The PRMT5 inhibitor C9 mitigates hypoxia-induced carboplatin resistance in lung cancer by inducing autophagy.

Hypoxia, a common feature of solid tumors, can promote chemoresistance in cancer cells. PRMT5 mediates various cellular processes involved in cancer development and progression. However, the role of PRMT5 in hypoxia-induced chemoresistance is unclear. In this study, hypoxia upregulated PRMT5 expression in lung cancer cells. Additionally, PRMT5 overexpression promoted cancer cell resistance to carboplatin. In carboplatin-resistant cancer cells, PRMT5 overexpression promoted the methylation of ULK1, a critical regulator of autophagy. ULK1 hypermethylation leads to the upregulation of autophagy, which can improve the survival of cancer cells under hypoxic conditions. Furthermore, this study demonstrated that the PRMT5 inhibitor C9 significantly enhanced the sensitivity of lung cancer cells to carboplatin. These findings suggest that targeting PRMT5-mediated autophagy with C9 can overcome hypoxia-induced carboplatin resistance and improve the efficacy of chemotherapy in patients with cancer.

Correlation between different types of malocclusions and body image issues in college students / 中国学校卫生

Objective@#To explore the correlation between malocclusion and body image issues in college students.@*Methods@#A total of 1 851 students in three universities in Jingmen were selected by using stratified cluster sampling method. Angle s classification of malocclusion was used to determine the number of three types of malocclusions. Body image issues were self reported and its relationship with different types of malocclusions was explored.@*Results@#The proportions of Classes Ⅰ, Ⅱ and Ⅲ malocclusion in college students with malocclusion were 71.21%, 16.32%, and 12.47%, respectively. The detection rates of body image issues among students with Classes Ⅰ,Ⅱ and III malocclusions were 36.64%, 54.78% and 65.83%, respectively. No significant difference were found in the detection rates of sexual organ issues and gender issues in college students with different types of malocclusions( χ 2= 0.75, 0.53, P >0.05). There were significant differences in the detection rates of appearance troubles (27.59%, 33.12%, 50.83% ) and stature troubles ( 24.09% , 31.21%, 44.17%) in students with Classes Ⅰ, Ⅱ and Ⅲ malocclusions( χ 2=5.62, 2.89, P <0.05).@*Conclusion@#The prevalence of body image issues in college students increases with severity of malocclusions. Appearance and stature troubles are issues mostly concerned among college students. Psychological evaluation for students with Class Ⅲ malocclusion should be especially emphasized when administrating orthodontic treatment.

Solubility and biological activity enhancement of docetaxel via formation of inclusion complexes with three alkylenediamine-modified ß-cyclodextrins.

Docetaxel (DTX) is an effective and commonly used chemotherapeutic drug for cancer. However, its efficacy is greatly compromised because of its toxicity and poor water solubility. In order to overcome these disadvantages, three inclusion complexes between DTX and alkylenediamine-modified ß-cyclodextrins (H1-3) with ethylene, propylene and butylene segments were prepared and characterized. The phase solubility studies demonstrated that the stoichiometry of the inclusion complexes between H1-3 and DTX were 1 : 1. The binding abilities of host H1-3 towards DTX decrease in the following order: H3 > H2 > H1, which had good consistency with the decreasing alkylene lengths of these hosts. The water solubility of DTX is remarkably increased 216, 242 and 253 times after forming inclusion complexes with H1-3, respectively. In vitro release studies of DTX from H1-3/DTX into NaAc-HAc buffer solution (pH 5.0) or PBS (pH 7.4) exhibited a preliminary stage burst effect and followed by a slow drug release. The cytotoxicity studies revealed that the H1-3/DTX inclusion complexes exhibited better cytotoxicity profiles against MCF-7, SW480 and A-549 cells than that of DTX. Furthermore, compared with the treatment of DTX, the H1/DTX inclusion complex significantly increased the cell apoptosis percentage from 17.2% to 30.2% (5 µg mL-1), 19.0% to 31.0% (10 µg mL-1), and 19.3% to 32.2% (15 µg mL-1), respectively. These results will provide useful information for H1-3/DTX inclusion complexes as safe and efficient anticancer drug formulations.

Serologic Response to SARS-CoV-2 in COVID-19 Patients with Different Severity.

The immense patient number caused by coronavirus disease 2019 (COVID-19) global pandemic brings the urge for more knowledge about its immunological features, including the profile of basic immune parameters. In this study, eighty-eight reported COVID-19 patients in Wuhan were recruited from January to February, 2020, including 32 severe/critical cases and 56 mild/moderate cases. Their mean age was 56.43 years (range 17-83) and gender ratio (male/female) was 43:45. We tested SARS-CoV-2 RNA with commercial kits, investigated the level of serologic IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using magnetic particle chemiluminescence immunoassays, and compared the results of serologic tests and nucleic acid test (NAT). Among 88 patients, 95.45% were confirmed as positive by the combination of NAT and antibody test, which was significantly higher (P < 0.001) than by single nucleic acid test (73.86%) or serologic test (65.91%). Then the correlation between temporal profile and the level of antibody response was analyzed. It showed that seroconversion started on day 5 after disease onset and IgG level was rose earlier than IgM. Comparison between patients with different disease severity suggested early seroconversion and high antibody titer were linked with less severe clinical symptoms. These results supported the combination of serologic testing and NAT in routine COVID-19 diagnosis and provided evidence on the temporal profile of antibody response in patients with different disease severity.

A label-free and sensitive photoluminescence sensing platform based on long persistent luminescence nanoparticles for the determination of antibiotics and 2,4,6-trinitrophenol.

The rapid detection of pollutants with high sensitivity and selectivity is of considerable significance for security screening, environmental safety, and human health. In this study, we prepared persistent luminescence nanoparticles (PLNPs) and constructed a label-free sensor for sensitive and selective detection of pollutants in real samples and test papers. Following excitation, PLNPs could store absorbed light energy and release it in the form of luminescence. Compared with a fluorescence-based technique, a PLNPs-based measurement could effectively avoid background interference. Under optimal conditions, the limit of detection for TNP was found to be 10 nM, while for an antibiotic it was 5 nM. The nanoprobe was successfully applied for the detection of pollutants in real samples including milk and Dianchi Lake water samples. Due to the long-lasting afterglow nature of PLNPs, the signal-to-noise ratio could be greatly increased in complex real samples. By hand-writing with TNP solution as ink on filter paper, the photoluminescence (PL) of the part stained with TNP was immediately quenched. Moreover, after direct exposure under a UV lamp for 10 min and without further excitation, the luminescence of the test paper was investigated to avoid interferents. This PLNP material could be potentially employed as a multi-responsive luminescent sensor. In addition, these easy-to-use visual techniques could provide a powerful tool for a convenient POC assay of organic pollutants.

A universal aptameric biosensor: Multiplexed detection of small analytes via aggregated perylene-based broad-spectrum quencher.

A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets.

Upregulation of microRNA-210 regulates renal angiogenesis mediated by activation of VEGF signaling pathway under ischemia/perfusion injury in vivo and in vitro.

BACKGROUND: MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs that regulate gene expression and function, but little is known about regulation of miRNAs in the kidneys under normal or pathologic conditions. Here, we sought to investigate the potential involvement of miRNAs in renal ischemia/reperfusion (I/R) injury and angiogenesis and to define some of the miRNAs possibly associated with renal angiogenesis. METHODS AND RESULTS: Male Balb/c mice were subjected to a standard renal I/R. CD31 immunostaining indicated a significant increase of microvessels in the ischemic region. VEGF and VEGFR2 expression were increased in renal I/R at both the mRNA and protein levels which were detected by qRT-PCR and Western blot, respectively. More importantly, 76 microRNAs exhibited more than 2-fold changes using Agilent microRNA microarray, which contains downregulation of 40 miRNAs and upregulation of 36 miRNAs. Upregulation of miR-210 was confirmed by qRT-PCR with prominent changes at 4 and 24 h after reperfusion. Furthermore, overexpression of miR-210 in HUVEC-12 cells enhances VEGF and VEGFR2 expression and promotes angiogenesis on Matrigel in vitro. CONCLUSION: These findings suggest miR-210 may be involved in targeting the VEGF signaling pathway to regulate angiogenesis after renal I/R injury, which provides novel insights into the angiogenesis mechanism of renal I/R injury.

[Change in expression of vascular endothelial growth factor in serum and wound tissue of rats with electrical burns].

OBJECTIVE: To observe the change in expression of vascular endothelial growth factor (VEGF) in serum and wound tissue of rats with electrical burn (EB), and to explore its regulation mechanism in the pathological changes of EB. METHODS: Sixty-four SD rats were divided into normal control group (n = 8) and EB group (n = 56) according to the random number table. Eight rats in EB group were sacrificed at post injury hour (PIH) 6 and on post injury day (PID) 1, 3, 7, 14, 21, and 28, to collect wound muscle tissue and serum samples. Histopathological changes in wound tissue were observed with HE staining. The serum content of VEGF was determined with double-antibody sandwich enzyme-linked immunosorbent assay. The expression level of VEGF in wound tissue was determined with Western blotting. VEGF expression intensity in wound tissue was observed with immunohistochemical staining. The microvessel density (MVD) was calculated. The correlation between VEGF expression intensity and MVD was analyzed. Muscle tissue of calf and serum of the rats in normal control group without any treatment were collected for above-mentioned observations and determinations. Data were processed with one-way analysis of variance and Spearman hierarchy correlation analysis, and LSD-t test was applied for paired comparison. RESULTS: (1) In EB group, breakage of muscle fiber, heavy infiltration of inflammatory cells, and obvious tissue edema were observed at PIH 6 and on PID 1; new vessels were observed on PID 3; amount of granulation tissue and number of new vessels were found to be increased on PID 7. (2) In EB group, the serum level of VEGF was (43 ± 11) pg/mL at PIH 6, (44 ± 11) pg/mL on PID 1, and (74 ± 27) pg/mL on PID 14, which were all significantly higher than that in normal control group [(15 ± 9) pg/mL, with t values from 4.001 to 5.724, P values all below 0.01]. (3) The protein expression level of VEGF of wound tissue in EB group was higher than that in normal control group (0.21 ± 0.09) at each time point. The protein expression level of VEGF in EB group peaked on PID 7 (0.63 ± 0.13, t = 4.965, P < 0.05). (4) In EB group, strongly positive expression of VEGF was observed in inflammatory cells at early stage and in new vascular endothelial cells at late stage. (5) The expression intensity of VEGF was positively correlated with MVD in wound tissue on PID 3, 7, 14, 21, and 28 in EB group (r(s) = 0.834, P < 0.01). CONCLUSIONS: Different expression levels of VEGF were observed in serum and wound tissue of rats at various stages after EB, and they were closely correlated with different stages of fluid exudation and wound healing process after EB.