Research progress of circular RNAs in myocardial ischemia.

Circular RNAs (circRNAs) are a type of single-stranded RNA that forms a covalently closed continuous loop. Its structure, stability, properties, and cell- and tissue-specificity have gained considerable recognition in the research and clinical sectors, as its role has been observed in different diseases, such as cardiovascular diseases, cancers, and central nervous system diseases, etc. Cardiovascular disease is still named as the number one cause of death globally, with myocardial ischemia (MI) accounting for 15 % of mortality annually. A number of circRNAs have been identified and are being studied for their ability to reduce MI by inhibiting the molecular mechanisms associated with myocardial ischemia reperfusion injury, such as inflammation, oxidative stress, autophagy, apoptosis, and so on. CircRNAs play a significant role as crucial regulatory elements at transcriptional levels, regulating different proteins, and at posttranscriptional levels, having interactions with RNA-binding proteins, ribosomal proteins, micro-RNAS, and long non-coding RNAS, making it possible to exert their effects through the circRNA-miRNA-mRNA axis. CircRNAs are a potential novel biomarker and therapeutic target for myocardial ischemia and cardiovascular diseases in general. The purpose of this review is to summarize the relationship, function, and mechanism observed between circRNAs and MI injury, as well as to provide directions for future research and clinical trials.

Expression of clMagR/clCry4 protein in mBMSCs provides T2-contrast enhancement of MRI.

Here, we propose for the first time the evaluation of magnetosensitive clMagR/clCry4 as a magnetic resonance imaging (MRI) reporter gene that imparts sensitivity to endogenous contrast in eukaryotic organisms. Using a lentiviral vector, we introduced clMagR/clCry4 into C57BL/6 mice-derived bone marrow mesenchymal stem cells (mBMSCs), which could specifically bind with iron, significantly affected MRI transverse relaxation, and generated readily detectable contrast without adverse effects in vivo. Specifically, clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which cells recruit exogenous iron and convert these stores into an MRI-detectable contrast; this is not achievable with control cells. Additionally, Prussian blue staining was performed together with ultrathin cell slices to provide direct evidence of natural iron-bearing granules being detectable on MRI. Hence, it was inferred that the sensitivity of MRI detection should be correlated with clMagR/clCry4 and exogenous iron. Taken together, the clMagR/clCry4 has great potential as an MRI reporter gene. STATEMENT OF SIGNIFICANCE: In this study, we propose the evaluation of magnetosensitive clMagR/clCry4 as an MRI reporter gene, imparting detection sensitivity to eukaryotic mBMSCs for endogenous contrast. At this point, the clMagR and clCry4 were located within the cytoplasm and possibly influence each other. The clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which protein could specifically bind with iron and convert these stores into MRI-detectable contrast; this is not achieved by control cells. The viewpoint was speculated that the clMagR/clCry4 and exogenous iron were complementary to each other. Additionally, Prussian blue staining was performed together with TEM observations to provide direct evidence that the iron-bearing granules were sensitive to MRI.

Morphology and deformity of the shoulder and pelvis in the entire spine radiographs of adolescent idiopathic scoliosis.

Background: To investigate the deformity and asymmetry of the shoulder and pelvis in adolescent idiopathic scoliosis (AIS) patients. Methods: This retrospective cross-sectional study enrolled 223 AIS patients with a right thoracic curve or left thoracolumbar/lumbar curve who underwent spine radiographs at the Third Hospital of Hebei Medical University between November 2020 and December 2021. The following parameters were measured: Cobb angle, clavicular angle, glenoid obliquity angle, acromioclavicular joint deviation, femoral neck-shaft projection angle, iliac obliquity angle, acetabular obliquity angle, coronal trunk deviation distance, and spinal deformity deviation distance. The Mann-Whitney U test, Kruskal-Wallis H test were used for inter-group comparisons, and Wilcoxon signed-rank test were used for intra-group left and right sides comparisons. Results: Shoulder and pelvic imbalances were found in 134 and 120 patients, respectively, and there were 87, 109, and 27 cases of mild, moderate, and severe scoliosis, respectively. Compared with mild scoliosis patients, the difference in the acromioclavicular joint offset on bilateral sides was significantly increased in moderate and severe scoliosis [11.04, 95% confidence interval (CI): 0.09-0.14 for mild, 0.13-0.17 for moderate, and 0.15-0.27 for severe scoliosis, P=0.004], and the difference in the femoral neck-shaft projection angle on bilateral sides was significantly enhanced with scoliosis aggravation (14.14, 95% CI: 2.34-3.41 for mild, 3.00-3.94 for moderate, and 3.57-6.43 for severe scoliosis, P=0.001). The acromioclavicular joint offset was significantly larger on the left than that on the right in patients with a thoracic curve or double curves (thoracic curve -2.75, 95% CI: 0.57-0.69 for the left and 0.50-0.63 for the right, P=0.006; double curve -3.27, 95% CI: 0.60-0.77 for the left and 0.48-0.65 for the right, P=0.001). The femoral neck-shaft projection angle was significantly larger on the left than right in patients with a thoracic curve (-4.46, 95% CI: 133.78-136.20 for the left and 131.62-134.01 for the right, P<0.001), but larger on the right than left in patients with thoracolumbar/lumbar curve (thoracolumbar -2.98, 95% CI: 133.75-136.70 for the left and 135.13-137.82 for the right, P=0.003; lumbar -3.24, 131.97-134.56 for the left and 133.76-136.26 for the right, P=0.001). Conclusions: In AIS patients, shoulder imbalance has a greater impact on coronal balance and spinal scoliosis above the lumbar segment, whereas pelvic imbalance has a greater impact on sagittal balance and spinal scoliosis below the thoracic segment.

Transfection of clMagR/clCry4 imparts MR-T2 imaging contrast properties to living organisms (E. coli) in the presence of Fe3+ by endogenous formation of iron oxide nanoparticles.

Rapid development of medical imaging, such as cellular tracking, has increased the demand for "live" contrast agents. This study provides the first experimental evidence demonstrating that transfection of the clMagR/clCry4 gene can impart magnetic resonance imaging (MRI) T2-contrast properties to living prokaryotic Escherichia coli (E. coli) in the presence of Fe3+ through the endogenous formation of iron oxide nanoparticles. The transfected clMagR/clCry4 gene markedly promoted uptake of exogenous iron by E. coli, achieving an intracellular co-precipitation condition and formation of iron oxide nanoparticles. This study will stimulate further exploration of the biological applications of clMagR/clCry4 in imaging studies.

Relationship between dysphagia and surgical treatment for supraglottic laryngeal carcinoma: A meta-analysis.

OBJECTIVE: To systematically evaluate differences in swallowing disorder-related manifestations in patients with supraglottic laryngeal cancer, who underwent traditional open partial horizontal laryngectomy (OPHL) and endoscopic supraglottic laryngectomy (ESL). METHODS: A systematic review of the literature and a meta-analysis were performed. The CNKI, Wan Fang, PubMed, EMBASE, Cochrane Library, Web of Science, and Clinical Trials databases for clinical studies data sources were investigated. The efficiency of recovery, postoperative swallowing function, and complications related to dysphagia were investigated to compare the effects of surgical procedures. RESULTS: The meta-analysis included 8 studies with 281 patients. ESL surgery played a positive role in the recovery of patients. Preservation of the anterior epiglottic space, ventricular band, and arytenoid cartilage without destroying the external framework of the larynx can effectively reduce the risk of aspiration pneumonia in patients. CONCLUSIONS: ESL has advantages in postoperative recovery and retention of swallowing function in patients with supraglottic laryngeal cancer.

Clinical study of poorly differentiated head and neck squamous cell carcinoma: a prospective cohort study in China.

Background: Although poorly differentiated is rare in head and neck squamous cell carcinoma (HNSCC), its prognosis are worse with high rate of local recurrence and distant metastasis (DS). Therefore, this study hopes to carry out prospective clinical research on different treatment options for poorly differentiated patients and explore the treatment scheme more suitable for these patients. Methods: This study is a prospective cohort study. We selected patients with poorly differentiated carcinoma in larynx or hypopharynx (stage I-IV, T1-4a, N0-2, M0). The intervention treatment methods for stage I-II patients are as follows: surgery, induction chemotherapy (IC) + surgery, surgery + adjuvant therapy; The intervention treatment methods for stage III-IV patients are as follows: surgery, IC + surgery + adjuvant therapy, surgery + adjuvant therapy. The patients were followed up for at least 1 year, and the disease progression and survival were counted. Results: From September 2016 to October 2020, 62 patients were included (29 patients in stage I/II and 33 patients in stage III/IV). We found that there was no significant difference in survival between treatment groups in stage I/II patients [overall survival (OS): P=0.447; progression free survival (PFS): P=0.504], but the surgery + adjuvant treatment group had a significant advantage in 3-year OS (100%). In stage III/IV patients, there were significant differences in DS, OS and PFS between different treatment groups (DS: P=0.013; OS: P=0.021; PFS: P=0.020). Among them, the survival rate of IC + surgery + adjuvant treatment group was the best, with 3-year OS of 78%. Conclusions: Our study found that postoperative radiotherapy may improve the OS rate of patients with early (stage I/II) poorly differentiated HNSCC; For advanced patients (stage III/IV), surgery combined with IC and postoperative adjuvant radiotherapy may better control DS and improve the survival rate. However, our study draws the above conclusions based on small sample data, and we will continue to summarize and expand the sample size for verification.

Quercetin loading CdSe/ZnS nanoparticles as efficient antibacterial and anticancer materials.

Quercetin (Qe) plays an important role in inflammation, antibacterial, anticancer, and aging. However, Qe has extremely low water solubility, which is a major challenge in drug absorption. In this study, we described a simple method for synthesis of Qe/CdSe/ZnS nanoparticles (QCZ NPs). The QCZ NPs had an average diameter of 10nm and prominent yellow emission under UV irradiation. We investigated the antibacterial activity of QCZ NPs against drug-resistant Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in vitro. Results showed that QCZ NPs had considerably more effective antibacterial activities than Qe or CdSe nanoparticles (CdSe NPs). Antibacterial experiment results showed that QCZ NPs acted against E. coli and B. subtilis by disrupting the bacterial cell wall and membrane. In vivo study, the QCZ NPs could cure inflammation and lesion which caused by E. coli. In anticancer assays, the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assays exhibited the cytotoxicity of QCZ NPs increased approximately 2-6 fold compared to raw Qe and CdSe NPs. Moreover, by using RT-CES (real-time cell electronic sensing) studies, we had demonstrated QCZ NPs have also an effect on migration and proliferation of BGC-823 cells. CdSe NPs loaded with Qe, these QCZ NPs exhibited excellent antibacterial (E. coli and B. subtilis) and anticancer (BGC-823) activities.

Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer's disease.

Dysfunctional interaction of amyloid-ß (Aß) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Hence, disruption of these metal-peptide interactions using nanoparticles (NPs) holds considerable promise as a therapeutic strategy to combat this incurable disease. Given that quercetin is a natural product, the biocompatibility and small size essential for permeating the blood-brain barrier make it a potential therapeutic drug candidate for treating AD. Nanocarriers formulated with the US Food and Drug Administration-approved biocompatible and biodegradable polymer PLGA are being widely explored for the controlled delivery of therapeutic drugs, proteins, peptides, oligonucleotides, and genes. With this background, the present study was undertaken to investigate the effects of PLGA-functionalized quercetin (PLGA@QT) NPs on inhibited and disassembled Aß42 fibrils and the PLGA@QT NPs have low cytotoxicity when tested on SH-SY5Y cells in vitro. As expected, the cytotoxicity studies of the PLGA@QT NPs led to a concentration-related behaviour on the SH-SY5Y human neuroblastoma cells. And, it has demonstrated that PLGA@QT NPs can inhibit the neurotoxicity of Zn2+-Aß42 system and enhance the viability of neuron cells. The results from behavioral tests indicate that injection of PLGA@QT NPs into APP/PS1 mice ameliorate cognition and memory impairments. Most encouragingly, the in vivo systemic toxicity of PLGA@QT NPs examined by histological analysis in major organs did not show any signs of adverse effect to mice. Thus, the prepared quercetin based nanoscale drug delivery carrier efficiently enhanced the therapeutic index and reduced the side effects. Our findings are highly encouraging, providing substantial evidence of the safety of PLGA@QT NPs for biomedical application. We expect these findings will be relevant for other NPs for treatment of AD and have broad implications in NP-based studies and applications.

Anti-tumor activity and mechanism of apoptosis of A549 induced by ruthenium complex.

Two new ruthenium (II) polypyridyl complexes [Ru(MeIm)4(pip)]2+ (1) and [Ru(MeIm)4(4-npip)]2+ (2) were synthesized under the guidance of computational studies (DFT). Their binding property to human telomeric G-quadruplex studied by UV-Vis absorption spectroscopy, the fluorescent resonance energy transfer (FRET) melting assay and circular dichroism (CD) spectroscopy for validating the theoretical prediction. Both of them were evaluated for their potential anti-proliferative activity against four human tumor cell lines. Complex 2 shows growth inhibition against all the cell lines tested, especially the human lung tumor cell (A549). The RTCA analysis not only validated the inhibition activity but also showed the ability of reducing A549 cells' migration. DNA-flow cytometric analysis, mitochondrial membrane potential (ΔΨm) and the scavenger measurements of reactive oxygen species (ROS) analysis carried out to investigate the mechanism of cell growth inhibition and apoptosis-inducing effect of complex 2. The results demonstrated that complex 2 induces tumor cells apoptosis by acting on both mitochondrial homeostasis destruction and death receptor signaling pathways. And those suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent against human tumor.

[Multiple myeloma with oral amyloidosis: report of a case and literature review].

Multiple myeloma is the most common type of multifocal plasma cell proliferation in the bone marrow, whereas cases with multiple amyloidosis of oral cavity are rarely documented. Clinically, the disease is easily miss- diagnosed and mistreated due to lack of specificity. This article reported a rare case with multiple myeloma and amyloidosis of tongue, gingiva, buccal mucosa, followed by a review of relevant literature.