Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

DDX39B protects against sorafenib-induced ferroptosis by facilitating the splicing and cytoplasmic export of GPX4 pre-mRNA in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main histological subtype of primary liver cancer and remains one of the most common solid malignancies globally. Ferroptosis was recently defined as an iron-catalyzed form of regulated necrosis. Because cancer cells exhibit higher iron requirements than noncancer cells, treatment with ferroptosis-inducing compounds may be a feasible strategy for cancer therapy. However, cancer cells develop acquired resistance to evade ferroptosis, and the mechanisms responsible for ferroptosis resistance are not fully clarified. In the current study, we reported that DDX39B was downregulated during sorafenib-induced ferroptosis in a dose- and time-dependent manner. Exogenous introduction of DDX39B ensured the survival of HCC cells upon exposure to sorafenib, while the opposite phenomenon was observed in DDX39B-silenced HCC cells. Mechanistically, we demonstrated that DDX39B increased GPX4 levels by promoting the splicing and cytoplasmic translocation of GPX4 pre-mRNA, which was sufficient to detoxify sorafenib-triggered excess lipid ROS production, lipid peroxidation accumulation, ferrous iron levels, and mitochondrial damage. Inhibition of DDX39B ATPase activity by CCT018159 repressed the splicing and cytoplasmic export of GPX4 pre-mRNA and synergistically assisted sorafenib-induced ferroptotic cell death in HCC cells. Taken together, our data uncover a novel role for DDX39B in ferroptosis resistance by modulating the maturation of GPX4 mRNA via a posttranscriptional approach and suggest that DDX39B inhibition may be a promising therapeutic strategy to enhance the sensitivity and vulnerability of HCC cells to sorafenib.

EEPD1 is identified as a predictor of prognosis and immune microenvironment through pan-cancer analysis and related to progression of colorectal cancer.

Background: EEPD1 is vital in homologous recombination, while its role in cancer remains unclear. Methods: We performed multiple pan-cancer analyses of EEPD1 with bioinformatics methods, such as gene expression, gene alterations, Prognosis and enrichment analysis, tumor microenvironment, immune cell infiltration, TMB, MSI, immunotherapy, co-expression of genes, and drug resistance. Finally, RT-qPCR, EdU, and transwell assays helped investigate the impact of EEPD1 on CRC cells. Results: EEPD1 was dysregulated and correlated with bad prognosis in several cancers. GSVA and GSEA revealed that EEPD1 was primarily associated with the "WNT_BETA_CATENIN_SIGNALING," "ribonucleoprotein complex biogenesis," "Ribosome," and "rRNA processing." The infiltration of CD8+ T cells, MAIT cells, iTreg cells, NK cells, Tc cells, Tex cells, Tfh cells, and Th1 cells were negatively correlated with EEPD1 expression. Additionally, EEPD1 is significantly associated with TMB and MSI in COAD, while enhanced CRC cell proliferation and migration. Conclusions: EEPD1 was dysregulated in human cancers and correlated with various cancer patient prognoses. The dysregulated EEPD1 expression can affect tumor-infiltrating immune cells and immunotherapy response. Therefore, EEPD1 could act as an oncogene associated with immune cell infiltration in CRC.

Neuroprotective effects of cordycepin on MPTP-induced Parkinson's disease mice via suppressing PI3K/AKT/mTOR and MAPK-mediated neuroinflammation.

Parkinson's disease (PD) is a prevalent progressive and multifactorial neurodegenerative disorder. Cordycepin is known to exhibit antitumor, anti-inflammatory, antioxidative stress, and neuroprotective effects; however, few studies have explored the neuroprotective mechanism of cordycepin in PD. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, we investigated the impact of cordycepin on PD and its underlying molecular mechanisms. The findings indicated that cordycepin significantly mitigated MPTP-induced behavior disorder and neuroapoptosis, diminished the loss of dopaminergic neurons in the striatum-substantia nigra pathway, elevated striatal monoamine levels and its metabolites, and inhibited the polarization of microglia and the expression of pro-inflammatory factors. Subsequent proteomic and phosphoproteomic analyses revealed the involvement of the MAPK, mTOR, and PI3K/AKT signaling pathways in the protective mechanism of cordycepin. Cordycepin treatment inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the expression of autophagy proteins in the striatum and substantia nigra. We also demonstrated the in vivo inhibition of the ERK/JNK signaling pathway by cordycepin treatment. In summary, our investigation reveals that cordycepin exerts neuroprotective effects against PD by promoting autophagy and suppressing neuroinflammation and neuronal apoptosis by inhibiting the PI3K/AKT/mTOR and ERK/JNK signaling pathways. This finding highlights the favorable characteristics of cordycepin in neuroprotection and provides novel molecular insights into the neuroprotective role of natural products in PD.

Combined exposure to multiple metals on abdominal aortic calcification: results from the NHANES study.

Exposure to metals increases the risk of many diseases and has become a public health concern. However, few studies have focused on the effect of metal on abdominal aortic calcification (AAC), especially the combined effects of metal mixtures. In this study, we aim to investigate the combined effect of metals on AAC risk and determine the key components in the multiple metals. We tried to investigate the relationship between multiple metal exposure and AAC risk. Fourteen urinary metals were analyzed with five statistical models as follows: generalized linear regression, weighted quantile sum regression (WQS), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) models. A total of 838 participants were involved, of whom 241 (28.8%) had AAC. After adjusting for covariates, in multiple metal exposure logistic regression, cadmium (Cd) (OR = 1.364, 95% CI = 1.035-1.797) was positively associated with AAC risk, while cobalt (Co) (OR = 0.631, 95% CI = 0.438-0.908) was negatively associated with AAC risk. A significant positive effect between multiple metal exposure and AAC risk was observed in WQS (OR = 2.090; 95% CI = 1.280-3.420, P < 0.01), Qgcomp (OR = 1.522, 95% CI = 1.012-2.290, P < 0.05), and BKMR models. It was found that the positive association may be driven primarily by Cd, lead (Pb), uranium (U), and tungsten (W). Subgroups analysis showed the association was more significant in participants with BMI ≥ 25 kg/m2, abdominal obesity, drinking, and smoking. Our study shows that exposure to multiple metals increases the risk of AAC in adults aged ≥ 40 years in the USA and that Cd, Pb, U, and W are the main contributors. The association is stronger in participants who are obese, smoker, or drinker.

Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells.

Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.

Prediction by a multiparametric magnetic resonance imaging-based radiomics signature model of disease-free survival in patients with rectal cancer treated by surgery.

Objective: The aim of this study was to assess the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics signature model to predict disease-free survival (DFS) in patients with rectal cancer treated by surgery. Materials and methods: We evaluated data of 194 patients with rectal cancer who had undergone radical surgery between April 2016 and September 2021. The mean age of all patients was 62.6 ± 9.7 years (range: 37-86 years). The study endpoint was DFS and 1132 radiomic features were extracted from preoperative MRIs, including contrast-enhanced T1- and T2-weighted imaging and apparent diffusion coefficient values. The study patients were randomly allocated to training (n=97) and validation cohorts (n=97) in a ratio of 5:5. A multivariable Cox regression model was used to generate a radiomics signature (rad score). The associations of rad score with DFS were evaluated using Kaplan-Meier analysis. Three models, namely a radiomics nomogram, radiomics signature, and clinical model, were compared using the Akaike information criterion. Result: The rad score, which was composed of four MRI features, stratified rectal cancer patients into low- and high-risk groups and was associated with DFS in both the training (p = 0.0026) and validation sets (p = 0.036). Moreover, a radiomics nomogram model that combined rad score and independent clinical risk factors performed better (Harrell concordance index [C-index] =0.77) than a purely radiomics signature (C-index=0.73) or clinical model (C-index=0.70). Conclusion: An MRI radiomics model that incorporates a radiomics signature and clinicopathological factors more accurately predicts DFS than does a clinical model in patients with rectal cancer.

The potential role of hydrogen sulfide in cancer cell apoptosis.

For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathological conditions. Currently, a large number of studies have shown that H2S mediates apoptosis through multiple signaling pathways to participate in cancer occurrence and development, for example, PI3K/Akt/mTOR and MAPK signaling pathways. Therefore, the regulation of the production and metabolism of H2S to mediate the apoptotic process of cancer cells may improve the effectiveness of cancer treatment. In this review, the role and mechanism of H2S in cancer cell apoptosis in mammals are summarized.

Expression of ADAM17 and its clinical value for patients with pernicious placenta previa: A retrospective study of 148 PPP patients underwent cesarean section.

To explore the expression and the diagnostic value of ADAM17 in pernicious placenta previa (PPP) combined placental accreta. A total of 148 PPP patients were enrolled and divided into 2 groups: 62 patients with placenta accrete (PPP with PA group) and 86 patients without placenta accrete (PPP without PA group). In the same period, 74 pregnant women without PPP who had undergone cesarean section were selected as controls. The levels of ADAM17 were detected by qt-PCR. Diagnostic efficiency of ADAM17 were evaluated by receiver operating characteristics curve. ADAM17 was higher expression in PPP patients. Multivariate analysis showed that ADAM17 was related to gravida times (HR = 2.43 95% CI, 1.25-3.31), history of cesarean delivery (HR = 3.44, 95% CI = 2.24-4.28), history of abortions (HR = 2.22, 95% CI = 1.57-3.06) for PPP with PA patients and gravida times (HR = 2.01, 95% CI = 1.45-2.86), history of cesarean delivery (HR = 1.89, 95% CI = 1.33-2.48) for PPP patients without PA. Diagnostic efficiency of ADAM17 indicated that the sensitivity and specificity of ADAM17 detection for PPP with PA were 74.41% and 67.21% and for PPP without PA were 89.29% and 85.52%. Area under curve were 0.7876 (0.7090-0.8661) for PPP with PA and 0.9443 (0.9136-0.9750) for PPP without PA. Insummary, ADAM17 was higher expression in patients with PPP. ADAM17 was associated with gravida times, history of cesarean delivery, history of abortions. It also indicated a better diagnostic efficiency for patients with PPP. Further larger sample, multicenter studies should be conducted to confirm the conclusion from our study.

TRAF2 decrease promotes the TGF-ß-mTORC1 signal in MAFLD-HCC through enhancing AXIN1-mediated Smad7 degradation.

According to recent research, metabolic-associated fatty liver disease (MAFLD) has emerged as an important underlying etiology of hepatocellular carcinoma (HCC). However, the molecular mechanism of MAFLD-HCC is still unclear. Tumor necrosis factor receptor-associated factor 2 (TRAF2) is the key molecule to mediate the signal of inflammatory NF-κB pathway. This study aims to investigate the potential dysregulation of TRAF2 and its biological function in MAFLD-HCC. Huh7 TRAF2-/- demonstrated increased tumor formation ability compared to huh7 TRAF2+/+ when stimulated with transforming growth factor-ß (TGF-ß). The decisive role of TGF-ß in the development of MAFLD-HCC was confirmed through the specific depletion of TGF-ß receptor II gene in the hepatocytes (Tgfbr2ΔHep) of mice. In TRAF2-/- cells treated with TGF-ß, both the glycolysis rate and lipid synthesis were enhanced. We proved the signal of the mechanistic target of rapamycin complex 1 (mTORC1) could be activated in the presence of TGF-ß, and was enhanced in TRAF2-/- cells. The coimmunoprecipitation (co-IP) experiments revealed that TRAF2 fortified the Smurf2-mediated ubiquitination degradation of AXIN1. Hence, TRAF2 depletion resulted in increased Smad7 degradation induced by AXIN1, thus promoting the TGF-ß signal. We also discovered that PLX-4720 could bind with AXIN1 and restrained the tumor proliferation of TRAF2-/- in mice fed with high-fat diet (HFD). Our findings indicate that TRAF2 plays a significant role in the pathogenesis of MAFLD-HCC. The reduction of TRAF2 expression leads to the enhancement of the TGF-ß-mTORC1 pathway by facilitating AXIN1-mediated Smad7 degradation.

Caroli disease combined with Banti syndrome in a woman: a case report.

Caroli disease is a rare congenital malformation that predisposes to segmental cystic dilatation of the intrahepatic bile ducts. Banti syndrome is characterized by persistent splenomegaly due to chronic congestion, resulting in a low hematocrit and ultimately leading to pancytopenia. In this report, we describe a 29-year-old woman who presented with a >20-year history of hepatitis B surface antigen positivity and a >1-year history of recurrent fatigue and malaise. On examination, the patient had abdominal distension with marked splenomegaly (7 cm below the ribs) and ascites with tenderness of the abdominal muscles to palpation. A complete blood count showed a low white blood cell count, red blood cell count, and hemoglobin concentration. During the course of treatment, the patient developed multiple symptoms of pancytopenia and concomitant splenomegaly, and she was discharged after total splenectomy with good recovery. The combination of Banti syndrome and Caroli disease results in severe symptoms of portal hypertension.

Digital protractor as an intraoperative guide to cup anteversion in total hip arthroplasty.

INTRODUCTION: To explore if digital protractor could guide the anteversion of acetabular cup during primary THA and make it consistent with preoperative. METHODS: We retrospectively reviewed 172 cases of primary THA with direct anterior approach (DAA) over 2 years. The anteversion of acetabular cup were measured from computed tomography (CT) scan preoperative and de-identified plain radiographs postoperative by two blinded investigators who were not involved in the surgery. The effect of the digital protractor on the anteversion was determined using regression analysis. RESULTS: The mean anteversion for the THAs in digital protractor group was 15.5°and 21.4°in control group (P < 0.01). The mean anteversion bias for the THAs in digital protractor group was 1.59° and 6.63° in control group (P < 0.01).Regression analysis identified a 10.7% difference in anteversion due to the use of digital protractor (P < 0.01), and THAs performed without digital protractor were six times more likely to result in anteversion of > 25°. The correlation coefficient for the interobserver reliability of the measurement of the two investigators was 0.94. CONCLUSION: The digital protractor is a practical tool in the DAA for THA to determine the anteversion of the acetabular prosthesis.

Construction of brain metastasis prediction model in limited stage small cell lung cancer patients without prophylactic cranial irradiation.

INTRODUCTION: Small cell lung cancer (SCLC) is a highly aggressive lung cancer variant known for its elevated risk of brain metastases (BM). While earlier meta-analyses supported the use of prophylactic cranial irradiation (PCI) to reduce BM incidence and enhance overall survival, modern MRI capabilities raise questions about PCI's universal benefit for limited-stage SCLC (LS-SCLC) patients. As a response, we have created a predictive model for BM, aiming to identify low-risk individuals who may not require PCI. METHODS: A total of 194 LS-SCLC patients without PCI treated between 2009 and 2021 were included. We conducted both univariate and multivariate analyses to pinpoint the factors associated with the development of BM. A nomogram for predicting the 2- and 3-year probabilities of BM was then constructed. RESULTS: Univariate and multivariate analyses revealed several significant independent risk factors for the development of BM. These factors include TNM stage, the number of chemotherapy (ChT) cycles, Ki-67 expression level, pretreatment serum lactate dehydrogenase (LDH) levels, and haemoglobin (HGB) levels. These findings underscore their respective roles as independent predictors of BM. Based on the results of the final multivariable analysis, a nomogram model was created. In the training cohort, the nomogram yielded an area under the receiver operating characteristic curve (AUC) of 0.870 at 2 years and 0.828 at 3 years. In the validation cohort, the AUC values were 0.897 at 2 years and 0.789 at 3 years. The calibration curve demonstrated good agreement between the predicted and observed probabilities of BM. CONCLUSIONS: A novel nomogram has been developed to forecast the likelihood of BM in patients diagnosed with LS-SCLC. This tool holds the potential to assist healthcare professionals in formulating more informed and tailored treatment plans.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

An integrative clinical and CT-based tumoral/peritumoral radiomics nomogram to predict the microsatellite instability in rectal carcinoma.

BACKGROUND: Microsatellite instability (MSI) is detected in approximately 15% of colorectal carcinoma (CRC) patients, which has emerged as a predictor of patient response to adjuvant chemotherapy. Rectal carcinoma (RC) is the most common type of CRC. Therefore, prediction of MSI status of RC is significant for personalized medication. The purpose of this article was to develop an integrative model that combines clinical characteristics and computed tomography-based (CT-based) tumoral/peritumoral radiomics to predict the MSI status in RC. METHODS: A cohort of 788 RCs with 97 high-MSI status (MSI-H) and 691 microsatellite stable status (MSS) were enrolled between January 2015 and January 2021 in this retrospective study. Clinical characteristics were recorded, and CT-based tumoral/peritumoral radiomic features were calculated after segmenting volume of interests. The patients were randomly divided into training and validation sets in a 7:3 proportion. Logistic models of single tumoral radiomics (LM-tRadio), peritumoral radiomics (LM-ptRadio), and combined tumoral/peritumoral radiomics (LM-Radio) were constructed to distinguish MSI-H from MSS, and a relevant radiomic score was calculated. An integrative nomogram (LM-Nomo) was developed, including significant clinical characteristics and CT-based tumoral/peritumoral radiomics. The area under receiver operator curve (AUC) was calculated to evaluate the efficacy of prediction. RESULTS: The AUCs of LM-Radio were 0.785 (95%CI 0.732-0.837) in the training set and were 0.628 (95%CI 0.528-0.723) in the validation set, which were higher than those of LM-tRadio and LM-ptRadio. The AUCs of single LM-ptRadio were slightly higher than those of LM-tRadio (0.724 vs. 0.708 in the training set, 0.613 vs. 0.602 in the validation set). The LM-Nomo containing carcinoembryonic antigen (CEA), hypertension, and CT-based tumoral/peritumoral radiomic score showed the highest AUCs of 0.796 (95%CI 0.748-0.843) in the training set and 0.679 (95%CI 0.588-0.771) in the validation set in predicting the MSI-H status of RC. CONCLUSION: The AUCs of LM-ptRadio were slightly higher than LM-tRadio to evaluate the MSI-H status of RC. The LM-Nomo, which includes significant clinical characteristics and CT-based tumoral/peritumoral radiomics score, demonstrated the best performance in predicting MSI-H status of RC.

A rare disease in adult women: Gaucher disease.

Gaucher disease is a rare, autosomal recessive disorder caused by inborn errors of metabolism. Globally, more than 27 million people are born each year, and approximately 19,000 neonates are born with lysosomal storage disease. We report a rare case of Gaucher disease in an adult female patient of non-consanguineous parents in a subtropical area of Jiangxi Province, China. This area has a high prevalence of schistosomiasis. The diagnosis of this case posed a great challenge because of the possible differential diagnoses of pancytopenia with hepatomegaly and giant splenomegaly. The key component of the patient's diagnosis was her medical history in which it was documented that her brother had died of hepatocellular carcinoma of unknown origin. We diagnosed the patient through a combination of a pathological biopsy and imaging plus the patient's medical history.

Value of ctDNA methylation biomarkers in diagnosis of colorectal tumors.

Tweetable abstract DNA methylation alterations have been identified as promising biological markers for early-stage colorectal cancer detection. Here, the authors highlight some recent advances in DNA methylation and its role in the early diagnosis and overall disease course management of colorectal tumors. New insights into DNA methylation biomarkers for colorectal cancer early diagnosis and management are discussed.

Public RNA-seq data-based identification and functional analyses reveal that MXRA5 retains proliferative and migratory abilities of dental pulp stem cells.

Dental pulp stem cells (DPSC) usually remain quiescent in the dental pulp tissue; however, once the dental pulp tissue is injured, DPSCs potently proliferate and migrate into the injury microenvironment and contribute to immuno-modulation and tissue repair. However, the key molecules that physiologically support the potent proliferation and migration of DPSCs have not been revealed. In this study, we searched publicly available transcriptome raw data sets, which contain comparable (i.e., equivalently cultured) DPSC and mesenchymal stem cell data. Three data sets were extracted from the Gene Expression Omnibus database and then processed and analyzed. MXRA5 was identified as the predominant DPSC-enriched gene associated with the extracellular matrix. MXRA5 is detected in human dental pulp tissues. Loss of MXRA5 drastically decreases the proliferation and migration of DSPCs, concomitantly with reduced expression of the genes associated with the cell cycle and microtubules. In addition to the known full-length isoform of MXRA5, a novel splice variant of MXRA5 was cloned in DPSCs. Recombinant MXRA5 coded by the novel splice variant potently induced the haptotaxis migration of DPSCs, which was inhibited by microtubule inhibitors. Collectively, MXRA5 is a key extracellular matrix protein in dental pulp tissue for maintaining the proliferation and migration of DPSCs.

Angelica sinensis polysaccharide improves mitochondrial metabolism of osteoarthritis chondrocytes through PPARγ/SOD2/ROS pathways.

Osteoarthritis (OA) is a common degenerative joint disease, which is characterized by wear of articular cartilage and narrow joint space, resulting in joint movement disorder. At present, accurate molecular mechanisms and effective interventions are still being explored. Here, we propose that angelica sinensis polysaccharide (ASP) alleviates OA progression by activating peroxisome proliferator-activated receptor gamma (PPARγ). Therapeutic effect of ASP improving mitochondrial metabolism of OA chondrocytes was evaluated in vitro and in vivo, respectively. During cell experiments, the concentration and time response of tert butyl hydroperoxide (TBHP) and ASP were determined by cell viability. Apoptosis was detected by flow cytometry. Mitochondrial metabolism was detected by reactive oxygen species (ROS), mitochondrial membrane potential (MMP), release of cytochrome C, adenosine triphosphate (ATP) production, and superoxide dismutase 2 (SOD2) activity. Expressions of Aggrecan, collagen type II (Col2a1), PPARγ, and SOD2 were detected by qRT-PCR and western blot. In animal experiments, we detected cell apoptosis and target protein expression separately through terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining and immunohistochemistry. Pretreatment of ASP significantly activated PPARγ and SOD2 in rat chondrocytes incubated with TBHP, cleared ROS, improved mitochondrial metabolism, increased chondrocytes viability, and alleviated chondrocytes apoptosis. In vivo, the administration of ASP could effectively ameliorate cartilage degeneration in OA rats, promote extracellular matrix synthesis, and decelerate the progress of OA. Our research identifies the role of ASP in mitochondrial metabolism of OA chondrocytes through PPARγ/SOD2/ROS pathways, which provides a new idea for the treatment of OA.