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.

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.

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.

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.

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.

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.

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.

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.

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.

Role of serum C1q/TNF-related protein family levels in patients with acute coronary syndrome.

Background: The C1q/TNF-related protein (CTRP) family affects inflammation regulation, energy metabolism, and insulin signaling. However, their role in acute coronary syndrome (ACS) development is unclear. In this cross-sectional study, we aimed to investigate the association between CTRP family and ACS. Methods: We enrolled 289 consecutive inpatients with suspected ACS. Serum CTRP family, tumor necrosis factor-α (TNF-α), and adiponectin (ADP) levels were assessed using enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and subgroup analyses were used to assess risk factors for ACS. Spearman's tests were used to analyze correlations between CTRP family and continuous variables. Results: Serum CTRP family levels differed significantly between ACS and Control groups (p < 0.05). After adjusting for confounding factors, CTRP family were independently associated with ACS (p < 0.05). The association between serum CTRP family levels and ACS was stable in various subgroups according to sex, age, diabetes mellitus, and dyslipidemia status (p for interaction > 0.05). Increasing tertiles of serum CTRP1 levels, significantly increased ACS risks, which decreased gradually with increasing CTRP2, CTRP12, and CTRP13 tertiles (p for trend < 0.05). Additionally, serum CTRP1, CTRP2, CTRP13, and CTRP15 levels were weakly correlated with the severity of coronary artery stenosis. Conclusion: CTRP1 and CTRP5 were identified as independent ACS risk factors, whereas CTRP2, CTRP3, CTRP9, CTRP12, CTRP13, and CTRP15 were independent protective factors for ACS. CTRP family, especially CTRP1 and CTRP3 could be novel potential clinical biomarkers of ACS.

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.

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.

Hinokitiol functions as a ferroptosis inhibitor to confer neuroprotection.

The intrinsic link of ferroptosis to neurodegeneration, such as Parkinson's disease and Alzheimer's disease, has set promises to apply ferroptosis inhibitors for treatment of neurodegenerative disorders. Herein, we report that the natural small molecule hinokitiol (Hino) functions as a potent ferroptosis inhibitor to rescue neuronal damages in vitro and in vivo. The action mechanisms of Hino involve chelating irons and activating cytoprotective transcription factor Nrf2 to upregulate the antioxidant genes including solute carrier family 7 member 11, glutathione peroxidase 4 and Heme oxygenase-1. In vivo studies demonstrate that Hino rescues the deficits of locomotor activity and neurodevelopment in zebrafishes. In addition, Hino shows the efficient blood-brain barrier permeability in mice, supporting the application of Hino for brain disorders. Paclitaxel is one of the most widely used broad-spectrum antineoplastic agents. However, its neurotoxic side effect is a severe concern. We demonstrate that the neurotoxicity of paclitaxel is ferroptosis-related and Hino also alleviates the paclitaxel-induced neurotoxicity without compromising its cytotoxicity to cancer cells. Hino also salvages the neurobehavioral impairment by paclitaxel in zebrafishes. Collectively, the discovery of Hino as a novel ferroptosis inhibitor and disclosure of its action mechanisms establish a foundation for the further development of Hino as a neuroprotective agent.

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.

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.

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.

Nomograms Based on the Advanced Lung Cancer Inflammation Index for the Prediction of Coronary Artery Disease and Calcification.

AIM: To develop and validate 3 nomograms incorporating the advanced lung cancer inflammation index (ALI) that can aid in predicting the risk of coronary artery disease (CAD) and coronary artery calcification (CAC). METHODS: The study enrolled 562 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography between September 2015 and June 2017. Independent risk factors for CAD, CAC, and CAD with CAC were identified via univariate and multivariate analysis, and nomograms were established based on the independent predictors identified. The area under the curve (AUC), calibration curve, and decision curve analysis were used to evaluate the nomograms. Correlations between ALI and other clinical indicators were examined via Spearman correlation analysis. RESULTS: In total, 549 patients with suspected CAD who underwent coronary computed tomographic angiography were included. Male sex, hypertension, diabetes, dyslipidemia, ischemic stroke, and ALI were independent predictors of both CAD and CAC. Male sex, hypertension, diabetes, dyslipidemia, and ALI were also identified as independent predictors of CAD with CAC. The AUC values for the nomograms developed using these risk factors were 0.739 (95% confidence interval [CI], 0.693-0.785), 0.728 (95% CI, 0.684-0.772), and 0.717 (95% CI 0.673-0.761), respectively. ALI was negatively correlated with neutrophil-to-lymphocyte ratio and CAC score and positively correlated with serum albumin levels and body mass index (all P < .05). CONCLUSIONS: ALI is an independent predictor of CAD, CAC, and CAD with CAC. Our ALI-based nomograms can provide accurate and individualized risk predictions for patients with suspected CAD.

Cynaropicrin Induces Cell Cycle Arrest and Apoptosis by Inhibiting PKM2 to Cause DNA Damage and Mitochondrial Fission in A549 Cells.

Metabolic reprogramming is critical for tumorigenesis. Pyruvate kinase M2 (PKM2) is overexpressed in lung carcinoma cells and plays a critical role in the Warburg effect, making the enzyme a research hotspot for anticancer drug development. Cynaropicrin (CYN), a natural sesquiterpene lactone compound from artichoke, has received increasing consideration due to its consumable esteem and pharmacological properties. Our data reveal that CYN not only inhibited the purified PKM2 activity but also decreased the cellular PKM2 expression in A549 cells. The inhibition of PKM2 leads to the upregulation of p53 and the downregulation of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP), and subsequently causes the cell cycle arrest. Additionally, CYN inhibits the interaction of PKM2 and Nrf2, resulting in the impairment of cellular antioxidant capacity, induction of oxidative stress, and mitochondrial damages. Overexpression of PKM2 attenuates the CYN-induced DNA damage, mitochondrial fission, and cell viability. Thus, targeting PKM2 provides an original mechanism for understanding the pharmacological impact of CYN and assists in the further development of CYN as an anticancer agent.

Prognostic value of peripheral blood inflammatory cell subsets in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: This study aimed to investigate the predictive value of inflammatory cells in peripheral blood on the prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: Patients (n=1558) were consecutively enrolled and the median follow-up was 1142 days. Patients were divided into the major adverse cardiac events (MACE) 1 group (n=63) (all-cause mortality [n=58] and rehospitalization for severe heart failure [n=5], no MACE1 group (n=1495), MACE2 group (n=38) (cardiac mortality [n=33] and rehospitalization for severe heart failure [n=5]), and no MACE2 group (n=1520). The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were analyzed. RESULTS: The NLR, MLR, and PLR were higher in the MACE groups than in the no MACE groups. Different subsets of inflammatory cells had similar diagnostic values for MACE. Kaplan-Meier curves showed that the survival time gradually decreased with an increase in the degree of risk as determined by the NLR, MLR, and PLR. The risk of MACE was highest in the extremely high-risk group. CONCLUSION: Peripheral blood inflammatory cell subsets can predict MACE in patients with ACS undergoing PCI. These cell subsets could be important laboratory markers for the prognosis and clinical treatment of these patients.

FOXO1 expression in chondrocytes modulates cartilage production and removal in fracture healing.

Fracture healing is a multistage process characterized by inflammation, cartilage formation, bone deposition, and remodeling. Chondrocytes are important in producing cartilage that forms the initial anlagen for the hard callus needed to stabilize the fracture site. We examined the role of FOXO1 by selective ablation of FOXO1 in chondrocytes mediated by Col2α1 driven Cre recombinase. Experimental mice with lineage-specific FOXO1 deletion (Col2α1Cre+FOXO1L/L) and negative control littermates (Col2α1Cre-FOXO1L/L) were used for in vivo, closed fracture studies. Unexpectedly, we found that in the early phases of fracture healing, FOXO1 deletion significantly increased the amount of cartilage formed, whereas, in later periods, FOXO1 deletion led to a greater loss of cartilage. FOXO1 was functionally important as its deletion in chondrocytes led to diminished bone formation on day 22. Mechanistically, the early effects of FOXO1 deletion were linked to increased proliferation of chondrocytes through enhanced expression of cell cycle genes that promote proliferation and reduced expression of those that inhibit it and increased expression of cartilage matrix genes. At later time points experimental mice with FOXO1 deletion had greater loss of cartilage, enhanced formation of osteoclasts, increased IL-6 and reduced numbers of M2 macrophages. These results identify FOXO1 as a transcription factor that regulates chondrocyte behavior by limiting the early expansion of cartilage and preventing rapid cartilage loss at later phases.