Polyphyllin II Induces Apoptosis in Fibrosarcoma Cells via Activating Pyruvate Kinase M2.

Aerobic glycolysis is a metabolic reprogramming of tumor cells that is essential for sustaining their phenotype of fast multiplication by continuously supplying energy and mass. Pyruvate kinase M2 (PKM2) has a vital role in this process, which has given it high interest as a target for anticancer drug development. With potent toxicity to many types of cancer cells, polyphyllin II (PP2), a steroidal saponin isolated from the herbaceous plant Rhizoma paridis, brought to our attention that it might interfere with the PKM2 activity. In this study, we discovered that PP2 was a novel agonist of PKM2. PP2 activated recombinant PKM2 and changed the protein's oligomeric state to activate intracellular PKM2. At the same time, PP2 suppressed its protein kinase function by decreasing the content of nuclear PKM2. The mRNA levels of its downstream genes, such as Glut1, LDHA, and MYC, were inhibited. In addition, PP2 induced oxidative stress by downregulating the expression and activity of antioxidant proteins such as NQO1, TrxR, and Trx in HT-1080 cells, which in turn led to mitochondrial dysfunction and ultimately induced apoptosis. Moreover, PP2 reduced the proliferation and migration of HT-1080 cells. Thus, targeting the glycolysis pathway offers an unprecedented mode of action for comprehending PP2's pharmacological impacts and advances PP2's further development in fibrosarcoma therapy.

Physiological occlusal force attenuates replacement root resorption of replanted teeth: an experimental animal study.

BACKGROUND: Tooth avulsion represents the most severe form of dental trauma, necessitating tooth replantation as the primary treatment. However, the risk of replacement root resorption (RRR) poses a significant threat to tooth retention following replantation. This study preliminarily aimed to investigate the effect of physiological occlusal force on RRR after the replantation of avulsed teeth and to explore the potential underlying mechanisms. METHODS: Thirty-six 4-week-old male Sprague-Dawley rats underwent extraction and immediate replantation of their left maxillary molars. The rats were randomly divided into two major groups: the occluded (n = 18) group, where the opposite mandibular teeth were preserved; non-occluded (n = 18) group, where the opposite mandibular teeth were extracted. Within each major group, there were three subgroups corresponding to 7 days, 14 days, and 2 months, resulting in a total of six subgroups, (n = 6 per subgroup). The right maxillary first molars served as the normal control. Various periodontal characteristics were assessed using haematoxylin-eosin (H&E), tartrate-resistant acid phosphatase (TRAP) staining, and micro-computed tomography (micro-CT). RESULTS: Histological staining revealed that under occlusal force, the early stage (day 7) after tooth replantation mainly manifested as root surface resorption, especially in the non-occluded group, which gradually diminished over time. Cementum and periodontal ligament (PDL) repair was observed on day 14. Micro-CT analysis indicated a significant decrease in PDL width in the non-occluded group two months after replantation, consistent with the histological findings, signifying severe RRR in the non-occluded group. CONCLUSIONS: This study provides preliminary evidence that physiological occlusal force may attenuate osteoclastogenesis during the early stage of tooth replantation, thereby reducing the occurrence of RRR and promoting periodontal healing.

Human epicardial adipose tissue inflammation correlates with coronary artery disease.

BACKGROUND AND AIMS: This study investigates the expression of novel adipocytokines and inflammatory cells infiltration in epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) between 27 coronary artery disease (CAD) and 21 non-CAD (NCAD) patients enrolled from September 2020 to September 2021. METHODS AND RESULTS: Serum, gene, and protein expression levels of the novel adipocytokines were determined using ELISA, RT-qPCR, and western blot analyses. The number of blood vessels and adipocytes morphology were measured via hematoxylin-eosin staining, and inflammatory cells infiltration was examined via immunohistochemistry. Serum ANGPTL8, CTRP5, and Wnt5a levels were higher in the CAD than in the NCAD group, while serum CTRP3, Sfrp5, and ZAG levels were lower in the CAD than in the NCAD group. Compared to the EAT of NCAD and SAT of CAD patients, the EAT of CAD patients had higher mRNA levels of ANGPTL8, CTRP5, and Wnt5a while lower levels of CTRP3, Sfrp5, and ZAG; higher protein expression levels of ANGPTL8 and CTRP5 but lower levels of CTRP3; more blood vessels; and higher infiltration rates of macrophages (CD68 + ), pro-inflammatory M1 macrophages (CD11c + ), mast cells (Tryptase + ), T lymphocytes (CD3 + ), and B lymphocytes (CD20 + ) but lower infiltration rates of anti-inflammatory M2 macrophages (CD206 + ). CONCLUSION: Novel adipocytokines and inflammatory cells infiltration are dysregulated in human EAT, and could be important pathophysiological mechanisms and novelly promising medicating targets of CAD.

Contribution of mitochondria to postmortem muscle tenderization: a review.

Postmortem meat tenderization is a process mediated by a series of biochemical reactions related to muscle cell death. Cell death is considered a sign that muscle has started to transform into meat. Mitochondria play a significant role in regulating and executing cell death, as they are an aggregation point for many cell death signals and are also the primary target organelle damaged by tissue anoxia. Mitochondrial damage is likely to have an expanded role in postmortem meat tenderization. This review presents current findings on mitochondrial damage induced by the accumulation of reactive oxygen species during postmortem anaerobic metabolism and on the impact of mitochondrial damage on proteolysis and discusses how this leads to improved tenderness during aging. The underlying mechanisms of mitochondrial regulation of postmortem muscle tenderization likely focus on the mitochondria's role in postmortem cell death and energy metabolism. The death process of postmortem skeletal muscle cells may exhibit multiple types, possibly involving transformation from autophagy to apoptosis and, ultimately, necroptosis or necrosis. Mitochondrial characteristics, especially membrane integrity and ATP-related compound levels, are closely related to the transformation of multiple types of dead postmortem muscle cells. Finally, a possible biochemical regulatory network in postmortem muscle tenderization is proposed.

Correlation between serum Dickkopf-1 (DKK1) levels and coronary artery stenosis.

BACKGROUND AND AIMS: To study the correlation between the level of serum Dickkopf-1 (DKK1) and the degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease. METHODS AND RESULTS: In 2018, general data and biochemical indexes of 311 patients who underwent coronary angiography were recorded. Before procedure, arterial blood was drawn and the concentrations of DKK1, retinol binding protein 4 (RBP4), plasminogen activator inhibitor (PAI-1) were measured. Based on coronary angiography results, subjects were divided into a coronary heart disease (CHD) group; and a non-coronary heart disease (non-CHD)group. The CHD group was divided into three subgroups: the low Gensini score; the middle Gensini score; and the high Gensini score subgroups. Compared with those of the non-CHD group, DKK1, RBP4 and PAI-1 of the CHD group were significantly higher, while the OC was lower. DKK1,RBP4 and PAI-1 levels of the middle and high Gensini subgroups were significantly higher, compared with that of the low Gensini subgroup. Differences between osteocalcin (OC), beta-isomerized C-terminal telopeptidase (ß-CTX), and 25(OH)2D3 of the three subgroups were not significant. Correlation between DKK1 and the inflammatory factors, RBP4 and PAI-1, was positive. Correlation between DKK1 and ß - CTX, 25(OH)2D3 and OC was not significant. DKK1 was a risk factor for CHD. The degree of coronary artery stenosis was related to DKK1 concentration. CONCLUSIONS: Serum DKK1 levels in coronary heart disease patients were significantly higher, and positively correlated with the degree of coronary artery stenosis. DKK1 level is an independent risk factor for coronary heart disease.

Hemin as a General Static Dark Quencher for Constructing Heme Oxygenase-1 Fluorescent Probes.

The development of small-molecule probes suitable for live-cell applications remains challenging yet highly desirable. We report the first fluorescent probe, RBH, for imaging the heme oxygenase-1 (HO-1) activity in live cells after discovering hemin as a universal dark quencher. Hemin works via a static quenching mechanism and shows high quenching efficiency (>97 %) with fluorophores across a broad spectrum (λex =400-700 nm). The favorable properties of RBH (e.g. long excitation/emission wavelengths, fast response rate and high magnitude of signal increase) enable its use for determining HO-1 activity in complex biological samples. As HO-1 is involved in regulating antioxidant defence, iron homeostasis and gasotransmitter carbon monoxide production, we expect RBH to be a powerful tool for dissecting its functions. Also, the discovery of hemin as a general static dark quencher provides a straightforward strategy for constructing novel fluorescent probes for diverse biological species.

Evaluation of conditioned medium from placenta-derived mesenchymal stem cells as a storage medium for avulsed teeth: An in vitro study.

BACKGROUND/AIM: The viability of periodontal ligament cells on the root surface is a major factor that influences the healing of replanted teeth. A suitable storage medium is necessary to preserve avulsed teeth before replantation. Conditioned medium from placenta-derived mesenchymal stem cells (PMSC-CM) contains a variety of growth factors. The aim of this study was to evaluate the effectiveness of PMSC-CM as a storage medium to maintain the cell viability of avulsed teeth. MATERIAL AND METHODS: Extracted premolars from healthy humans were randomly stored in Hank's balanced salt solution (HBSS) and PMSC-CM for 6, 12 and 24 hours, respectively, at room temperature, and then the ratio of apoptosis of the periodontal ligament (PDL) cells was identified by flow cytometry. Human periodontal ligament stem cells (PDLSCs) were incubated with HBSS and PMSC-CM, respectively, for 6, 12, 24 and 48 hours in 5% CO2 at 37°C. Then, the cell viability of PDLSCs was determined using the cell counting kit-8 (CCK-8) and a cell cycle assay was performed. RESULTS: The apoptosis rate of PDL cells in PMSC-CM was significantly lower than that in HBSS at 24 hours (P < .001), while the two groups showed similar cell apoptosis rates at 6 and 12 hours (P > .05). The cell proliferation of PDLSCs treated with PMSC-CM significantly increased compared with the HBSS group (P < .05). The cell cycle assay revealed that the PDLSCs treated with HBSS were arrested at the G1 phase, while there was no difference between the PMSC-CM group and the control group (P > .05). CONCLUSIONS: Compared with HBSS, PMSC-CM showed better inhibition of apoptosis of PDL cells and promoted the proliferation of PDLSCs. Thus, PMSC-CM could be a promising storage medium for avulsed teeth.

The impact of diabetes on periodontal diseases.

The susceptibility and severity of periodontal diseases is made more severe by diabetes, with the impact on the disease process inversely proportional to the level of glycemic control. Although type 1 diabetes mellitus and type 2 diabetes mellitus have different etiologies, and their impact on bone is not identical, they share many of the same complications. Studies in animals and humans agree that both forms of diabetes increase inflammatory events in periodontal tissue, impair new bone formation, and increase expression of RANKL in response to bacterial challenge. High levels of glucose, reactive oxygen species, and advanced glycation end-products are found in the periodontium of diabetic individuals and lead to increased activation of nuclear factor-kappa B and expression of inflammatory cytokines such as tumor necrosis factor and interleukin-1. Studies in animals, moreover, suggest that there are multiple cell types in periodontal tissues that are affected by diabetes, including leukocytes, vascular cells, mesenchymal stem cells, periodontal ligament fibroblasts, osteoblasts, and osteocytes. The etiology of periodontal disease involves the host response to bacterial challenge that is affected by diabetes, which increases the expression of RANKL and reduces coupled bone formation. In addition, the inflammatory response also modifies the oral microbiota to render it more pathogenic, as demonstrated by increased inflammation and bone loss in animals where bacteria are transferred from diabetic donors to germ-free hosts compared with transfer from normoglycemic donors. This approach has the advantage of not relying upon limited knowledge of the specific bacterial taxa to determine pathogenicity, and examines the overall impact of the microbiota rather than the presumed pathogenicity of a few bacterial groups. Thus, animal studies have provided new insights into pathogenic mechanisms that identify cause-and-effect relationships that are difficult to perform in human studies.

Poly lactic-co-glycolic acid scaffold loaded with plasmid DNA encoding fibroblast growth factor-2 promotes periodontal ligament regeneration of replanted teeth.

OBJECTIVE: This study investigated the effects of poly lactic-co-glycolic acid (PLGA) loaded with plasmid DNA encoding fibroblast growth factor-2 (pFGF-2) on human periodontal ligament cells (hPDLCs) in vitro and evaluated the ability of the PLGA/pFGF-2 scaffold to promote periodontal ligament (PDL) regeneration in a beagle dog teeth avulsion animal model. BACKGROUND: Growth factor and scaffold play important roles in PDL regeneration. PLGA is a kind of biodegradable and biocompatible polymer that can be used as a carrier to deliver growth factors or genes. FGF-2 can induce potent proliferative responses, promote cell migration and regulate the production of extracellular matrix. Therefore, a gene-activated matrix composed of scaffold and genes is supposed to be a superior approach for promoting tissue regeneration. METHODS: In this study, PLGA and PLGA/pFGF-2 scaffolds were fabricated using electrospinning. The characterization of scaffolds was shown by scanning electron microscope (SEM) and transmission electron microscope (TEM). dsDNA HS was used to test the plasmid release of PLGA/pFGF-2 scaffold. The viability and proliferation of hPDLCs on the two kinds of scaffolds were evaluated by the CCK-8 assay, and the expression of collagen I and scleraxis were analysed by RT-qPCR. The roots of avulsed teeth were covered by the two types of scaffolds and replanted into the alveolar pockets in beagles. Haematoxylin-eosin and Masson staining were used to evaluate the effects of PLGA/pFGF-2 scaffold on promoting PDL regeneration. RESULTS: The smooth and uniform fibres can be observed in both scaffolds, and the plasmids were randomly distributed in the PLGA/pFGF-2 scaffold. dsDNA HS analysis demonstrated that the PLGA/pFGF-2 scaffold released up to 123 ng pFGF-2 over 21 days in a sustained manner without any obvious burst release. The PLGA/pFGF-2 scaffold promoted the proliferation of hPDLCs and increased the expression levels of collagen I and scleraxis compared with PLGA scaffold. Animal experiments showed that more regular PDL-like tissues and less root surface resorption occurred in the PLGA/pFGF-2 scaffold group compared with the PLGA scaffold group. CONCLUSIONS: The PLGA/pFGF-2 scaffold promoted hPDLCs proliferation and facilitated periodontal ligament-related differentiation. The PLGA/pFGF-2 scaffold possesses excellent biological characteristics and could be used as a promising biomaterial for improving the treatment prognosis of replanted tooth.

Effect of mitochondrial calcium homeostasis-mediated endogenous enzyme activation on tenderness of beef muscle based on MCU modulators.

The mitochondrial calcium uniporter (MCU) occupies a noteworthy position in the regulation of mitochondrial calcium uptake. This study investigated the effects of MCU modulator-mediated mitochondrial calcium on mitochondrial dysfunction, oxidative stress, endogenous enzyme activities, and tenderness during postmortem aging. Spermine, as an activator of MCU, resulted in an increase in mitochondrial calcium levels, not only disrupting mitochondrial morphology but also triggering mitochondrial oxidative stress and downregulation of antioxidant factors. Additionally, the spermine group underwent later activation of calpain and earlier activation of caspases, as well as the myofibril fragmentation index was initially lower and then higher compared with control group, indicating that endogenous enzymes played an indispensable role in different aging periods. Interestingly, the results of the Ru360 (an inhibitor of MCU) group were opposite to those aforementioned findings. Our data provide a novel perspective on the regulatory mechanism of mitochondrial calcium homeostasis mediated by MCU on tenderness.

Unveiling the anticancer potential of plumbagin: targeting pyruvate kinase M2 to induce oxidative stress and apoptosis in hepatoma cells.

Pyruvate kinase M2 (PKM2), a crucial enzyme in the glycolysis pathway, is commonly documented as being overexpressed in cancer cells. Inhibiting PKM2, a strategy to mitigate cancer cell-dependent glycolysis, has demonstrated efficacy in anticancer treatment. In this study, plumbagin, which was originally extracted from the plant Plumbago zeylanica L., was discovered as a novel PKM2 inhibitor and it could bind to PKM2 to inhibit the enzymatic activity. Treatment with plumbagin in HepG2 cells resulted in the decrease of PKM2 expression, which in turn reduced the protein kinase function. The mRNA levels of its downstream genes, such as LDHA and MYC, were suppressed. Additionally, plumbagin downregulated the expression of intracellular antioxidant proteins, which induced oxidative stress and mitochondrial damage, ultimately triggering apoptosis. Moreover, plumbagin also reduced the migration and proliferation of HepG2 cells. This study offered valuable insights into the molecular mechanism of plumbagin and advocated for the exploration of PKM2 inhibitors as viable possibilities for anticancer therapeutics.

Enhancing the stability of O/W emulsions by the interactions of casein/carboxymethyl chitosan and its application in whole nutrient emulsions.

The influence of Carboxymethyl chitosan (CMCS) on the emulsification stability mechanism of casein (CN) and its effects on the stability of whole nutrient emulsions were investigated. The complex solutions of CN and CMCS were prepared and the turbidity, ultraviolet (UV) absorption spectrum, fluorescence spectrum, circular dichroism (CD) spectrum, Fourier transform infrared (FTIR) spectrum, interfacial tension and microstructural observations were used to study the inter-molecular interaction of CMCS and CN. The effects of CMCS on the emulsion stability of CN were further analyzed by particle size, ζ-potential, instability index and rheological properties. Moreover, the accelerated stability of whole nutrient emulsions prepared by CMCS and CN was evaluated. The results revealed that CN-CMCS complexes were mainly formed by hydrogen bonding. The stability of the CN-CMCS composite emulsions were improved, as evidenced by the interfacial tension decreasing from 165.96 mN/m to 158.49 mN/m, the particle size decreasing from 45.85 µm to 12.98 µm, and the absolute value of the potential increasing from 29.8 mV to 33.5 mV. The stability of whole nutrient emulsion was also significantly enhanced by the addition of CN-CMCS complexes. Therefore, CN-CMCS complex could be served as a novel emulsifier to improve the stability of O/W emulsions.

Morphological changes of mitochondria-related to apoptosis during postmortem aging of beef muscles.

This study aimed to investigate how postmortem muscle cells' mitochondria changed in morphology from three aspects: the outer membrane, cristae, and fission/fusion. Atomic force microscopy (AFM) results showed that mitochondria underwent a morphology transformation from normal to swelling and collapse. Meanwhile, the cleavage of OPA1, upregulation of OMA1, downregulation of Mic60 and transmission electron microscope micrographs revealed that mitochondrial cristae ruptured with an aging time extended. Additionally, the increased expressions of Fis1 and Drp1, and the AFM topographic images mutually confirmed mitochondrial fission. These results further proved from the perspective of mitochondrial morphology that the degree of mitochondrial damage increased with the postmortem aging time extended, which was consistent with the results of the release of cytochrome c caused by the increase of mitochondrial permeability transition pore opening and the decrease of mitochondrial membrane permeability, and further induced the apoptosis of postmortem muscle cells.

Nomograms Based on the Albumin/Neutrophil-to-Lymphocyte Ratio Score for Predicting Coronary Artery Disease or Subclinical Coronary Artery Disease.

Purpose: To develop and validate two nomograms incorporating the albumin/neutrophil-to-lymphocyte ratio score (ANS) for predicting the risk of coronary artery disease (CAD) or subclinical CAD. Patients and Methods: Four hundred fifty patients with suspected CAD who underwent coronary computed tomographic angiography were consecutively enrolled between September 2015 and June 2017. Nomograms were established based on independent predictors of CAD or subclinical CAD. Results: In total, 437 patients with suspected CAD who underwent coronary computed tomographic angiography were included. Male sex, age ≥65 years, smoking, hypertension, diabetes, dyslipidemia, ischemic stroke, and ANS were independent predictors of CAD and subclinical CAD. The areas under the curve of each nomogram were 0.799 (95% CI: 0.752-0.846) and 0.809 (95% CI: 0.762-0.856), respectively. The calibration curve and decision curve analysis showed good performance for the diagnostic nomograms. The prediction of CAD or subclinical CAD by the ANS was not modified by the independent predictors (all, p for interaction >0.05). Conclusion: Our ANS-based nomograms can provide accurate and individualized risk predictions for patients with suspected CAD or subclinical CAD.

The Quality Changes and Proteomic Analysis of Cattle Muscle Postmortem during Rigor Mortis.

Rigor mortis occurs in a relatively early postmortem period and is a complex biochemical process in the conversion of muscle to meat. Understanding the quality changes and biomarkers during rigor mortis can provide a theoretical basis for maintaining and improving meat quality. Herein, a tandem mass tag proteomic method is used to investigate the effects of differentially expressed proteins on the meat quality of cattle Longissimus lumborum muscle postmortem (0, 6, and 24 h). The pH, total sulfhydryl content and sarcomere length decrease significantly during storage. In contrast, meat color values (L*, a*, and b*) and the myofibril fragmentation index increase significantly. Altogether, 147 differentially expressed proteins are identified, most being categorized as metabolic enzymes, mitochondrial proteins, necroptosis and ferroptosis proteins and structural proteins. The results also reveal additional proteins that are potentially involved in rigor mortis, such as cardiac phospholamban, acetyl-coenzyme A acyltransferase, and ankyrin repeat domain 2. The current results provide proteomic insights into the changes in meat quality during rigor mortis.

Comparison of oxidative stress-mitochondria-mediated tenderization in two different bovine muscles during aging.

The aim of this study was to investigate the differences in the effects of mitochondria-involved energy metabolism and caspases activation on postmortem tenderness in different muscle fiber types. Beef Longissimus thoracis (LT) and Psoas major (PM) muscles showed significant difference in mitochondrial function. Our data revealed that PM suffered from higher levels of reactive oxygen species (ROS) earlier than LT, causing faster mitochondrial swelling and rupture. Additionally, faster metabolism of ATP-related compounds and activation of caspase-9 appeared in PM, but the activity of caspase-3 in PM was lower than that in LT. Differences in myofibril fragmentation index (MFI) of LT and PM at different aging stages suggested that energy metabolism and caspases activities may play a role in tenderness at different aging stages. These results indicated that oxidative stress-mitochondria-mediated tenderization process could be muscle-specific.

The Association of Triglyceride Glucose index for Coronary Artery Disease in Postmenopausal Women.

This study aimed to explore the association between the triglyceride glucose (TyG) index and coronary artery disease (CAD) in postmenopausal women. This study enrolled 869 postmenopausal women and classified them into two groups: CAD group (n = 538) and control group (n = 331). The TyG index was significantly higher in patients with CAD than in controls (P < 0.05).Receiver operator characteristic curves showed that the TyG index was more discriminative for CAD than for control group, and after adjusting for the traditional clinical prognostic factors, including age (>60 years), diabetes, ischemic stroke, systolic blood pressure (≥140), and ejection fraction (<50%), we found that the TyG index could be an independent risk factor for CAD (P < 0.05). The risk of increased TyG index was greater in the <50 years subgroup than in the >50 years subgroup (P < 0.05). The TyG index may be a valuable clinical predictor of CAD risk in postmenopausal women.

Establishment of a Predictive Model for Poor Prognosis of Incomplete Revascularization in Patients with Coronary Heart Disease and Multivessel Disease.

OBJECTIVE: To establish a predictive model for poor prognosis after incomplete revascularization (ICR) in patients with multivessel coronary artery disease (MVD). METHODS: Clinical data of 757 patients with MVD and ICR after percutaneous coronary intervention (PCI) in the Affiliated Hospital of Chengde Medical University from January 2020 to August 2021 were retrospectively collected. The least absolute shrinkage and selection operator regression method was used to screen variables, and multivariate logistic regression was used to establish a predictive model. An independent cohort was used to validate the model. The C-statistic was used to verify and evaluate the discriminative ability of the model; the calibration curve was drawn, and the decision curve analysis (DCA) was performed to evaluate the calibration degree, the clinical net benefit, and the practicability of the model. RESULTS: The predictive factors included female, age, unconjugated bilirubin, uric acid, low-density lipoprotein, hyperglycemia, total occlusion, and severe tortuosity lesion on coronary angiography. The C-statistic of the training and validation sets were 0.628 and 0.745, respectively. The statistical value of the Hosmer-Lemeshow test for the calibration curve of the training and validation sets were 5.27(P = 0.873) and 6.27 (P = 0.792), respectively. DCA showed that the model was clinically applicable when the predicted probability value of major adverse cardiovascular events(MACEs) ranged from 0.07 to 0.68. CONCLUSIONS: We established a predictive model for poor prognosis after ICR in patients with MVD. The predictive and calibration ability and the clinical net benefit of the predictive model were good, indicating that it can be used as an effective tool for the early prediction of poor prognosis after ICR in patients with MVD.

Association Between Novel Pro- and Anti- Inflammatory Adipocytokines in Patients with Acute Coronary Syndrome.

BACKGROUND AND AIMS: Novel pro- and anti-inflammatory adipocytokines affect inflammation, energy metabolism, and insulin signaling. However, their role in acute coronary syndrome (ACS) development is unclear. We evaluated the diagnostic and risk predictive value of such adipocytokines for ACS. METHODS: We enrolled 168 consecutive inpatients with suspected ACS and detected serum PLIN1, PLIN2, PLIN5, CTRP6, CTRP7, CTRP11, WISP1, FAM19A5, TNF-α, and adiponectin levels. Multivariate logistic regression analysis and Spearman's test were used to assess risk factors for ACS and correlations between serum adipocytokines and continuous variables, respectively. RESULTS: Serum levels of the adipocytokines differed between ACS and Non-ACS groups (p < 0.05). After adjusting for confounding factors, serum PLIN1, PLIN2, PLIN5, CTRP6, CTRP7, CTRP11, WISP1, and FAM19A5 levels were independently associated with ACS (p < 0.05). Increasing tertiles of serum PLIN1, PLIN2, CTRP7, CTRP11, and WISP1 levels increased the ACS risk, which decreased gradually with increasing PLIN5 and CTRP6 tertiles (p for trend <0.05). Serum PLIN1, PLIN5, CTRP6, CTRP7, CTRP11, WISP1, and FAM19A5 levels correlated with ACS severity. CONCLUSIONS: PLIN1, PLIN2, CTRP7, CTRP11, and WISP1 were identified as independent ACS risk factors, whereas PLIN5, CTRP6, and FAM19A5 were independent protective factors for ACS. These serum adipocytokines are novel potential clinical biomarkers of ACS.

Emodin ameliorates antioxidant capacity and exerts neuroprotective effect via PKM2-mediated Nrf2 transactivation.

Pyruvate kinase M2 (PKM2) is overexpressed in neuronal cells. However, there are few studies on the involvement of PKM2 modulators in neurodegenerative diseases. Emodin, a dominating anthraquinone derivative extracting from the rhizome of rhubarb, has received expanding consideration due to its pharmacological properties. Our data reveal that emodin could resist hydrogen peroxide- or 6-hydroxydopamine-mediated mitochondrial fission and apoptosis in PC12 cells (a neuron-like rat pheochromocytoma cell line). Notably, emodin at nontoxic concentrations significantly inhibits PKM2 activity and promotes dissociation of tetrameric PKM2 into dimers in cells. The PKM2 dimerization enhances the interaction of PKM2 and NFE2-related factor 2 (Nrf2), which further triggers the activation of the Nrf2/ARE pathway to upregulate a panel of cytoprotective genes. Modulating the PKM2/Nrf2/ARE axis by emodin unveils a novel mechanism for understanding the pharmacological functions of emodin. Our findings indicate that emodin is a potential candidate for the treatment of oxidative stress-related neurodegenerative disorders.