Association of waist-to-hip ratio adjusted for body mass index with cognitive impairment in middle-aged and elderly patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. METHODS: A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. RESULTS: WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261-1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032-4.371, P for trend < 0.001). CONCLUSIONS: Our study illustrated that higher WHRadjBMI is likely to be associated with an increased risk of CI among patients with T2DM. These findings support the detrimental effects of excess visceral fat accumulation on cognitive function in middle-aged and elderly T2DM patients.

Predictive effect of lipopolysaccharide-stimulated inflammatory cytokines on symptoms of generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is a relatively common mental disorder. Recently, inflammation, an important factor for the development of depression, has attracted increasing attention. Several studies have shown that inflammatory cytokines can affect the pathophysiological processes of several nervous system diseases. We hypothesized that there is a correlation between the levels of lipopolysaccharide (LPS)-stimulated inflammatory cytokines and the clinical symptoms of GAD. AIM: To investigate the predictive effect of LPS-stimulated inflammatory cytokines on symptoms of GAD. METHODS: This was a cross-sectional study in which 89 patients with GAD diagnosed at The First Hospital of Hebei Medical University from January 2022 to December 2022 and 70 individuals without anxiety and depression (controls) during the same period were included. Fasting venous blood was collected from all the subjects in heparin tubes, and another 3 ml of blood was supplemented with LPS (10 ng/ml). The plasma levels of 12 cytokines [Interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17A, IL-12p70, and IFN-α] were detected. RESULTS: Post-LPS stimulation, the levels of IL-1ß, IL-6, IL-8, IL-10, and TNF-α in both the control and GAD groups were significantly elevated above those in the nonstimulated groups, with IL-6 and IL-8 showing marked increases. Increases in IL-8 and TNF-α were statistically significant in the GAD group (P < 0.05). IL-1ß, IL-6, IL-8, IL-10, and TNF-α were found to be significantly correlated with Hamilton Anxiety Rating Scale (HAMA) scores (P < 0.05). A negative correlation was observed between IL-10 levels and HAMA scores. Further analysis revealed that TNF-α was associated with mental anxiety, whereas IL-1ß, IL-8, and IL-10 were associated with physical anxiety symptoms, with IL-10 showing a negative correlation with physical anxiety. IL-6 was associated with both mental and physical aspects of anxiety. CONCLUSION: The physical symptoms of GAD are related to inflammatory factors. IL-1ß, IL-8, IL-10, and TNF-a can be used as predictors of physical or mental anxiety in patients with GAD.

Single-cell RNA-seq Reveals that Methamphetamine Inhibits Liver Immunity with Involvement of Dopamine Receptor D1.

Methamphetamine (METH) is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder, especially in the liver that contains a significant number of immune cells. Dopamine, a key neurotransmitter in METH addiction and immune regulation, plays a crucial role in this process. Here, we developed a chronic METH administration model and conducted single-cell RNA sequencing (scRNA-seq) to investigate the effect of METH on liver immune cells and involvement of dopamine receptor D1 (DRD1). Our findings reveal that chronic exposure to METH induces immune cell identity shifts from Ifitm3+Macrophage (Mac) and Ccl5+Mac to Cd14+Mac, and from Fyn+CD4+T effector (Teff), CD8+T, and natural killer T cells (NKT) to Fos+CD4+T and Rora+ group 2 innate lymphoid cells (ILC2), along with suppression of multiple functional immune pathways. DRD1 is implicated in regulating certain pathways and identity shifts among the hepatic immune cells. Our results provide valuable insights into development of targeted therapies to mitigate METH-induced immune impairment.

Genetic Characterization of Two Novel Insect-Infecting Negative-Sense RNA Viruses Identified in a Leaf Beetle, Aulacophora indica.

Herbivorous insects harbor a variety of insect-specific viruses (ISVs) some of which are considered to be valuable biological agents for potential applications in biological defense and control strategies. Leaf beetles with chewing mouthparts are particularly known for their capacity to disrupt plant tissue while feeding, often creating openings that can act as entry points for plant pathogens. In this study, we have identified two new negative-sense RNA viruses infecting the leaf beetle Aulacophora indica, an important member of the Chrysomelidae family. These recently discovered viruses belong to the viral families Nyamiviridae and Chuviridae and have been preliminarily named Aulacophora indica nyami-like virus 1 (AINlV1) and Aulacophora indica chu-like virus 1 (AIClV1), respectively. The complete genomic sequences of these viruses were obtained using rapid amplification of cDNA ends (RACE) techniques. Detailed analysis of their genomic structures has confirmed their similarity to other members within their respective families. Furthermore, analysis of virus-derived small interfering RNA (vsiRNA) demonstrated a high abundance and typical vsiRNA pattern of AINlV1 and AIClV1, offering substantial evidence to support their classification as ISVs. This research enhances our understanding of viral diversity within insects.

Identification and Characterization of Three Novel Solemo-like Viruses in the White-Backed Planthopper, Sogatella furcifera.

Agricultural insects play a crucial role in transmitting plant viruses and host a considerable number of insect-specific viruses (ISVs). Among these insects, the white-backed planthoppers (WBPH; Sogatella furcifera, Hemiptera: Delphacidae) are noteworthy rice pests and are responsible for disseminating the southern rice black-streaked dwarf virus (SRBSDV), a significant rice virus. In this study, we analyzed WBPH transcriptome data from public sources and identified three novel viruses. These newly discovered viruses belong to the plant-associated viral family Solemoviridae and were tentatively named Sogatella furcifera solemo-like virus 1-3 (SFSolV1-3). Among them, SFSolV1 exhibited a prevalent existence in different laboratory populations, and its complete genome sequence was obtained using rapid amplification of cDNA ends (RACE) approaches. To investigate the antiviral RNA interference (RNAi) response in WBPH, we conducted an analysis of virus-derived small interfering RNAs (vsiRNAs). The vsiRNAs of SFSolV1 and -2 exhibited typical patterns associated with the host's siRNA-mediated antiviral immunity, with a preference for 21- and 22-nt vsiRNAs derived equally from both the sense and antisense genomic strands. Furthermore, we examined SFSolV1 infection and distribution in WBPH, revealing a significantly higher viral load of SFSolV1 in nymphs' hemolymph compared to other tissues. Additionally, in adult insects, SFSolV1 exhibited higher abundance in male adults than in female adults.

Etiology including epigenetic defects of retinoblastoma.

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1 is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1 mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1 biallelic loss are rare, yet epigenetic changes driven by RB1 loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis.

Evidence for causal effects of neuropsychiatric conditions on risk of venous thromboembolism: A univariable and multivariable Mendelian randomization study.

BACKGROUND: Substantial observational evidence suggests an association between neuropsychiatric conditions and venous thromboembolism (VTE). However, the causal relationship between these two conditions requires further investigation. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the bidirectional causal effects between four neuropsychiatric conditions and VTE, deep vein thrombosis, and pulmonary embolism (PE). METHODS: Genetic variants associated with four neuropsychiatric conditions (ie, schizophrenia, major depressive disorder [MDD], bipolar disorder, and epilepsy) and VTE, deep vein thrombosis, and PE were selected. Bidirectional univariable and multivariable MR methods were applied to evaluate the causal relationships among these conditions. The primary causal estimates were obtained using the inverse variance weighted method with multiplicative random effects, supplemented by MR Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analysis was conducted using the MR pleiotropy residual sum, funnel plots, and outlier (MR pleiotropy and residual sum and outlier) method. RESULTS: Univariable MR results showed that genetic susceptibility to MDD increases the risk of VTE and PE (VTE: odds ratio [OR], 1.25; 95% confidence interval [CI], 1.08-1.46; P = .004; PE: OR, 1.36; 95% CI, 1.09-1.69; P = .006) and that PE has an adverse causal effect on MDD (OR, 1.02; 95% CI, 1.00-1.04; P = .026). Adjustment for confounders such as obesity, sleep duration, smoking, physical activity, and alcohol consumption revealed that increased genetic susceptibility to MDD is also associated with VTE and PE. CONCLUSIONS: Our results suggest that genetic susceptibility to MDD might have an adverse causal effect on the risk of VTE and PE and that PE has a reverse causal effect on MDD. Prevention and early diagnosis of depression are crucial in the management of VTE and PE.

Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1+ epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition.

The impact of dietary acid load on super-agers with exceptional cognitive abilities: a propensity score analysis of national health and nutrition examination survey (NHANES) 2011-2014.

OBJECTIVES: 'Super-agers,' individuals over 80 with memory abilities comparable to those 20-30 years younger. The relationship between super-agers and dietary acid load (DAL) is an area that warrants further investigation. We aim to examine the link between DAL and super-agers and assess DAL's effects on cognitive functions across different age groups and cognitive domains. DESIGN: Employing a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination Survey (NHANES) data, we utilized propensity score analysis and multivariate-adjusted regression to mitigate confounding factors. SETTING: Older adults aged 60 and above in the United States. PARTICIPANTS: Our primary analysis encompassed 985 older adults, supplemented by a sensitivity analysis with 2,522 participants. MEASUREMENTS: DAL was assessed through potential renal acid load (PRAL), estimated net acid excretion (NAEes), and net endogenous acid production (NEAP) indices. RESULTS: Super-agers demonstrate a preference for alkaline diets, shown by their lower DAL indices. After inverse probability of treatment weighting (IPTW), multivariate-adjusted logistic regression reveals that each unit reduction in NAEes and PRAL increases the chances of being a super-ager by 3.9% and 3.0%, respectively. The DAL's impact on cognitive function becomes more pronounced with age. Lower PRAL and NAEes scores are significantly linked to higher situational memory and overall cognitive performance scores in those over 70, with these effects being even more pronounced in participants over 80. CONCLUSION: This research pioneers in demonstrating that super-agers prefer an alkaline diet, highlighting the potential role of alkaline diet in countering cognitive decline associated with aging.

Effect of Sarcopenia on 10-Year Risk of Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

Effects of predictive nursing interventions on pressure ulcer in older bedridden patients: A meta-analysis.

To evaluate the effect of predictive nursing interventions on pressure ulcers in elderly bedridden patients by meta-analysis. Applied computer searches of PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases for randomised controlled trials (RCTs) on the effect of predictive nursing in preventing pressure ulcers in elderly bedridden patients from the database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on inclusion and exclusion criteria. Stata 17.0 software was utilised for data analysis. Eighteen RCTs involving 6504 patients were finally included. The analysis revealed the implementation of predictive nursing interventions had a significant advantage in reducing the incidence of pressure ulcers in elderly bedridden patients compared with conventional nursing (odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.15-0.28, p < 0.001), while the patients' satisfaction with nursing care was higher (OR = 3.70, 95% CI: 2.99-4.57, p < 0.001). This study shows that the implementation of a predictive nursing interventions for elderly bedridden patients can effectively reduce the occurrence of pressure ulcers and significantly improve patients' satisfaction with nursing care, which is worthy of clinical promotion and application.

Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study.

BACKGROUND: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. METHODS: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. RESULTS: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. CONCLUSIONS: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

Risk factors for cognitive impairment in middle-aged type 2 diabetic patients: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate risk factors for cognitive impairment (CI) and explore the relationship between obesity and cognition in hospitalised middle-aged patients with type 2 diabetes (T2DM). METHODS: Subjects were divided into normal cognitive function (NCF) (n=320) and CI (n=204) groups based on the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The risk factors for CI were determined by logistic regression analysis and generalised linear modelling. The associations between obesity parameters (body mass index (BMI) and waist circumference (WC)) and cognitive ability were studied with the use of linear regression analysis, piecewise regression modelling and interaction analysis. The receiver operating characteristic curve analysis was used to examine the diagnostic value of influencing factors for cc RESULTS: The prevalence of CI was 38.9% in hospitalised middle-aged T2DM patients (median age, 58 years). Age, WC, hypoglycaemic episode within past 3 months and cerebrovascular disease (CVD) were identified as independent risk factors for CI, while the independent protective factors were education, diabetic dietary pattern, overweight and obesity. BMI was a protective factor for the MoCA score within a certain range, whereas WC was a risk factor for the MMSE and MoCA scores. The area under the curve for the combination of BMI and WC was 0.754 (p<0.001). CONCLUSION: Age, education, diabetic dietary pattern, WC, overweight, obesity, hypoglycaemic episode in 3 months and CVD may be potential influencing factors for the occurrence of CI in hospitalised middle-aged population with T2DM. The combination of BMI and WC may represent a good predictor for early screening of CI in this population. Nevertheless, more relevant prospective studies are still needed.

ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers.

Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies. Activation of the ADORA2A signaling rewires the proline metabolism via an ERK/MYC/PYCR cascade. Increased proline synthesis promotes deacetylases SIRT6/7-mediated deacetylation of histone H3 at lysine 27 (H3K27), and thereby biases a global transcriptional output toward a neuroendocrine lineage profile. Ablation of Adora2a in genetically engineered mouse models inhibits the development and progression of neuroendocrine prostate and lung cancers, and, intriguingly, prevents the adenocarcinoma-to-neuroendocrine phenotypic transition. Importantly, pharmacological blockade of ADORA2A profoundly represses neuroendocrine prostate and lung cancer growth in vivo. Therefore, we believe that ADORA2A can be used as a promising therapeutic target to govern the epigenetic reprogramming in neuroendocrine malignancies.

The ELAVL3/MYCN positive feedback loop provides a therapeutic target for neuroendocrine prostate cancer.

Neuroendocrine prostate cancer is a rapidly progressive and lethal disease characterized by early visceral metastasis, poor prognosis, and limited treatment options. Uncovering the oncogenic mechanisms could lead to the discovery of potential therapeutic avenues. Here, we demonstrate that the RNA-binding protein ELAVL3 is specifically upregulated in neuroendocrine prostate cancer and that overexpression of ELAVL3 alone is sufficient to induce the neuroendocrine phenotype in prostate adenocarcinoma. Mechanistically, ELAVL3 is transcriptionally regulated by MYCN and subsequently binds to and stabilizes MYCN and RICTOR mRNA. Moreover, ELAVL3 is shown to be released in extracellular vesicles and induce neuroendocrine differentiation of adenocarcinoma cells via an intercellular mechanism. Pharmacological inhibition of ELAVL3 with pyrvinium pamoate, an FDA-approved drug, effectively suppresses tumor growth, reduces metastatic risk, and improves survival in neuroendocrine prostate cancer mouse models. Our results identify ELAVL3 as a critical regulator of neuroendocrine differentiation in prostate cancer and propose a drug repurposing strategy for targeted therapies.

Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.

Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.

Relationships Between Body Composition and Cognitive Impairment in Hospitalised Middle-Aged Type 2 Diabetic Patients.

Objective: The aim of this study was to elucidate the relationship between specific body composition and the risk of Cognitive Impairment (CI) in middle-aged Type 2 Diabetes Mellitus (T2DM) patients. Methods: This cross-sectional study included 504 hospitalized patients with T2DM from the Department of Endocrinology and Metabolism of the Tianjin Union Medical Center. Subjects were grouped by sex, and cognitive status was assessed using the Montreal Cognitive Assessment (MoCA). The relationship between body composition and cognitive ability was investigated with the use of linear regression analysis. The association between body composition and CI risk was determined by logistic regression analysis. Results: The prevalence of CI was 39.3% in middle-aged T2DM patients. After adjusting for age, education, marriage status, carotid atherosclerosis, cerebrovascular disease and hemoglobin, multiple linear regression analysis showed that lean mass index (LMI), body mass index (BMI) and appendicular skeletal muscle index (SMI) were significant predictors for the MoCA scores in men (p < 0.05). In addition, BMI (OR 0.913, 95% CI 0.840-0.992) and LMI (OR 0.820, 95% CI 0.682-0.916) were independent protective factors for CI in males. After adjusted for age, education, marriage status, dietary control of diabetes and cerebrovascular disease, visceral obesity (VO, OR 1.950, 95% CI 1.033-3.684) and abdominal obesity (AO, OR 2.537, 95% CI 1.191-5.403) were risk factors for CI in female patients. Conclusion: The results suggest that there may be different mechanisms underlying the relationship of body compositions and cognitive performance between middle-aged male and female patients with T2DM. In addition, our finding of potential determinants of cognitive impairment may facilitate the development of intervention programs for middle-aged type 2 diabetic patients. Nevertheless, more large prospective studies looking at cognition and changes in body composition over time are needed in the future to further support their association.

Kangfuxin alleviates ulcerative colitis in rats by inhibiting NF-κB p65 activation and regulating T lymphocyte subsets.

Objectives: Ulcerative colitis (UC) remains an enduring, idiopathic inflammatory bowel disease marked by persistent mucosal inflammation initiating from the rectum and extending in a proximal direction. An ethanol extract of Periplaneta americana L., namely Kangfuxin (KFX), has a significant historical presence in Traditional Chinese Medicine and has been broadly utilized in clinical practice for the treatment of injury. Here, we aimed to determine the effect of KFX on 2,4,6-trinitro'benzene sulfonic acid (TNBS)-induced UC in Sprague-Dawley rats. Materials and Methods: We established the UC model by TNBS/ethanol method. Then, the rats were subject to KFX (50, 100, 200 mg/kg/day) for 2 weeks by intragastric gavage. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), and histopathological score were evaluated. The colonic tissue interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-1 (TGF-ß1), and epidermal growth factor (EGF) were determined by Elisa. To study T-lymphocyte subsets, flow cytometry was performed. In addition, the expression level of NF-κB p65 was evaluated by immunohistochemistry and western blot analysis. Results: Compared with the TNBS-triggered colitis rats, the treatment of rats with KFX significantly increased the body weight, and decreased DAI, CMDI, and histopathological score. Also, KFX elicited a reduction in the secretion of colonic pro-inflammatory cytokines, namely IL-1ß, IL-6, and TNF-α, concomitant with up-regulation of IL-10, TGF-ß1, and EGF levels. Upon KFX treatment, the CD3+CD4+/CD3+CD8+ ratio in the spleen decreased, while the CD3+CD8+ subset and the CD3+CD4+CD25+/CD3+CD4+ ratio demonstrated an increase. In addition, the expression of NF-κB p65 in the colon was decreased. Conclusion: KFX effectively suppresses TNBS-induced colitis by inhibiting the activation of NF-κB p65 and regulating the ratio of CD4+/CD8+.

Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.

Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation. We find that GHRH-R is not expressed in naïve CD4+ T cells, while its expression is induced throughout Th17 cell differentiation in vitro. Mechanistically, GHRH-R activates the JAK-STAT3 pathway, increases the phosphorylation of STAT3, enhances both non-pathogenic and pathogenic Th17 cell differentiation and promotes the gene expression signatures of pathogenic Th17 cells. Enhancing this signaling by GHRH agonist promotes, while inhibiting this signaling by GHRH antagonist or GHRH-R deficiency reduces, Th17 cell differentiation in vitro and Th17 cell-mediated ocular and neural inflammation in vivo. Thus, GHRH-R signaling functions as a critical factor that regulates Th17 cell differentiation and Th17 cell-mediated autoimmune ocular and neural inflammation.