Severe COVID-19 post pregnancy complicated by acute thromboemboli resulting in ST-elevation myocardial infarction - A case report.

Introduction: It has been shown that pregnancy can cause alterations in the severity of COVID-19 infection. We demonstrate an immediate post-partum patient diagnosed with severe COVID-19 and subsequently developed acute thrombosis of coronary artery.Case Summary: 35-year-old female unvaccinated for COVID-19 presented in labor and delivered on the same day. Several hours later, she was found to be in respiratory distress and tested positive for COVID-19. On day 7, computerized tomography (CT) of chest revealed bilateral pneumonia and pneumomediastinum. On day 8, she developed chest pain with electrocardiogram (EKG) showing inferior STelevations with troponin I of 0.6 ng/mL. She was intubated for airway protection and emergent diagnostic angiogram revealed thrombus occlusion of the third right posterolateral segment that resulted in thrombolysis in myocardial infarction (TIMI) 0 flow without evidence of underlying atherosclerotic disease in the remaining vessels. Intracoronary IIb/IIIa inhibitor was administered. Arterial blood gas in the lab revealed profound hypoxia despite being on 100% inspired oxygen. Multidisciplinary decision was made to cannulate patient for venovenous extracorporeal membrane oxygenation (ECMO) to treat severe COVID-19 pneumonia. She was finally decannulated from ECMO on day 65. After prolonged hospital stay, she eventually recovered and was discharged to rehabilitation.Conclusions: The center for disease control (CDC) surveillance has reported that pregnant patients with COVID-19 are more likely to require invasive ventilation and ECMO, and die given the immunological changes during pregnancy. Hypercoagulable state caused by combination of pregnancy and COVID-19 resulting in coronary thrombosis is rarely described in literature, our case demonstrated the paucity of this phenomenon.

Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice.

Although neuronal Toll-like receptors (TLRs) (e.g., TLR2, TLR3, and TLR7) have been implicated in itch sensation, the roles of keratinocyte TLRs in chronic itch are elusive. Herein, we evaluated the roles of keratinocyte TLR2 and TLR7 in chronic itch under dry skin and psoriasis conditions, which was induced by either acetone-ether-water treatment or 5% imiquimod cream in mice, respectively. We found that TLR2 and TLR7 signaling were significantly upregulated in dry skin and psoriatic skin in mice. Chronic itch and epidermal hyperplasia induced by dry skin or psoriasis were comparably reduced in TLR2 and TLR7 knockout mice. In the dry skin model, the enhanced messenger RNA (mRNA) expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, TNF-α, and IFN-γ were inhibited in TLR2-/- mice, while CXCL2, IL-31, and IL-6 were inhibited in TLR7-/- mice. In psoriasis model, the enhanced mRNA expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, and TNF-α were inhibited in TLR2-/- mice, while CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, and TNF-α were inhibited in TLR7-/- mice. Incubation with Staphylococcus aureus (S. aureus) peptidoglycan (PGN-SA) (a TLR2 agonist), imiquimod (a TLR7 agonist), and miR142-3p (a putative TLR7 agonist) were sufficient to upregulate the expression of pruritic cytokines or chemokines in cultured keratinocyte HaCaT cells. Finally, pharmacological blockade of C-X-C Motif Chemokine Receptor 1/2 and high mobility group box protein 1 dose-dependently attenuated acute and chronic itch in mice. Together, these results indicate that keratinocyte TLR2 and TLR7 signaling pathways are distinctly involved in the pathogenesis of chronic itch.

Extracellular vesicles derived from human bone marrow mesenchymal stem cells protect rats against acute myocardial infarction-induced heart failure.

Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stem cells (BMSCs) are suggested to promote angiogenesis in a rat model of acute myocardial infarction (AMI). This study aimed to explore the underlying mechanism of BMSCs-EVs in AMI-induced heart failure (HF). BMSCs were isolated and verified, and EVs were purified and identified. After establishment of AMI-induced HF models, rats were treated with BMSCs-EVs and/or overexpressing (ov)/knocking down (kd) bone morphogenetic protein 2 (BMP2). Cardiac function, myocardial histopathological changes, angiogenesis, and vascular regeneration density were measured. Levels of pro-angiogenesis factors and cardiomyocyte apoptosis were detected. The viability and angiogenesis of hypoxic human umbilical vein endothelial cells (HUVECs) were measured. After BMSCs-EV treatment, the cardiac function of HF rats was improved, myocardial fibrosis and inflammatory cell infiltration were decreased, angiogenesis was increased, and cardiomyocyte apoptosis was inhibited. BMP2 was significantly upregulated in the myocardium. Ov-BMP2-BMSCs-EVs alleviated myocardial fibrosis and inflammatory cell infiltration, and promoted angiogenesis of HF rats, and improved the activity and angiogenesis of hypoxic HUVECs, while kd-BMP2-BMSCs-EVs showed limited protection against AMI-induced HF. BMSCs-EVs deliver BMP2 to promote angiogenesis and improve cardiac function of HF rats.

Melatonin alleviates doxorubicin-induced mitochondrial oxidative damage and ferroptosis in cardiomyocytes by regulating YAP expression.

Doxorubicin (Dox) is a high-efficiency agent for cancer therapy. However, it causes cardiotoxicity which limits its clinical application. Despite more efforts has been made to seek protective decisions, unfortunately, the poor prognosis suggests the need for new treatments. As a powerful mitochondrial antioxidant, melatonin (Mel) has been found to confer cardioprotection against various cardiovascular diseases. Currently, the mechanism through which Mel confers protection is not well understood. In this study, we established a Dox-induced cardiotoxicity model in H9c2 cardiomyocytes, zebrafish, and SD rats to explore the mechanism by which Mel alleviates Dox-induced cardiotoxicity. In vivo and in vitro experiments showed that Dox significantly decreased the viability of H9c2 cells, induced apoptosis, myocardial injury, and effectively up-regulated the expression of p-YAP but down-regulated the expression of YAP. Furthermore, we found that Dox significantly up-regulated the expression of ferroptosis-associated protein ACSL4 and down-regulated expression of GPX4. Interestingly, these effects of Dox were reversed following treatment with Mel, indicating that ferroptosis mediated the protective effects of Mel against Dox-induced cardiomyocyte injury. Furthermore, we used YAP-siRNA in vitro and verteporfin (Ver) in vivo to down-regulate the expression level of YAP. The results showed that YAP down-regulation abolished the protective effects of Mel including apoptosis, mitochondrial lipid peroxidation, and ferroptosis. Collectively, these results show that Mel regulates ferroptosis by modulating YAP expression to counteract Dox-induced cardiotoxicity.

Silenced long non-coding RNA activated by DNA damage elevates microRNA-495-3p to suppress atherosclerotic plaque formation via reducing Krüppel-like factor 5.

OBJECTIVE: Atherosclerosis (AS) is an inflammatory disease and the formation of atherosclerotic plaque plays a critical role in AS progression. We aimed to investigate the effect of long non-coding RNA (lncRNA) activated by DNA damage (NORAD)/microRNA-495-3p (miR-495-3p)/Krüppel-like factor 5 (KLF5) axis on atherosclerotic plaque formation. METHODS: The ApoE-/- mice were fed a high-fat diet to construct AS mouse models and the modeled mice were treated with altered NORAD, miR-495-3p or KLF5. NORAD, miR-495-3p and KLF5 expression in mouse aorta tissues were evaluated, and the levels of inflammatory factors, oxidative stress factors, endothelial function indices and blood lipid in mice were all determined. The atherosclerotic plaque area, lipid deposition area, collagen fibers and CD68 expression in mouse aorta tissues were assessed. The regulatory relation between NORAD and miR-495-3p, and the target relation between miR-495-3p and KLF5 were confirmed. RESULTS: NORAD and KLF5 were increased whereas miR-495-3p was decreased in atherosclerotic mouse aortas. Inhibited NORAD or elevated miR-495-3p suppressed inflammation, oxidative stress, endothelial dysfunction, blood lipid level, atherosclerotic plaque area, collagen fibers and CD68 expression in atherosclerotic mouse aortas. Effects of elevated miR-495-3p on atherosclerotic mice could be reversed by up-regulation of KLF5. NORAD served as a sponge of miR-495-3p and miR-495-3p directly targeted KLF5. CONCLUSION: Silenced NORAD elevated miR-495-3p to suppress atherosclerotic plaque formation via reducing KLF5. Findings in our research may be helpful for exploring molecular mechanisms of AS.

Anxiety and depression and their interdependent influencing factors among medical students in Inner Mongolia: the cross-sectional survey.

BACKGROUND: Mental health has become a global problem, among which anxiety and depression disorder were ranked as the first and sixth leading causes of disability, respectively, according to the World Health Organization (WHO). Medical students experienced higher levels of anxiety and depression than the general population. But there was a lack of research on the emotional situation among medical students in Inner Mongolia. The main objectives of this study were to investigate the prevalence of anxiety and depression symptoms as well as the factors that influence them among medical students in Inner Mongolia. METHODS: A cross-sectional study was conducted on 1282 students from a university in Inner Mongolia, China, ranging in age from 16 to 27 years. They were assessed demographic indicators, the disorder of anxiety and depression using Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale (SAS and SDS) by an anonymous, self-administered questionnaire. The internal reliability and validity of the questionnaire were determined using Cronbach's alpha coefficient, Kaiser-Meyer-Olkin (KMO), and Bartlett's sphericity. T-tests and one-way ANOVA were used to explore factors, including demographic and behavioral information influencing anxiety and depression disorder. According to the above results of exploring the influencing factors based on univariate analysis, significant factors (p < 0.05) were entered into multiple linear regressions that sequentially fitted to predictors associated with anxiety and depression. The collected data were entered into EpiData for windows and analyzed using SPSS 26.0. The p < 0.05 was considered to be significantly different. RESULTS: The questionnaire was completed by 1187 students with a 92.59% response rate. The prevalence of anxiety and depression symptoms among medical students were 10.36% and 24.43%, and the mean ± standard deviation (M ± SD) anxiety and depression scores were 39.60 ± 7.81 and 48.23 ± 9.06, respectively, among the medical students. The specific contributions of the two scales with good reliability and validity were 60.58% and 63.59%, respectively. For univariate analysis, age, whether the daily meal was at a fixed time, grade, the birthplace of students, average daily eating habits, were the factors that influenced both the total score of SAS and SDS (p < 0.05). For further analysis, the results showed that "Birthplace of students" and "Whether daily meals at a fixed time" were significantly associated with anxiety and depression. Furthermore, "Age" and "Mode of delivery" were independent risk factors for depressive disorder. CONCLUSION: Our findings revealed that high prevalence of mental health problems among medical students in Inner Mongolia. The Ministry of Medical Education should make a targeted intervention for specific risk factors of this study to improve psychological well-being and face uncertain future challenges among university students in Inner Mongolia.

Molecular basis of cross-resistance to acetohydroxy acid synthase-inhibiting herbicides in Sagittaria trifolia L.

Acetohydroxy acid synthase (AHAS)-inhibiting herbicides are one of the most commonly used herbicides for controlling the growth of Sagittaria trifolia L. in paddy fields in Northeastern China. In this study, we collected five suspected resistant populations of S. trifolia (R1-R5) from three different provinces of Northeastern China. The results of whole-plant bioassays revealed that those populations showed high level of resistance to bensulfuron-methyl with resistance index (GR50 R/S) ranging from 39.90 to 88.50. The results of AHAS-activity assays were consistent with the results of the whole-plant bioassays. The AHAS gene analysis showed that R2 and R3 populations contained Pro-197-Leu mutations that were highly resistant to penoxsulam; R1 and R4 populations contained Pro-197-Ser mutations that were highly resistant to bispyribac­sodium; R5 population contained Trp-574-Leu mutation that showed high resistance to IMI, PT, PTB and SU herbicides. The AHAS with resistance mutations showed less sensitivity to feedback inhibition by BCAAs and R genotypes had increased free BCAAs.

Non-target-site resistance to ALS-inhibiting herbicides in a Sagittaria trifolia L. population.

Sagittaria trifolia L. is one of the most competitive weeds in rice fields in northeastern China. The continuous use of acetolactate synthase (ALS)-inhibitors has led to the evolution of herbicide resistant S. trifolia. A subpopulation BC1, which was derived from the L1 population, was analyzed using DNA sequencing and ALS enzyme activity assays and levels of resistance to five ALS-inhibiting herbicides was determined. DNA sequencing and ALS enzyme assays revealed no amino acid substitutions and no significant differences in enzyme sensitivity between susceptible and resistant populations. Whole-plant dose-response experiments showed that the BC1 population exhibited different levels of resistance (resistance ratios ranging from 2.14 to 51.53) to five ALS herbicides, and the addition of malathion (P450 inhibitor) to bensulfuron-methyl, penoxsulam and bispyribac-sodium strongly reduced the dry weight accumulation of the BC1 population compared with the effects of the three herbicides alone. The results of the present study demonstrated that the BC1 population has evolved non-target-site resistance to ALS-inhibiting herbicides.

Sensing patches for biomarker identification in skin-derived biofluids.

In conventional clinical disease diagnosis and screening based on biomarker detection, most analysis samples are collected from serum, blood. However, these invasive collection methods require specific instruments, professionals, and may lead to infection risks. Additionally, the diagnosis process suffers from untimely results. The identification of skin-related biomarkers plays an unprecedented role in early disease diagnosis. More importantly, these skin-mediated approaches for collecting biomarker-containing biofluid samples are noninvasive or minimally invasive, which is more preferable for point-of-care testing (POCT). Therefore, skin-based biomarker detection patches have been promoted, owing to their unique advantages, such as simple fabrication, desirable transdermal properties and no requirements for professional medical staff. Currently, the skin biomarkers extracted from sweat, interstitial fluid (ISF) and wound exudate, are achieved with wearable sweat patches, transdermal MN patches, and wound patches, respectively. In this review, we detail these three types of skin patches in biofluids collection and diseases-related biomarkers identification. Patch classification and the corresponding manufacturing as well as detection strategies are also summarized. The remaining challenges in clinical applications and current issues in accurate detection are discussed for further advancement of this technology (Scheme 1).

The HPE1 RNA-binding protein modulates chloroplast RNA editing to promote photosynthesis under cold stress in Arabidopsis.

Cold stress has severe negative consequences for plant growth and crop yield. Here, we report that an Arabidopsis thaliana mutant that lacks the HPE1 gene, which encodes an RNA-binding protein, maintains higher photosynthetic activity under cold stress, together with higher accumulation of thylakoid proteins. We showed that HPE1 interacts with MORF2 and MORF9 and thereby mediates RNA editing in chloroplasts. Loss of HPE1 function increased the editing efficiency at four RNA editing sites, rpoC-488, ndhB-149, ndhB-746 and matK-706, under cold stress and altered the expression of nuclear photosynthesis-related genes and cold-responsive genes. We propose that HPE1-mediated RNA editing acts as a trigger for retrograde signaling that affects photosynthesis under cold stress.

Microgel-Modified Bilayered Hydrogels Dramatically Boosting Load-Bearing and Lubrication.

Hydrogel-based articular cartilage replacement materials are promising candidates for their potential to provide both high load-bearing capacity and low friction performance, similar to natural cartilage. Nevertheless, the design of these materials presents a significant challenge in reconciling the conflicting demands of the load-bearing capacity and lubrication. Despite extensive research in this area, there is still room for improvement in the creation of hydrogel-based materials that effectively meet these demands. Herein, a facile strategy is provided to realize simultaneously high load-bearing and low friction properties on the proposed hydrogel by modifying the surface of mechanically strong annealled PVA-PAAc hydrogel with a high hydration potential PAAm-co-PAMPS microgel. Consequently, a bilayer hydrogel with a porous surface and a compact substrate has been obtained. Compressive experiments confirmed that the bilayer hydrogel exhibited excellent mechanical strength with a compressive strength of 32.23 MPa at 90% strain. A high load-bearing (applied load up to 30 N), extremely low friction coefficiency (0.01-0.05) and excellent wear resistance (COF low to 0.03 after a 4 h test at 10 N using a steel ball as the contact pair) are successfully achieved. These findings provide new perspectives for the design of articular cartilage materials.

A Case of Complex Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction Caused by Extension of Type A Aortic Dissection into the Left Main Coronary Artery.

Aortic dissection extending into the left main coronary artery is rare and carries high mortality, especially when resulting in extensive myocardial infarction. Here we report a case of retrograde extension of type A aortic dissection into the left main coronary artery causing ST-segment elevation myocardial infarction managed by complex percutaneous coronary intervention, which resulted in temporary stabilization of the patient. We briefly review current literature on this approach.

Oxymatrine attenuated isoproterenol-induced heart failure via the TLR4/NF-κB and MAPK pathways in vivo and in vitro.

Oxymatrine (OMT) is a quinoline alkaloid isolated from the root of the Sophora flavescens that has a variety of biological activities. However, the effect and potential mechanism of OMT on isoproterenol (ISO)-induced heart failure (HF) are not clear. In this study, we found that OMT improved the survival of HL-1 cells induced by ISO. We also demonstrated that OMT significantly inhibited the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). OMT decreased the levels of the TLR4 and reduced the phosphorylation levels of nuclear factor-κB (NF-κB) inhibitor (IκB), p65, c-Jun N-terminal kinases (JNK) and p38. The inhibitory effect of the TLR4 inhibitor TAK242 on HL-1 cells was evaluated. The results showed that the effect of OMT on the phosphorylation levels of IκBα and p65 was enhanced in HL-1 cells treated with TAK242. Using animal models, OMT significantly reduced ISO-induced cardiac injury, myocardial necrosis, interstitial edema, and fibrosis. In addition, OMT attenuated TNF-α and IL-6 and inhibited the expression of TLR4/NF-κB and MAPK pathway-related proteins. This finding suggests that OMT may alleviate HF by interfering with the TLR4/NF-κB and MAPK pathways.

Comparative clinical-related outcomes of Chinese patent medicines for cardiac hypertrophy: A systematic review and network meta-analysis of randomized clinical trials.

Background: Persistent pathological cardiac hypertrophy has been associated with increased risk of heart failure and even sudden death. Multiple Chinese patent medicines (CPMs) have gained attention as alternative and complementary remedies due to their high efficiency and few side effects. However, the effects of CPM-related treatment regimens for cardiac hypertrophy had not been systematically evaluated. Aim: The objective of this study was to estimate and compare the effectiveness of different mechanisms of CPMs to improve clinical outcomes, including clinical efficacy and echocardiographic indices, in the treatment of cardiac hypertrophy patents. Methods: A network meta-analysis was conducted on CPM-related randomized controlled trials (RCTs) published between 2012 and 2022 involving cardiac hypertrophy patients from four foreign and four Chinese databases. The outcomes concerned efficacy and related indicators, including echocardiographic indices, cardiac biomarkers, and functional exercise capacity, which were evaluated as odds ratios, mean differences, and 95% credible intervals. Network plots, league tables, surface-under-the-cumulative ranking (SUCRA), and funnel plots were created for each outcome, and all analyses were conducted using Stata 16.0 software. Results: A total of 25 RCTs were evaluated; these involved 2395 patients in a network meta-analysis (NMA). The results from existing evidence indicate that blood-activating and stasis-removing Chinese patent medicine (BASR-CPM) + Western medicine (WM) showed a good improvement in clinical efficacy (OR = 8.27; 95%CI = 0.97, 70.73). A combined treatment regimen of CPM with a function of qi-replenishing, blood-activating and stasis-removing, and Western medicine was an effective treatment regimen for echocardiographic indices such as decreasing left ventricular end-systolic dimension (LVESD) (SMD = -2.35; 95%CI = -3.09, -1.62) and left ventricular mass index (LVMI) (SMD = -1.73; 95%CI = -2.92, -0.54). Furthermore, KWYR-CPM + WM and BASR-CPM also showed good improvement for echocardiographic indices of LVEDD (SMD = -1.84; 95%CI = -3.46, -0.22) and left ventricular ejection fraction (SMD = 1.90; 95%CI = -0.46, -3.35), respectively. Conclusion: The study showed that BASR-CPM + WM may be the potentially superior treatment regimen for improving clinical efficacy among cardiac hypertrophy patients. QR&BASR-CPM + WM might be the optimal treatment for decreasing LVESD and LVMI. However, due to potential risks from bias and limited RCTs, further studies with larger samples and high-quality RCTs are needed to support these findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329589],identifier [CRD42022329589].

Eco-friendly photothermal hydrogel evaporator for efficient solar-driven water purification.

The field of solar vapor generation has developed rapidly in recent years, but achieving the goals of a high evaporation rate, eco-friendliness and rapid preparation with low-cost raw materials is still a challenge. In this work, a type of photothermal hydrogel evaporator was prepared by blending eco-friendly poly(vinyl alcohol), agarose, Fe3+ and tannic acid (TA) together, in which the tannic acid-ferric ion (TA*Fe3+) complexes served as photothermal materials and effective gelators. The results indicate that the TA*Fe3+ complex exhibits excellent gelatinization ability and light-absorption performance, which leads to a compressive stress of 0.98 MPa at 80% strain and up to 85% light absorption ratio in the photothermal hydrogel. For interfacial evaporation, a high rate of 1.897 ± 0.11 kg·m-2·h-1 corresponding to an energy efficiency of 89.7 ± 2.73% under 1 sun irradiation is achieved. Moreover, the hydrogel evaporator exhibits high stability in a 12-hour test and a 20-cycle test without a decline in evaporation performance. The outdoor testing results show that the hydrogel evaporator can achieve an evaporation rate of > 0.70 kg/m2 and effectively purify wastewater treatment and seawater desalination.

Defining levels of care in cardiogenic shock.

Background: Expert opinion and professional society statements have called for multi-tier care systems for the management of cardiogenic shock (CS). However, little is known about how to pragmatically define centers with different levels of care (LOC) for CS. Methods: Eleven of 23 hospitals within our healthcare system sharing a common electronic health record were classified as different LOC according to their highest mechanical circulatory support (MCS) capabilities: Level 1 (L-1)-durable left ventricular assist device, Level 1A (L-1A)-extracorporeal membrane oxygenation, Level 2 (L-2)-intra-aortic balloon pump and percutaneous ventricular assist device; and Level 3 (L-3)-no MCS. All adult patients treated for CS (International Classification of Diseases, ICD-10 code R57.0) between 2016 and 2022 were included. Etiologies of CS were identified using associated diagnostic codes. Management strategies and outcomes across LOC were compared. Results: Higher LOC centers had higher volumes: L-1 (n = 1): 2,831 patients, L-1A (n = 4): 3,452, L-2 (n = 1): 340, and L-3 (n = 5): 780. Emergency room admissions were more common in lower LOC (96% at L-3 vs. 46% L-1; p < 0.001), while hospital transfers were predominant at higher LOC (40% at L-1 vs. 2.7% at L-3; p < 0.001). Men comprised 61% of the cohort. Patients were younger in the higher LOC [69 (60-78) years at L-1 vs. 77 (67-85) years at L-3; p < 0.001]. Patients with acute myocardial infarction (AMI)-CS and acute heart failure (AHF)-CS were concentrated in higher LOC centers while other etiologies of CS were more common in L-2 and L-3 (p < 0.001). Cardiac arrest on admission was more prevalent in lower LOC centers (L-1: 2.8% vs. L-3: 12.1%; p < 0.001). Patients with AMI-CS received more percutaneous coronary intervention in lower LOC (51% L-2 vs. 29% L-1; p < 0.01) but more coronary arterial bypass graft surgery at higher LOC (L-1: 42% vs. L-1A: 23%; p < 0.001). MCS use was consistent across levels for AMI-CS but was more frequent in higher LOC for AHF-CS patients (L-1: 28% vs. L-2: 10%; p < 0.001). Despite increasing in-hospital mortality with decreasing LOC, no significant difference was seen after multivariable adjustment. Conclusion: This is the first report describing a pragmatic classification of LOC for CS which, based on MCS capabilities, can discriminate between centers with distinct demographics, practice patterns, and outcomes. This classification may serve as the basis for future research and the creation of CS systems of care.

CircUBR5 acts as a ceRNA for miR-1179 to up-regulate UBR5 and to promote malignancy of triple-negative breast cancer.

UBR5 is an E3 ubiquitin ligase and an oncogene in a panel of human cancers. However, little is known on its impacts in triple-negative breast cancer (TNBC) and even less on its relationship to circUBR5 (hsa_circ_0001819), a circular RNA derived from exons 2, 3, 4, and 5 of UBR5 gene. In this study, we detected higher expressions of both circUBR5 and UBR5 in TNBC tissues, which were associated with worse prognosis, and also in a panel of breast cancer cells, particularly in TNBC cells. Functionally, circUBR5 was crucial for sustaining the malignant growth and metastasis of TNBC cells both in vitro and in vivo. Mechanistically, the oncogenic phenotypes of circUBC5 were mediated through sponging miR-1179 and up-regulating UBR5. Concomitant silencing circUBR5 and miR-1179 abolished the anti-tumor effects of targeting circUBR5 alone. Therefore, targeting circUBR5/miR-1179/UBR5 axis may benefit the treatment of TNBCs.

Long non-coding RNA Sox2OT promotes coronary microembolization-induced myocardial injury by mediating pyroptosis.

OBJECTIVE: As a common complication of coronary microembolization (CME), myocardial injury (MI) implies high mortality. Long non-coding RNAs (lncRNAs) are rarely studied in CME-induced MI. Herein, this study intended to evaluate the role of lncRNA Sox2 overlapping transcript (Sox2OT) in CME-induced MI. METHODS: The CME rat models were successfully established by injection of microemboli. Rat cardiac functions and MI were observed by ultrasonic electrocardiogram, HE staining, and HBFP staining. Functional assays were utilized to test the inflammatory responses, oxidative stress, and pyroptosis using reverse transcription quantitative polymerase chain reaction, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. Dual-luciferase reporter gene assay and RNA immunoprecipitation were conducted to clarify the targeting relations between Sox2OT and microRNA (miRNA)-23b and between miR-23b and toll-like receptor 4 (TLR4). RESULTS: Rat CME disrupted the cardiac functions and induced inflammatory responses and oxidative stress, and activated the nuclear factor-kappa B (NF-κB) pathway and pyroptosis (all P < 0.05). An NF-κB inhibitor downregulated the NF-κB pathway, reduced pyroptosis, and relieved cardiomyocyte injury and pyroptosis. Compared with the sham group (1.05 ± 0.32), lncRNA Sox2OT level (4.41 ± 0.67) in the CME group was elevated (P < 0.05). Sox2OT acted as a competitive endogenous RNA (ceRNA) of miR-23b to regulate TLR4. Silencing of Sox2OT favoured miR-23b binding to 3'UTR of TLR4 mRNA leading to suppressed TLR4-mediated NFKB signalling and pyroptosis in myocardial tissues harvested from CME rat models. In addition, miR-23b overexpression could supplement the cytosolic miR-23b reserves to target TLR-4 and partially reverse Sox2OT-mediated pyroptosis in LPS-treated H9C2 cells. CONCLUSIONS: This study supported that silencing Sox2OT inhibited CME-induced MI by eliminating Sox2OT/miR-23b binding and down-regulating the TLR4/NF-κB pathway. This investigation may provide novel insights for the treatment of CME-induced MI.