Isosilybin A exhibits anti-inflammatory properties in rosacea by inhibiting MAPK pathway and M1 macrophage polarization.

Rosacea is a chronic inflammatory skin disease, which is prone to flares and requires continuous management and treatment. However, long-term use of drugs can lead to additional adverse drug reactions. Based on the comorbid relationship between rosacea and Parkinson's disease, bioinformatics and network pharmacology analysis were used to identify a safer drug for rosacea. It has been demonstrated that ISA has an ameliorative impact on the symptoms of Parkinson's disease. The results demonstrated that ISA exhibited anti-inflammatory properties, including reducing erythema areas and inflammatory cell infiltration in rosacea-like mice models, and inhibiting the expression of inflammatory factors in cellular inflammation models. Furthermore, the anti-inflammatory effect of ISA was associated with inhibition of the Erk, p38 and NF-κB signaling pathways and inhibition of macrophage polarization to M1 type. In addition, molecular docking and drug affinity responsive target stability experiment results indicated that VEGFA and RELA were the direct targets of ISA in the treatment for rosacea. In conclusion, these results suggested that ISA may be a potential therapeutic agent for rosacea.

Association of triglyceride glucose index and triglyceride glucose-body mass index with sudden cardiac arrest in the general population.

BACKGROUND: Insulin resistance (IR) significantly contributes to cardiovascular disease (CVD) development. Triglyceride glucose (TyG) index and triglyceride glucose-body mass index (TyG-BMI) are recognised as convenient proxies for IR. However, their relationship with sudden cardiac arrest (SCA) remains unclear. METHODS: This prospective cohort analysis included 355,242 UK Biobank participants with available TyG index and TyG-BMI data and no history of CVD. Cox proportional risk models assessed the association between the TyG index, TyG-BMI and SCA risk. Additionally, Accelerated Failure Time (AFT) models were employed to investigate the timing of SCA onset. The impact of dynamic increases in TyG index and TyG-BMI levels on SCA risk was examined using restricted cubic spline. RESULTS: Over a median follow-up period of 165.4 months (interquartile range 156.5-174 months), 1,622 cases of SCA were recorded. Multivariate Cox regression analysis revealed a 9% increase in SCA risk per standard deviation increase in TyG index (adjusted hazard ratio (aHR) = 1.09, 95% confidence interval (CI) 1.04-1.15) and an 14% increase per standard deviation increase in TyG-BMI (aHR 1.14, 95% CI 1.09-1.2). AFT models indicated earlier median times to SCA occurrence with increasing quintiles of TyG index and TyG-BMI compared to the lowest quintile (P for trend < 0.05). SCA risk was linearly (P = 0.54) and non-linearly (P = 0.007) correlated with gradual increases in TyG index and TyG-BMI levels, respectively. Sex-stratified analyses showed stronger associations in women. CONCLUSIONS: Higher TyG index and TyG-BMI levels are associated with an increased SCA risk and earlier onset, particularly in women.

The Effects of VR-assisted and Overground Gait Adaptation Training on Balance and Walking Ability in Stroke Patients.

OBJECTIVE: This study compared the effects of virtual reality(VR)-assisted gait adaptation training with the overground gait adaptation training on balance and walking in patients with stroke. METHODS: Fifty-four eligible patients were enrolled. All patients were randomly divided into a VR and control group, with 27 patients in each group. The VR group received VR-assisted training on the treadmill, whereas the control group received overground training in a physical therapy room. After the intervention, patients were assessed using walking speed, obstacle avoidance ability, timed up and go (TUG) test, postural stability, and the Barthel Index (BI). RESULTS: Significant improvements in walking speed, obstacle avoidance ability, TUG test and eye-opening center of pressure (COP) speed were observed after the intervention (P < 0.05). No statistically significant differences were found in eye-closing COP speed, tandem COP speed, single-leg COP speed, and BI (P > 0.05). CONCLUSIONS: Stroke patients may benefit from VR-assisted gait adaptation training in improving walking and static balance function and reducing the risk of falls.

Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord

We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC

Morvan syndrome associated with LGI1 antibody: a case report.

BACKGROUND: Morvan syndrome (MoS) is a rare autoimmune syndrome associated with antibodies against two kinds of potassium channel proteins, contactin associated protein-like 2 (CASPR2) and leucine-rich glioma inactivated protein 1 (LGI1). MoS patients with only LGI1-antibody seropositivity have rarely been reported. Here, we describe a 64-year-old male MoS patient with only LGI1-antibody seropositivity. CASE PRESENTATION: A 64-year-old male patient was referred to our hospital due to limb pain, widespread myokymia, insomnia, constipation, and hyperhidrosis for 1 month. The patient was diagnosed with MoS based on the clinical symptoms and positive LGI1-antibody in serum. He was treated with intravenous immunoglobulin (IVIG), intravenous methylprednisolone followed by oral prednisone, and other drugs for symptomatic relief. Several days later, myokymia and insomnia symptoms improved. After 60 days of follow-up, all the drugs had been stopped for 2 weeks, and the patient achieved complete remission without any medical side effects. CONCLUSION: We report the clinical characteristics of a Chinese MoS patient with only LGI1-antibody seropositivity, and further support the view that non-neoplasm MoS patients respond well to immunotherapy.

Correlation Between SIRT2 3'UTR Gene Polymorphism and the Susceptibility to Alzheimer's Disease.

The purpose of this study is to investigate the correlation between single-nucleotide polymorphism (SNP) at the 3' end of the untranslated region (UTR) of Sirtuin 2 (SIRT2) gene and the risk of developing Alzheimer's disease (AD), and to explore its underlying mechanisms. In total, 260 patients with AD and 260 healthy controls were recruited in this study. The genotype of rs2015 and rs2241703 loci of the SIRT2 gene was analyzed by Sanger sequencing for all participants. Quantitative real-time Polymerase chain reaction (qRT-PCR) was used to analyze microRNAs (miRNAs) and SIRT2 mRNA levels. Western blotting was used to analyze the expression level of SIRT2 protein. The dual luciferase reporter gene assay and cell transfection were performed to examine the role of miRNAs in regulating SIRT2 expression. Carriers of the SIRT2 gene rs2015 locus A allele were 0.69 times less likely to develop AD than the carriers of the C allele (95% confidence interval (CI): 0.59-0.80, p < 0.01). The carriers of the SIRT2 gene rs2241703 locus A allele were 1.43 times more likely to develop AD than the carriers of the G allele (95% CI: 1.23-1.61, p < 0.01). The rs2015 locus single-nucleotide polymorphism (SNP) affected the binding efficiency between miR-376a-5p and miR-8061 and the 3'UTR of the SIRT2 gene, and miR-376a-5p and miR-8061 bound to SIRT2 rs2015 A allele to down-regulate the expression of the SIRT2 protein. The rs2241703 SNP affected the binding efficiency between miR-486-3p and the 3'UTR of SIRT2 gene, and miR-486-3p bound to SIRT2 rs2241703 A allele to down-regulate SIRT2 protein expression. The SIRT2 gene rs2015 and rs2241703 loci SNPs are associated with the risk of AD. The rs2015 locus SNP affects regulation of miR-376a-5p and miR-8061 in SIRT2 expression and the rs2241703 locus SNP affects regulation of miR-486-3p in SIRT2, but further studies are needed to verify this mechanism.

Long noncoding RNA eosinophil granule ontogeny transcript inhibits cell proliferation and migration and promotes cell apoptosis in human glioma.

Glioma is the most common primary brain tumor and represents one of the most aggressive and lethal types of human cancer. Recent advances have implicated long noncoding RNAs (lncRNAs) as crucial mediators of cancer development and progression. The present study aimed to investigate the role of a newly-discovered lncRNA, termed eosinophil granule ontogeny transcript (EGOT), in the aggressive abilities of cells in human glioma. It was initially found that the relative transcription level of EGOT in glioma cancerous tissues was significantly lower than that in adjacent non-cancerous tissues. EGOT was differentially expressed in a series of glioma cell lines, with its lowest level in high aggressive U251 and U87 cells. When EGOT was overexpressed by an expression plasmid, cell viability was significantly inhibited in U251 and U87 cells. Furthermore, with EGOT overexpression, the cell cycle was arrested at G0/G1 phase and consequently, cell apoptosis was significantly promoted along with the activities of caspase-3 and caspase-9. The migration abilities of EGOT-overexpressed cells were inhibited by 71.4% in U251 cells and by 69.5% in U87 cells. These data suggest that overexpression of EGOT inhibits cell proliferation and migration, and promotes cell apoptosis in glioma. Therefore, EGOT has potent anticancer activity and may function as a tumor suppressor in human glioma.

[Observation on effect of Wuling Capsule in treating poststroke depression].

OBJECTIVE: To evaluate the efficacy of Wuling Capsule (WLC) in treating patients with poststroke depression. METHODS: One hundred and eight patients with poststroke depression were randomly assigned to three groups, 36 in each. All were treated with routine medicine, but to the WLC group and the FLX group, additional WLC and fluoxetine was given respectively, while to the combined group, both of the two were given. Patients' neurological and cognitive function were estimated by HAMI) scale, MMSE scale, SSS scale and Barthel index (BI) before treatment and at 4 weeks and 12 weeks after treatment. RESULTS: HAMD score and SSS score significantly decreased (P < 0.01) while MMSE score and BI score significantly increased (P <0.05) in all the three groups, but the improvement in decrease of HAMD score and in increase of BI score in the combined group was more significant than those in the other two groups respectively (P<0.05). CONCLUSIONS: WLC is effective in treating patients with poststroke depression and shows synergism with fluoxetine.