Decreased levels of PTCSC3 promote the deterioration of prostate cancer and affect the prognostic outcome of patients through sponge miR-182-5p.

BACKGROUND: Prostate cancer, characterized by its insidious onset and short overall survival, and has seen a rise in incidence over recent decades. This study aims to investigate the expression and molecular mechanism of lncRNA PTCSC3 (PTCSC3) in prostate cancer in order to develop new prognostic and therapeutic biomarkers. METHODS: The level of PTCSC3 in serum and cell samples of prostate cancer was quantitatively measured using RT-qPCR assays. The correlation between the variation in PTCSC3 levels and clinical indicators of patients was evaluated. The survival status of the prostate cancer patients included in the study was evaluated using Kaplan-Meier curve and multivariable Cox analysis. The impact of PTCSC3 overexpression on cell growth and activity was revealed by CCK-8 and Transwell assays. The targeting relationship between PTCSC3 and miR-182-5p was determined by bioinformatics prediction and luciferase activity. RESULTS: PTCSC3 was found to be downregulated in prostate cancer, and its low levels were associated with short overall survival in patients. It influenced the progression of prostate cancer by targeting miR-182-5p. Increasing PTCSC3 levels suppressed the proliferation, migration and invasion levels of cells, and miR-182-5p mimic counteracted PTCSC3's effects on cells. CONCLUSIONS: As a potential prognostic biological factor for prostate cancer, PTCSC3 may regulate the progression of prostate cancer by sponging miR-182-5p and affect the prognosis of patients.

The clinical application of V-Y advanced flap pedicled with freestyle perforator flap for repairing small range defects in the anterior knee region.

Introduction: This study aims to investigate the clinical efficacy of V-Y advanced flap pedicled with freestyle perforator flap for repairing small range defects in the anterior knee region. Methods: 8 patients with skin and soft tissue defect/necrosis in the anterior knee area admitted to the Changshu No.1 People's Hospital from January 2021 to January 2022 were selected, with a defect range of 4 cm × 3 cm-9 cm × 6 cm, designed a V-Y advanced flap pedicled with freestyle perforator flap to repair the wound in the anterior knee area. Adjust the size and position of the flap according to the number and position of perforating branches found during the surgery, with a cutting area of 6 cm × 5 cm-14 cm × 10 cm and the supply area was directly pulled and sutured. Results: 4 patients were repaired by flaps pedicled with 2 perforating branches, 2 patients were repaired by flaps pedicled with 1 perforating branch and 2 patients were repaired by flaps pedicled with 3 perforating branches. 4 patients were repaired by flaps pedicled with 2 perforating branches, 2 patients were repaired by flaps pedicled with 1 perforating branch and 2 patients were repaired by flaps pedicled with 3 perforating branches. All flaps survived and following up for 6-15 months, the blood supply, appearance, and color of the flap were satisfactory, and the functions of knee joint flexion and extension were well preserved. Discussion: The V-Y advancement flap pedicled with freestyle perforator flap has the advantages of reliable blood supply, simple surgical operation, texture and thickness similar to the skin of the anterior knee area, and direct suture of the donor area. It is a perforator flap with good repair effect for small scale defects in the anterior knee area.

Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

DSCAM-AS1 promotes the development of prostate cancer.

PURPOSE: The purpose of this study was to investigate the role of lncRNA DSCAM-AS1 in prostate cancer to find new therapeutic targets and promote the research progress of prostate cancer. METHODS: RT-qPCR was used to detect DSCAM-AS1 expression in prostate cancer tissues, normal tissues, human normal prostate epithelial cells (RWPE), and four prostate cancer cell lines. The clinical and prognostic role of DSCAM-AS1 was evaluated by the Kaplan-Meier curve and chi-square test. Secondly, a dual luciferase reporter gene assay was used to study the regulatory mechanism between miR-338-3p and DSCAM-AS1. Finally, the roles of DSCAM-AS1 and miR-338-3p in prostate cancer cell proliferation and metastasis were explored by CCK-8 and Transwell assays. RESULTS: It was found that DSCAM-AS1 upregulation could serve as a warning of deterioration and poor prognosis in prostate cancer patients, and that knockdown of DSCAM-AS1 expression inhibited the progression of prostate cancer cells. In addition, miR-338-3p, a target of DSCAM-AS1, was found to be down-regulated in prostate cancer cells and miR-338-3p knockdown could reverse the inhibitory effect of DSCAM-AS1 silencing on prostate cancer. CONCLUSION: DSCAM-AS1 is up-regulated in prostate cancer and regulates the progression of prostate cancer cells by targeting miR-338-3p.

Emerging roles of O-GlcNAcylation in protein trafficking and secretion.

The emerging roles of O-GlcNAcylation, a distinctive post-translational modification, are increasingly recognized for their involvement in the intricate processes of protein trafficking and secretion. This modification exerts its influence on both conventional and unconventional secretory pathways. Under healthy and stress conditions, such as during diseases, it orchestrates the transport of proteins within cells, ensuring timely delivery to their intended destinations. O-GlcNAcylation occurs on key factors, like coat protein complexes (COPI and COPII), clathrin, SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), and GRASP55 (Golgi reassembly stacking protein of 55 kDa) that control vesicle budding and fusion in anterograde and retrograde trafficking and unconventional secretion. The understanding of O-GlcNAcylation offers valuable insights into its critical functions in cellular physiology and the progression of diseases, including neurodegeneration, cancer, and metabolic disorders. In this review, we summarize and discuss the latest findings elucidating the involvement of O-GlcNAc in protein trafficking and its significance in various human disorders.

ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Single amino acid-based PROTACs trigger degradation of the oncogenic kinase BCR-ABL in chronic myeloid leukemia (CML).

Proteolysis-targeting chimera (PROTAC) that specifically targets harmful proteins for destruction by hijacking the ubiquitin-proteasome system is emerging as a potent anticancer strategy. How to efficiently modulate the target degradation remains a challenging issue. In this study, we employ a single amino acid-based PROTAC, which uses the shortest degradation signal sequence as the ligand of the N-end rule E3 ubiquitin ligases to degrade the fusion protein BCR (breakpoint cluster region)-ABL (Abelson proto-oncogene), an oncogenic kinase that drives the progression of chronic myeloid leukemia. We find that the reduction level of BCR-ABL can be easily adjusted by substituting different amino acids. Furthermore, a single PEG linker is found to achieve the best proteolytic effect. Our efforts have resulted in effective degradation of BCR-ABL protein by the N-end rule pathway and efficient growth inhibition of K562 cells expressing BCR-ABL in vitro and blunted tumor growth in a K562 xenograft tumor model in vivo. The PROTAC presented has unique advantages including lower effective concentration, smaller molecular size, and modular degradation rate. Demonstrating the efficacy of the N-end rule-based PROTACs in vitro and in vivo, our study further expands the limited degradation pathways currently available for PROTACs in vivo and is easily adapted for broader applications in targeted protein degradation.

Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway.

Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genes Heme Oxygenase-1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1), and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment.

Artificial dermis combined with split-thickness skin autograft in the treatment of hand thermal compression wounds: a single center case-control study.

Objective: To explore the clinical effect of artificial dermis combined with split-thickness skin autograft in treating hand thermal compression wounds. Methods: Forty-two patients in our hospital from January 2016 to October 2022 with thermal compression wounds were divided into two groups. The survival rate of autologous skin grafts seven days after skin grafting, the number of operations, total hospital stay, total hospitalization cost, and bacterial culture results of secretions were recorded. The visual analog scale was used to evaluate the wound pain. The condition of skin graft rupture was recorded and the scar status of the donor site was evaluated by the Vancouver Scar Scale. Results: It showed combination of artificial dermis, split-thickness skin autograft, and vacuum sealing drainage improves the treatment of hand thermal compression wounds by enhancing the survival rate of skin grafting (95.24% > 66.67%), reducing the number of operations (P < 0.001), relieving wound pain (P < 0.001), effectively controlling wound infection (4.76% < 9.52%), and reducing the skin graft rupture rate after surgery (4.8% < 28.6%). There was no evident scar hyperplasia in the donor (P = 0.003) and skin graft areas (P < 0.001), which had a good recovery of hand function (P = 0.037); however, this treatment strategy may prolong the hospital stay (P = 0.030) and increase the total hospitalization cost (P = 0.030). Conclusion: The composite transplantation of artificial dermis and split-thickness skin combined with the VSD significantly improves treatment and aesthetic outcomes in patients with thermal compression wounds to the hand, which is worth promoting and applying in clinical practice.

Evaluating the Diagnostic Potentials of Circulating Tumor DNA against Melanoma: A Systematic Review and Meta-Analysis.

Background: The accurate detection of circulating tumor (ct) DNA is affected by multiple factors, and several controversies still persists regarding clinical applications. In order to assess the consistency of ctDNA gene mutation detection findings in matched melanoma tissue samples and peripheral blood, a meta-analysis was performed and provided evidence-based analysis for its clinical applications. Method: As of May 20, 2019, the database has been searched using the Embase, PubMed, and Cochrane Library search engines. The ctDNA investigations mentioned in this review may be used to directly or indirectly get the true positive (TP), true negative (TN), false positive (FP), and false negative (FN) values of melanoma patients. To be excluded from the study are duplicate publications, research that do not offer a full text, inadequate material or an inability to extract data, and animal trials. Results: Overall, the pooled specificity, sensitivity, NLR, PLR, and DOR were 0.94 (95% CI: 0.91-0.96), 0.73 (95% CI: 0.70-0.75), 0.32 (95% CI: 0.22-0.45), 8.21 (95% CI: 4.67-14.43), and 32.72 (95% CI: 14.81-72.30), respectively. Additionally, we calculated AUC by drawing the SROC curve, and the value of AUC is 0.9287, which indicates that the accuracy of ctDNA in diagnosing melanoma is 92.87% of the gold standard. Furthermore, we conducted a subgroup analysis for different countries, sample sources, and ctDNA detection methods. The pooled results showed that different countries, sample sources, and ctDNA detection methods showed significantly large differences in terms of sensitivity of ctDNA in diagnosing melanoma, while the specificity basically remained the same. Conclusion: We discovered that the diagnostic outcomes between matched tumor samples and ctDNA remained more reliable in melanoma patients. ctDNA has the advantages of low trauma, convenient dynamic monitoring, and simple operation. ctDNA is expected to become an auxiliary method for the diagnosis of melanoma gene mutations.

GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway.

The mannose-6-phosphate (M6P) biosynthetic pathway for lysosome biogenesis has been studied for decades and is considered a well-understood topic. However, whether this pathway is regulated remains an open question. In a genome-wide CRISPR/Cas9 knockout screen, we discover TMEM251 as the first regulator of the M6P modification. Deleting TMEM251 causes mistargeting of most lysosomal enzymes due to their loss of M6P modification and accumulation of numerous undigested materials. We further demonstrate that TMEM251 localizes to the Golgi and is required for the cleavage and activity of GNPT, the enzyme that catalyzes M6P modification. In zebrafish, TMEM251 deletion leads to severe developmental defects including heart edema and skeletal dysplasia, which phenocopies Mucolipidosis Type II. Our discovery provides a mechanism for the newly discovered human disease caused by TMEM251 mutations. We name TMEM251 as GNPTAB cleavage and activity factor (GCAF) and its related disease as Mucolipidosis Type V.

Prognostic Nutritional Index as a Novel Predictor of Long-Term Prognosis in Patients with Coronary Artery Disease After Percutaneous Coronary Intervention.

BACKGROUND: The Prognostic Nutritional Index (PNI) has been reported to be correlated with long-term outcomes after gastrointestinal tumor surgery. However, to our knowledge, only a few studies have shown that the PNI is related to cardiovascular diseases. Therefore, we aimed to assess the association between the PNI and long-term outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: This was retrospective observational study. A total of 3561 patients with CAD after PCI were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients (3519) were divided into three groups according to PNI tertiles: the first tertile (PNI < 47.12, n = 1173), the second tertile (47.12 ≤ PNI < 51.50, n = 1185), and the third tertile (PNI ≥ 51.50, n = 1161). The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM).Secondary endpoints were major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs). RESULT: In our study, the incidences of ACM in the first, second, and third tertiles were 3.8%, 1.8% and 1.4%, respectively (P < 0.001). The incidences of CM occurring in the first, second, and third tertiles were 1.7%, 3.1% and 2.1%, respectively (P < 0.001).There was statistically significant different in primary endpoints incidence. MACEs occurred in 139 patients (11.8%) in the first tertile, 121 patients(11.1%) in the second tertile and 123 patients(10.8%) in the third tertile(P = 0.691). MACCEs occurred in 183 patients (15.6%) in the first tertile, 174 patients(14.7%) in the second tertile and 160 patients(13.85%) in the third tertile(P = 0.463).There was no statistically significant different in secondary endpoints incidence. Kaplan-Meier analyses showed that elevated PNI was significantly related to long-term CM (log rank, P < 0.001) and long-term ACM (log-rank, P < 0.001). Cox regression analyses suggested that compared with the patients in the first tertile, the risk of ACM was decreased to 60.9% (HR = 0.609, 95% CI: 0.398-0.932, P = 0.029) in the second tertile and 40.3%(HR = 0.403, 95% CI: 0.279-0.766, P = 0.003) in the third tertile, while the risk of CM was decreased to 58.8%(HR = 0.588, 95% CI: 0.321-0.969, P = 0.038) in the second tertile and 46.6%(HR = 0.466, 95% CI: 0.250-0.870, P = 0.017) in the third tertile. Multivariate Cox regression analyses showed that the PNI was an independent predictor of long-term ACM and CM. CONCLUSION: Our finding shown that PNI is an independent predictor in CAD patients after PCI，the higher the PNI, the less occurring adverse event. Therefore，PNI may be an new biomarker to predict long-term outcome of CAD patients after PCI.

Effects of Momordica charantia exosomes on platelet activation, adhesion, and aggregation.

The platelets play a crucial role in the progression of multiple medical conditions, such as stroke and tumor metastasis, where antiplatelet therapy may be a boon for treating these diseases. In this study, we have attempted to study the effects of extracted Momordica charantia exosomes (MCEs) on platelet activation, adhesion, and aggregation. Adult platelets isolated from healthy individuals were dose-dependently treated with MCEs (0.1, 40, and 200 µg/ml). We performed flow cytometry to detect the expression of platelet activation protein marker-activated GP IIb/IIIa (PAC-1) and P-selectin (CD62P). Platelet adhesion was analyzed through fluorescence labeling assays. The effect of MCEs on platelet-mediated cell migration of HCT116 cells was observed by transwell. Furthermore, the MCAO model of Sprague-Dawley rats was used to observe the effect of MCEs (200, 400, and 800 µg/kg) on platelet aggregation and maximum thrombotic agglutination in vivo . The results showed that 200 µg/ml MCEs exerted the most pronounced effect on platelet activation, adhesion, and aggregation. Experiments on animals showed that MCEs significantly inhibited platelet aggregation and attenuated the maximum thrombus agglutination. We concluded that MCEs inhibited platelet activation, adhesion, aggregation, and platelet-mediated migration of HCT116 cells, indicating the potential role MCEs may play in the treatment of stroke and tumor metastasis.

Adaptor-Specific Antibody Fragment Inhibitors for the Intracellular Modulation of p97 (VCP) Protein-Protein Interactions.

Protein-protein interactions (PPIs) form complex networks to drive cellular signaling and cellular functions. Precise modulation of a target PPI helps explain the role of the PPI in cellular events and possesses therapeutic potential. For example, valosin-containing protein (VCP/p97) is a hub protein that interacts with more than 30 adaptor proteins involved in various cellular functions. However, the role of each p97 PPI during the relevant cellular event is underexplored. The development of small-molecule PPI modulators remains challenging due to a lack of grooves and pockets in the relatively large PPI interface and the fact that a common binding groove in p97 binds to multiple adaptors. Here, we report an antibody fragment-based modulator for the PPI between p97 and its adaptor protein NSFL1C (p47). We engineered these antibody modulators by phage display against the p97-interacting domain of p47 and minimizing binding to other p97 adaptors. The selected antibody fragment modulators specifically disrupt the intracellular p97/p47 interaction. The potential of this antibody platform to develop PPI inhibitors in therapeutic applications was demonstrated through the inhibition of Golgi reassembly, which requires the p97/p47 interaction. This study presents a unique approach to modulate specific intracellular PPIs using engineered antibody fragments, demonstrating a method to dissect the function of a PPI within a convoluted PPI network.

The PRMT5-LSD1 axis confers Slug dual transcriptional activities and promotes breast cancer progression.

BACKGROUND: Downregulation of epithelial markers and upregulation of mesenchymal markers are the characteristics of the epithelial to mesenchymal transition (EMT) program, which provides the metastatic advantage of breast cancer. However, the mechanism underlying the switch of EMT markers remains poorly understood. METHODS: In this study, we used the affinity purification and mass spectrometry coupled approach to identify the interactome of Slug. CoIP, GST-pulldown, ChIP, Re-ChIP, qPCR and Immunoblot were used to investigate the underlying mechanism of Slug-PRMT5-LSD1 complex. The role of PRMT5 and LSD1 in breast cancer progression was evaluated both in vivo and in vitro. RESULTS: Here we found that the transcription factor Slug associates with PRMT5 and LSD1 in a complex and facilitates the breast cancer invasion in vitro. Mechanistically, PRMT5 and LSD1 work with Slug to exert dual transcriptional activities to inhibit E-cadherin expression by PRMT5-catalyzed H4R3me2s and LSD1-mediated demethylation of H3K4me2 on the E-cadherin (CDH1) promoter, and activate vimentin (VIM) expression via PRMT5-driven H3R2me2s and LSD1-mediated removal of H3K9me2. Importantly, PRMT5 and LSD1 are coordinately expressed in breast cancer patients and pharmacologic perturbation of both PRMT5 and LSD1 shows a synergetic effect on the inhibition of breast tumor growth and metastasis in vivo. CONCLUSIONS: Our study suggests that PRMT5 and LSD1 function as a dual epigenetic modifier to promote Slug induced EMT program, suggesting that the inhibition of PRMT5 and LSD1 presents a potential therapeutic strategy against cancer metastasis.

Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro.

Background: The incidence of cutaneous squamous cell carcinoma (CSCC), a malignant tumor that threatens human life, is increasing every year, and yet its pathogenesis is still unclear. This study found that long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) was abnormally expressed in CSCC. However, the biochemical mechanisms of lncRNA NEAT1 in carcinogenesis and the development of cancer remain unclear. Methods: Fluorescence quantitative polymerase chain reaction (qPCR) was conducted to determine lncRNA NEAT1 expression in CSCC and paracarcinoma tissues and investigate the correlation between NEAT1 levels and patients' clinicopathological features. The invasion, proliferation, and migration of CSCC cells were measured using colony formation, Cell Counting Kit-8, and Transwell assays. Western blot assay was conducted to test whether NEAT1 knockdown affected invasion and migration-related proteins. In addition, a nude mouse subcutaneous tumorigenesis experiment was performed to determine whether the knockdown of NEAT1 affected the proliferation ability of CSCC cells. Results: Changes in lncRNA NEAT1 expression in CSCC tissues were correlated with the degree of lymph node metastasis and the tumor, regional lymph nodes, and distant metastasis (TNM) grade of patients. The downregulation of NEAT1 lncRNA significantly impeded cell invasion, proliferation, and migration in CSCC. Through lncRNA NEAT1 knockdown, significant reductions in metalloproteinase-2, metalloproteinase-9, N-cadherin, and vimentin expression were observed, and the level of E-cadherin increased. In vivo experiments in nude mice revealed that knockdown of lncRNA NEAT1 greatly inhibited cell proliferation in CSCC. Conclusions: In CSCC tissues, NEAT1 lncRNA was expressed at high levels and correlated with lymph node metastasis and TNM stage. The knockdown of NEAT1 lncRNA could significantly impede CSCC proliferation, metastasis, and invasion. Additionally, by measuring the expression level of lncRNA NEAT1, we may be able to detect the clinical and pathological characteristics of CSCC.

Exosomes as a messager to regulate the crosstalk between macrophages and cardiomyocytes under hypoxia conditions.

Recent studies have confirmed that cardiomyocyte-derived exosomes have many pivotal biological functions, like influencing the progress of coronary artery disease via modulating macrophage phenotypes. However, the mechanisms underlying the crosstalk between cardiomyocytes and macrophages have not been fully characterized. Hence, this study aimed to observe the interaction between cardiomyocytes under hypoxia and macrophages through exosome communication and further evaluate the ability of exosomes derived from cardiomyocytes cultured under hypoxic conditions (Hypo-Exo) to polarize macrophages, and the effect of alternatively activated macrophages (M2) on hypoxic cardiomyocytes. Our results revealed that hypoxia facilitated the production of transforming growth factor-beta (TGF-ß) in H9c2 cell-derived exosomes. Moreover, exosomes derived from cardiomyocytes cultured under normal conditions (Nor-Exo) and Hypo-Exo could induce RAW264.7 cells into classically activated macrophages (M1) and M2 macrophages respectively. Likewise, macrophage activation was induced by circulating exosomes isolated from normal human controls (hNor-Exo) or patients with acute myocardial infarction (hAMI-Exo). Thus, our findings support that the profiles of hAMI-Exo have been changed, which could regulate the polarization of macrophages and subsequently the polarized M2 macrophages reduced the apoptosis of cardiomyocytes in return. Based on our findings, we speculate that exosomes have emerged as important inflammatory response modulators regulating cardiac oxidative stress injury.

ADS Score as a Novel Predictor of Outcomes in Patients Who Underwent Percutaneous Coronary Intervention.

Objectives: A novel AFR- albumin-derived neutrophil to lymphocyte ratio (dNLR) score (ADS) were reported to associate with clinical outcome in various malignancies, However, the relation between the ADS score and outcomes in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) has not been investigated. Methods: Three thousand five hundred and sixty-one patients were divided into two groups according to ADS score: low group (ADS score <2; n = 2,682) and high group (ADS score ≥ 2; n = 879). Overall, there were 133 all-cause mortality (ACM) during the following up. The incidence of ACM in the low group is 2.7% (72/2,682) and high group is 6.9% (61/879). The ACM incidence was significantly higher in high group compared to that in the low group (P < 0.001). Cardiac mortality (CM) occurred in 82 patients: 44(1.6%) in the low group and 38 (4.3%) in the high group. There was significant difference in the CM incidence between the low group and high group (P < 0.001). Major adverse cardiac and cerebrovascular events (MACCE) occurred in 520 patients: 366 (13.6%) in the low group and 154 (17.5%) in the high group. There was significant difference in the MACCE incidence between the low group and high group (P = 0.005). Major adverse cardiac and events (MACE) occurred in 395 patients: 281(10.5%) in the low group and 114 (13.0%) in the high group. There was significant difference in the MACE incidence between the low group and high group (P = 0.041). The multivariate Cox proportional hazards model showed that ADS score was independently correlated with the ACM [adjusted HR = 2.031 (1.357-3.039), P = 0.001]; CM [adjusted HR = 1.883 (1.127-3.147), P = 0.016]; MACCE [adjusted HR = 1.352 (1.096-1.668), P = 0.005], and MACE [adjusted HR = 1.260 (0.987-1.608), P = 0.063]. Conclusion: The present study indicated that the ADS score was associated with long-term mortality, the MACCE, and the MACE in CAD patients underwent PCI.

RGB Three-Channel SWE-Based Ultrasomics Model: Improving the Efficiency in Differentiating Focal Liver Lesions.

OBJECTIVE: To explore a new method for color image analysis of ultrasomics and investigate the efficiency in differentiating focal liver lesions (FLLs) by Red, Green, and Blue (RGB) three-channel SWE-based ultrasomics model. METHODS: One hundred thirty FLLs were randomly divided into training set (n = 65) and validation set (n = 65). The RGB three-channel and direct conversion methods were applied to the same color SWE images. Ultrasomics features were extracted from the preprocessing images establishing two feature data sets. The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied for feature selection and model construction. Two models, named RGB model (based on RGB three-channel conversion) and direct model (based on direct conversion), were used to differentiate FLLs. The diagnosis performance of the two models was evaluated by area under the curve (AUC), calibration curves, decision curves, and net reclassification index (NRI). RESULTS: In the validation cohort, the AUC of the direct model and RGB model in characterization on FLLs were 0.813 and 0.926, respectively (p = 0.038). Calibration curves and decision curves indicated that the RGB model had better calibration efficiency and provided greater clinical benefits. NRI revealed that the RGB model correctly reclassified 7% of malignant cases and 25% of benign cases compared to the direct model (p = 0.01). CONCLUSION: The RGB model generated by RGB three-channel method yielded better diagnostic efficiency than the direct model established by direct conversion method. The RGB three-channel method may be promising on ultrasomics analysis of color images in clinical application.