Prevalence and risk factors of pre-frailty and frailty in hemodialysis patients in central China.

The current study was to explore the prevalence and risk factors elements of pre-frailty and frailty among patients undergoing hemodialysis (HD) in central China. A cross-sectional, multi-institutional investigation was conducted. From March to May 2024, using the convenience sampling method, a total of 408 HD patients from four hospitals in Xiangyang, China, were recruited for this study.

Individual-based morphological brain network changes in children with Rolandic epilepsy.

Objective: To investigate the local cortical morphology and individual-based morphological brain networks (MBNs) changes in children with Rolandic epilepsy (RE).

Methods: Based on the structural MRI data of 56 children with RE and 56 healthy controls (HC), we constructed four types of individual-based MBNs using morphological indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]). The global and nodal properties of the brain networks were analyzed using graph theory.

Association between hearing ability and cortical morphology in the elderly: multiparametric mapping, cognitive relevance, and neurobiological underpinnings.

Background: Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking.

Methods: We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments.

Aberrant single-subject morphological brain networks in first-episode, treatment-naive adolescents with major depressive disorder.

Background: Neuroimaging-based connectome studies have indicated that major depressive disorder (MDD) is associated with disrupted topological organization of large-scale brain networks. However, the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD.

Objective: To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD.

DeepHBV: a deep learning model to predict hepatitis B virus (HBV) integration sites.

Background: The hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer. HBV integration is one of the key steps in the virus-promoted malignant transformation.

Results: An attention-based deep learning model, DeepHBV, was developed to predict HBV integration sites.

DeepEBV: a deep learning model to predict Epstein-Barr virus (EBV) integration sites.

Motivation: Epstein-Barr virus (EBV) is one of the most prevalent DNA oncogenic viruses. The integration of EBV into the host genome has been reported to play an important role in cancer development. The preference of EBV integration showed strong dependence on the local genomic environment, which enables the prediction of EBV integration sites.

Compromised IGF signaling causes caspase-6 activation in Huntington disease.

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expansion of a polyglutamine repeat in the huntingtin (HTT) protein. Aberrant activation of caspase-6 and cleavage of mutant HTT generating the toxic N-terminal 586 HTT fragment are important steps in the pathogenesis of HD. Similarly, alterations in the insulin-like growth factor 1 (IGF-1) signaling pathway have been implicated in the disease as a result of decreased plasma IGF-1 levels in HD patients.

Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound.

Aberrant activation of caspase-6 (C6) in the absence of other hallmarks of apoptosis has been demonstrated in cells and tissues from patients with Huntington disease (HD) and animal models. C6 activity correlates with disease progression in patients with HD and the cleavage of mutant huntingtin (mHTT) protein is thought to strongly contribute to disease pathogenesis. Here we show that the mHTT fragment generated by C6 cleavage interacts with the zymogen form of the enzyme, stabilizing a conformation that contains an active site and is prone to full activation.

Constitutive ablation of caspase-6 reduces the inflammatory response and behavioural changes caused by peripheral pro-inflammatory stimuli.

Traditionally, the family of caspases has been subcategorised according to their respective main roles in mediating apoptosis or inflammation. However, recent studies have revealed that caspases participate in diverse cellular functions beyond their canonical roles. Caspase-6 (C6) is one such protease known for its role as a pro-apoptotic executioner caspase and its aberrant activity in several neurodegenerative diseases.

Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62.

HACE1 is essential for astrocyte mitochondrial function and influences Huntington disease phenotypes in vivo.

Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels of hace1 (HECT domain and Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis of HD. Hace1 promotes the stability of Nrf2 and thus plays an important role in antioxidant response mechanisms, which are dysfunctional in HD. Moreover, hace1 overexpression mitigates mutant huntingtin (mHTT)-induced oxidative stress in vitro through promotion of the Nrf2 antioxidant response.

Palmitoylation of caspase-6 by HIP14 regulates its activation.

Caspase-6 (CASP6) has an important role in axonal degeneration during neuronal apoptosis and in the neurodegenerative diseases Alzheimer and Huntington disease. Decreasing CASP6 activity may help to restore neuronal function in these and other diseases such as stroke and ischemia, where increased CASP6 activity has been implicated. The key to finding approaches to decrease CASP6 activity is a deeper understanding of the mechanisms regulating CASP6 activation.

Laquinimod decreases Bax expression and reduces caspase-6 activation in neurons.

Laquinimod is an immunomodulatory compound that has shown neuroprotective benefits in clinical trials for multiple sclerosis. Laquinimod ameliorates both white and gray matter damage in human patients, and prevents axonal degeneration in animal models of multiple sclerosis. Axonal damage and white matter loss are a common feature shared between different neurodegenerative diseases.

A Huntingtin-based peptide inhibitor of caspase-6 provides protection from mutant Huntingtin-induced motor and behavioral deficits.

Over the past decade, increasing evidence has implied a significant connection between caspase-6 activity and the pathogenesis of Huntington's disease (HD). Consequently, inhibiting caspase-6 activity was suggested as a promising therapeutic strategy to reduce mutant Huntingtin toxicity, and to provide protection from mutant Huntingtin-induced motor and behavioral deficits. Here, we describe a novel caspase-6 inhibitor peptide based on the huntingtin caspase-6 cleavage site, fused with a cell-penetrating sequence.

Partial rescue of some features of Huntington Disease in the genetic absence of caspase-6 in YAC128 mice.

Huntington Disease (HD) is a progressive neurodegenerative disease caused by an elongated CAG repeat in the huntingtin (HTT) gene that encodes a polyglutamine tract in the HTT protein. Proteolysis of the mutant HTT protein (mHTT) has been detected in human and murine HD brains and is implicated in the pathogenesis of HD. Of particular importance is the site at amino acid (aa) 586 that contains a caspase-6 (Casp6) recognition motif.

Somatostatin receptor-2 negatively regulates β-adrenergic receptor mediated Ca(2+) dependent signaling pathways in H9c2 cells.

In the present study, we report that somatostatin receptor 2 (SSTR2) plays a crucial role in modulation of β1AR and β2AR mediated signaling pathways that are associated with increased intracellular Ca(2+) and cardiac complications. In H9c2 cells, SSTR2 colocalizes with β1AR or β2AR in receptor specific manner. SSTR2 selective agonist inhibits isoproterenol and formoterol stimulated cAMP formation and PKA phosphorylation in concentration dependent manner.

p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin.

Activation of caspase-6 in the striatum of both presymptomatic and affected persons with Huntington's disease (HD) is an early event in the disease pathogenesis. However, little is known about the role of caspase-6 outside the central nervous system (CNS) and whether caspase activation might play a role in the peripheral phenotypes, such as muscle wasting observed in HD. We assessed skeletal muscle tissue from HD patients and well-characterized mouse models of HD.

Isoproterenol induced hypertrophy and associated signaling pathways are modulated by somatostatin in H9c2 cells.

Background: Somatostatin (SST), a growth hormone inhibitory peptide plays key role in regulation of cell proliferation via modulation of mitogen activated protein kinases (MAPKs) and cell survival pathway. In cardiac physiology, β-Adrenergic receptors (β-ARs) play crucial role in regulation of downstream signaling pathways in receptor specific manner. The aim of the current study was to delineate the mechanistic insight for the role of SST on β-AR mediated signaling which promotes hypertrophy and apoptosis in rat fetal cardiomyocytes (H9c2 cells).

Heterodimerization of β2 adrenergic receptor and somatostatin receptor 5: Implications in modulation of signaling pathway.

Background: In the present study, we describe heterodimerization between human-Somatostatin Receptor 5 (hSSTR5) and β2-Adrenergic Receptor (β2AR) and its impact on the receptor trafficking, coupling to adenylyl cyclase and signaling including mitogen activated protein kinases and calcineurin-NFAT pathways.

Methods: We used co-immunoprecipitation, photobleaching- fluorescence resonance energy transfer and Fluorescence assisted cell sorting analysis to characterize heterodimerization between SSTR5 and β2AR.

Results: Our results indicate that hSSTR5/β2AR exist as preformed heterodimers in the basal condition which is enhanced upon co-activation of both receptors.

Role of somatostatin receptor 1 and 5 on epidermal growth factor receptor mediated signaling.

Epidermal growth factor (EGF) regulates normal and tumor cell proliferation via epidermal growth factor receptor (EGFR) phosphorylation, homo- or heterodimerization and activation of mitogen-activated protein kinases (MAPKs) and PI3K/AKT cell survival pathways. In contrast, SST via activation of five different receptor subtypes inhibits cell proliferation and has been potential target in tumor treatment. To gain further insight for the effect of SSTRs on EGFR activated signaling, we determine the role of SSTR1 and SSTR1/5 in human embryonic kidney (HEK) 293 cells.

Receptor specific crosstalk and modulation of signaling upon heterodimerization between β1-adrenergic receptor and somatostatin receptor-5.

In the present study we describe heterodimerization, trafficking, coupling to adenylyl cyclase and signaling in HEK-293 cells cotransfected with human-somatostatin receptor 5 (hSSTR5) and β(1)-adrenergic receptor (β(1)AR). hSSTR5/β(1)AR exists as heterodimers in basal conditions which was further enhanced upon synergistic activation of both receptors. Activation of either β(1)AR or hSSTR5 displayed dissociation of heterodimerization.

Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the presence of somatostatin receptor 5 modulate signaling pathways.

Epidermal growth factor through the stimulation of epidermal growth factor receptor (EGFR) plays a critical role in the activation of MAPKs and phosphatidylinositol-3-protein kinase/AKT cell survival pathways attributed in many pathological conditions. At the cellular level, such functions involve EGFR overactivation and phosphorylation. In the present study, we describe that human embryonic kidney-293 cells transfected with somatostatin (SST) receptor 5 (SSTR5) exhibit inhibition of EGFR phosphorylation and modulate MAPK and phosphatidylinositol-3-protein kinase/AKT cell survival signaling.

Endothelin-1 expression in vascular adventitial fibroblasts.

Endothelial cells are a major source of endothelin (ET)-1, but the possibility that vascular adventitial fibroblasts generate ET-1 has not been explored. We hypothesized that aortic adventitial fibroblasts have the ability to produce ET-1, which may contribute to extracellular matrix synthesis. Vascular adventitial fibroblasts were isolated from mouse aorta and incubated with various concentrations of angiotensin II (ANG II).