Relationship between CD274 gene polymorphism and systemic lupus erythematosus risk in a Chinese Han population.

OBJECTIVE: Relationship between surface antigen differentiation cluster 274 (CD274) gene polymorphism and systemic lupus erythematosus (SLE) risk is limited. This study aims to discuss whether in a Chinese Han population, CD274 gene polymorphisms may relate to SLE susceptibility. METHODS: Three hundred and ten SLE patients and 390 healthy controls were included in this case-control study. Using the Kompetitive Allele-Specific PCR (KASP) approach, five single nucleotide polymorphisms (SNPs), including rs2890658, rs4143815, rs822339, rs2282055, and rs2297137, were genotyped for CD274 gene polymorphisms. Correlation between the polymorphisms and clinical, laboratory features in SLE patients were discussed. RESULTS: Frequency of C allele was substantially lower in SLE patients than in healthy controls (p = .015), and CC genotype was significantly negatively related to developing SLE at locus rs4143815 (p = .013). At locus rs822339, frequency of GA genotype was higher than that of the healthy controls (p = .006). At locus rs2282055, frequency of GG genotype was lower than that of healthy controls (p = .024). According to subgroup analysis, the CD274 gene polymorphisms rs2890658, rs4143815, rs822339, rs2282055, and rs2297137 were partly linked to some clinical symptoms of SLE patients, such as Complement 4 (C4), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). CONCLUSION: CD274 gene polymorphisms may be susceptible to SLE in the Chinese Han people.

Biology of endophilin and it's role in disease.

Endophilin is an evolutionarily conserved family of protein that involves in a range of intracellular membrane dynamics. This family consists of five isoforms, which are distributed in various tissues. Recent studies have shown that Endophilin regulates diseases pathogenesis, including neurodegenerative diseases, tumors, cardiovascular diseases, and autoimmune diseases. In vivo, it regulates different biological functions such as vesicle endocytosis, mitochondrial morphological changes, apoptosis and autophagosome formation. Functional studies confirmed the role of Endophilin in development and progression of these diseases. In this study, we have comprehensively discussed the complex function of Endophilin and how the family contributes to diseases development. It is hoped that this study will provide new ideas for targeting Endophilin in diseases.

Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.

RATIONALE: Deregulated attack behaviors have devastating social consequences; however, satisfactory clinical management for the behavior is still an unmet need so far. Social isolation (SI) has been common during the COVID-19 pandemic and may have detrimental effects on mental health, including eliciting heightened attack behavior. OBJECTIVES: This study aims to explore whether injection of ZL006 can alleviate SI-induced escalation of attack behavior in mice. METHODS: Pharmacological tools, biochemical methods, and behavioral tests were used to explore the potential therapeutic effects of ZL006 targeting postsynaptic density 95 (PSD95)/neuronal nitric oxide synthase (nNOS) pathway on escalation of attack behavior induced by SI in mice. RESULTS: ZL006 mitigated SI-induced escalated attack behaviors and elevated nitric oxide (NO) level in the cortex of the SI mice. The beneficial effects of ZL006 lasted for at least 72 h after a single injection of ZL006. Potentiation of NO levels by L-arginine blocked the effects of ZL006. Moreover, a sub-effective dose of 7-NI in combination with a sub-effective dose of ZL006 decreased both SI-induced escalated attack behaviors and NO levels in mice subjected to SI. CONCLUSIONS: Our study highlights the importance of the PSD95/nNOS pathway in mediating SI-induced escalation of attack behavior. ZL006 may be a promising therapeutic strategy for treating aggressive behaviors.

[Rapid determination of 25 drug residues in aquatic products by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry].

An ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UPLC-Q Orbitrap HRMS) method was developed for the rapid screening of 25 drug residues in aquatic products by the application of a novel enhanced matrix removal of lipids (EMR-Lipid). The samples were extracted with acetonitrile, cleaned-up with EMR-Lipid, and salted out with 3.0 g sodium chloride and 3.0 g sodium sulfate. The separation of the 25 drug residues was performed on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) with gradient elution. Acetonitrile containing 0.1% (v/v) formic acid and 0.1% (v/v) formic acid aqueous solution were used as mobile phases. The compounds were detected by Full scan/date dependent MS/MS (Full MS/dd-MS2) via heated electrospray ionization (HESI) source. The calibration curves were linear with correlation coefficients (r) greater than 0.997. The limits of detection (LODs) ranged from 0.1 µg/kg to 1.0 µg/kg. The average spiked recoveries of the 25 target compounds were between 70.1% and 108.9% with relative standard derivations (RSDs) from 2.1% to 13.8%. Compared with the previous methods, this method has characteristics of simpler sample preparation and higher sensitivity.

[Rapid screening of 24 tranquillizer drugs in fish and fishery products by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectroscopy].

A method was developed for the simultaneous determination of 24 tranquillizer drugs in fish and fishery products using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). The samples were extracted with acetonitrile. Then, the extracts were concentrated, dissolved by 50% (v/v) methanol aqueous solution, cleaned up with hexane saturated by acetonitrile. The separation was performed on an ACQUITY UPLC® BEH C18 column (100 mm×2.1 mm, 1.7 µm) with the gradient elution using acetonitrile and water both containing 0.1% (v/v) formic acid as mobile phases. The drugs were analyzed by full MS scan/data dependent MS2 (Full MS/dd-MS2)(Top 1) mode by heating electrospray ion (HESI) source. The results were quantified by external standard method. The calibration curves of the 24 tranquillizer drugs were linear in their respective linear range, the decision coefficients (r2) were no less than 0.9968. The average spiked recoveries of the 24 tranquillizer drugs were 58.9%-122.9%, and the relative standard deviations (RSDs) were 0.1%-16.4% in the six kinds of fish and fishery products at three spiked levels. The limits of quantification (LOQs) of the 24 tranquillizer drugs were 0.1-5.0 µg/kg. The method is simple, rapid, sensitive, reliable and suitable for the screening of the 24 tranquillizer drugs in fish and fishery products.

[Determination of 11 mycotoxins in baked foods and raw materials by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry].

A method for the determination of 11 mycotoxins in baked foods and raw materials by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-HRMS) is reported in this paper. The samples were extracted with 20 mL 90% (v/v) acetonitrile aqueous solution containing 1% (v/v) formic acid, and the extracts were salted out by 2.0 g MgSO4 and 0.5 g NaCl, cleaned up by 300 mg C18. The analytes were carried out on a CORTECS C18 column (100 mm×2.1 mm, 1.6 µ m) by gradient elution with 2 mmol/L ammonium acetate with 0.1% (v/v) formic acid aqueous solution and 2 mmol/L ammonium acetate methanol with 0.1% (v/v) formic acid. The results showed that the 11 mycotoxins had good linear relationships in their respective mass concentration ranges. The correlation coefficients were not less than 0.9960 and the limits of quantitation (LOQs) were from 0.15 to 20.00 µ g/kg. The recoveries of the 11 mycotoxins in bread ranged from 64.38% to 122.61% with the relative standard deviations (RSDs) from 1.52% to 12.99% at three spiked levels (n=6). The method is demonstrated to be simple, fast, highly sensitive, reliable and it is effective to detect common mycotoxins in baked foods and raw materials.

Comparative effects of EtOH consumption and thiamine deficiency on cognitive impairment, oxidative damage, and ß-amyloid peptide overproduction in the brain.

The effects of chronic EtOH consumption, associated or not with thiamine deficiency (TD), on cognitive impairment, oxidative damage, and ß-amyloid (Aß) peptide accumulation in the brain were investigated in male C57BL/6 mice. We established an alcoholic mouse model by feeding an EtOH liquid diet, a TD mouse model by feeding a thiamine-depleted liquid diet, and an EtOH treatment associated with TD mouse model by feeding a thiamine-depleted EtOH liquid diet for 7 weeks. The learning and memory functions of the mice were detected through the Y-maze test. Biochemical parameters were measured using corresponding commercial kits. The Aß expression in the hippocampus was observed by immunohistochemical staining. Several results were obtained. First, EtOH significantly reduced cognitive function by significantly decreasing the Glu content in the hippocampus; increasing the AChE activity in the cortex; and reducing the thiamine level, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and choline acetyltransferase (ChAT) activities in both the hippocampus and cortex. The treatment also increased the levels of malondialdehyde (MDA), protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), and nitric oxide (NO) and the activities of total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), and monoamine oxidase B (MAO-B). Furthermore, EtOH enhanced the expression levels of Aß1-42 and Aß1-40 in the hippocampus. Second, TD induced the same dysfunctions caused by EtOH in the biochemical parameters, except for learning ability, 8-OHdG content, and GPx, tNOS, and AChE activities in the cortex. Third, the modification of MDA, protein carbonyl and NO levels, and GPx, iNOS, ChAT, and MAO-B activities in the brain induced by chronic EtOH treatment associated with TD was greater than that induced by EtOH or TD alone. The synergistic effects of EtOH and TD on Aß1-40 and Glu release, as well as on SOD activity, depended on their actions on the hippocampus or cortex. These findings suggest that chronic EtOH consumption can induce TD, cognitive impairment, Aß accumulation, oxidative stress injury, and neurotransmitter metabolic abnormalities. Furthermore, the association of chronic EtOH consumption with TD causes dramatic brain dysfunctions with a severe effect on the brain.

[Determination of 64 veterinary drug residues in aquatic products by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry].

A method has been developed for the simultaneous determination of 64 veterinary drugs in aquatic products using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry. The samples were extracted with an acetonitrile/water mixture (80/20, v/v), cleaned up by normal hexane saturated with acetonitrile and primary secondary amine (PSA) adsorbent, quantified with external standard method. The drugs were analyzed in full scan/data dependent mass spectrum 2 (Full MS/ddMS2) Top 1 mode. The calibration curves of the 64 drugs were linear with the correlation coefficients more than 0. 9967. The average recoveries of the 64 analytes ranged from 56.2% to 124.6%, and the relative standard deviations (RSDs) were 1.3%-29.8% in the three kinds of matrixes (fish, shrimp and shell) at three levels. The limits of quantification were 0.2-10 µg/kg. The method is simple, rapid, sensitive, reliable and suitable for the screening of residues in aquatic products.