MiR-93/HMGB3 regulatory axis exerts tumor suppressive effects in colorectal carcinoma cells.

OBJECTIVE: MicroRNA (miR)-93 has been proven to mediate the initiation and progression of colorectal carcinoma (CRC); however, the mechanisms by which miR-93 mediates CRC development need deeper elucidation. The present study is designed to investigate the association between miR-93 and high mobility group box 3 (HMGB3), as well as the functions of miR-93, in CRC. METHODS: miR-93 expression was quantified by RT-qPCR. CRC cells were transfected or cotransfected with miR-93 mimic, miR-93 inhibitor, pcDNA3.1-HMGB3 and sh-HMGB3, and then the proliferative, migratory and invasive capacities were detected in addition to the apoptotic rate. Western blotting assessed the expression levels of HMGB3, PI3K, p-PI3K, AKT and p-AKT. The interaction between miR-93 and HMGB3 was identified. RESULTS: In CRC tissues, miR-93 was downregulated and HMGB3 was upregulated. LOVO and SW480 cells transfected with miR-93 mimic exhibited reduced proliferation, invasion and migration as well as increased apoptosis. The ratios of p-PI3K/PI3K and p-AKT/AKT were declined after miR-93 mimic was introduced into the CRC cell lines. miR-93 negatively downregulated HMGB3, and introduction of pcDNA3,1-HMGB3 could counteract, in part, the inhibitory effects of miR-93 on the malignant properties of CRC cells as well as the ratios of p-PI3K/PI3K and p-AKT/AKT. CONCLUSION: miR-93 targeted HMGB3 to block the activation of the PI3K/AKT pathway and thus enhance CRC cell apoptosis.

Co-Infection with Common Respiratory Pathogens and SARS-CoV-2 in Patients with COVID-19 Pneumonia and Laboratory Biochemistry Findings: A Retrospective Cross-Sectional Study of 78 Patients from a Single Center in China.

BACKGROUND This retrospective study aimed to investigate co-infections with common respiratory pathogens and SARS-CoV-2 and laboratory biochemistry findings in patients with COVID-19 in the Zhuzhou area of China, in order to provide a reference for the disease assessment and clinical treatment of COVID-19. MATERIAL AND METHODS The clinical data of COVID-19 patients admitted to the hospital of Zhuzhou City from January 28 to March 15, 2020, as well as laboratory test results for respiratory pathogens and biochemical indicators, were collected to conduct correlation analyses. All patients were diagnosed based on fluorescence-based PCR assay for SARS-CoV-2. RESULTS Eleven of the 78 patients (14.1%) were co-infected with other respiratory pathogens, among which Mycoplasma pneumoniae (n=5, 45.5%) and respiratory syncytial virus (n=4, 36.4%) were the most frequent. There were 8 patients co-infected with 1 other pathogen and 3 patients co-infected with 2 other pathogens. Compared with mono-infected COVID-19 patients, patients with co-infections had significantly higher levels of procalcitonin (P=0.002). CONCLUSIONS The findings showed that Mycoplasma pneumonia and respiratory syncytial virus were the most common co-infections in patients with COVID-19 pneumonia. Increased levels of PCT in patients with COVID-19 pneumonia were associated with co-infection.

[Screening of interacting proteins of idiopathic gonadotropin-releasing hormone deficiency pathogenic gene RNF216].

OBJECTIVE: To screen proteins interacting with ring finger protein 216(RNF216) through yeast two hybrid experiment, and further clarify the role of RNF216 in the pathogenesis of gonadotropin-releasing hormone deficiency. METHODS: A recombinant expression vector pGBKT7-RNF216 was constructed and transformed into yeast Y2HGold, which was hybridized with a human cDNA library in order to screen proteins interacting with RNF216. The interaction was verified in yeast Y2HGold. RESULTS: A recombinant expression vector pGBKT7-RNF216 was successfully constructed and expressed in yeast Y2HGold. Filamin B (FLNB) was identified by yeast two hybrid experiment, and their interaction was verified in yeast Y2HGold. CONCLUSION: An interaction between FLNB and RNF216 was identified through yeast two hybrid experiment. RNF216 may affect the proliferation and migration of GnRH neurons by regulating FLNB or FLNB/FLNA heterodimers.

C-type Lectin Domain Family 4 Member G (CLEC4G) Is a Negative Marker for CD34 in the Evolution of Liver Pathogenesis.

OBJECTIVE: This study aimed to explore the expression of the C-type lectin domain family 4 member G (CLEC4G) gene in the liver sinusoidal endothelial cells (LSECs) during liver pathogenesis, and to evaluate its correlation with CD34 and clinical significance in hepatocellular carcinoma patients. METHODS: We conducted bioinformatics analysis of the differential expression of CLEC4G in various human organs, carcinomatous and adjacent tissues. Then, mRNA and protein expression levels of CD34 in hepatocellular carcinoma (HCC) samples were detected via real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical (IHC), respectively. ELISA was applied to detect serum levels of CLEC4G in healthy controls, liver fibrosis and HCC patients. RESULTS: The expressions of mRNA and protein levels of CLEC4G were higher in normal liver tissues, moderately expressed in cirrhotic and para-cancerous tissues (P<0.001), and lowest in HCC tissues (P<0.001). We also found high CD34 expression in tumors, which was negatively correlated with CLEC4G at both mRNA and protein levels. Compared to the healthy controls, the CLEC4G levels in liver fibrosis patients and HCC patients gradually became lower (P<0.001). CONCLUSIONS: The low expression of CLEC4G is potentially correlated with LSEC capillarization and the appearance of micro-vessels. Such a phenomenon may serve as a reliable diagnostic marker for hepatocellular carcinoma.

HPMA Polymeric Nanocarriers for Anticancer Drugs with Tumor Microenvironment-Responsive Extracellular Biodegradation and Intracellular Drug Release.

The balance between systemic toxicity and circulation time for a polymeric nanocarrier to deliver antitumor drugs has been trialed. A new approach to break the balance was proposed in this study by significantly improving its biosafety and prolonging the circulation time, hence, to enhance its anti-tumor efficacy. A matrix metalloproteinases (MMPs)-sensitive peptide (PVGLIGK) was introduced to cross-link the N-(2-hydroxypropyl) methylacrylamide polymer-doxorubicin conjugates (HPMA-Dox) conjugate to construct a nano-size polymeric nanocarrier-Dox assembly (PMD) with a molecular weight (MW) of 73 kDa and this modification has resulted in a prolonged circulation time (a half-time of 20.1 h) and enhanced accumulation of PMD at the tumor site, while negligible systemic toxicity and excellent biocompatibility were displayed after injection of PMD into the mice. The cross-linked nanoassembly was unpacking in the presence of MMPs in the extracellular microenvironment, and the conjugated Dox was released from the nanoassembly in the lysosome/endosome due to an intracellular low pH microenvironment. The released Dox from PMD inhibited tumor cells very efficiently with a tumor growth inhibition of around 70%. The outstanding performance of the dual stimuli-responsive biodegradable polymeric nanocarriers may open a door for other hydrophobic anti-tumor drugs.

Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Dihydromyricetin (DHM), a Rattan tea extract, has been shown to have antitumor activity with no obvious toxicity to normal cells in vitro and in vivo. However, its efficacy in the treatment of CSCC and the underlying antitumor mechanism has not been fully elucidated yet. In our study, DHM increased autophagic flux in the A431 cells, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blocking autophagy decreased DHM-induced cell death, indicating DHM triggered autophagic cell death in A431 cells. Specifically, DHM induced TFEB(Ser142) de-phosphorylation, activated TFEB nuclear translocation and increased of TFEB reporter activity, which contributed to the expression of autophagy-related genes and subsequent initiated autophagic cell death in A431 cells. Importantly, DHM decreased lncRNA MALAT1 expression and MALAT1 overexpression abrogated the effects of DHM on TFEB-dependent autophagy both in vitro and in vivo. Taken together, DHM induces CSCC cell death via inducing excessive autophagy, which is mediated through the MALAT1-TFEB pathway. Therefore, DHM may be beneficial for the development of chemotherapy for CSCC.

Effects of sintering temperature on sensing properties of WO3 and Ag-WO3 electrode for NO2 sensor.

Pure WO3 and Ag-WO3 (mixed solid solutions Ag with WO3) have been successfully synthesized by sol-gel method and the influences of calcination temperature on the particle size, morphology of the WO3 and Ag-WO3 nanoparticles were investigated. Powder X-ray diffraction results show that the hexagonal to monoclinic phase transition occurs at calcination temperature varying from 300°C to 500°C. SEM images show that calcination temperature plays an important role in controlling the particle size and morphology of the as-prepared WO3 and Ag-WO3 nanoparticles. The NO2 gas sensing properties of the sensors based on WO3 and Ag-WO3 nanoparticles calcined at different temperatures were investigated and the experimental results exhibit that the gas sensing properties of the Ag-WO3 sensors were superior to those of the pure WO3. Especially, the sensor based on Ag-WO3 calcined at 500°C possessed larger response, better selectivity, faster response/recovery and better longer-term stability to NO2 than the others at relatively low operating temperature (150°C).