Relationship between social isolation and glycaemic control of people previously diagnosed with diabetes: secondary analysis from the CHARLS.

OBJECTIVES: Social isolation may affect diabetes self-management. This study aimed to explore the relations between social isolation and glycaemic control in patients with diabetes and to explore lifestyle differences among individuals with different levels of social isolation. METHODS: The relevant data of 665 people previously diagnosed with diabetes included in the China Health and Retirement Longitudinal Study from 2011 to 2015 were extracted and analysed. The study included patient general information, blood glucose, lipids, glycosylated haemoglobin, social isolation index, health-related lifestyle factors and diabetes-related factors. Differences in metabolic abnormalities and modifiable lifestyles were compared among patients with varying levels of social isolation. RESULTS: Multiple linear regression analysis demonstrated that among men aged 45-64 years, the high social isolation group had significantly higher glycosylated haemoglobin levels compared with the low isolation group (7.29±1.81 vs 6.59±1.63, p=0.026). A positive correlation was observed between social isolation and blood glucose (ß=14.16; 95% CI 2.75 to 25.57; p=0.015) and glycosylated haemoglobin (ß=0.35; 95% CI 0.10 to 0.60; p=0.006), indicating that higher social isolation was associated with higher fasting blood glucose and glycosylated haemoglobin levels. However, no significant associations were observed in other age groups. Notably, men aged 45-65 years with high social isolation had higher depression rates (44.10% vs 24.60%, p=0.024), lower engagement in moderate exercise (5.70% vs 23.50%, p=0.019) and shorter 10-minute walks (17.10% vs 36.80%, p=0.027). Differences in other health-related and diabetes-related factors were not statistically significant. CONCLUSION: Middle-aged men with diabetes with higher social isolation tend to have higher blood glucose and glycosylated haemoglobin levels. This subset of patients requires targeted attention to provide social support from family and friends for improved glycaemic control. If necessary, education on diabetes should be made available to family members and friends.

Genetic Association of Lipid-Lowering Drugs with Aortic Aneurysms: A Mendelian Randomization Study.

AIMS: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA. METHODS: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. RESULTS: The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, p = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, p = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, p = 1.78 × 10-04). PCSK9 (Proprotein convertase subtilisin/kexin type 9) and CETP (Cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, p = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, p = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA. CONCLUSIONS: This study provides causal evidence for the genetic association between lipid-lowering drugs and aortic aneurysms. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.

This Mendelian Randomization study used publicly available data involving over 1 million individuals to demonstrate the causal relationship between five target genes of LDL-C-lowering medicines and the risk of aortic aneurysms, and implied one lipid-lowering drug may link with the lumen size of aortic aneurysms. Key findings High expression of HMGCR, PCSK9, and CETP was positively correlated with the risk of aortic aneurysms, highlighting that the corresponding lipid-lowering drugs may be preferred for preventing arterial aneurysms in high-risk individuals with dyslipidemia. We found that genetically predicted HMGCR inhibitors were positively associated with smaller aortic lumen size, which is the first time to support the causal association of gene HMGCR on the lumen size of aortic aneurysms.

Identification of Adipogenesis Subgroups and Immune Infiltration Characteristics in Diabetic Peripheral Neuropathy.

Dysregulation of adipogenesis is related to diabetic peripheral neuropathy (DPN) pathogenesis, which may be mediated by immune infiltration. Nevertheless, the expression patterns of multiple adipogenesis-related genes and the differences of immune infiltration in different lipid metabolism levels remain unknown. GSE95849, a gene expression matrix containing DPN patients and healthy participants, was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed adipogenesis-related genes (DEARGs) were screened by overlapping the adipogenesis-related genes with differentially expressed genes (DEGs). DPN patients from GSE24290 and GSE148059 were divided into two adipogenesis subgroups according to the expression of DEARGs. The single-sample gene set enrichment analysis (ssGSEA) was used to estimate the abundance of the immune cells between two subgroups. The analysis of immune infiltration suggested that a variety of immune cells and immune processes were elevated in the high expression group of DEARGs. The differentially expressed genes of the two subgroups were mainly enriched in biological processes and signaling pathways related to lipid metabolism. PPARG, FABP4, LIPE, FASN, SCD, DGAT2, PNPLA2, ADIPOQ, LEP, and CEBPA were identified as the hub genes of the two subgroups, whose related transcription factors (TFs) and miRNAs were predicted. An immunohistochemical assay was used to verify the expression of hub genes in DPN nerve tissues. Our comprehensive analysis of adipogenesis subgroups in DPN illustrated that different expression patterns of DEARGs may lead to different immune and inflammatory states. The identification of DEARGs may help to further distinguish the different characteristics of DPN patients and lay the foundation for targeted treatment. Our findings may bring a novel perspective to the diagnosis and treatment of DPN patients.

[Relationship Between Social Isolation and Health Behaviors and Ulcer Severity in Diabetic Foot Patients].

Objective: To explore the relationship between social isolation and health behaviors and ulcer severity in patients with diabetic foot. Methods: A cross-sectional study was conducted with 160 patients suffering from type 2 diabetes mellitus combined with diabetic foot. The patients received treatment at the Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University between September 2020 and December 2021. Patient information was collected, including the scores for Lubben Social Network Scale and the Wagner classification of foot ulcers. Analysis was conducted to study the characteristics of the patients' health behaviors, including whether they received information and education on diabetic foot, whether there were delays in their attempt to access medical service, the frequency of foot examinations, etc. In addition, patient demographic data were collected, including sex, age, education, and employment status. According to their scores for Lubben Social Network Scale, the patients were divided into a social isolation group ( n=60) and a non-social-isolation group ( n=100). The severity of the foot ulcers and the health behaviors of the two groups were compared to identify differences. Results: The findings suggest that, compared with the non-social-isolation group, the social isolation group had a higher proportion of diabetic foot patients with Wagner grade 3-5 diabetic foot ulcers ( P<0.05). Analysis of the health behaviors showed that the social isolation group had a higher proportion of diabetes foot patients who had never undergone examination of their feet and those who had delayed attempts to access medical service for their condition ( P<0.05). There were no significant differences between the two groups in terms of whether the patients had received information and education concerning diabetic foot, causes of foot injury, self-treatment of wounds, smoking, and drinking. Correlational analysis suggested that the scores of Lubben Social Network Scale were negatively correlated with the delayed attempts to access medical service ( r=-0.353, P=0.001), that is, the higher the degree of social isolation, the longer the delay in patients' attempt to access medical service for their diabetic foot. Conclusions: Social isolation is correlated to health behaviors and ulcer severity in patients with diabetic foot. Giving more attention to the problem of social isolation of diabetic foot patients and increasing their ties with the social environment and the members of their social network may have a positive effect on improving the delays in diabetic foot patients' attempt to access medical service, which is particularly important for follow-up treatment.

Discovery of physalin biosynthesis and structure modification of physalins in Physalis alkekengi L. var. Franchetii.

Physalins, active ingredients from the Physalis alkekengi L. var. franchetii (P. alkekengi) plant, have shown anti-inflammatory, antioxidant and anticancer activities. Whereas the bioactivity of physalins have been confirmed, their biosynthetic pathways, and those of quite a few derivatives, remain unknown. In this paper, biosynthesis and structure modification-related genes of physalins were mined through transcriptomic and metabolomic profiling. Firstly, we rapidly and conveniently analyzed physalins by UPLC-Q-TOF-MS/MS utilizing mass accuracy, diagnostic fragment ions, and common neutral losses. In all, 58 different physalin metabolites were isolated from P. alkekengi calyxes and berries. In an analysis of the physalin biosynthesis pathway, we determined that withanolides and withaphysalins may represent a crucial intermediate between lanosterol and physalins. and those steps were decanted according to previous reports. Our results provide valuable information on the physalin metabolites and the candidate enzymes involved in the physalins biosynthesis pathways of P. alkekengi. In addition, we further analyzed differential metabolites collected from calyxes in the Jilin (Daodi of P. alkekengi) and others. Among them, 20 physalin metabolites may represent herb quality biomarkers for Daodi P. alkekengi, providing an essential role in directing the quality control index of P. alkekengi.

Two novel compounds from green walnut husks (Juglans mandshurica Maxim.).

Phytochemical investigation on the ethanol extract of green walnut husks (Juglans mandshurica Maxim.) led to the isolation of two previously unknown compounds, including a macrolide compound (13S)-8-oxo-(9E, 11E)-8-oxo-octadeca-9,11-dien-13-olide (1) and a diarylheptanoid compound 1-(3'-methoxy-4'-hydroxyphenyl)-7-(3″,4″-dimethoxyphenyl)heptan-3-one (2), together with 19 known compounds. The structures of these 21 compounds were elucidated by extensive analyses of NMR and HR-MS data, and the basis of spectroscopic analysis.

Tongmai granules improve rat hippocampal injury by regulating TLR4/MyD88/AP-1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongmai granules (TMG) is composed of Salvia miltiorrhiza Bge., Radix puerariae Lobata., and Ligusticum chuanxiong hort. TMG is mainly used for ischemic cardiovascular, cerebrovascular diseases, atherosclerosis, coronary heart disease, cerebral infarction and cerebral ischemia. TMG is a kind of traditional compound granule, which has a protective effect on brain injury. However, the potential protective mechanism of the TMG has not been elucidated. AIM OF THE STUDY: TMG has a good effect on brain injury, but its brain protective mechanism is still unclear. The purpose of this study was to confirm the neuroprotective mechanism of TMG, reveal its target genes and identify the active components of TMG. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to identify the fingerprint of TMG. UPLC-Q-TOF-MSE was used to analyze the base peak intensity (BPI) chromatograms of TMG. TMG was pre-administered for one week, brain injury and edema were induced by injection of glutamate (Glu) into the lateral ventricles of rats. HE staining was used to investigate the pathological damage caused by Glu in the hippocampus of rats, and the RNA-seq was used to analyze the changes of different genes before and after TMG treatment. Finally, changes of related proteins were analyzed by qRT-PCR, Western blot, and other molecular biological methods. Dosage of TMG were set to 0.6 g/kg, 1.2 g/kg and 2.4 g/kg. RESULTS: We found that TMG contained many active components, including salvianolic acid, puerarin, ferulic acid, etc. TMG could improve cerebral edema and brain injury induced by Glu. After TMG treatment, differential gene analysis showed that differential genes were significantly enriched in toll-like receptor signaling pathway. qRT-PCR validation results were consistent with RNA-Seq analysis results. Combined with Western blot analysis, we found that TMG ultimately regulated the expression of inflammatory cytokines by affecting the TLR4/MyD88/AP-1 pathway. CONCLUSIONS: In this study, we combined TMG with RNA-seq analysis to demonstrate that TMG may play a neuroprotective role by regulating Toll-like receptor signaling pathway and down-regulating the expression of inflammatory cytokine. TMG may become a kind of traditional Chinese medicine with neuroprotective potential.

Porous Molecular Conductor: Electrochemical Fabrication of Through-Space Conduction Pathways among Linear Coordination Polymers.

The first porous molecular conductor (PMC), which exhibits porosity, a through-space conduction pathway and rich charge carriers (electrons), was prepared through electrocrystallization from Cd2+ and N, N'-di(4-pyridyl)-1,4,5,8-naphthalenetetracarboxdiimide (NDI-py). [Cd(NDI-py)(OH2)4](NO3)1.3±0.1· nDMA (PMC-1) was assembled by π-π stacking among one-dimensional (1D) linear coordination polymers. The NDI cores were partially reduced into radical anions to form conductive π-stacked columns, yielding (1.0-3.3) × 10-3 S cm-1 at room temperature. Moreover, the electrical conductivity was significantly enhanced by removing the solvent molecules from PMC-1, indicating that PMCs are promising as molecule-responsive conductive materials.

Rhein ameliorates adenomyosis by inhibiting NF-κB and ß-Catenin signaling pathway.

In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and ß-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of ß-catenin during canonical Wnt signaling, we found that the degradation complex of ß-catenin was improved by rhein. In addition, ß-catenin nuclear translocation and its downstream genes were markedly suppressed by different doses of rhein. At the same time, decreased activation of epithelial-mesenchymal transition (EMT)-associated proteins including Snail and ZEB1 was detected in rhein-treated mice, indicating that the activation of Wnt signaling pathway was suppressed by rhein. The in vitro study verified a negative regulation of rhein on ß-catenin in stromal cells. Stimulation of IL-1ß significantly increased the nuclear translocation of ß-catenin and improved its target genes expressions. While, rhein remarkably abolished the enhancement in a dose dependent manner. Taken together, our results demonstrated the ability of rhein to inhibit Wnt/ß-catenin activation and its potential use in the treatment of adenomyosis and other abnormal activation of ß-catenin -associated diseases.