Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: Most previous studies suggested obesity deteriorates the functional outcome after ischemic stroke. But there are researches claiming that obesity is associated with lower mortality, recurrence, and readmission rates, which is known as the obesity paradox. Our current research aimed to investigate the correlation between genetically obesity and the post-stroke outcome with the Mendelian randomization (MR) method. METHODS: The UK Biobank and the GIANT consortium provided instrumental variables for body mass index (BMI, 806,834 individuals) and waist-to-hip ratio (WHR, 697,734 individuals). Data of functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network (6012 individuals). Inverse-variance weighted approach was utilized as the primary analyses. Sensitivity analyses involved the utilization of different MR methods. The heterogeneity among genetic variants was assessed by I2 and Q value statistics. RESULTS: In univariable analysis, there was a significant connection between genetic susceptibility to WHR and worse functional outcome (modified Rankin Scale 3) after ischemic stroke (OR [95%CI] = 1.47 [1.07, 2.02], P = 0.016). Genetic liability to BMI and was not associated with post-stroke functional outcome (all P > 0.05). The overall patterns between genetic liability to WHR and functional outcome post-ischemic outcome no longer existed in the multivariable MR analysis after adjusting for BMI (OR [95%CI] = 1.26[0.76,1.67], P = 0.56). CONCLUSION: The current MR study provided evidence that WHR was correlated to unfavorable outcome post-ischemic stroke. Exploring interventions against obesity may potentially improve recovery after ischemic stroke.

Genotype-phenotype correlation of WT1 mutation-related nephropathy in Chinese children.

Introduction: This study aimed to analyze the clinical characteristics of nephropathy associated with WT1 gene mutations in Chinese children and explore the relationship between genotype and clinical phenotype. Methods: Cases diagnosed at the Guangzhou Women and Children's Medical Center, were combined with those retrieved from PubMed and China National Knowledge Infrastructure (CNKI) databases from January 2015 to June 2022 and integrated into a study cohort; grouped according to gene mutation sites, clinical phenotype, and renal pathological types. The clinical characteristics between groups were compared, and the relationship between genotype and age of onset, clinical phenotype, and pathological type were retrospectively analyzed. Results: The center enrolled 15 confirmed children: seven cases of non-simple nephropathy, including Denys-Drash syndrome (DDS) and Frasier syndrome (FS); eight cases of isolated steroid-resistant nephrotic syndrome (ISRNS); and 13 cases (86.7%) that progressed to end-stage renal disease (ESRD). The initial hemoglobin and bicarbonate levels of patients with clinical non-simple nephropathy were significantly lower than those with simple nephropathy, whereas the serum creatinine levels were higher than those of patients with simple nephropathy. A total of 75 cases of nephropathy associated with WT1 mutations in the study cohort met the inclusion and exclusion criteria. The most common clinical manifestations of WT1 mutations in this cohort were DDS (29/75, 38.7%) and ISRNS (37/75, 49.3%). A renal biopsy was performed in 43 patients, and the common types of renal pathology were focal segmental glomerulosclerosis (23/43, 53.5%) and DMS (13/43, 30.2%). Within the cohort, there were 12 cases (16.0%) in the exon 8 mutation group, 32 (42.6%) in the exon 9 group, 19 (25.3%) in the intron 9 group, and 12 (16.0%) in other gene site mutation groups. Common sites of WT1 mutations in Chinese children were exons 9 and intron 9. Exon 8 mutations were uniquely correlated with the age of onset within three months [5/7; 71.4%; Adjusted standardized residual (AR) = 4.2]. The renal survival time in the exon 8 mutation group was the shortest (P = 0.003). Discussion: The molecular and biological characteristics of WT1 mutation-related nephropathy determine the clinical type, pathological features, and renal survival time of the disease; and there was a strong correlation between the genotype and clinical phenotype.

Sex differences in the association between serum α-Klotho and depression in middle-aged and elderly individuals: A cross-sectional study from NHANES 2007-2016.

BACKGROUND: Klotho is a well-known anti-aging protein that exerts pleiotropic effects; however, little is known regarding serum α-Klotho in the context of depression. Here, we evaluated the association between serum α-Klotho levels and depression in middle-aged and older individuals. METHODS: In this cross-sectional study, data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 with a total of 5272 participants who were ≥40 years of age. Depression was evaluated using the 9-item Patient Health Questionnaire (PHQ-9). The association between serum α-Klotho levels and depression was determined on the basis of multivariable logistic regression models. RESULTS: The mean age of the enrolled adults was 58.94 ± 10.54 years, of which 49.5 % were female. When serum α-Klotho was log10-transformed, it was significantly inversely associated with depression in females in the final adjusted model (odds ratio [OR], 0.32; 95 % confidence interval [CI], 0.12-0.85). In the contrast, serum α-Klotho (log10) was significantly positively associated with depression in males in one of the adjusted models (OR, 3.71; 95 % CI, 1.17-11.8), and this disappeared after adjusting other covariates (all P > 0.05). Based on further stratified respective analyses of females and males, the results were stable. LIMITATIONS: The cross-sectional study could not yield any conclusions regarding causality. CONCLUSIONS: In the present study, serum α-Klotho levels were negatively related to the prevalence of depression in middle-aged and elderly women. This study provides new evidence of sex differences in the association between serum α-Klotho levels and depression.

Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice.

Hyperuricemia (HUA), a common metabolic disease, is treated as the second-largest metabolic disease after diabetes in China. Cortex Phellodendri (CP) is one of the most frequently used herbal medicines for treating gout or HUA. However, the mechanism underlying the anti-HUA effect of CP is still unrevealed. Hence, this study aimed to explore the pharmacological mechanism of CP against HUA using network pharmacology coupled with in vivo experimental validation. Active compounds and potential targets of CP, as well as the potential targets related to HUA, were retrieved from multiple open-source databases. The drug-disease overlapping targets were obtained by Venn diagram analysis and used to construct the herb-component-target (HCT), protein-protein-interaction (PPI), and component-target-pathway (CTP) networks. The functional enrichment analysis was also performed for further study. Furthermore, a HUA mouse model was induced by a combination of intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) and intragastric administration of hypoxanthine (HX, 300 mg/kg) daily for 10 days. Different dosages of CP (200, 400, and 800 mg/kg) were orally given to mice 1 h after modeling. The results showed that 12 bioactive compounds and 122 drug-disease overlapping targets were obtained by matching 415 CP-related targets and 679 HUA-related targets, and berberine was one of the most important compounds with the highest degree value. The core targets of CP for treating HUA were TP53, MAPK8, MAPK3, IL-6, c-Jun, AKT1, xanthine oxidase (XOD), and ATP-binding cassette subfamily G member 2 (ABCG2). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that the anti-HUA effect of CP mainly involved the pathways of inflammation and apoptosis, such as PI3K/Akt, TNF, MAPK, TLR, AMPK, NF-κB, and NLRP3 signaling pathways. In vivo animal experiment further confirmed the hypouricemic effect of CP in a HUA mouse model, as evidenced by significantly restored kidney histological deteriorations, and considerably decreased levels of serum uric acid (sUA), creatinine (Cre), blood urea nitrogen (BUN), and hepatic UA. Furthermore, the hypouricemic action of CP in vivo might be attributed to its suppression of XOD activity in the liver, rather than ABCG2 in the kidney. Real-time qPCR (RT-qPCR) and Western blot analysis also confirmed the key roles of the hub genes in CP against HUA. In conclusion, CP exhibited therapeutic effect against HUA via multi-compounds, multi-targets, and multi-pathways. It possessed anti-HUA and nephroprotective effects via suppressing XOD activity, and reversed the progression of renal injury by exerting anti-inflammatory and anti-apoptotic effects.

Association between Geriatric Nutritional Risk Index and Depression after Ischemic Stroke.

BACKGROUND: Malnutrition is associated with poor outcomes after stroke. However, the association between malnutrition and post-stroke depression (PSD) remains unelucidated. We aimed to explore the association between geriatric nutritional risk index (GNRI) and depression after ischemic stroke. METHODS: In total, 344 patients with ischemic stroke were included in this analysis. The GNRI was calculated from serum albumin level, weight, and height at admission. Malnutrition was defined using the GNRI cutoff points. A lower GNRI score indicates an elevated nutritional risk. The outcome was depression, measured 14 days after ischemic stroke. Logistic regression models were used to estimate the association between the GNRI and risk of PSD. RESULTS: A total of 22.9% developed PSD 14 days after stroke. The mean GNRI was 99.3 ± 6.0, and 53.8% of the patients had malnutrition. After adjusting for covariates, baseline malnutrition was not associated with risk of PSD (OR, 0.670; 95%CI, 0.370-1.213; p = 0.186). The restricted cubic splines revealed a U-shaped association between the GNRI and PSD. Compared to moderate GNRI, higher GNRI (OR, 2.368; 95%CI, 0.983-5.701; p = 0.085) or lower GNRI (OR, 2.226; 95%CI, 0.890-5.563; p = 0.087) did not significantly increase the risk of PSD. CONCLUSION: A low GNRI was not associated with an increased risk of depression after ischemic stroke.

Increasing agar content improves the sol-gel and mechanical features of starch/agar binary system.

Starch/agar systems are highly potential for versatile applications such as packaging and biomedical materials. Here, how combined factors affect the features of a starch/agar binary system were explored. An increase of starch amylose/amylopectin ratio from 0/100 to 50/50 increased the sol-gel transition temperature and gel hardness of the aqueous starch/agar mixture. An increased agar content (mainly from 30% to 70%) allowed increases in both the tensile strength (reaching 50-60 MPa) and elongation at break of the starch/agar binary films. This phenomenon should be related to the strengthened crystalline structure and the weakened hydrogen bonding between starch chains (reflected by infrared spectroscopy). Furthermore, a higher relative humidity (from 30% to 70%) allowed enhanced chain interactions and probably nanoscale molecular order but weakened the crystalline structure, leading to reduced tensile strength and increased elongation at break. This work could facilitate the design of starch/agar binary systems with improved sol-gel and mechanical performance.

Deacetylation enhances the properties of konjac glucomannan/agar composites.

From a microstructural point of view, this work concerns how deacetylation improves the practical characteristics of deacetylated-konjac glucomannan/agar (DK/A) composite films. As disclosed by infrared spectroscopy and X-ray diffraction, the deacetylation of konjac glucomannan (KGM) enhanced the chain interactions in DK/A composites and suppressed the realignment of agar molecules into crystallites. The enhanced associations between acetyl-free regions of KGM and agar reduced the exposure of OH groups and thus increased the hydrophobicity of the composites. Besides, the partial removal of acetyl groups allowed shortened distances between chains; consequently, denser composite matrices emerged with lower water vapor permeability and higher tensile strength. Also, the KGM deacetylation increased the matrix flexibility and elongation at break for DK/A composites, associated with the hindered rearrangement of agar chains. Thus, altering the deacetylation degree of KGM may be an effective way to design KGM-based composites with improved hydrophobicity and mechanical performance.