prot M enhanced the Zn absorption in the small intestine partially via upregulating the expression of ZnT4, ZnT7, ZnT9, ZIP3, ZIP5, y + LAT2, and rBAT in the duodenum of broilers.

The Effect of Bone Morphogenetic Protein 2 or Extracellular Signal-Regulated Kinase 1 Silencing on Phosphorus Utilization and Related Parameters in Primary Broiler Osteoblasts.

Two experiments were conducted to study the effect of bone morphogenetic protein 2 (BMP2) or extracellular signal-regulated kinase 1 (ERK1) silencing on phosphorus (P) utilization and related parameters in primary broiler osteoblasts. Experiment 1 was carried out to select the most efficacious siRNAs against BMP2 or ERK1 for the subsequent experiment. In experiment 2, with or without the siRNA against BMP2 or ERK1, primary broiler osteoblasts were incubated in the medium supplemented with 0.0 or 2.0 mmol/L of P as NaH2PO4 for 12 days. The osteoblastic P utilization and related parameters were determined. The results showed that the si980 and si1003 were the most effective (P < 0.05) in inhibiting BMP2 and ERK1 expressions, respectively. The BMP2 silencing reduced (P < 0.004) the osteoblastic P retention rate, alkaline phosphatase (ALP) activity, BMP2 mRNA and protein expressions. Supplemental P increased (P = 0.0008) ALP activity. Significant interactions (P < 0.04) between the gene silencing and supplemental P level were observed in both mineralization formation and bone gal protein (BGP) content. The BMP2 silencing decreased (P < 0.05) mineralization formation at both 0.0 and 2.0 mmol/L of added P levels, but the decreased degree was greater at 2.0 mmol/L of added P level, while BMP2 silencing reduced (P < 0.05) BGP content at only 2.0 mmol/L of added P level. The ERK1 silencing decreased (P < 0.004) mineralization formation, ALP activity, BGP content, ERK1 mRNA, ERK1 and p-ERK1 protein expressions. Supplemental P increased (P < 0.03) mineralization formation, ALP activity, BGP content and p-ERK1 protein expression, but inhibited (P = 0.014) ERK1 protein expression. There was an interaction (P < 0.03) between the gene silencing and supplemental P level in the osteoblastic P retention rate. The ERK1 silencing decreased (P < 0.05) it regardless of 0.0 or 2.0 mmol/L of added P level, but the reduced degree was greater at 2.0 mmol/L of added P level. It was concluded that either BMP2 or ERK1 silencing suppressed P utilization, and thus either of them participated in regulating P utilization in primary broiler osteoblasts.

Graphene-ophicalcite heterogeneous composite sponge for rapid hemostasis.

Synergistic functionalization of interface coagulation stimulation and liquid absorption capacity is the key to improve the hemostatic efficiency of hemostats. Herein, we prepared a graphene-ophicalcite (OPH) heterogeneous composite sponge (GOCS) by using the heterogeneous gradient composite strategy. The sponge took cross-linked graphene sponge (CGS) as the main skeleton, allowing the OPH to be controllably positioned on the surface of GOCS. The heterogeneous strategy gave full play to the advantages of the material. On the one hand, GOCS had excellent liquid absorption ability, which enriched blood cells and other coagulation components at the wound interface after contacting blood. On the other hand, the OPH at the interface obviously activated platelets and rapidly triggered coagulation cascade reactions, exhibiting fast response and feedback characteristics for coagulation signals. Under the synergistic effects, the blood clotting index value of GOCS was reduced to 33.87 ± 9.97%, which was significantly lower than those of OPH (46.33 ± 16.85%) and CGS (67.53 ± 5.35%). Importantly, GOCS rapidly stopped bleeding within 51 s in the rat femoral artery model, suggesting its great potential in the field of hemostasis. Therefore, this study provides a new idea for the design and preparation of hemostatic materials via heterogeneous strategy.

Naringenin alleviates myocardial ischemia/reperfusion injury by regulating the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) /System xc-/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis.

Ferroptosis is an important form of myocardial cell death in myocardial ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has a significant advantage in improving MIRI. But the regulatory effect and mechanism of NAR on ferroptosis in MIRI have not been reported. After the rats were given NAR and induced to form myocardial ischemia-reperfusion (MI/R) injury, Tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats, and Hematoxylin-eosin (H&E) staining was used to detect myocardial injury. The markers of tissue inflammation were detected by ELISA. Serum creatine kinase Serum creatin kinase (CPK), Lactate dehydrogenase (LDH), and lipid peroxide (LPO) and oxidative stress related levels were measured. In addition, iron detection kits were used to detect total iron and Fe2+ levels in cardiac tissues, and western blot was used to detect the expression of ferroptosis-related proteins and the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). At the cellular level, H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and ferroptosis inducer Erastin was administered to detect cell viability, ferroptosis-related indicators, oxidative stress related indicators, and expressions of Nrf2 and GPX4, to explore the mechanisms involved. NAR alleviated MI/R-induced pathological damage, inflammation and lipid peroxidation in myocardial tissue of rats. NAR adjusted the NRF2 /System xc - /GPX4 axis and improved ferroptosis. At the cellular level, ferroptosis inducer Erastin reversed the protective effect of NAR on H/R-induced H9C2 cardiomyocytes. In conclusion, NAR can alleviate MIRI by regulating the Nrf2/System xc-/GPX4 axis to inhibit ferroptosis.

Effect of aspirin in takotsubo syndrome: protocol of a systematic review and meta-analysis.

INTRODUCTION: Takotsubo syndrome (TTS) is a sudden reversible weakening of the left ventricle function induced by severe stress and resembles many features as acute coronary syndrome. Even though many guidelines had been published about TTS, there is no consensus regarding the long-term treatment. Aspirin is one of the most common prescribed medicines at discharge for patients with the intention to reduce thrombus events and improve the overall prognosis. However, existing studies yielded conflicting results concerning its effects. This study aims to evaluate the impact of long-term maintenance treatment of aspirin in TTS and provides insights in clinical management. METHODS AND ANALYSIS: After searching through electronic databases (PubMed, Embase, Cochrane Library, Web of Science, National Library of Medicine Gateway, CNKI, Wanfang and VIP), grey literatures, conference abstract and trial registries for clinical studies investigating the impact of aspirin on patients with TTS, a systemic review and meta-analysis will be conducted. The search will be limited from inception of each database to 1 August 2020. The outcomes including all-cause death, TTS recurrence, stroke, transient ischaemic attack or myocardial infarction at 30-day and 5-year follow-up will be examined. Risk of bias will be assessed by Newcastle-Ottawa quality assessment scale for observational studies and Cochrane Effective Practice and Organization of Care evaluation tool for interventional studies. Grading of Recommendations Assessment, Development and Evaluations method will be applied to assess the quality of evidence. If available, the effects of aspirin on the above outcomes for patients with TTS will be evaluated using random-effect modelling with relative risk at 95% CIs. Subgroup analysis and sensitivity analysis will also be performed when possible. ETHICS AND DISSEMINATION: Ethics approval was not required due to the retrospective nature of the study. Results of the review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020212729.

Understanding the Benefits of Standing and Sitting Baduanjin Based on Cardiopulmonary Exercise Testing: An Observational Study.

Objectives: Although Baduanjin (a traditional Chinese physical activity) has been reported to promote general health, the optimal exercise intensity and kinematic characteristics of this intervention remain poorly understood. This investigation aimed to quantify and compare the exercise intensities of traditional standing Baduanjin (TB) and sitting Baduanjin (SB) using cardiopulmonary exercise testing, to further clarify the sources of the previously observed benefits of this modality. Study design: Observational study. Interventions: Healthy individuals were recruited to perform TB, SB, and cycling (in order) until they reached their ventilatory threshold. Intensity-relevant parameters based on type of exercise and specific time points (exercise start and the end of the 2nd, 4th, 6th, and 8th set of motion) were compared between TB and SB with ventilatory threshold as control. Results: Forty individuals (18 male and 22 female) completed the trial. Significant differences in peak oxygen uptake, metabolic equivalent of task, and Borg scale existed among the three exercise types, indicating a decreasing overall exercise intensity in the order of ventilatory threshold, TB, and SB. All parameters except the respiratory exchange ratio fluctuated significantly across the time points. Conclusions: Both TB and SB resulted in a significantly lower exercise intensity when compared with the ventilatory threshold established through cycling exercise. The benefits of Baduanjin might be explained partly by its appropriate exercise intensity and intermittent intensity pattern. Baduanjin might be a potential alternative to existing schemes for exercise rehabilitation.

Efficacy and safety of the classic Chinese herbal prescription Sanpian decoction on migraine: A meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of the classic Chinese herbal prescription Sanpian decoction for curing migraine. METHODS: Scopus, PubMed, EMBASE, SPRINGER LINK, China National Knowledge Infrastructure (CNKI), Weipu Database and WanFang Database were searched from inception through January 2019 to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of Sanpian decoction. RESULTS: Fifteen RCTs with a total of 1377 participants were identified. Compared with the control drugs, Sanpian decoction and Sanpian decoction combined with Sibelium significantly improved the clinical efficacy separately (relative risk [RR] 4.19, 95% confidence intervals [CI] 2.91 to 6.04, P < 0.00001; RR 1.29, 95% CI 1.09 to 1.54, P = 0.003 separately); the Sanpian decoction significantly improved the visual analogue scale score (VAS) (mean differences [MD] -1.83, 95% CI -2.69 to -0.97, P < 0.0001), headache score (MD -3.77, 95% CI -7.20 to -0.34, P = 0.03) and reduced the frequency of headache attacks (MD -1.61, 95% CI -2.07 to -1.14, P < 0.00001) and the concentration of endothelin (ET) (MD -11.90, 95% CI -23.22 to -0.58, P = 0.04) when compared with control drugs. There were minor side effects related to Sanpian decoction which were well tolerated. CONCLUSIONS: Sanpian decoction is of significant benefits and relative safety in treating migraine. However, more rigorous studies with larger sample sizes are needed due to methodological flaws and low quality of the included trials in this meta-analysis.

Intervention Treatment for Myocardial Infarction With Tai Chi: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the efficacy of Tai Chi (TC) in patients with myocardial infarction and provide up-to-date evidence for its application. DATA SOURCES: Three English databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) and 3 Chinese databases (China Knowledge Resource Integrated, Wanfang, Weipu) were screened for the time period between January 1, 1976 and May 31, 2019. STUDY SELECTION: Seven randomized and controlled experiments were included. DATA EXTRACTION: Two independent researchers under 2 independent advisors extracted and classified the data from all relevant studies based on the prespecified inclusion criteria and rules for data extraction. DATA SYNTHESIS: A total of 615 patients were included in this study. The TC group was comprised of 294 patients, and the control group included 261 patients. The results revealed that TC has significant effects on the outcomes of the 6-minute walk (standardized mean difference, 1.30; 95% confidence interval, 0.50-2.11) and left ventricular ejection fraction (standardized mean difference, 1; 95% confidence interval, 0.43-1.57) compared with no or low-density exercise. Also, TC positively affected the quality of life, pro-B type natriuretic peptide, and short form-36. However, TC did not significantly affect activities of daily living (P=.060), sense of coherence-13 (P=.057) and N-terminal-pro-brain natriuretic peptide (P=.081). A moderate to high heterogeneity was observed across all comparisons. CONCLUSIONS: Compared with no exercise or other types of low-intensity physical activities, TC improved the outcome of the 6-minute walk, left ventricular ejection fraction, quality of life, and short form-36 scores, but reduced the outcome of pro-B type natriuretic peptide in patients with myocardial infarction. Therefore, TC could be an effective exercise option for cardiac rehabilitation. More research should be done to identify the effects of TC on academic functioning and to determine ways of motivating patients to use preventive TC interventions.