ENO1 regulates IL-1ß-induced chondrocyte inflammation, apoptosis and matrix degradation possibly through the potential binding to CRLF1.

In this study, we aim to investigate the role of enolase 1 (ENO1) in osteoarthritis (OA) pathogenic process and to uncover the underlying mechanism. To this end, we used IL-1ß to induce an in vitro OA­like chondrocyte model in human immortalized chondrocyte C-28/I2 cells. We manipulated the expression of ENO1 and cytokine receptor-like factor 1 (CRLF1) in IL-1ß-induced C-28/I2 cells using siRNA and/or overexpression and tested their effects on IL-1ß-induced pathologies including cell viability, apoptosis and inflammatory cytokine levels (IL-6 and TNF-α), and the expression of extracellular matrix-related enzymes and major mediators in the NF-κB signaling pathway (p-p65, p65, p-IκBα and IκBα). We used co-immunoprecipitation and immunofluorescence imaging to study a possible binding between ENO1 and CRLF1. Our data showed that IL-1ß induction elevated ENO1 and CRLF1 expression in C-28/I2 cells. Silencing ENO1 or CRLF1 inhibited the IL-1ß-induced cell viability damage, apoptosis, inflammation, and extracellular matrix degradation. The inhibitory effect of silencing ENO1 was reversed by CRLF1 overexpression, suggesting a functional connection between ENO1 and CRLF1, which could be attributed to a binding between these two partners. Our study could help validate the role of ENO1 in OA pathogenies and identify novel therapeutic targets for OA treatment.

Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.

Mammalian cytosolic selenoprotein thioredoxin reductase (TXNRD1) is crucial for maintaining the reduced state of cellular thioredoxin 1 (TXN1) and is commonly up-regulated in cancer cells. TXNRD1 has been identified as an effective target in cancer chemotherapy. Discovering novel TXNRD1 inhibitors and elucidating the cellular effects of TXNRD1 inhibition are valuable for developing targeted therapies based on redox regulation strategies. In this study, we demonstrated that butein, a plant-derived small molecule flavonoid, is a novel TXNRD1 inhibitor. We found that butein irreversibly inhibited recombinant TXNRD1 activity in a time-dependent manner. Using TXNRD1 mutant variants and LC-MS, we identified that butein modifies the catalytic cysteine (Cys) residues of TXNRD1. In cellular contexts, butein promoted the accumulation of reactive oxygen species (ROS) and exhibited cytotoxic effects in HeLa cells. Notably, we found that pharmacological inhibition of TXNRD1 by butein overcame the cisplatin resistance of A549 cisplatin-resistant cells, accompanied by increased cellular ROS levels and enhanced expression of p53. Taken together, the results of this study demonstrate that butein is an effective small molecule inhibitor of TXNRD1, highlighting the therapeutic potential of inhibiting TXNRD1 in platinum-resistant cancer cells.

Early predictors of Epstein-Barr virus infection in patients with severe fever with thrombocytopenia syndrome.

BACKGROUND: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients. METHODS: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression. RESULTS: A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG < 12.5 g/l, IgM < 1.1 g/l, C4 < 0.3 g/l, and CD56+ cell counts > 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients. CONCLUSIONS: SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.

Comparison of Autolumo A2000 Plus and Architect i2000 for detection of hepatitis B virus serological markers.

Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p < 0.0001. HBV marker consistency test results show perfect consistency between the two analyzers, with Kappa values ranging from 0.854 to 1.000. For specific samples, including Hepatitis B patients with Genotype C, chronic hepatitis B, hepatitis B-related cirrhosis, and hepatocellular carcinoma, spearman correlation analysis showed HBsAg correlation coefficients ranging from 0.8532 to 0.9745, p < 0.001 in both analyzers. In conclusion, Autolumo A2000Plus diagnostic performance in consistency and correlation is comparable to Abbott Architect i2000 when detecting markers of hepatitis B infection. The Autolumo A2000Plus system can be used as a reliable instrument for HBV marker detection.

Clinical Characteristics and Comparative Proteomics Analysis of COVID-19-Related Atrioventricular Block.

Background: Atrioventricular block (AVB) is thought to be a rare cardiovascular complication of the coronavirus disease 2019 (COVID-19), though limited data are available beyond case reports. We aim to describe the baseline characteristics, proteomics profile, and outcomes for patients with COVID-19-related AVB. Methods: We prospectively recruited patients diagnosed with COVID-19-related AVB between November 2022 and March, 2023. Inclusion criteria were hospitalization for COVID-19 with the diagnosis of AVB. A total of 24 patients diagnosed with COVID-19 without AVB were recruited for control. We analyzed patient characteristics and outcomes and performed a comparative proteomics analysis on plasma samples of those patients and controls. Results: A total of 17 patients diagnosed with COVID-19-related AVB and 24 individuals diagnosed with COVID-19 infection without AVB were included. Among patients with COVID-19-related AVB, the proportion of concurrent pneumonia was significantly higher than controls (7/17 versus 2/24, p < 0.05). All 17 AVB patients (9 of permanent AVB, 8 of paroxysmal AVB) received permanent pacemaker implantation. No procedural-related complication occurred. In laboratory tests, the level of biomarkers indicating myocardial damage were substantially higher than controls, including high-sensitivity cardiac troponin-I (median 0.005 versus 0.002 ng/mL, p < 0.05), myoglobulin (median 39.0 versus 27.6 ng/mL, p < 0.05), and MB isoenzyme of creatine kinase (median 1.2 versus 0.8 U/L, p < 0.05). The level of N-terminal pro-b-type natriuretic peptide (median 241.0 versus 33.5 pg/mL, p < 0.05), C-reactive protein (median 4.8 versus 2.0 mg/L, p < 0.05), D-dimer (median 1.2 versus 0.2 µg/mL, p < 0.05), left ventricular end-diastolic diameter (median 49.3 versus 45.7 mm, p < 0.05) in patients with COVID-19-related AVB were significantly higher than controls. The level of albumin (median 41.9 versus 44.5 g/L, p < 0.05) was significantly lower than controls. In comparative proteomics analysis, we identified 397 human proteins. Several significantly altered plasma proteins related to inflammatory response (Serum amyloid A protein, C-reactive protein, Protein Adenosine 5'-monophosphate-activated protein kinase (AMPK), Alpha-2-macroglobulin), complement and coagulation cascades (Tetranectin, haptoglobin), and immune response (Neutrophil defensin 3, Fibrinogen beta chain) may contribute to the pathogenesis of COVID-19-related AVB. Conclusions: Patients with COVID-19-related AVB are more prone to have myocardial damage and concurrent pneumonia. Through laboratory tests and comparative proteomics analysis, we identified several differential expressed proteins (Serum amyloid A protein, Tetranectin, Neutrophil defensin 3) releated to the inflammatory response, complement and coagulation cascades, and immune response, which provides evidence of potential biomarkers and sheds light on the pathogenesis of COVID-19-related AVB.

A survey of breastfeeding among women with previous surgery for benign breast disease: a descriptive exploratory study.

BACKGROUND: Surgery is the primary treatment for benign breast disease and causes some disruption to the normal physiology of the breast, even when this disruption is localised, it remains unclear whether it affects women's ability to breastfeed. There are only a few studies describing the experience of breastfeeding in women who have undergone benign breast disease (BBD) surgery. METHODS: We retrospectively analysed data from patients aged 20-40 years in Guangdong, China, who underwent breast lumpectomy for BBD in our department between 01 January 2013 and 30 June 2019, with a follow-up date of 01 February 2022. Patients were included who had a history of childbirth between the time of surgery and the follow-up date. By collecting general information about this group of patients and information about breastfeeding after surgery, we described the breastfeeding outcomes of women of a fertile age who had previously undergone surgery for benign breast disease. RESULTS: With a median follow-up of 5.9 years, a total of 333 patients met the inclusion criteria. From the breastfeeding data of the first child born postoperatively, the mean duration of 'exclusive breastfeeding' was 5.1 months, and the mean duration of 'any breastfeeding' was 8.8 months. The rate of 'ever breastfeeding' is 91.0%, which is lower than the national average of 93.7%, while the exclusive breastfeeding rate at six months was 40.8%, was higher than the 29.2% national average. The any breastfeeding rate at 12 months was 30.0%, which was well below the 66.5% national average. The common reason for early breastfeeding cessation was insufficient breast milk. A total of 29.0% of patients who had ever breastfed after surgery voluntarily reduced the frequency and duration of breastfeeding on the operated breast because of the surgery. CONCLUSIONS: There are some impacts of BBD surgery on breastfeeding and some may be psychological. Institutions should provide more facilities for mothers who have undergone breast surgery to help them breastfeed, such as conducting community education on breastfeeding after breast surgery, training professional postoperative lactation consultants in hospitals, and extending maternity leave. Families should encourage mothers to breastfeed with both breasts instead of only the non-operated breast.

Spontaneous Dislocation of the Lens Nucleus Into the Anterior Chamber Observed in a Patient With Overmature Senile Cataract.

Overmature cataract refers to the advanced stage of cataract where timely surgical intervention is not performed, leading to further progression characterized by decreased water content in the lens, degradation of fibers, and liquefaction within its structure, which can cause a reduction in volume, wrinkling of the capsule, as well as calcification or cholesterol crystallization on its surface. In addition, it may result in deepening of the anterior chamber. If left promptly untreated, these complications may result in visual impairment or even blindness. The occurrence of spontaneous complete dislocation of the lens nucleus into the anterior chamber in overmature cataracts is extremely uncommon. The authors present a case study involving a 74-year-old female patient who was diagnosed with complete dislocation of the lens nucleus in an overmature senile cataract without any apparent ocular injury or any relevant medical records. After undergoing cataract removal combined with anterior vitrectomy, the patient experienced relief from eye discomfort and expressed satisfaction with the surgical outcome; however, her visual acuity did not show significant improvement.

Central Retinal Artery Occlusion after Peribulbar Injection of Triamcinolone Acetonide in Thyroid-associated Ophthalmopathy.

Central retinal artery occlusion (CRAO) is a form of acute ocular ischemic syndrome that causes visual loss. Timely treatment is of great importance for visual recovery, but the prognosis is usually poor. By analyzing the pathogenesis, diagnosis, and treatment process of a CRAO case after peribulbar injection of triamcinolone acetonide in thyroid-associated ophthalmopathy (TAO), this study aims to investigate the association of CRAO with hemodynamics and orbital pressure, thereby providing references in safety improvement of diagnosis and treatment on TAO.

DKK1 Activates the PI3K/AKT Pathway via CKAP4 to Balance the Inhibitory Effect on Wnt/ß-Catenin Signaling and Regulates Wnt3a-Induced MSC Migration.

Wnt/ß-catenin signaling plays a crucial role in the migration of mesenchymal stem cells (MSCs). However, our study has revealed an intriguing phenomenon where Dickkopf-1 (DKK1), an inhibitor of Wnt/ß-catenin signaling, promotes MSC migration at certain concentrations ranging from 25 to 100 ng/mL while inhibiting Wnt3a-induced MSC migration at a higher concentration (400 ng/mL). Interestingly, DKK1 consistently inhibited Wnt3a-induced phosphorylation of LRP6 at all concentrations. We further identified cytoskeleton-associated protein 4 (CKAP4), another DKK1 receptor, to be localized on the cell membrane of MSCs. Overexpressing the CRD2 deletion mutant of DKK1 (ΔCRD2), which selectively binds to CKAP4, promoted the accumulation of active ß-catenin (ABC), the phosphorylation of AKT (Ser473) and the migration of MSCs, suggesting that DKK1 may activate Wnt/ß-catenin signaling via the CKAP4/PI3K/AKT cascade. We also investigated the effect of the CKAP4 intracellular domain mutant (CKAP4-P/A) that failed to activate the PI3K/AKT pathway and found that CKAP4-P/A suppressed DKK1 (100 ng/mL)-induced AKT activation, ABC accumulation, and MSC migration. Moreover, CKAP4-P/A significantly weakened the inhibitory effects of DKK1 (400 ng/mL) on Wnt3a-induced MSC migration and Wnt/ß-catenin signaling. Based on these findings, we propose that DKK1 may activate the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/ß-catenin signaling and thus regulate Wnt3a-induced migration of MSCs. Our study reveals a previously unrecognized role of DKK1 in regulating MSC migration, highlighting the importance of CKAP4 and PI3K/AKT pathways in this process.

Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer.

BACKGROUND: Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies. METHODS: In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer. RESULTS: Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging. CONCLUSION: CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.

Single-cell sequencing reveals the heterogeneity of B cells and tertiary lymphoid structures in muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. B cells are crucial factors in tumor suppression, and tertiary lymphoid structures (TLSs) facilitate immune cell recruitment to the tumor microenvironment (TME). However, the function and mechanisms of tumor-infiltrating B cells and TLSs in MIBC need to be explored further. METHODS: We performed single-cell RNA sequencing analysis of 11,612 B cells and 55,392 T cells from 12 bladder cancer patients and found naïve B cells, proliferating B cells, plasma cells, interferon-stimulated B cells and germinal center-associated B cells, and described the phenotype, gene enrichment, cell-cell communication, biological processes. We utilized immunohistochemistry (IHC) and immunofluorescence (IF) to describe TLSs morphology in MIBC. RESULTS: The interferon-stimulated B-cell subtype (B-ISG15) and germinal center-associated B-cell subtypes (B-LMO2, B-STMN1) were significantly enriched in MIBC. TLSs in MIBC exhibited a distinct follicular structure characterized by a central region of B cells resembling a germinal center surrounded by T cells. CellChat analysis showed that CXCL13 + T cells play a pivotal role in recruiting CXCR5 + B cells. Cell migration experiments demonstrated the chemoattraction of CXCL13 toward CXCR5 + B cells. Importantly, the infiltration of the interferon-stimulated B-cell subtype and the presence of TLSs correlated with a more favorable prognosis in MIBC. CONCLUSIONS: The study revealed the heterogeneity of B-cell subtypes in MIBC and suggests a pivotal role of TLSs in MIBC outcomes. Our study provides novel insights that contribute to the precision treatment of MIBC.

miR-345-3p Modulates M1/M2 Macrophage Polarization to Inhibit Inflammation in Bone Infection via Targeting MAP3K1 and NF-κB Pathway.

Infection after fracture fixation (IAFF), a complex infectious disease, causes inflammatory destruction of bone tissue and poses a significant clinical challenge. miR-345-3p is a biomarker for tibial infected nonunion; however, the comprehensive mechanistic role of miR-345-3p in IAFF is elusive. In this study, we investigated the role of miR-345-3p in IAFF pathogenesis through in vivo and in vitro experiments. In vivo, in a rat model of IAFF, miR-345-3p expression was downregulated, accompanied by increased M1 macrophage infiltration and secretion of proinflammatory factors. In vitro, LPS induced differentiation of primary rat bone marrow-derived macrophages into M1 macrophages, which was attenuated by miR-345-3p mimics. miR-345-3p promoted M1 to M2 macrophage transition-it reduced the expression of cluster of differentiation (CD) 86, inducible NO synthase, IL-1ß, and TNF-α but elevated those of CD163, arginase-1, IL-4, and IL-10. MAPK kinase kinase 1 (MAP3K1), a target mRNA of miR-345-3p, was overexpressed in the bone tissue of IAFF rats compared with that in those of the control rats. The M1 to M2 polarization inhibited MAP3K1 signaling pathways in vitro. Conversely, MAP3K1 overexpression promoted the transition from M2 to M1. miR-345-3p significantly inhibited NF-κB translocation from the cytosol to the nucleus in a MAP3K1-dependent manner. In conclusion, miR-345-3p promotes the polarization of M1 macrophages to the M2 phenotype by inhibiting the MAP3K1 and NF-κB pathways. These findings provide insight into the pathogenesis and immunotherapeutic strategies for IAFF and offer potential new targets for subsequent research.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Discovery a series of novel inhibitors of human dihydroorotate dehydrogenase: Biological activity evaluation and molecular docking.

Human dihydroorotate dehydrogenase (hDHODH) is a key enzyme that catalyzes the de novo synthesis of pyrimidine. In recent years, various studies have shown that inhibiting this enzyme can treat autoimmune diseases such as rheumatoid arthritis (RA) and cancer. This study designed and synthesized a series of novel thiazolidone hDHODH inhibitors. Through biological activity evaluation, Compound 14 was found to have high inhibitory activity, with an IC50 value reaching nanomolar level. Preliminary structure-activity relationship studies found that the carboxyl group in R1 and the naphthalene in R2 are key factors in improving activity. Through molecular docking, the binding mode between inhibitors and proteins was elucidated. This study provides an important reference for further optimizing hDHODH inhibitors.

N-acetylcysteine and Hydroxychloroquine Ameliorate ADMA-Induced Fetal Growth Restriction in Mice via Regulating Oxidative Stress and Autophagy.

Fetal growth restriction (FGR) seriously threatens perinatal health. The main cause of FGR is placental malperfusion, but the specific mechanism is still unclear, and there is no effective treatment for FGR. We constructed a FGR mouse model by adding exogenous asymmetric dimethylarginine (ADMA) through in vivo experiments and found that ADMA could cause placental dysplasia and induce the occurrence of FGR. Compared with the control group, reactive oxygen species (ROS) production in the placenta was increased in mice with FGR, and the expression of autophagy-related proteins p-AKT/AKT, p-mTOR/mTOR, and P62 was significantly decreased, while the expression of Beclin-1 and LC3-II was significantly increased in the FGR group. Furthermore, ADMA had a favorable effect in promoting the formation of autophagosomes. Hydroxychloroquine (HCQ) and N-acetylcysteine (NAC) improved ADMA-induced disorders of placental development and alleviated ADMA-induced FGR. This study found that ADMA could cause excessive autophagy of trophoblasts by increasing the level of oxidative stress, ultimately leading to the occurrence of FGR, and HCQ and NAC had therapeutic effects on ADMA-induced FGR.

Engineering Immunomodulatory Stents Using Zinc Ion-Lysozyme Nanoparticle Platform for Vascular Remodeling.

Rapid endothelialization of cardiovascular materials can enhance the vascular remodeling performance. In this work, we developed a strategy for amyloid-like protein-assembly-mediated interfacial engineering to functionalize a biomimetic nanoparticle coating (BMC). Various groups (e.g., hydroxyl and carboxyl) on the BMC are responsible for chelating Zn2+ ions at the stent interface, similar to the glutathione peroxidase-like enzymes found in vivo. This design could reproduce the release of therapeutic nitric oxide gas (NO) and an aligned microenvironment nearly identical with that of natural vessels. In a rabbit abdominal aorta model, BMC-coated stents promoted vascular healing through rapid endothelialization and the inhibition of intimal hyperplasia in the placement sites at 4, 12, and 24 weeks. Additionally, better anticoagulant activity and immunomodulation in the BMC stents were also confirmed, and vascular healing was mainly dependent on cell signaling through the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) cascade. Overall, a metal-polypeptide-coated stent was developed on the basis of its detailed molecular mechanism of action in vascular remodeling.

Polyphenol-mediated sandwich-like coating promotes endothelialization and vascular healing.

Drug-eluting stents have become one of the most effective methods to treat cardiovascular diseases. However, this therapeutic strategy may lead to thrombosis, stent restenosis, and intimal hyperplasia and prevent re-endothelialization. In this study, we selected 3-aminophenylboronic acid-modified hyaluronic acid and carboxylate chitosan as polyelectrolyte layers and embedded an epigallocatechin-3-gallate-tanshinone IIA sulfonic sodium (EGCG-TSS) complex to develop a sandwich-like layer-by-layer coating. The introduction of a functional molecular EGCG-TSS complex improved not only the biocompatibility of the coating but also its stability by enriching the interaction between the polyelectrolyte coatings through electrostatic interactions, hydrogen bonding, π-π stacking, and covalent bonding. We further elucidated the effectiveness of sandwich-like coatings in regulating the inflammatory response, smooth muscle cell growth behavior, stent thrombosis and restenosis suppression, and vessel re-endothelialization acceleration via in vivo and in vitro. Conclusively, we demonstrated that sandwich-like coating assisted by an EGCG-TSS complex may be an effective surface modification strategy for cardiovascular therapeutic applications.

MicroRNA-411-3p motivates methotrexate's cellular uptake and cytotoxicity via targeting Yin-yang 1 in leukemia cells.

This study aimed to figure out how microRNA (miR)-411-3p's impacts on methotrexate (MTX)'s cellular uptake and cytotoxicity in acute lymphoblastic leukaemia (ALL) CEM-C1 cells by targeting Yin-yang 1 (YY1). miR-411-3p and YY1 were detected by RT-qPCR or Western blot. Intracellular MTX concentration was measured by enzyme-linked immunosorbent assay. Cell viability and apoptosis were evaluated by CCK-8, clonal formation assay, and flow cytometry. Verification of miR-411-3p and YY1's targeting link was manifested. It came out that miR-411-3p mimic or si-YY1 elevated intracellular MTX, MTX-induced cytotoxicity and apoptosis rate in CEM-C1. However, the inverse results were noticed in cells introduced with miR-411-3p inhibitor or oe-YY1. Meanwhile, it was found that cell relative luciferase activity was reduced after co-transfection of miR-411-3p mimic with YY1-WT, indicating that miR-411-3p targeted YY1. Elevation of YY1 could turn around elevating miR-411-3p's impacts on MTX's cellular uptake and cytotoxicity in CEM-C1 cells. These findings convey that miR-411-3p motivated MTX's cellular uptake and cytotoxic impacts via targeting YY1 in leukemia cells. This study is helpful for learning about the mechanisms underlying MTX responses in ALL patients.

Association between obesity and risk of delayed discharge and unplanned readmission for day surgery: A systematic review and meta-analysis.

AIMS: This work aims to investigate the association between obesity and risk of delayed discharge and unplanned readmission in day surgery patients. BACKGROUND: Day surgeries are well received and developing rapidly. Associations between obesity and delayed discharge and unplanned readmission, which are clinically relevant outcomes in day surgeries, are complex. DESIGN: A systematic review and meta-analysis was conducted. DATA SOURCES: The PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, VIP, and Wan Fang databases were comprehensively searched from inception until January 2021. REVIEW METHODS: Two independent reviewers assessed the studies and extracted data. Pooled estimates were obtained using a random-effects model. RESULTS: Eleven articles published between 2007 and 2020 were finally included. Obesity appeared not to increase the risk of delayed discharge. However, morbid obesity seemed to be associated with a higher risk of delayed discharge. The meta-analysis revealed no relationship between higher body mass index (BMI) and unplanned readmission for day surgery patients. CONCLUSIONS: Obesity appeared not to increase the risk of delayed discharge except in patients with morbid obesity. Additionally, a higher BMI was not associated with increased risk of unplanned readmission after day surgery. Future studies are required to address this issue further in different types of surgery and areas.