Effect of YKL-40 RNA Interference on VEGF Gene Polymorphism Expression in Atherosclerotic Mice

Aims: To investigate the effect of YKL-40 RNA interference on VEGF gene polymorphism expression in atherosclerotic mice. Methods: After the atherosclerosis models in mice were built, the mice were divided into three groups including control group, negative control group and observation group, which were separately given to normal saline, negative virus (5 × 107 TU) and YKL-40 RNA interference lentivirus. Then the whole blood DNA was extracted and genotyped in each group of mice and the expression of VEGF in each group of mice was detected by PCR, while the expression level of inflammatory factors in each group of mice was detected by ELISA. Meanwhile, the aortas of mice in each group were pathologically analyzed and the atherosclerosis of mice was detected. Results: Compared with the control group, the VEGF content in both the virus negative control group and the observation group was significantly increased（P<0.05）. The detection rates of CC genotype and C allele at rs699947 of VEGF gene in the observation group were significantly higher than those in the control group and the virus negative control group, and the difference was statistically significant. There were no significant changes for the expression of HDL-C, LDL-C, TC and TG in mice of each group（P>0.05）. Moreover, the levels of Lp-PLA2 and MCP-1 in the negative control group were significantly increased (P < 0.05), while those in the observation group were significantly decreased (P < 0.05) compared to that in control group. What’s more, the histomorphology of the observation group was significantly different from that of the control group and the virus negative control group. The thickness of the fibrous cap of the as plaque was significantly higher than that of the control group and the virus negative control group, but the plaque area and fat content were significantly lower than that of the control group and the virus negative control group and the NC group. Besides, there was no significant difference in lipid content, fiber cap thickness and plaque area between the control group and the virus negative control group. Conclusion: YKL-40 RNAi could improve the VEGF polymorphism, reduce the expression of LPâƒPLA2 and MCPâƒ1, and significantly inhibit the occurrence and development of atherosclerosis, which was expected to provide a new target for the prevention and treatment of atherosclerosis

FUS-NLS/Transportin 1 complex structure provides insights into the nuclear targeting mechanism of FUS and the implications in ALS

The C-terminal nuclear localization sequence of FUsed in Sarcoma (FUS-NLS) is critical for its nuclear import mediated by transportin (Trn1). Familial amyotrophic lateral sclerosis (ALS) related mutations are clustered in FUS-NLS. We report here the structural, biochemical and cell biological characterization of the FUS-NLS and its clinical implications. The crystal structure of the FUS-NLS/Trn1 complex shows extensive contacts between the two proteins and a unique α-helical structure in the FUS-NLS. The binding affinity between Trn1 and FUS-NLS (wide-type and 12 ALS-associated mutants) was determined. As compared to the wide-type FUS-NLS (K(D) = 1.7 nM), each ALS-associated mutation caused a decreased affinity and the range of this reduction varied widely from 1.4-fold over 700-fold. The affinity of the mutants correlated with the extent of impaired nuclear localization, and more importantly, with the duration of disease progression in ALS patients. This study provides a comprehensive understanding of the nuclear targeting mechanism of FUS and illustrates the significance of FUS-NLS in ALS

The enzymatic activity of Arabidopsis protein arginine methyltransferase 10 is essential for flowering time regulation

Arabidopsis AtPRMT10 is a plant-specific type I protein arginine methyltransferase that can asymmetrically dimethylate arginine 3 of histone H4 with auto-methylation activity. Mutations of AtPRMT10 derepress FLOWERING LOCUS C (FLC) expression resulting in a late-flowering phenotype. Here, to further investigate the biochemical characteristics of AtPRMT10, we analyzed a series of mutated forms of the AtPRMT10 protein. We demonstrate that the conserved "VLD" residues and "double-E loop" are essential for enzymatic activity of AtPRMT10. In addition, we show that Arg54 and Cys259 of AtPRMT10, two residues unreported in animals, are also important for its enzymatic activity. We find that Arg13 of AtPRMT10 is the auto-methylation site. However, substitution of Arg13 to Lys13 does not affect its enzymatic activity. In vivo complementation assays reveal that plants expressing AtPRMT10 with VLD-AAA, E143Q or E152Q mutations retain high levels of FLC expression and fail to rescue the late-flowering phenotype of atprmt10 plants. Taken together, we conclude that the methyltransferase activity of AtPRMT10 is essential for repressing FLC expression and promoting flowering in Arabidopsis

Oral mucosal manifestations of Sweet’s syndrome: a case report and literature review

Objective To explore the oral mucosal manifestations of Sweet’s syndrome and provide a reference for its early detection and correct diagnosis. Methods The oral mucosal manifestations of a 60-year-old female patient with Sweet’s syndrome are described in detail, followed by a discussion of the related literature. Results The patient had skin erythema of both lower extremities, which was accompanied by oral mucosal ulceration and pain for 3 days. The patient presented with mild cutaneous lesions and diffuse large-scale erosion in the oral mucosa with obvious pain. During the onset of the disease, the patient was accompanied by fever with a temperature of 38.5°C. After visiting the Department of Stomatology, laboratory tests showed an increase in C-reactive protein (35.2 mg/L) and an accelerated erythrocyte sedimentation rate (77.00 mm/h). Scattered red plaques and mild tenderness were observed in the knees and lower limbs. Histopathological examination of the skin lesions revealed scattered infiltration of immature neutrophils across the entire dermis. The patient responded well to glucocorticoid therapy. According to the clinical signs and laboratory examination, combined with the lesion histopathological results, a diagnosis of Sweet’s syndrome was given. The patient was administered 1 mL compound Betamethasone injection only once intramuscularly. In the meantime, the patient was asked to gargle with compound chlorhexidine solution and topically apply recombinant bovine basic fibroblast growth factor solution to the damaged mucosa three times a day for 1 week. After 4 days of medication, the patient’s body temperature had returned to normal and the oral lesions were significantly reduced. After 2 weeks, the erythema in the leg and knee had almost all subsided, and the oral mucosal lesions had disappeared. The patient was followed up 6 months after treatment, with no recurrence of skin lesions. After 2 years of follow-up, the disease was stable with no recurrence. A review of the relevant literature shows that Sweet’s syndrome is a rare inflammatory reactive dermatosis with unknown etiology, which can be divided into three clinical types: specific, tumor-related, and drug-induced. The male/female prevalence ratio is 1:4. The salient clinical manifestations are abrupt onset of painful erythematous plaques or nodules most commonly involving the extremities, often accompanied by pyrexia, elevated neutrophil count, elevation of the erythrocyte sedimentation rate, and positive C-reactive protein. The use of glucocorticoids is the most common treatment for this disease, and most patients see a rapid improvement in skin lesions; however, some may experience infection or recurrence after withdrawal. Some patients with Sweet’s syndrome are accompanied by oral lesions, but cases of oral mucosal damage have been rarely reported, and this condition is easily misdiagnosed. Conclusion Oral mucosal lesions may be extraterritorial manifestations of Sweet’s syndrome, and the patient’s systemic condition should be comprehensively considered. Skin biopsy should be completed as soon as possible to make a clear diagnosis, so as not to delay the disease