Traditional Chinese Medicine Monomers Are Potential Candidate Drugs for Cancer-Induced Cardiac Cachexia.

BACKGROUND: Cardiovascular diseases are now the second leading cause of death among cancer patients. Heart injury in patients with terminal cancer can lead to significant deterioration of left ventricular morphology and function. This specific heart condition is known as cancer-induced cardiac cachexia (CICC) and is characterized by cardiac dysfunction and wasting. However, an effective pharmacological treatment for CICC remains elusive. SUMMARY: The development and progression of CICC are closely related to pathophysiological processes, such as protein degradation, oxidative responses, and inflammation. Traditional Chinese medicine (TCM) monomers offer unique advantages in reversing heart injury, which is the end-stage manifestation of CICC except the regular treatment. This review outlines significant findings related to the impact of eleven TCM monomers, namely Astragaloside IV, Ginsenosides Rb1, Notoginsenoside R1, Salidroside, Tanshinone II A, Astragalus polysaccharides, Salvianolate, Salvianolic acids A and B, and Ginkgolide A and B, on improving heart injury. These TCM monomers are potential therapeutic agents for CICC, each with specific mechanisms that could potentially reverse the pathological processes associated with CICC. Advanced drug delivery strategies, such as nano-delivery systems and exosome-delivery systems, are discussed as targeted administration options for the therapy of CICC. KEY MESSAGE: This review summarizes the pathological mechanisms of CICC and explores the pharmacological treatment of TCM monomers that promote anti-inflammation, antioxidation, and pro-survival. It also considers pharmaceutical strategies for administering TCM monomers, highlighting their potential as therapies for CICC.

Cardioprotection of voluntary exercise against breast cancer-induced cardiac injury via STAT3.

Exercise is an effective way to alleviate breast cancer-induced cardiac injury to a certain extent. However, whether voluntary exercise (VE) activates cardiac signal transducer and activator of transcription 3 (STAT3) and the underlying mechanisms remain unclear. This study investigated the role of STAT3-microRNA(miRNA)-targeted protein axis in VE against breast cancer-induced cardiac injury.VE for 4 weeks not only improved cardiac function of transgenic breast cancer female mice [mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT +)] compared with littermate mice with no cancer (MMTV-PyMT -), but also increased myocardial STAT3 tyrosine 705 phosphorylation. Significantly more obvious cardiac fibrosis, smaller cardiomyocyte size, lower cell viability, and higher serum tumor necrosis factor (TNF)-α were shown in MMTV-PyMT + mice compared with MMTV-PyMT - mice, which were ameliorated by VE. However, VE did not influence the tumor growth. MiRNA sequencing identified that miR-181a-5p was upregulated and miR-130b-3p was downregulated in VE induced-cardioprotection. Myocardial injection of Adeno-associated virus serotype 9 driving STAT3 tyrosine 705 mutations abolished cardioprotective effects above. Myocardial STAT3 was identified as the transcription factor binding the promoters of pri-miR-181a (the precursor of miR-181a-5p) and HOX transcript antisense RNA (HOTAIR, sponged miR-130b-3p) in isolated cardiomyocytes. Furthermore, miR-181a-5p targeting PTEN and miR-130b-3p targeting Zinc finger and BTB domain containing protein 20 (Zbtb20) were proved in AC-16 cells. These findings indicated that VE protects against breast cancer-induced cardiac injury via activating STAT3 to promote miR-181a-5p targeting PTEN and to promote HOTAIR to sponge miR-130b-3p targeting Zbtb20, helping to develop new targets in exercise therapy for breast cancer-induced cardiac injury.

Achieving Colorful Ultralong-Lifetime Room-Temperature Phosphorescence Based on Benzocarbazole Derivatives through Resonance Energy Transfer.

It is of practical significance to develop polymer-based room-temperature phosphorescence (RTP) materials with ultralong lifetime and multicolor afterglow. Herein, the benzocarbazole derivatives were selected and combined with a poly(vinyl alcohol) (PVA) matrix by a coassembly strategy. Owing to the hydrogen-bonding interactions between benzocarbazole derivatives and the PVA matrix, the nonradiative transition and the quenching of triplet excitons are effectively inhibited. Therefore, the maximum phosphorescence emission lifetime of 2202.17 ms from ABfCz-PVA and the maximum phosphorescence quantum efficiency of 34.97% from ABtCz-PVA were obtained, respectively. In addition, commercially available dye molecules were selected to construct phosphorescent resonance energy transfer (PRET) systems for energy acceptors, enabling full-color afterglow emission in blue, green, yellow, red, and even white. Based on the characteristics of prepared RTP materials, multifunctional applications to flexibility, information encryption, and erasable drawing were deeply explored.

M6A Demethylase Inhibits Osteogenesis of Dental Follicle Stem Cells via Regulating miR-7974/FKBP15 Pathway.

N6-methyladenosine (m6A) is the most abundant RNA modification, regulating gene expression in physiological processes. However, its effect on the osteogenic differentiation of dental follicle stem cells (DFSCs) remains unknown. Here, m6A demethylases, the fat mass and obesity-associated protein (FTO), and alkB homolog 5 (ALKBH5) were overexpressed in DFSCs, followed by osteogenesis assay and transcriptome sequencing to explore potential mechanisms. The overexpression of FTO or ALKBH5 inhibited the osteogenesis of DFSCs, evidenced by the fact that RUNX2 independently decreased calcium deposition and by the downregulation of the osteogenic genes OCN and OPN. MiRNA profiling revealed that miR-7974 was the top differentially regulated gene, and the overexpression of m6A demethylases significantly accelerated miR-7974 degradation in DFSCs. The miR-7974 inhibitor decreased the osteogenesis of DFSCs, and its mimic attenuated the inhibitory effects of FTO overexpression. Bioinformatic prediction and RNA sequencing analysis suggested that FK506-binding protein 15 (FKBP15) was the most likely target downstream of miR-7974. The overexpression of FKBP15 significantly inhibited the osteogenesis of DFSCs via the restriction of actin cytoskeleton organization. This study provided a data resource of differentially expressed miRNA and mRNA after the overexpression of m6A demethylases in DFSCs. We unmasked the RUNX2-independent effects of m6A demethylase, miR-7974, and FKBP15 on the osteogenesis of DFSCs. Moreover, the FTO/miR-7974/FKBP15 axis and its effects on actin cytoskeleton organization were identified in DFSCs.

Ginseng Saponin Rb1 Attenuates Cigarette Smoke Exposure-Induced Inflammation, Apoptosis and Oxidative Stress via Activating Nrf2 and Inhibiting NF-κB Signaling Pathways.

Objective: Cigarette smoke exposure is one of the major risk factors for the development of chronic obstructive pulmonary disease (COPD). Ginseng saponin Rb1 (Rb1) is a natural extract from ginseng root with anti-inflammatory and anti-oxidant effects. However, the underlying mechanism of the Rb1 in COPD remains unknown. Therefore, we sought to explore the role of Rb1 in cigarette smoke-induced damage and to reveal the potential mechanism. Methods: The cell viability and lactose dehydrogenase (LDH) activity were analyzed using cell counting kit-8 (CCK-8) and LDH release assays. We further investigated the inflammation, apoptosis and oxidative stress markers and analyzed the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid-2-related factor 2 (Nrf2) pathways in BEAS-2B cells and COPD rat model following cigarette smoke extract (CSE) exposure. Results: Our results showed that CSE promoted inflammation, apoptosis and oxidative stress in BEAS-2B cells. Rb1 suppressed the inflammatory response by inhibiting expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß and inhibiting the NF-κB signaling pathway. Rb1 possessed the ability to hinder cell apoptosis induced by CSE. In addition, Rb1 concurrently reduced CSE-induced oxidative reactions and promoted Nrf2 translocation to nucleus. For in vivo study, Rb1 treatment alleviated CSE-induced lung injury, apoptosis, reactive oxygen species (ROS) release and inflammatory reactions. Also, Rb1 treatment activated Nrf2 signaling and inactivated NF-κB signaling in COPD rats. Conclusion: Rb1 attenuates CSE-induced inflammation, apoptosis and oxidative stress by suppressing NF-κB and activating Nrf2 signaling pathways, which provides novel insights into the mechanism underlying CSE-induced COPD.

Identification and analysis of type 2 diabetes-mellitus-associated autophagy-related genes.

Introduction: Autophagy, an innate safeguard mechanism for protecting the organism against harmful agents, is implicated in the survival of pancreatic â cells and the development of type 2 diabetes mellitus (T2DM). Potential autophagy-related genes (ARGs) may serve as potential biomarkers for T2DM treatment. Methods: The GSE25724 dataset was downloaded from the Gene Expression Omnibus (GEO) database, and ARGs were obtained from the Human Autophagy Database. The differentially expressed autophagy-related genes (DEARGs) were screened at the intersection of ARGs and differentially expressed genes (DEGs) between T2DM and non-diabetic islet samples, which were subjected to functional enrichment analyses. A protein-protein interaction (PPI) network was constructed to identify hub DEARGs. Expressions of top 10 DEARGs were validated in human pancreatic â-cell line NES2Y and rat pancreatic INS-1 cells using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell viability and insulin secretion were measured after cell transfection with lentiviral vector EIF2AK3 or RB1CC1 into islet cells. Results: In total, we discovered 1,270 DEGs (266 upregulated and 1,004 downregulated genes) and 30 DEARGs enriched in autophagy- and mitophagy-related pathways. In addition, we identified GAPDH, ITPR1, EIF2AK3, FOXO3, HSPA5, RB1CC1, LAMP2, GABARAPL2, RAB7A, and WIPI1 genes as the hub ARGs. Next, qRT-PCR analysis revealed that expressions of hub DEARGs were consistent with findings from bioinformatics analysis. EIF2AK3, GABARAPL2, HSPA5, LAMP2, and RB1CC1 were both differentially expressed in the two cell types. Overexpression of EIF2AK3 or RB1CC1 promoted cell viability of islet cells and increased the insulin secretion. Discussion: This study provides potential biomarkers as therapeutic targets for T2DM.

Hydrogen peroxide preconditioning is of dual role in cardiac ischemia/reperfusion.

Moderate reactive oxygen species (ROS) at reperfusion would trigger cardioprotection and various antioxidants for pharmacological preconditioning failed to achieve cardioprotection. The causes for different roles of preischemic ROS during cardiac ischemia/reperfusion (I/R) require reevaluation. We investigated the precise role of ROS and its working model in this study. Different doses of hydrogen peroxide (H2O2, the most stable form of ROS) were added 5 min before ischemia using isolated perfused rat hearts, only moderate-dose H2O2 preconditioning (H2O2PC) achieved contractile recovery, whereas the low dose and high dose led to injury. Similar results were observed in isolated rat cardiomyocytes on cytosolic free Ca2+ concentration ([Ca2+]c) overload, ROS production, the recovery of Ca2+ transient, and cell shortening. Based on the data mentioned above, we set up a mathematics model to describe the effects of H2O2PC with the fitting curve by the percentage of recovery of heart function and Ca2+ transient in I/R. Besides, we used the two models to define the initial thresholds of H2O2PC achieving cardioprotection. We also detected the expression of redox enzymes and Ca2+ signaling toolkits to explain the mathematics models of H2O2PC in a biological way. The expression of tyrosine 705 phosphorylation of STAT3, Nuclear factor E2-related factor 2, manganese superoxide dismutase, phospholamban, catalase, ryanodine receptors, and sarcoendoplasmic reticulum calcium ATPase 2 were similar with the control I/R and low-dose H2O2PC but were increased in the moderate H2O2PC and decreased in the high-dose H2O2PC. Thus, we concluded that preischemic ROS are of dual role in cardiac I/R.

Establishment of a Beagle Dog Model of Dry Eye Disease.

Purpose: To establish a Beagle dog model of dry eye disease (DED). Methods: DED models were induced by surgical removal of orbital lacrimal glands and entire resection of third eyelids in the left eyes of six Beagle dogs. Intact right eyes served as self-controls. Non-anaesthetized Schirmer test (STT), tear break-up time (TBUT), and fluorescein staining grading were performed monthly after operation. Interleukin (IL)-1ß, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) levels were detected in tears and conjunctiva tissues. Six months after surgery, conjunctiva and cornea were collected and histopathologically analyzed. Results: Signs of DED appeared within one month after surgery and then remained stable. STT values were significantly reduced by 88% within 3 weeks after operation and remained stable over months with 1.6 ± 0.4 mm. Mean TBUT decreased significantly within two months after operation and maintained 5.2 ± 1.1 seconds. The mean fluorescein staining score was highest at the first month and then was reduced, eventually reaching a balance with 11.0 ± 1.3 points. Elevated levels of IL-1ß, IL-8, IL-10, and TNF-α were detected in tears and conjunctivas of operated eyes. Hematoxylin and eosin staining showed cornea neovascularization in the corneal stroma with thickened stroma layer and disorganized collagen bundles. Periodic acid-Schiff staining revealed a reduced function of conjunctival goblet cells. Conclusions: A combined type of DED model on the Beagle dog was established by removal of the orbital lacrimal gland and resection of the third eyelid. This DED model is easily accessible and is stable at six-month observation. Translational Relevance: The surgery-induced Beagle dog DED model is easily accessible and stable over a relatively long time.

Updated information regarding management of hepatic epithelioid hemangioendothelioma.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare hepatic vascular tumor with a borderline biological behavior between hemangioma and hemangiosarcoma. It tends to be multiple or diffuse subcapsular lesions across the liver but has no characteristic clinical manifestations or imaging findings. On computed tomography and magnetic resonance imaging, these lesions usually have a hypodense appearance with heterogeneous enhancement and a "halo sign" or "lollipop sign" may be evident in some cases. HEHE is diagnosed mainly based on a pathological examination along with differential immunohistochemical markers such as CAMTA1, CD31, CD34, CD10, vimentin, and factor VIII antigen. Currently, there are no standardized treatment guidelines for HEHE, and surgery (curative resection and liver transplantation) remains the mainstay of treatment. Studies have indicated that extra-hepatic metastasis might not be a contraindication for resection or transplantation. Systemic chemotherapeutic agents including doxorubicin, vincristine, interferon-a, 5-fluorouracil, and thalidomide, as well as VEGF-related agents are being investigated, but no agents have been approved for the treatment of HEHE.

Pillar[n]arene-Mimicking/Assisted/Participated Carbon Nanotube Materials.

The recent progress in pillar[n]arene-assisted/participated carbon nanotube hybrid materials were initially summarized and discussed. The molecular structure of pillar[n]arene could serve different roles in the fabrication of attractive carbon nanotube-based materials. Firstly, pillar[n]arene has the ability to provide the structural basis for enlarging the cylindrical pillar-like architecture by forming one-dimensional, rigid, tubular, oligomeric/polymeric structures with aromatic moieties as the linker, or forming spatially "closed", channel-like, flexible structures by perfunctionalizing with peptides and with intramolecular hydrogen bonding. Interestingly, such pillar[n]arene-based carbon nanotube-resembling structures were used as porous materials for the adsorption and separation of gas and toxic pollutants, as well as for artificial water channels and membranes. In addition to the art of organic synthesis, self-assembly based on pillar[n]arene, such as self-assembled amphiphilic molecules, is also used to promote and control the dispersion behavior of carbon nanotubes in solution. Furthermore, functionalized pillar[n]arene derivatives integrated carbon nanotubes to prepare advanced hybrid materials through supramolecular interactions, which could also incorporate various compositions such as Ag and Au nanoparticles for catalysis and sensing.

The crosstalk between STAT3 and microRNA in cardiac diseases and protection.

Signal transducer and activator of transcription 3 (STAT3), an important transcription factor and signaling molecule, play an important role in cardiac disease and protection. As a transcription factor, STAT3 upregulates anti-oxidative and anti-apoptotic genes but suppresses anti-inflammatory and anti-fibrotic genes in cardiac disease and protection. As a signaling molecule, STAT3 is the downstream or upstream of other molecules for signaling transduction, also activated in cardiac disease and protection. MicroRNAs (miRNAs) are endogenous short non-coding RNAs that regulate mRNA expression at the transcriptional level and prevent protein translation. Recently, STAT3 is reported to be not only the target of miRNA but also the inhibitor or inducer of miRNA to modify the mRNA expression profiles in cardiomyocytes resulting in different effects on cardiac disease and protection. We summarize the current knowledge on STAT3 regulation of individual miRNAs and the modulation of STAT3 by miRNAs in cardiac diseases and protection.

Development and assessment of deep learning system for the location and classification of rib fractures via computed tomography.

PURPOSE: The purpose of this study was to evaluate the performance of a deep learning system for the automatic diagnosis and classification of rib fractures. METHODS: This retrospective study analyzed computed tomography (CT) data of patients diagnosed with a rib fracture between 1 January 2019 and 23 July 2020 in two hospitals, including 591 patients from Suzhou TCM hospital and 75 patients from Jintan TCM hospital. A deep learning system (Dr.Wise@ChestFracture v1.0) based on a convolutional neural network framework was used as a diagnostic tool, and a human-model comparison experiment was designed to compare the diagnostic efficiencies of the deep learning system and radiologists. Furthermore, a secondary classification model was established to distinguish the different types of fracture. First, a classification model to differentiate between fresh and old fractures was developed. Second, a submodel to determine any misalignment in fresh fractures was established. RESULTS: For all fracture types, the detection efficiency (recall) of the system was statistically significantly better than that of radiologists with different levels of experience (all p < 0.0167 except for senior radiologists). The F1-score of the system for diagnosing rib fractures was similar to that of the radiologists. The system was much faster than the radiologists in assessing rib fractures (all p < 0.0167). The two classification models can distinguish between fresh and old fractures (accuracy = 87.63%) and determine whether there is any misalignment in fresh fractures (accuracy = 95.22%) or not. CONCLUSION: The use of a deep learning system can accurately, automatically, and rapidly diagnose and classify rib fractures, helping doctors improve the diagnostic efficiency and reducing their workload. The classification models can distinguish different types of rib fracture well.

Hybrid Macrocyclic Polymers: Self-Assembly Containing Cucurbit[m]uril-pillar[n]arene.

Supramolecular self-assembly by hybrid macrocycles containing both cucurbit[m]uril (CB[m]) and pillar[n]arene was discussed and summarized in this review. Due to different solubility, diverse-sized cavities, and various driving forces in recognizing guests, the role of CB[m] and pillar[n]arene in such hybrid macrocyclic systems could switch between competitor in capturing specialized guests, and cooperator for building advanced hybridized macrocycles, by controlling their characteristics in host-guest inclusions. Furthermore, both CB[m] and pillar[n]arene were employed for fabricating advanced supramolecular self-assemblies such as mechanically interlocked molecules and supramolecular polymers. In those self-assemblies, CB[m] and pillar[n]arene played significant roles in, e.g., microreactor for catalyzing particular reactions to bridge different small pieces together, molecular "joint" to connect different monomers into larger assemblies, and "stabilizer" in accommodating the guest molecules to adopt a favorite structure geometry ready for assembling.

The YAP signaling pathway promotes the progression of lymphatic malformations through the activation of lymphatic endothelial cells.

BACKGROUND: To investigate whether the YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ binding motif) pathway contributes to the pathogenesis of lymphatic malformations (LMs). METHODS: YAP, TAZ, CTGF (connective tissue growth factor), and Ki-67 were detected in LMs by immunohistochemistry. The colocalization of YAP and Ki-67 was analyzed by double immunofluorescence. Pearson's correlation and cluster analyses were performed to analyze the relationships between these proteins. Human dermal lymphatic endothelial cells (HDLECs) were used for mechanistic investigation. Rat models of LMs were established to investigate the role of the YAP pathway in LM development. RESULTS: Compared with those in normal skin, the expression levels of YAP, TAZ, CTGF, and Ki-67 were significantly upregulated in lymphatic endothelial cells (LECs) of LMs. Interestingly, YAP and CTGF presented much higher expression levels in infected LMs. In experiments in vitro, lipopolysaccharide (LPS) enhanced the expression of YAP in a concentration- and time-dependent manner via the increased phosphorylation of Erk1/2 (extracellular signal-regulated kinase 1/2). Moreover, the proliferation, invasion, and tubule formation of HDLECs increased significantly in accordance with the activation of the YAP signaling pathway. Furthermore, LM rat models validated that LPS facilitated the development of LMs, which was dependent on the activation of YAP. CONCLUSIONS: The data reveal that activation of the YAP signaling pathway in LECs may play a crucial role in the progression of LMs. IMPACT: Compared with that in normal skin, the YAP signaling pathway was activated in LECs of LMs. Inhibiting the YAP signaling pathway attenuated the proliferation, invasion, and tubule formation of HDLECs. Additionally, the activation of the YAP signaling pathway could promote LM development in a rat model. Activation of the YAP signaling pathway in LECs may play a crucial role in the progression of LMs. The YAP signaling pathway was activated in LMs. Inhibition of the YAP signaling pathway could promote regression of the lesions.

Bleomycin: A novel osteogenesis inhibitor of dental follicle cells via a TGF-ß1/SMAD7/RUNX2 pathway.

BACKGROUND AND PURPOSE: Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown. EXPERIMENTAL APPROACH: Human dental follicle cells (hDFCs) were treated by bleomycin or exogenous TGF-ß1 or transfected by plasmids loading SMAD7 or shRNA targeting SMAD7, followed by osteogenesis induction assay and signalling analysis. Human fresh DF tissues and Wistar rats were used to further confirm bleomycin function. KEY RESULTS: Bleomycin decreased expression of RUNX2 and osteogenic genes in hDFCs, reducing osteogenic capacity. TGF-ß1 expression was up-regulated in bleomycin-treated hDFCs. The effects of exogenous TGF-ß1 were similar to those of bleomycin in hDFCs. Additionally, compared to SMAD2/3, SMAD7 expression increased more in bleomycin- or TGF-ß1-treated hDFCs. Overexpression of SMAD7 likewise significantly decreased RUNX2 expression and osteogenic capacity of hDFCs. Knockdown of SMAD7 markedly attenuated the inhibitory effects of bleomycin and TGF-ß1 on osteogenic capacity and RUNX2 expression of hDFCs. Most importantly, changes in TGF-ß1, SMAD7, and RUNX2 expressions were similar in the DF of rats and humans treated with bleomycin. CONCLUSION AND IMPLICATIONS: SMAD7 was a negative regulator of osteogenic differentiation in DFCs through suppressing RUNX2 expression. Bleomycin or TGF-ß1 inhibited osteogenic differentiation of DFCs via a TGF-ß1/SMAD7/RUNX2 pathway. Our findings might be beneficial for enhancing the osteogenic activity of DFCs or inhibiting the eruption of undesirable teeth.

Effects of bleomycin on tooth eruption: a novel potential application.

There are many kinds of potentially undesirable teeth. At present, surgical extraction is the most efficient way to eliminate these teeth, but it's very complex and invasive. In this study, we investigated the effects of bleomycin (BLM) on dental follicle and tooth eruption as a potential conservative therapy for undesirable teeth. Our data showed that local injection of 0.2 U/kg BLM had no significant effects on tooth eruption compared to the control group in Wistar rats. With higher dose of BLM (0.5 or 2 U/kg), the eruption of treated teeth was interrupted and their root formation failed until 4 weeks postnatal without significant systemic toxicity. Additionally, those effects were not depending on the toxicity of overdose evidenced by TUNEL assay. In summary, injecting BLM into dental follicle at an early stage could interrupt tooth development and eruption, and may prevent the potentially clinical problems resulting from undesirable teeth instead of surgical removal.

Elevated ATF4 Expression in Odontogenic Keratocysts Epithelia: Potential Involvement in Tissue Hypoxia and Stromal M2 Macrophage Infiltration.

The aim of this study was to investigate the expression of the activating transcription factor 4 (ATF4) in odontogenic keratocysts (OKC), its association with hypoxia and M2-polarized macrophages infiltration, and its potential relationships with angiogenesis in OKC. The expression of ATF4, hypoxia-inducible factor 1α (HIF-1α), macrophage colony-stimulating factor (M-CSF), and receptor activator of nuclear factor κ-B ligand (RANKL) in OKC samples and normal oral mucosa (OM) was detected by immunohistochemistry. Meanwhile, microvessel density (MVD) was measured using antibody against CD31. M2-polarized macrophages were identified using double-staining for CD68+ and CD163+. The correlations of ATF4 with HIF-1α, M-CSF, and M2-polarized macrophages infiltration were determined by Spearman's rank correlation test and hierarchical clustering. Human immortalized oral epithelial cells (HIOECs) were used in in vitro experiments. Our data showed that the expression of HIF-1α, ATF4, and M-CSF was significantly upregulated in the epithelium of OKC when compared with the OM. The expression of ATF4 was positively correlated with that of HIF-1α, M-CSF, MVD, and M2-polarized macrophages infiltration. Elevated expression of ATF4 in the epithelial lining of OKC may facilitate the M2 macrophages infiltration in response to hypoxia, leading to the development of OKC.

Mammography and MRI manifestations of breast angiosarcoma.

BACKGROUND: Breast angiosarcoma is rare and previous studies only focus on its pathology. This study aimed to summarize its imaging features. METHODS: Overall 17 patients pathologically confirmed with breast angiosarcoma were recruited. Eight patients underwent preoperative mammography, and 13 received preoperative MRI scan. The mammography and MRI findings were classified according to the ACR-BI-RADS-mammography/MR lexicon. RESULTS: Mammography showed that 3 cases developed diffuse asymmetry occupying two or more quadrants of the affected breast and that 5 patients had lobulated or oval masses. The 13 patients' lesions presented as diffuse and slightly/significantly high homogeneous or heterogeneous signals on T1-weighted images, while the necrotic and cystic parts had relatively low signals. The hemorrhagic lesions in 7 cases had high signals on both T1- and T2-weighted images. A hemosiderin ring at the edge of an old hemorrhagic lesion had long and short signals on the T1- and T2-weighted images, respectively. Contrast-enhanced MRI revealed that the 13 patients' lesions had significant heterogeneous enhancement. Significant enhancement was observed in the early phase, and varying degrees of concentric enhancement was seen in the delayed phase. CONCLUSIONS: The mammography findings are nonspecific. MRI scan is helpful in determining the malignancy of the lesions. Breast angiosarcoma usually shows heterogeneous signals on both T1-weighted and T2-weighted images. Due to their incomplete lumens and lack of thrombocytes, patients with angiosarcoma have a higher incidence of bleeding (nearly 50% in this study) than those with other malignant tumors. The pattern of the enhancement curve helps to distinguish this disease from the typical types of breast cancer.

Ultrasound-Targeted Microbubble Destruction (UTMD) Combined with Liposome Increases the Effectiveness of Suppressing Proliferation, Migration, Invasion, and Epithelial- Mesenchymal Transition (EMT) via Targeting Metadherin (MTDH) by ShRNA.

BACKGROUND Reports show that ultrasound-targeted microbubble destruction (UTMD) is a promising method of gene therapy, and metadherin (MTDH) is related to the development of breast cancer. Thus, we investigated the role of MTDH in breast cancer and compared the effect of suppressing MTDH by shRNA using liposome, UTMD, or the combination of these 2 methods. MATERIAL AND METHODS Graphing of survival curves of MTDH was analyzed by bioinformatics. UTMD was conducted using an ultrasonic therapeutic apparatus. Cell counting kit-8 (CCK-8) assay was used to measure cell viability. Migration and invasion rates were measured by wound healing test and Transwell invasion assay, respectively. The expression of MTDH, E-cadherin, metastasis-associated protein-1 (MTA-1), matrix metalloproteinase (MMP)-2, and MMP-9 were measured by Western blot and qPCR. RESULTS The prognosis of breast cancer can be decreased by the high expression of MTDH, and elevated expression of MTDH was discovered in MCF-7, MCF-10A, and T47D cell lines. UTMD combined with liposome is most efficient in transfecting shRNA, clearly suppressing the expression of MTDH and thereby decreasing cell viability, migration, invasion rate, and epithelial- mesenchymal transition (EMT) processes in the MCF-7 cell line. CONCLUSIONS UTMD combined with liposome could be used as a more efficient way to transfect shRNA into cells to suppress the expression of MTDH and thus lead to the downregulation of proliferation, migration, and EMT processes of the MCF-7 cell line, showing the potential for use in gene therapy.