Effect of hexavalent chromium exposure on the reproductive status and biomarker responses of female Geloina erosa.

Hexavalent chromium (Cr (VI)) is widely distributed in the marine environment of Hainan Province, China and poses a potential threat to its mangrove ecosystems. However, the mechanisms underlying Cr-induced stress and reproductive toxicity in clams remain largely unknown. In this study, the clams, Geloina erosa, were exposed to 4.34, 8.69, 17.38 and 34.76 mg/L Cr (VI) for 24, 48 and 72 h. The gonad-somatic index (GSI) was determined and histological alterations of the ovaries were quantified by light microscopy. The micronucleus test was performed which quantifies the genotoxic presence of small cytoplasmic bodies in eukaryotic cells. Enzymatic assays for catalase (CAT), glutathione reductase (GR), and malondialdehyde (MDA) activities were done. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of glutathione-S-transferase (GST), heat shock protein 70 (HSP70) and vitellogenin (Vtg) in ovaries of G. erosa. The results showed that the micronucleus frequency was significantly increased when clams were exposed to Cr (VI). Cr (VI) exposure induced the accumulation of MDA and affected CAT and GR enzyme activities. The high Cr (VI) concentration of 34.76 mg/L significantly increased the levels of GR activity, GST expression and HSP70 expression and inhibited Vtg expression and CAT activity. MDA content was significantly increased after 72 h at the high Cr (VI) exposure (34.76 mg/L). Therefore, Cr (VI) exposure may be toxic to the development of ovaries of G. erosa.

Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge

The ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer protective immune responses against SARS-CoV-2 challenge due to the insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pulmonary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). Not only displays the pSpike/PP-sNp superior gene-transfection and favorable biocompatibility in the mouse airway, but pSpike/PP-sNp promotes a tripartite immunity consisting of systemic, cellular and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp might be a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.

Speciation Analysis of Chromium in Chromium-Enriched Yeast by Ion Chromatography-Inductively Coupled Plasma Mass Spectrometry.

Chromium-enriched yeast (CrY) is a popular Cr dietary supplement, but suitable speciation analysis of highly toxic Cr(VI) in CrY is not available. Ion chromatography-inductively coupled plasma mass spectrometry method was firstly developed and validated for the quantification of Cr(III) and Cr(VI). Ultrasound-assisted weakly alkaline EDTA solution combined with boiling was used to extract two Cr species in CrY. Two species were separated on two successive anion-exchange columns using a mobile phase of 0.6 mmol/L EDTA and 76 mmol/L NH4NO3 solution. The method was sensitive, accurate (92.4-100.9%), and precise (0.8-3.1%). Species of Cr(VI) were not found in CrY.

Application value of self-made perianal skin nursing strategy of device in the severe diarrhea or fecal incontinence / 中国实用护理杂志

Objective@#To explore the application effect of self-made nursing strategy of device in the severe diarrhea or fecal incontinence.@*Methods@#A total of 60 patients with severe diarrhea or fecal incontinence were randomly divided into study group and control group according to the order of admission, each with 30 patients. The control group received traditional nursing strategy, while the study group was applied self-made perianal skin nursing strategy of device. The change of perianal skin injury, nursing workload and patients′ pain index of two groups were compared.@*Results@#The study group perianal skin injury, nursing workload and patients pain index were (0.40±0.11) points, (2.14±0.22) times/day, (1.36±0.40) points, which were better than (0.84±0.14) points, (3.58±0.29) times/day, (3.28±0.60) points in the control group (t=2.475, 3.934, 2.652, P<0.05).@*Conclusion@#self-made perianal skin nursing strategy of device could reduce the incidence of perianal skin injury, liberation of nursing work, reduce the pain of patients. Which is worthy of clinical application for its convenience.

Study on fentanyl effect in promoting the stemness of breast cancer cell via Wnt3a/β-catenin signaling pathway / 中国医师进修杂志

Objective:To explore the effect and mechanism of fentanyl on promoting the stemness of breast cancer cell.Methods:From January 2018 to October 2019, human breast cancer cell line BT549 was used as the in vitro research object. Breast cancer cell BT549 was pretreated with 0.01 and 0.10 μmol/L fentanyl. Sphere formation assay and colony formation assay were performed to investigate the role of fentanyl on breast cancer cell stemness. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was used to detect the mRNA level of stemness-related transcription factors gender-determining area Y box protein 2 (Sox2), octamer binding transcription factor 4 (Oct4) and Nanog. Western blotting assay was performed to determine the level of Wnt3a/β-catenin pathway-related markers Wnt3a, phosphorylated glycogen synthase kinase-3β (p-GSK-3β), glycogenase kinase-3β (GSK-3β) and β-catenin. After down-regulating Wnt3a, western blotting assay and sphere formation assay were performed.Results:The sphere diameter, colony formation rate and the expression of Sox2 mRNA, Oct4 mRNA, Nanog mRNA, Wnt3a, p-GSK-3β, GSK-3β and β-catenin in 0.01 and 0.10 μmol/L fentanyl-treated breast cancer cell were significant higher than those in blank control: (131.22 ± 1.06) and (636.37 ± 0.02) μm vs. (72.68 ± 0.13) μm, (41.33 ± 0.03)% and (60.58 ± 1.08)% vs. (20.93 ± 0.15)%, 2.25 ± 0.20 and 3.82 ± 0.84 vs. 1.00, 1.87 ± 1.06 and 3.35 ± 0.04 vs. 1.00, 2.85 ± 0.03 and 4.36 ± 0.50 vs. 1.00, 1.82 ± 0.03 and 2.57 ± 0.42 vs. 1.00, 2.04 ± 0.13 and 2.81 ± 0.05 vs. 1.00, 1.62 ± 0.17 and 2.93 ± 0.06 vs. 1.00, 2.15 ± 0.02 and 3.54 ± 0.21 vs. 1.00, the indexes in 0.10 μmol/L fentanyl-treated breast cancer cell were significantly higher than those in 0.01 μmol/L fentanyl-treated breast cancer cell, and there were statistical differences ( P<0.01). After down-regulating Wnt3a, the expressions of p-GSK-3β, GSK-3β, β-catenin, Sox2, Oct4 and sphere diameter were significantly lower than those in blank control: 0.12 ± 0.05 vs. 1.00, 0.53 ± 0.06 vs. 1.00 and 0.24 ± 0.21 vs. 1.00, 0.28 ± 0.10 vs. 1.00 and 0.06 ± 0.01 vs. 1.00, (18.14 ± 0.30) μm vs. (74.32 ± 0.12) μm, and there were statistical differences ( P<0.01). Conclusions:Fentanyl promotes breast cancer cell stemness by Wnt3a/β-catenin signaling pathway.

Application value of self-made perianal skin nursing strategy of device in the severe diarrhea or fecal incontinence / 中国实用护理杂志

Objective:To explore the application effect of self-made nursing strategy of device in the severe diarrhea or fecal incontinence.Methods:A total of 60 patients with severe diarrhea or fecal incontinence were randomly divided into study group and control group according to the order of admission, each with 30 patients. The control group received traditional nursing strategy, while the study group was applied self-made perianal skin nursing strategy of device. The change of perianal skin injury, nursing workload and patients ′ pain index of two groups were compared. Results:The study group perianal skin injury, nursing workload and patients pain index were (0.40±0.11) points, (2.14±0.22) times/day, (1.36±0.40) points, which were better than (0.84±0.14) points, (3.58±0.29) times/day, (3.28±0.60) points in the control group ( t=2.475, 3.934, 2.652, P<0.05). Conclusion:self-made perianal skin nursing strategy of device could reduce the incidence of perianal skin injury, liberation of nursing work, reduce the pain of patients. Which is worthy of clinical application for its convenience.

MYC modulators in cancer: a patent review.

INTRODUCTION: The important role of MYC in tumorigenesis makes it particularly important to design MYC modulators. Over the past decade, researchers have raised a number of strategies for designing MYC modulators, some of which are already in clinical trials. This paper aims to review the patents of MYC modulators. AREAS COVERED: The important biological relevance of c-MYC and the regulation pathways related to c-MYC are briefly introduced. Base on that, the MYC modulators reported in published patents and references primarily for cancer treatment are outlined, highlighting the structures and biological activities. EXPERT OPINION: There has been a growing awareness of finding and designing MYC modulators as novel anticancer drugs over recent years. Patents involving the discovery, synthesis, and application of MYC modulators are particularly important for further development in this field. Although finding direct MYC inhibitors or binders is challenging, MYC cannot be simply defined as an undruggable target. There is still substantial evidence proving the concept that MYC modulators can benefit to the treatment of both human hematological malignancies and solid tumors. More efforts should be taken to improve the activity and specificity of MYC modulators.

Developing Novel G-Quadruplex Ligands: from Interaction with Nucleic Acids to Interfering with Nucleic Acid⁻Protein Interaction.

G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.

Effects of fentanyl on proliferation and apoptosis of H1299 cells by modulating AKT activation / 中国医师进修杂志

Objective To explored the effects of fentanyl on cell proliferation of H1299 cells, Methods After treating H1299 cells with different concentrations of fentanyl (0.001, 0.010, 0.100, 1.000 μM) for 12, 24, 48, 72 h, cell viability was detected by CCK-8 assay; the rate of cell apoptosis was determined by DAPI staining; the expression levels of Bax, Bcl-2, p-AKT and AKT protein were measured by Western blotting; Caspase-3 activity was determined by Caspase-3 activity assay kit. Results Compared with the control group, fentanyl obviously inhibited the viability of H1299 cells in a dose and time dependent way. Moreover, treatment with different concentrations of fentanyl(0.001, 0.010, 0.100, 1.000 μM) for 12, 24, 48, 72 h, the apoptosis rate of H1299 cells were significantly increased, The level of Bcl-2 protein reduced the level of Bax protein, and the activity of Caspase-3 in H1299 cells were increased after treatment with fentanyl (0.010, 0.100, 1.000 μM) for 48 h, Furthermore, fentanyl markedly inhibited p-AKT/AKT activity of H1299 cells. Conclusions Fentanyl can inhibit cell proliferation and promote cell apoptosis of human lung cancer, and its mechanism may be related to inhibition of AKT activation ,

Design, Synthesis, and Evaluation of Novel p-(Methylthio)styryl Substituted Quindoline Derivatives as Neuroblastoma RAS (NRAS) Repressors via Specific Stabilizing the RNA G-Quadruplex.

The human proto-oncogene neuroblastoma RAS ( NRAS) contains a guanine-rich sequence in the 5'-untranslated regions (5'-UTR) of the mRNA that could form an RNA G-quadruplex structure. This structure acts as a repressor for NRAS translation and could be a potential target for anticancer drugs. Our previous studies found an effective scaffold, the quindoline scaffold, for binding and stabilizing the DNA G-quadruplex structures. Here, on the basis of the previous studies and reported RNA-specific probes, a series of novel p-(methylthio)styryl substituted quindoline (MSQ) derivatives were designed, synthesized, and evaluated as NRAS RNA G-quadruplex ligands. Panels of experiments turned out that the introduction of p-(methylthio)styryl side chain could enhance the specific binding to the NRAS RNA G-quadruplex. One of the hits, 4a-10, showed strong stabilizing activity on the G-quadruplex and subsequently repressed NRAS's translation and inhibited tumor cells proliferation. Our finding provided a novel strategy to discover novel NRAS repressors by specifically binding to the RNA G-quadruplex in the 5'-UTR of mRNA.

Comparison of the Oral Absorption, Distribution, Excretion, and Bioavailability of Zinc Sulfate, Zinc Gluconate, and Zinc-Enriched Yeast in Rats.

SCOPE: The oral absorption, distribution, excretion, and bioavailability of zinc sulfate (ZnS), zinc gluconate (ZnG), and zinc-enriched yeast (ZnY) in rats are fully and systemically compared for the first time. METHODS AND RESULTS: After zinc compounds were orally administered to rats at a single dose of 4 mg Zn kg-1 , blood, tissues, urine, and feces at different time points were collected for the quantification of zinc concentration. Blood was also harvested for the zinc assay in the multiple-dose administration. Plasma zinc levels among three zinc compounds showed no difference, and zinc was widely distributed in various tissues with the level sequence of bone > liver > pancreas > testes. The net Zn balance was 2.993, 5.125, and 7.482% for ZnS, ZnG, and ZnY, respectively. CONCLUSION: ZnS, ZnG, and ZnY show equivalent bioavailability based on plasma and tissues zinc levels, although ZnY was statistically more absorbed and retained than ZnS and ZnG based on the excretion amount.

Effect of intrathecal parecoxib sodium in bone tumor pain of rats / 中国医师进修杂志

Objective To investigate the effect of intrathecal parecoxib sodium in bone tumor pain of rats. Methods Bone tumor pain was induced by injection of MRMT-1 tumor cells (1 × 104/L) into the tibia of female SD rats under sevoflurane anesthesia. The development of bone tumor was monitored by radiological study, and histological sections stained with hematoxylin and eosin. At 3 d after MRMT-1 tumor cell injection, a PE-10 catheter was inserted into the intrathecal space for drug administration. At 10 d after MRMT-1 tumor cell injection, rats were randomly divided into 5 equal groups, control group, parecoxib sodium 0.1, 0.3, 1.0 and 3.0 g/L group. For pain assessment, a withdrawal threshold was measured using von Frey filament being applied to the tumor cell inoculation site. The effects of intrathecal saline or parecoxib sodium were investigated. Results Intra-tibial injection of MRMT-1 tumor cells produced a bone tumor in radiologic and pathologic findings.Also, the paw withdrawal threshold was significantly decreased(mechanical allodynia).Percentage of the maximal possible effect (% MPE) of control group and parecoxib sodium 0.1, 0.3, 1.0 and 3.0 g/L group was (13.89 ± 4.17)%,(7.54 ± 3.91)%,(57.47 ± 11.47)%,(85.72 ± 9.42)% and(100.00 ± 0.00)%,compared with control group, intrathecal parecoxib sodium dose-dependently increased the withdrawal threshold (P<0.05).Conclusions Intrathecal parecoxib sodium reduces bone tumor-related pain behavior.

Investigating quality of life and self-stigma in Hong Kong children with specific learning disabilities.

BACKGROUND: Children with specific learning disabilities (SpLD) are likely to develop self-stigma and have a poor quality of life (QoL) because of their poor academic performance. Although both self-stigma and poor QoL issues are likely to be found in low academic achievers without SpLD, children with SpLD have worse situation because their diagnosis of SpLD suggests that their learning struggles are biological and permanent. Specifically, students' perception of own capabilities may be affected more by the diagnosis of SpLD than their own actual performance. AIMS: We examined the self-stigma and QoL of children with SpLD in Hong Kong, a region with an academics-focused culture. METHODS AND PROCEDURES: Children with SpLD (n=49,Mage±SD=9.55±1.21; SpLD group) and typically developing children (n=32,Mage±SD=9.81±1.40; TD group) completed a Kid-KINDL to measure QoL and a Modified Self-Stigma Scale to measure self-stigma. All parents completed a parallel Kid-KINDL to measure QoL of their children. OUTCOMES AND RESULTS: Compared with the TD group, the SpLD group had a higher level of self-stigma (p=0.027) and lower QoL (child-reported Kid-KINDL: p=0.001; parent-reported Kid-KINDL: p<0.001). CONCLUSIONS AND IMPLICATIONS: In the academics-focused environment in Hong Kong, SpLD was associated with impaired QoL and higher self-stigma. Treatments targeting the learning process of children with SpLD may be designed to overcome self-stigma and to improve QoL. In addition, the program may involve parents of the children with SpLD or other people (e.g., the peer of the children with SpLD) for improving their understanding and perceptions of SpLD.