The value of PET/CT in the diagnosis and differential diagnosis of Parkinson's disease: a dual-tracer study.

Positron emission tomography/computed tomography (PET/CT) is a molecular imaging method commonly used to diagnose and differentiate Parkinson's disease (PD). This study aimed to evaluate the performance of PET/CT with 11C-2ß-Carbomethoxy-3ß-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) tracers in the differential diagnosis between PD, multiple system atrophy parkinsonian type (MSA-P), progressive supranuclear palsy (PSP) and vascular parkinsonism (VP) using the data of 220 patients with clinical PD-like symptoms. Of the 220 enrolled patients, 166 (PD, n = 80; MSA-P, n = 54; PSP, n = 15; VP, n = 17) completed the motor, cognitive and PET/CT assessment and were included in this study. 11C-CFT and 18F-FDG PET/CT images were analyzed using the SNBPI toolbox and CortexID Suite software. The uptake values of 11C-CFT and 18F-FDG PET/CT were compared among the groups after controlling for covariates using generalized linear models. Receiver operating characteristic (ROC) curves were generated to estimate the diagnostic values. Patients with PSP showed the most significant reduction on 11C-CFT PET/CT, while patients with PD and MSA-P showed similar reductions, and patients with VP did not show any significant reduction in 11C-CFT uptake. The areas under the curve (AUCs) for 11C-CFT PET/CT for distinguishing PD from VP, PSP, and MSA-P were 0.902, 0.830, and 0.580, respectively, and 0.728 for distinguishing advanced-stage PD from PSP. On 18F-FDG PET/CT, the AUCs for distinguishing PD from PSP and MSA-P were 0.968 and 0.963, respectively. These results suggest that 11C-CFT and 18F-FDG PET/CT complement each other in improving the accuracy in differential diagnosis of PD.

Tribological Effects of Quaternary Ammonium-Functionalized Montmorillonite as Water-Based Additives.

In this study, a water-soluble quaternary ammonium salt (QAS)-functionalized montmorillonite (MMT) was fabricated using a mechanochemical method as a high-performance water lubrication additive. The intercalation of QAS into the MMT layer expands the layer spacing of MMT, but does not affect the hydrophilicity of MMT. The ultrathin layer QAS-functionalized montmorillonite (QAS-MMT) demonstrated excellent water-stable dispersion and can be used as a water-based lubrication additive. Only 0.1% addition can reduce the friction coefficient by more than 71.4% and the wear volume by about 58.8% when compared to water, demonstrating its excellent friction reduction and antiwear performance. The frictional mechanism indicates that the physical adsorption film, together with the chemical reaction film, endows the QAS-MMT additives with outstanding tribological performance, provides excellent lubrication for the contact of steel/steel pairs, and prevents the steel surface from being further worn.

Nepetoidin B Alleviates Liver Ischemia/Reperfusion Injury via Regulating MKP5 and JNK/P38 Pathway.

Background: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear. Methods: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5). Results: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway. Conclusion: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.

The PD-1 /PD-L1 signaling pathway regulates decidual macrophage polarization and may participate in preeclampsia.

The pathogenesis of preeclampsia (PE) has not been elucidated, but immune imbalance is known to be one of the main pathogeneses. Dysfunction of decidual macrophages can lead to PE, and the PD-1/PD-L1 signaling pathway is associated with macrophage polarization. However, the relationship between the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization and the onset of PE has not been fully elucidated. In this study, we analyzed the expression of CD68, iNOS, CD206, PD-1 and PD-L1 and the coexpression of CD68+PD-1+ and CD68+PD-L1+ in the decidual tissue of PE patients (n= 18) and healthy pregnant women (n=20). We found that CD68 and iNOS expression was increased in the decidua of PE patients (P < 0.001) and that CD206, PD-1 and PD-L1 expression and CD68+PD-1+ and CD68+PD-L1+ coexpression were decreased (P < 0.001). To assess the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization, we added an anti-PD-1 mAb (pembrolizumab) or an anti-PD-L1 mAb (durvalumab) during THP-1 differentiation into M1 macrophages. Then, we detected the polarization of CD68+CD80+ macrophages and the expression of iNOS. To examine the effect of macrophage polarization on the invasion ability of trophoblast cells, macrophages were cocultured with HTR8/SVneo cells, and the invasion ability of HTR8/SVneo cells was detected via transwell assays. We found that CD68+CD80+ macrophage polarization was enhanced (P<0.05) and that iNOS expression was greater (P<0.01) in the pembrolizumab group. In the durvalumab group, CD68+CD80+ macrophage polarization and iNOS expression were also increased (P<0.05 and P<0.001). Compared with that in the untreated group, the aggressiveness of HTR8/SVneo cells was decreased in both the pembrolizumab group (P < 0.01) and the durvalumab group (P < 0.001). These findings indicate that the PD-1/PD-L1 signaling pathway may play an important role in the pathogenesis of PE by influencing macrophage polarization and reducing the invasion ability of trophoblasts.

6-Gingerol attenuates hepatic ischemia/reperfusion injury through regulating MKP5-mediated P38/JNK pathway.

6-Gingerol, the main bioactive compound of ginger, has antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, it is unclear whether 6-Gingerol has protective effects against hepatic ischemia/reperfusion (I/R) injury. In this study, the mouse liver I/R injury model and the mouse AML12 cell hypoxia/reoxygenation (H/R) model were established by pretreatment with 6-Gingerol at different concentrations to explore the potential effects of 6-Gingerol. Serum transaminase levels, liver necrotic area, cell viability, inflammatory response, and cell apoptosis were used to assess the effect of 6-Gingerol on hepatic I/R or cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the mRNA and protein expression. The results show that 6-Gingerol decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, liver necrosis, inflammatory cytokines IL-1ß, IL-6, MCP-1, TNF-α expression, Ly6g+ inflammatory cell infiltration, protein phosphorylation of NF-κB signaling pathway, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, cell apoptosis rate, the protein expression of pro-apoptotic protein BAX and C-Caspase3, increased cell viability, and expression of anti-apoptotic protein BCL-2. Moreover, 6-Gingerol could increase the mRNA and protein expression of mitogen activated protein kinase phosphatase 5 (MKP5) and inhibit the activation of P38/JNK signaling pathway. In MKP5 knockout (KO) mice, the protective effect of 6-gingerol and the inhibition of P38/JNK pathway were significantly weakened. Therefore, our results suggest that 6-Gingerol exerts anti-inflammatory and anti-apoptotic effects to attenuate hepatic I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.

Mobile recognition and positioning for multiple visible light communication cells using a convolutional neural network: publisher's note.

This publisher's note contains a correction to Opt. Lett.48, 6468 (2024)10.1364/OL.503007.

Mobile recognition and positioning for multiple visible light communication cells using a convolutional neural network.

The industrial Internet of Things (IIoT) environment involves multiple production items, such as robots and automated guided vehicles (AGVs), among others. The practical industrial scenario requires communication of production items while also considering mobile recognition and positioning. Hence the perception approach requires not only combining communications but also realizing the recognition and positioning of multiple communication cells. This Letter proposes a multi-optical cell recognition and positioning framework based on LED image features. The LED images are obtained by a CMOS image sensor. This framework utilizes convolutional neural networks (CNN) to train LED images for recognition between multiple optical cells and locates precise positions through region recognition within the optical cells. The experimental results show that the mean accuracy of the CNN model for two LED cells is above 99%, and the mean accuracy of region recognition within the optical cell is as high as 100%, which is significantly better than other traditional recognition algorithms. Therefore, the proposed framework can provide location-aware services for visible light communication and has a wide application prospect in IIoT.

LED lighting area recognition for visible light positioning based on convolutional neural network in the industrial internet of things.

In the industrial environment, the positioning of mobile terminals plays an important role in production scheduling. Visible light positioning (VLP) based on a CMOS image sensor has been widely considered as a promising indoor positioning technology. However, the existing VLP technology still faces many challenges, such as modulation and decoding schemes, and strict synchronization requirements. In this paper, a visible light area recognition framework based on convolutional neural network (CNN) is proposed, where the training data is the LED images acquired by the image sensor. The mobile terminal positioning can be realized from the perspective of recognition without modulating LED. The experimental results show that the mean accuracy of the optimal CNN model is as high as 100% for the two-class and the four-class area recognitions, and is more than 95% for the eight-class area recognition. These results are obviously superior to other traditional recognition algorithms. More importantly, the model has high robustness and universality, which can be applied to various types of LED lights.

Editable 3D Micro-Supercapacitor with High Energy Density Based on Mortise-Tenon Joint Structures.

Three-dimensional micro-supercapacitors (3D MSCs) have accelerated the development of microenergy-storage modules for miniaturized and portable electronics. However, the low energy density, complex construction strategy, and low assembly accuracy of a 3D MSC restrict its practical application. Herein, we design a simple construction strategy for a 3D MSC with high energy density by mortise and tenon structures. Wood-derived carbon modified by nitrogen-doped carbon nanotube arrays (N-CNT-WDC) provides an ordered ion transport channel and a large active specific surface area, availing the improvement of the energy density of a 3D MSC. Its strong carbon skeleton structure supports the construction of 3D interdigital electrodes with a tenon structure by laser, realizing precise and regulable assembly of 3D MSCs through a mortise and tenon joint. The prepared 3D MSC based on N-CNT-WDC shows an excellent volumetric capacitance of 93.66 F cm-3, a high volumetric energy density of 12 mW h cm-3 at 600 mA cm-3, and an 85% retention rate of capacitance after 10,000 cycles of charge and discharge at 1000 mA cm-3. Furthermore, the mortise and tenon structure realizes diversified integration of 3D MSCs, making the integrated manufacturing of 3D microdevices more convenient and promoting their application in microelectronic devices.

[Effects of moxibustion on serum levels of ß-EP, SP and expression of IL-1ß and COX-2 protein in brainstem in rats with migraine].

OBJECTIVE: To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of ß-endorphin (ß-EP), substance P (SP) and expression of interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine. METHODS: Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of ß-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1ß in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem. RESULTS: Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of ß-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of ß-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of ß-EP was increased and COX-2 protein expression was decreased (P<0.05). CONCLUSION: Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1ß and COX-2 protein expression in brainstem, and increase the serum level of ß-EP, and the optimal effect is observed in the PT group.

Excessive Immune Activation and the Correlation with Decreased Expression of PD-1 at the Maternal-Fetal Interface in Preeclampsia.

The etiology of preeclampsia (PE) is still unknown, and excessive immune activation is an important component of its pathogenesis. Programmed cell death protein 1 (PD-1) is one of immune checkpoints which may prevent overactivated immune attack and lead to a tolerant immune microenvironment. Little is known about the involvement of PD-1-mediated immunoregulation at the maternal-fetal interface in PE. To investigate the inflammatory pattern and the involvement of PD-1 in the decidua of women with PE, decidual tissues were obtained from PE and control pregnant women. Quantitative RT-PCR analysis of the mRNA levels of the inflammatory cytokines was performed. PD-1 expression was detected by immunohistochemistry, western blot analysis, and flow cytometry. To prove the role of PD-1, decidual immune cells were incubated with blocking antibodies, and the inflammatory cytokines were detected by ELISA. We observed that the mRNA levels of IL-1ß, IL-6, TNF-α, and IFN-γ were higher in the decidua of the PE group than in the decidua of the control group. The mRNA levels of IL-4 and IL-10 were lower in PE. The expression level of PD-1 was significantly downregulated, and the proportion (%) of PD-1 + CD45 + cells was significantly lower in PE. There was a significant linear correlation between PD-1 expression and common proinflammatory cytokines in the decidua. Anti-PD-1 blocking antibody significantly increased the secretion of proinflammatory cytokines. Our data suggested that the inflammatory pattern and decreased PD-1 expression in the decidua might play an active role in the local immunoregulatory mechanisms of PE. The PD-1 pathway in the maternal-fetal interface possibly function to break the tolerant immune microenvironment in PE via inflammatory cytokines.

Visible light sensing based on shadow features using multi-scale region convolutional neural network.

There are various production items in the industrial internet of things (IIoT) environment, such as pedestrians, robots, automated automated guided vehicles, etc. The practice industrial environment requires simultaneous communication and sensing of production items to achieve intelligent production and control. Thus, sensing methods not only require the integration of communication but also achieve sensing tasks such as recognition and positioning. Compared with traditional sensing media, visible light sensing has the advantages of high-speed communication, high sensing accuracy, and security, low energy consumption, and has become a potential sensing technology. Based on the strong directivity of visible light spatial radiation and the consistency of light intensity and position, this paper proposes a multi-scale visible light sensing-region convolutional neural network (VLS-RCNN) framework based on shadow features for multiple target sensing. The framework enables the recognition and positioning to use shared visible light shadow features to assist each other, and the multi-scale compensation strategy of the shadow region makes the framework more robust. The simulation results show that positioning results in the sensing area improve the recognition accuracy. The recognition results also reduce the positioning error without additional overhead. Therefore, this paper provides a new perspective for the sensing technology in the future IIoT, which should be considered to sense objects of interest by utilizing the inherent characteristics of visible light.

LncRNA Airn maintains LSEC differentiation to alleviate liver fibrosis via the KLF2-eNOS-sGC pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases. The dysregulation of liver sinusoidal endothelial cell (LSEC) phenotype is a critical early event in the fibrotic process. However, the biological function of lncRNAs in LSEC still remains unclear. METHODS: The expression level of lncRNA Airn was evaluated in both human fibrotic livers and serums, as well as mouse fibrotic livers. Gain- and loss-of-function experiments were performed to detect the effect of Airn on LSEC differentiation and hepatic stellate cell (HSC) activation in liver fibrosis. Furthermore, RIP, RNA pull-down-immunoblotting, and ChIP experiments were performed to explore the underlying mechanisms of Airn. RESULTS: We have identified Airn was significantly upregulated in liver tissues and LSEC of carbon tetrachloride (CCl4)-induced liver fibrosis mouse model. Moreover, the expression of AIRN in fibrotic human liver tissues and serums was remarkably increased compared with healthy controls. In vivo studies showed that Airn deficiency aggravated CCl4- and bile duct ligation (BDL)-induced liver fibrosis, while Airn over-expression by AAV8 alleviated CCl4-induced liver fibrosis. Furthermore, we revealed that Airn maintained LSEC differentiation in vivo and in vitro. Additionally, Airn inhibited HSC activation indirectly by regulating LSEC differentiation and promoted hepatocyte (HC) proliferation by increasing paracrine secretion of Wnt2a and HGF from LSEC. Mechanistically, Airn interacted with EZH2 to maintain LSEC differentiation through KLF2-eNOS-sGC pathway, thereby maintaining HSC quiescence and promoting HC proliferation. CONCLUSIONS: Our work identified that Airn is beneficial to liver fibrosis by maintaining LSEC differentiation and might be a serum biomarker for liver fibrogenesis.

STARD5 as a potential clinical target of hepatocellular carcinoma.

To reveal whether STARD5 is a potential biomarker for diagnosis and prognosis of HCC. Using gene expression omnibus and the cancer genome atlas (TCGA) to screen differentially expressed genes in HCC and STARD5 was selected by LASSO algorithm. Then, we analyzed the association between STARD5 and clinical characteristics of HCC patients in TCGA and International Cancer Genome Consortium. Meanwhile, the mRNA and protein level of STARD5 was also verified by collecting 87 cases of HCC patients' liver tissues using qRT-PCR and WB. Next, we applied gene set enrichment analysis (GSEA) for pathways analysis of STARD5. Finally, TIMER1.0 and TISIDB were used to explore the correlation of STARD5 with immune cell infiltration. The expression of STARD5 was lower in HCC and negatively correlated with tumor grade (p < 0.05), while high expression of STARD5 suggested a better prognosis for HCC patients (p < 0.01) and it could be an independent prognostic predictor (p < 0.001). Meanwhile, STARD5 also had strong diagnostic accuracy for HCC patients. GSEA revealed that STARD5-related genes were mainly enriched in E2F targets, G2M checkpoint and KRAS signaling. The TIMER1.0 and TISIDB databases found a negative correlation between STARD5 and tumor immune infiltrating cells. STARD5 could be used as a potential target for HCC diagnosis and prognosis.

Romidepsin (FK228) improves the survival of allogeneic skin grafts through downregulating the production of donor-specific antibody via suppressing the IRE1α-XBP1 pathway.

Antibody-mediated rejection (AMR) is one of the major causes of graft loss after transplantation. Recently, the regulation of B cell differentiation and the prevention of donor-specific antibody (DSA) production have gained increased attention in transplant research. Herein, we established a secondary allogeneic in vivo skin transplant model to study the effects of romidepsin (FK228) on DSA. The survival of grafted skins was monitored daily. The serum levels of DSA and the number of relevant immunocytes in the recipient spleens were evaluated by flow cytometry. Then, we isolated and purified B cells from B6 mouse spleens in vitro by magnetic bead sorting. The B cells were cultured with interleukin-4 (IL-4) and anti-clusters of differentiation 40 (CD40) antibody with or without FK228 treatment. The immunoglobulin G1 (IgG1) and IgM levels in the supernatant were evaluated by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the corresponding levels of messenger RNA (mRNA) and protein expression in cultured cells and the recipient spleens. The results showed that FK228 significantly improved the survival of allogeneic skin grafts. Moreover, FK228 inhibited DSA production in the serum along with the suppression of histone deacetylase 1 (HADC1) and HDAC2 and the upregulation of the acetylation of histones H2A and H3. It also inhibited the differentiation of B cells to plasma cells, decreased the transcription of positive regulatory domain-containing 1 (Prdm1) and X-box-binding protein 1 (Xbp1), and decreased the expression of phosphorylated inositol-requiring enzyme 1 α (p-IRE1α), XBP1, and B lymphocyte-induced maturation protein-1 (Blimp-1). In conclusion, FK228 could decrease the production of antibodies by B cells via inhibition of the IRE1α-XBP1 signaling pathway. Thus, FK228 is considered as a promising therapeutic agent for the clinical treatment of AMR.

An injectable superior depot of Telratolimod inhibits post-surgical tumor recurrence and distant metastases.

The clinical success of Toll-like receptor (TLR) agonists is based on their capacity to efficiently mobilize both innate and adaptive immunity. However, rapid distribution of TLR agonists into the systemic circulation may result in systemic cytokine storms. Telratolimod (Tel) is a TLR 7/8 agonist whose structure has a hydrophobic long chain that helps to prolong its release. Despite this, the phase I study of Tel showed cytokine release syndromes in 3/35 patients. Herein, we designed an injectable phase transition gel (PGE) that served as a superior drug depot for fatty acid-modified drugs. PGE further minimized the systemic drug exposure of Tel and the possible cytokine storms. In vivo studies demonstrated that Tel@PGE facilitated the recruitment of effector CD8+ T lymphocytes (T cells) and the polarization of myeloid-derived suppressor cells (MDSCs) and immunosuppressive M2-like macrophages to tumoricidal antigen-presenting cells. The reshaping of the tumor microenvironment (TME) by Tel@PGE elicited systematic immune responses to significantly prevent B16F10 or 4T-1 tumor postoperative recurrence and metastasis. Therefore, this platform of Tel is expected to provide a clinically available option for effective postoperative combined therapy. STATEMENT OF SIGNIFICANCE: A series of prodrugs or conjugates containing hydrophobic blocks were designed to achieve sustained release at the injection site by reducing the water solubility. However, this strategy sometimes failed short of expectations. Thus, we constructed a biocompatible and biodegradable injectable phase transition gel (PGE) with superior release properties that can be injected subcutaneously into the surgery site. In the long-lasting treatment, the melanoma and breast cancer immunotherapeutic effect significantly enhanced and the risk of cancer metastasis and relapse was reduced. Crucially, for some immune agonists, a superior release control can significantly reduce adverse effects which was decisive for the availability of the drugs.

LncRNA-Airn alleviates acute liver injury by inhibiting hepatocyte apoptosis via the NF-κB signaling pathway.

Acute liver injury is a common and serious syndrome caused by multiple factors and unclear pathogenesis. If the injury persists, liver injury can lead to cirrhosis and liver failure and ultimately results in the development of liver cancer. Emerging evidence has indicated that long noncoding RNAs (lncRNAs) play an important role in the development of liver injury. However, the role of antisense Igf2r RNA (Airn) in acute liver injury and its underlying mechanism remain largely unclear. In this study, we show that Airn is upregulated in liver tissue and primary hepatocytes from an acute liver injury mouse model. Consistently, Airn is also overexpressed in serum samples of patients with acute-on-chronic liver failure and is negatively correlated with the Model for End-Stage Liver Disease (MELD) score. Moreover, gene knockout and rescue assays reveal that Airn alleviates CCl 4-induced liver injury by inhibiting hepatocyte apoptosis and oxidative stress in vivo. Further investigation reveals that Airn decreases H 2O 2-induced hepatocyte apoptosis in vitro. Mechanistically, we reveal that Airn represses CCl 4- and H 2O 2-induced enhancement of phosphorylation of p65 and IκBα, suggesting that Airn inhibits hepatocyte apoptosis by inactivating the NF-κB pathway. In conclusion, our results demonstrate that Airn can alleviate acute liver injury by inhibiting hepatocyte apoptosis via inactivating the NF-κB signaling pathway, and Airn could be a potential biomarker for acute liver injury.

Identification of CDCA2 as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear. METHODS: The differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator Cox regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both bioinformatic analysis and in vitro experiments. RESULTS: The level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis, and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant upregulation of p53 and the downstream PUMA and NOXA and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2. CONCLUSIONS: CDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage, and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.

Oridonin Prolongs the Survival of Mouse Cardiac Allografts by Attenuating the NF-κB/NLRP3 Pathway.

Background: Oridonin (Ori), the main bioactive ingredient of the natural anti-inflammatory herb Rabdosia rubescens, could be a covalent inhibitor of the NLRP3 inflammasome. Solid organ transplantation provides a life-saving optional therapy for patients with end-stage organ dysfunction. The long-term survival of solid organ transplantation remains restricted because of the possibility of rejection and the toxicity, infection, cardiovascular disease, and malignancy related to immunosuppressive (IS) drugs. However, the pathogenic mechanisms involved remain unclear. The ideal IS drugs to prevent allograft rejection have not been identified. Here, we investigated whether Ori could prolong the in vivo survival of completely mismatched cardiac allografts. Methods: The cardiac transplantation models were conducted among three groups of mice from C57BL/6NCrSlc (B6/N) or C3H/HeNSlc (C3H) to C3H: the syngeneic and the allogeneic group, whose recipients were treated with vehicle of Ori, and the Ori treatment group, in which the recipients were transplanted hearts from MHC-I mismatched donors and treated with different dosages of Ori from post-operative day (POD) 0 to 7. Then, we investigated the effect of Ori on bone marrow-derived dendritic cell (BMDC) and allogeneic mixed lymphocyte reaction in vitro. Results: Ori with 3, 10, and 15 mg/kg Ori could prolong the survival (MST = 22.8, 49.2, and 65.3 days, respectively). We found that infiltrating CD8+ T cells and macrophages were decreased, and regulatory T cells (Tregs) were expanded in allografts on POD7. The mRNA level of IL-1ß and IFN-γ of allografts was downregulated. Mechanistically, Ori-treated BMDCs suppressed T-cell proliferation and IFN-γ+CD4+ T-cell differentiation, along with the expansion of Tregs and IL-10+CD4+ T cells. Ori inhibited NOD, LRR-, and pyrin domain-containing protein 3 (NLRP3) expression; attenuated NF-κB and IκBα phosphorylation in LPS-activated BMDCs; downregulated NLRP3, Caspase-1, IL-1ß, IL-18, and IFN-γ; and upregulated IL-10 expression. Conclusions: Our findings highlight the potential of Ori as a novel and natural IS agent to improve transplant tolerance. Ori could exert IS activity through decreasing IL-1ß and IL-18 production and Th1 differentiation and proliferation and expanding Tregs via inhibiting the NF-κB/NLRP3 signaling pathway.

MiR-301a-5p/SCIN promotes gastric cancer progression via regulating STAT3 and NF-κB signaling.

Objective: Gastric cancer (GC) is a type of highly malignant cancer. Although the diagnostic and therapeutic methods are innovating, the outcome of GC patients is still poor. Therefore, our research was carried out to explore potential molecular mechanism in the diagnosis of GC. Materials and methods: Bioinformatics analyses were used to obtain microRNA and target mRNA of interest. The expression level of miR-301a-5p and Scinderin (SCIN) mRNA were detected by quantitative real-time PCR (qRT-PCR). Western blot assay was used to investigate SCIN protein level. Cell Counting Kit-8 assay (CCK-8) and colony formation assay were used to investigate cell proliferation ability. Transwell assay was employed to examine cell motility. The interaction between miR-301a-5p and SCIN mRNA was verified by dual-luciferase reporter assay. Results: The qRT-PCR analysis revealed that the expression of miR-301a-5p was higher in gastric cancer tissues than para-cancer tissues (P<0.05). Cox regression analysis showed upregulated miR-301a-5p was associated with larger tumor size (P=0.036) and more advanced TNM stage (P=0.048). The Kaplan-Meier analysis showed a correlation between increased miR-301a-5p expression and shorter overall survival (OS)(P=0.018). By using bioinformatic analysis, SCIN was predicted as one of the targets of miR-301a-5p. Overexpressing miR-301a-5p promoted proliferation and motility of GC cells while knockdown of SCIN exhibited the same performance. Further, we verified the alteration of miR-301a-5p and SCIN expression level could affect the epithelial-mesenchymal transition (EMT) progression on GC cells via STAT3 and NF-κB signaling. Conclusion: Highly expressed miR-301a-5p was associated with aggressiveness of GC. Upregulation of miR-301a-5p promoted malignant phenotype of GC by targeting SCIN. The present results indicated miR-301a-5p might be a promising molecule in the prognosis of GC.