Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neutralizing antibodies, as they struggle to keep up with the increased viral transmissibility and immune evasion. However, there is hope in targeting the CD147-spike protein, which serves as an alternative point for the entry of SARS-CoV-2 into host cells. This protein has emerged as a promising therapeutic target for the development of drugs against COVID-19. Here, we demonstrate that the RNA-binding protein Human-antigen R (HuR) plays a crucial role in the post-transcriptional regulation of CD147 by directly binding to its 3′-untranslated region (UTR). We observed a decrease in CD147 levels across multiple cell lines upon HuR depletion. Furthermore, we identified that niclosamide can reduce CD147 by lowering the cytoplasmic translocation of HuR and reducing CD147 glycosylation. Moreover, our investigation revealed that SARS-CoV-2 infection induces an upregulation of CD147 in ACE2-expressing A549 cells, which can be effectively neutralized by niclosamide in a dose-dependent manner. Overall, our study unveils a novel regulatory mechanism of regulating CD147 through HuR and suggests niclosamide as a promising therapeutic option against COVID-19

HAb18G/CD147 Promotes pSTAT3-Mediated Pancreatic Cancer Development via CD44s

Purpose STAT3 plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 is failure in clinic. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo. Experimental Design The expression of HAb18G/CD147, pSTAT3 and CD44s were determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 was assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot, immunofluorescence staining, immunoprecipitation, and in vivo tumor formationusing loss or gain-of-function strategies. Results Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. CyPA, a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147 dependent mechanisms. HAb18G/CD147 was associated and co-localized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high co-expression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer. Conclusions We identified HAb18G/CD147 as a novel upstream activator of STAT3 via interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies

CTGF: A potential therapeutic target for Bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that often occurs in preterm infants. However, there is still no effective treatment for BPD. Recent studies demonstrated that connective tissue growth factor (CTGF) is involved in the development of BPD in experimental models. CTGF, also known as CCN2, is the second member of the CCN family and is necessary for normal lung development. The expression of CTGF is increased in lung tissues in infants with BPD. Hyperoxia, inflammation and mechanic ventilation increase CTGF expression which may promote fibroblast proliferation, matrix production and vascular remodeling. Conditional overexpression of CTGF in alveolar epithelial type II cells disrupts alveolarization and vascular development, induces vascular remodeling, and results in pulmonary hypertension, the pathological hallmarks of severe BPD. Further studies have shown that inhibition of CTGF by a CTGF monoclonal antibody improved alveolarization and vascular development, and decreased pulmonary vascular remodeling and pulmonary hypertension in a rodent model of BPD induced by hyperoxia. CTGF may be a novel target for BPD therapy in preterm infants

Robot-Assisted Autonomous Reduction of a Displaced Pelvic Fracture: A Case Report and Brief Literature Review

Displaced pelvic fracture is among the most complicated fractures in traumatic orthopedics, with high mortality and morbidity. Reduction is considered a complex procedure as well as a key part in surgical treatment. However, few robotic techniques have been employed in the reduction of pelvic fracture, despite the rapid advancement of technologies. Recently, we designed a robot surgery system specialized in the autonomous reduction of displaced pelvic fracture and applied it in the true patient for the first time. In this paper, we report its successful clinical debut in the surgery of a displaced pelvic fracture. Total surgery time was 110 min and an anatomic reduction was achieved. We then present a brief overview of the literature about reduction techniques in pelvic fracture and introduce related principles involved in our robot-assisted reduction system

Condition Assessment of Concrete Structures by Dynamic Signature Tests

This paper focuses on the correlation between frequency of a structure and degree of damage by testing a full-scale beam both statically and dynamically. To improve the quality of test data and reduce the effort for identifying the fundamental frequency of the beam, preloads are applied to the beam before conducting the dynamic tests. Test results have confirmed that the frequency of the beam itself depends on the load history while that of the beam plus sufficient preloads can be identified independently. This is because preloads can keep cracks open so that the cracked beam vibrates in a linear fashion

Minimally Invasive Plating Osteosynthesis in the Treatment of Humeral Shaft Fractures: A Meta-Analysis

Background: Whether minimally invasive plating osteosynthesis (MIPO) or other operative interventions is superior in the treatment of humeral shaft fractures remains controversial. Therefore, we conducted a meta-analysis to quantitatively compare the clinical outcomes of MIPO and other operative interventions in the treatment of humeral shaft fractures. Methods: Pubmed, Embase, and Web of Science were systematically searched to identify all available studies comparing clinical outcomes between patients receiving MIPO and other operative interventions. The weight mean difference (WMD) was pooled to compare the operative time, union time, University of California, Los Angeles (UCLA) score, and Mayo elbow performance index (MEPI).The risk ratio (RR) was pooled to compare the union rate, and incidence of complications. Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, according to the heterogeneity among studies. Results: Nine studies were included in this meta-analysis. Our results suggest that both MIPO and other operative interventions can achieve similar union time, UCLA score, MEPI, and union rate. However, MIPO is associated with better outcomes including shorter operation time, and lower incidence of radial nerve injury. Conclusion: Evidence from this meta-analysis demonstrated that, MIPO is effective but safer than other operative interventions in the treatment of humeral shaft fracture. However, due to the potential limitations in this meta-analysis, randomized controlled trials with larger sample sizes using appropriate blinding methods are needed to confirm these findings