Chronic Disorder Research Articles

Influence of Qigong Wuqinxi on Pain, Sleep, and Tongue Features in Older Adults

ABSTRACT Background Chronic pain and sleep disorders are commonly seen symptoms in community-dwelling older adults at traditional Chinese medicine (TCM) clinics. TCM modalities such as herbal medication and acupuncture have side effects and usage limitations. Therefore, nonpharmacological and noninvasive interventions may be applied to relieve the symptoms of these conditions. Purpose This study was designed to test the effect of Qigong Wuqinxi exercise on chronic pain, sleep quality, TCM constitutions, and tongue features in community-dwelling older adults. Methods This was a cluster randomized controlled trial. Older adults in two community care centers who met the inclusion criteria were assigned by drawing lots to either the experimental group (n = 32) or the control group (n = 31). Experimental group members practiced the Qigong Wuqinxi exercise for 50 minutes three times each week for 12 weeks, whereas those in the control group maintained their normal daily routine. Before and after the 12-week study, data on chronic pain, sleep quality, TCM constitutions, and tongue features were collected from all participants to assess the effectiveness of the intervention. Between-group pretest and posttest comparisons were analyzed using independent samples t tests, and within-group differences were analyzed using paired t tests. Results The experimental group reported significantly greater average posttest improvements in chronic pain, yang deficiency, phlegm-stasis, thick fur, and red dots than the control group (all ps < .05). The maximum change in pretest to posttest pain scores favored the experimental group (−0.56 ± 0.76 vs. 0.39 ± 1.91, p = .011). Also, the experimental group had a significantly better change in the pain interference index (−3.31 ± 3.30 vs. −0.58 ± 1.91, p < .001). In addition, the experimental group exhibited greater improvements in yang-deficiency tendency (−2.38 ± 4.89 vs. 0.35 ± 4.67, p = .027), phlegm and stasis tendency (−2.19 ± 4.52 vs. 1.77 ± 2.47, p < .001), thick fur (1.44 ± 11.28 vs. 6.03 ± 6.04, p = .049), and red dots (−5.09 ± 21.45 vs. 2.81 ± 4.03, p = .048). However, no significant between-group difference in posttest sleep quality (p = .357) was observed. Conclusions/Implications for Practice The Qigong Wuqinxi exercise was found to positively improve chronic pain and TCM constitutions in community-dwelling older adults and may be promoted in community care centers to improve the health status of older adults.

Sjögren’s Disease and Gastroesophageal Reflux Disease: What Is Their Evidence-Based Link?

Sjögren’s disease (SjD), or primary Sjögren’s syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin’s lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sjögren’s Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren’s syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sjögren’s disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sjögren’s disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords ‘Sjögren’s syndrome’ OR ‘Sjögren’s disease’ AND ‘gastroesophageal reflux disease’ AND ‘microbiota’ OR microbiota dysbiosis’. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sjögren’s disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sjögren’s disease and the personalized management of the disease.

How to Utilize University Nursing Clinic Resources Successfully to Transition Autistic Adolescents into Higher Education

ABSTRACTAutism Spectrum Disorder (ASD) is complex neurodevelopmental disorder that is exhibited through a wide‐range of symptoms including social interactions, communication deficits, limited interests, and repetitive behaviors (e.g., stimming). The prevalence of autism amongst children and adolescents continues to grow with 1 in 36 diagnosed annually (CDC, 2024). Because autism often comes with a myriad of comorbidities (e.g., sleep disorders, seizure activity, nutritional imbalances, gastrointestinal issues, and mental health disorders), children and adolescents are often prescribed medications and/or treatments to help with the management of these chronic diseases. Croen et al., (2006) found that adolescents are six times more likely to be hospitalized than their neuro‐typical peers. Managing autism takes a multi‐disciplinary approach. Navigating a large university system, academics, and being away from home can be challenging for any teenager. But, adding the complexity of managing a chronic neurodevelopmental disorder on top of the new environment could potentially be overwhelming for the autistic adolescent. It makes sense to use all available resources when transitioning into a college setting. Registered nurses (RN) and advanced practice nurses (APN) are employed at university clinics to help manage student healthcare issues including acute healthcare problems (e.g., viruses), traumatic issues, and chronic healthcare issues. This paper will examine how nursing professionals can assist autistic adolescents when they are entering into a college environment by managing medications and other treatment modalities while being a student advocate within a multi‐disciplinary team.

Herbacetin ameliorates lipopolysaccharide-elicited inflammatory response by suppressing NLRP-3/AIM-2 inflammasome activation, PI3K/Akt/MAPKs/NF-κB redox inflammatory signalling, modulating autophagy and macrophage polarization imbalance.

Herbacetin, a flavonol abundant in traditional medicines, is documented as an anti-inflammatory agent. However, information regarding its attributes on lipopolysaccharide (LPS)-induced inflammatory immunopathies has not been delineated yet. The present study aimed to comprehend herbacetin effects on LPS-induced aspects of unwarranted, non-resolving inflammation, particularly via targeting the vicious circle of oxi-inflammatory stress, autophagy-apoptosis, macrophages polarization, impaired inflammasome activation, and inflammatory cascades. In-vitro model of LPS-stimulated RAW 264.7 macrophage was recapitulated to investigate different inflammatory anomalies using enzyme-linked immunosorbent assay, qRT-PCR (Real-Time Quantitative Reverse Transcription PCR), immunoblotting. Concanavalin A challenged splenocytes and in silico studies were performed to measure Tregs population and binding affinity, respectively. Herbacetin administration caused remarkable reduction in nitric oxide, reactive oxygen species, mitochondrial membrane potential hyperpolarization, tumor necrosis factor-α, interferon-γ, interleukin-6, inducible nitric oxide synthase and ratio of M1/M2 markers (inducible nitric oxide synthase/arginase-1/macrophage scavenger receptor-1/mannose receptor C type-1) in in vitro model of persistent inflammation. Suppression of interleukins-5,17 and matrix metalloproteinases-2,3,9,13 and proliferating cell nuclear antigen, signifies its anti-inflammatory attributes. Noticeable decline in monodansylcadaverine-Lysotracker staining, caspase-6, and enhanced p62, B-cell lymphoma-2 expression indicates apoptosis-autophagosome accumulation inhibition and lysosomal destabilization. These were accompanied by reduced NLRP3 activation, caspase-1, AIM-2 expression, and interleukin-1β release. Subsequently, up-regulated activation of TLR-4, NF-κB, PI3K, Akt, ERK1/2, and JNK was decisively thwarted by herbacetin. In silico investigation signified the interaction of herbacetin with these targets. Decreased cytokines and enhanced Tregs conferred its role in extenuating inflammation facilitated by T-cells depletion. Collectively, these findings comprehend attributes of herbacetin as an alternative therapeutic strategy in relieving LPS-associated chronic inflammatory disorders.

The impact of diet on the inflammatory bowel disease course – a literature review

Introduction and Objective. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic gastrointestinal disorder marked by relapsing symptoms. Current treatments mainly involve immunosuppressive therapies, which are effective but may have significant side effects. Diet as an adjunctive treatment is appealing due to its accessibility, low cost, and minimal adverse effects. This review explores the role of diet in managing IBD, focusing on dietary strategies during both active disease and remission. Methods. A literature review was conducted using PubMed and Google Scholar with search terms like "inflammatory bowel disease", "Crohn’s disease", "ulcerative colitis", "diet", "IBD treatment", "anti-inflammatory food" and related variations. Articles published within the last five years were prioritized. Brief description of the state of Knowledge. Ulcerative colitis and Crohn’s disease cause gastrointestinal inflammation. Crohn’s disease symptoms include abdominal pain, fistulas and rectal lesions, while UC is characterized by diarrhea, severe discomfort, and blood in the stool. Certain foods often exacerbate IBD symptoms. Proper nutrition during disease stages can improve patients’ quality of life. Diets high in processed foods, sugar, and red meat may increase IBD risk, while fiber and vitamin D3 are associated with fewer flare-ups. Regular malnutrition screening is essential for all IBD patients. Conclusions. Understanding the dietary components that influence inflammation in IBD could lead to better treatment outcomes and longer-lasting symptom relief. Integrating nutrition into personalized treatment strategies should become standard practice for managing IBD.

Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis.

Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.

Depression in patients with chronic otolaryngology symptoms - A vicious cycle.

Depression is a common comorbidity among individuals with otolaryngologic disorders, particularly those with longstanding conditions. This study aims at analysing the sociodemographic profile of depressive disorders in patients with chronic otolaryngology symptoms or conditions, and the correlation with PHQ-9 score. A cross-sectional study was conducted on a hundred patients presenting to the outpatient department with chronic otolaryngology symptoms or conditions. They were requested to fill in the PHQ-9 questionnaire, containing questions based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for major depressive disorder (MDD). Median age was 39, male: female ratio was 1.17. Nasal obstruction (29%), ear discharge (25%), and headache (17%) were the common presenting complaints. Mean and median PHQ-9 scores were 5.03 and 4 respectively. Seven patients (7%) had MDD, while eleven (11%) had other depressive disorder; 9% of cases were found to have no significant otolaryngologic problem despite presenting with symptoms, two of which were found to have depressive disorder. Thirty-five (35%) and thirty-six (36%) patients had minimal and mild depressive symptoms respectively, while one (1%) had severe depressive symptoms. Statistical significance was noted for the duration of symptoms (p-value 0.005); high statistical significance was found for occupation and otolaryngology diagnosis (p-value < 0.001 each). PHQ-9 score showed statistical significance in comparison with gender and duration of symptoms (p-value 0.046 and 0.005 respectively). Correlation of severity of depressive disorder revealed statistical significance with gender (p-value 0.049) and high statistical significance with duration of symptoms (p-value < 0.001). Chronic otolaryngology conditions are associated with significant morbidity, attributable to longstanding disturbing symptoms and prolonged treatment protocols, leading to depression. Nevertheless, depression in chronic otolaryngology disorders may aggravate or overlap the clinical symptoms or may go undetected. Hence it may be worthwhile to evaluate for depressive disorders in chronic patients presenting to otolaryngology.

A SYSTEMATIC REVIEW ON ADHERENCE TO ORAL ANTIDIABETIC DRUGS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder in which prevalence has been increasing steadily all over the world and one of the main reason for this is poor adherence to oral anti-diabetic drugs, which can lead to therapy failure and increase risk of complications. So we planned this systematic review with an aim to get an adherence estimation to oral anti-diabetic drugs in type 2 diabetes mellitus patients for which a literature search was performed in pubmed, Google Scholar, scopus, and central databases to find observational studies on therapeutic adherence in users of oral anti-diabetic drugs. Our analyses showed that adherence rate to oral anti-diabetic drugs therapy ranged from 23 to 90%. This review confirms that many patients for whom diabetes medication was prescribed were poor compliers with treatment of oral anti-diabetic drugs.

Physiological and Psychological Stress Reactivity in Narcolepsy Type 1.

Narcolepsy type 1 (NT1) is a chronic sleep-wake disorder, characterized by a loss of hypocretin production. Unexpectedly, in post-mortem tissue of people with NT1 there is a loss of corticotrophin-releasing hormone (CRH) in the paraventricular nucleus. CRH is known as activator of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. This activation results in the release of the stress hormones adrenocorticotropic hormone (ACTH) and cortisol. We hypothesize an altered physiological and psychological stress response in NT1. Participants were people with NT1 (n=14) and matched healthy controls (n=12). The Trier Social Stress Test for Groups (TSST-G), a validated socially evaluated stress test in controlled settings, induced acute stress. We measured ACTH and cortisol levels in blood before and at three timepoints after the TSST-G. We also measured subjective stress and heart rate levels. In both groups, acute stress led to increases in ACTH (p=0.006), cortisol (p<0.001), heart rate (p<0.001) and subjective stress (p<0.001). Subjectively, people with NT1 experienced more stress than controls (p<0.001). No differences were found in heart rate, cortisol, and ACTH between people with NT1 and controls at any timepoint. Secondary analyses showed that men with NT1 had lower cortisol levels immediately after stress induction than men in the control group (p=0.002). People with NT1 show an increased subjective stress response, but no changes in their endocrine or cardiovascular stress reactivity. Further research is required to determine the impact of reduced CRH production and gender in NT1.

A review of epilepsy detection and prediction methods based on EEG signal processing and deep learning

Epilepsy is a chronic neurological disorder that poses significant challenges to patients and their families. Effective detection and prediction of epilepsy can facilitate patient recovery, reduce family burden, and streamline healthcare processes. Therefore, it is essential to propose a deep learning method for efficient detection and prediction of epileptic electroencephalography (EEG) signals. This paper reviews several key aspects of epileptic EEG signal processing, focusing on epilepsy detection and prediction. It covers publicly available epileptic EEG datasets, preprocessing techniques, feature extraction methods, and deep learning-based networks used in these tasks. The literature is categorized based on patient independence, distinguishing between patient-independent and non-patient-independent studies. Additionally, the evaluation methods are classified into general classification indicators and specific epilepsy prediction criteria, with findings organized according to the prediction cycles reported in various studies. The review reveals several important insights. Despite the availability of public datasets, they often lack diversity in epilepsy types and are collected under controlled conditions that may not reflect real-world scenarios. As a result, signal preprocessing methods tend to be limited and may not fully represent practical conditions. Feature extraction and network designs frequently emphasize fusion mechanisms, with recent advances in Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs) showing promising results, suggesting that new network models warrant further exploration. Studies using patient-independent data generally produce better results than those relying on non-patient-independent data. Metrics based on general classification methods typically perform better than those using specific epilepsy prediction criteria, though future research should focus on the latter for more accurate evaluation. Epilepsy prediction cycles are typically kept under 1 h, with most studies concentrating on intervals of 30 min or less.

The antimicrobial and antibiofilm effects of gentamicin, imipenem, and fucoidan combinations against dual-species biofilms of Staphylococcus aureus and Acinetobacter baumannii isolated from diabetic foot ulcers.

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin production or utilization, leading to severe health complications. Diabetic foot ulcers (DFUs) represent a major complication, often exacerbated by polymicrobial infections involving Staphylococcus aureus and Acinetobacter baumannii. These pathogens, notorious for their resistance to antibiotics, complicate treatment efforts, especially due to biofilm formation, which enhances bacterial survival and resistance. This study explores the synergistic effects of combining gentamicin, imipenem, and fucoidan, a sulfated polysaccharide with antimicrobial properties, against both planktonic and biofilm forms of S. aureus and A. baumannii. Isolates of S. aureus and A. baumannii were collected from DFUs and genetically confirmed. Methicillin resistance in S. aureus was identified through disk diffusion and PCR. Biofilm formation, including dual-species biofilms, was analyzed using the microtiter plate method. The antimicrobial efficacy of gentamicin, imipenem, and fucoidan was assessed by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC). Synergistic interactions were evaluated using the fractional inhibitory concentration index (FICi) and fractional bactericidal concentration index (FBCi). The expression of biofilm-associated genes (icaA in S. aureus and bap in A. baumannii) was analyzed, and the cytotoxicity of fucoidan was assessed. The study revealed that 77.4% of S. aureus and all A. baumannii isolates showed multidrug resistance. Among 837 tested conditions for dual-species biofilm formation, 72 resulted in strong biofilm formation and 67 in moderate biofilm formation. The geometric mean MIC values for gentamicin were 12.2µg/mL for S. aureus, 22.62µg/mL for A. baumannii, and 5.87µg/mL for their co-culture; for imipenem, they were 19.84, 9.18, and 3.70µg/mL, respectively, and for fucoidan, 48.50, 31.20, and 19.65µg/mL, respectively. The MBC values for gentamicin were 119.42, 128, and 11.75µg/mL; for imipenem, they were 48.50, 14.92, and 8µg/mL; and for fucoidan, they were 88.37, 62.62, and 42.48µg/mL. The MBIC values were 55.71, 119.42, and 18.66µg/mL for gentamicin; 68.59, 48.50, and 25.39µg/mL for imipenem; and 153.89, 101.49, and 53.53µg/mL for fucoidan. The MBEC values were 315.17, 362.03, and 59.25µg/mL for gentamicin; 207.93, 157.58, and 74.65µg/mL for imipenem; and 353.55, 189.46, and 99.19µg/mL for fucoidan. When cultured in planktonic form, the geometric mean FICi and FBCi values indicated additive effects, while co-culture showed FICi values of ≤ 0.5, suggesting a synergistic interaction. Treatment with gentamicin and fucoidan led to significant downregulation of the icaA and bap genes in both single-species and dual-species biofilms of S. aureus and A. baumannii. The reductions in gene expression were more pronounced in dual-species biofilms compared to single-species biofilms. Additionally, treatment with imipenem and fucoidan also resulted in significant downregulation of these genes in both biofilm types. Cytotoxicity assessments indicated that higher concentrations of fucoidan were toxic, yet no harmful effects were noted at the optimal synergistic concentrations used with antibiotics. In our investigation, we found that combining gentamicin, imipenem, and fucoidan had a synergistic effect on dual-species biofilms of S. aureus and A. baumannii, suggesting potential benefits for treating such infections effectively. This underscores the importance of understanding microbial interactions, antibiotic susceptibility, and biofilm formation in DFUs.

The altered hypothalamic network functional connectivity in chronic insomnia disorder and regulation effect of acupuncture: a randomized controlled neuroimaging study.

The hypothalamus has been recognized as a core structure in the sleep-wake cycle. However, whether the neuroplasticity of the hypothalamus is involved in the acupuncture treatment of insomnia remains elusive. We recruited 42 patients with chronic insomnia disorder (CID) and 23 matched healthy controls (HCs), with CID patients randomly assigned to receive real acupuncture (RA) or sham acupuncture (SA) for four weeks. Insomnia severity was evaluated using the Pittsburgh Sleep Quality Index (PSQI) score, and the resting-state functional connectivity (rsFC) of the hypothalamus was assessed via functional magnetic resonance imaging (fMRI). In the cross-sectional investigation, CID patients showed increased rsFC between the medial hypothalamus (MH) and left lateral orbital frontal cortex (LOFC), and bilateral medial orbital frontal cortex (MOFC) compared to HCs. In the longitudinal experiment, PSQI scores significantly decreased in the RA group (p = 0.03) but not in the SA group. Interestingly, the increased MH-LOFC connectivity was found to be reduced following RA treatment. In addition, the altered rsFC of MH-LOFC significantly correlated with clinical improvement in the RA group (r = -0.692, p = 0.006). This randomized neuroimaging study provides preliminary evidence that acupuncture may improve insomnia symptoms by restoring circuits associated with hypothalamic subregions. This trial has been registered on the Chinese Clinical Trial Registry ( www.chictr.org.cn ) with the identifier (ChiCTR1800017092). Registered date: 11/07/2018.

A new clinical entity bridging the cardiovascular system and the kidney: The Chronic Cardiovascular-Kidney Disorder.

Background The complex relationship between heart and kidney dysfunction has been a subject of medical inquiry since the 19th century. The term "cardio-renal syndrome" (CRS) was introduced in the early 2000s and has since become a focal point of research. CRS is typically categorized into five subtypes based on the sequence of cardiovascular and kidney disease events. Summary The Cardiovascular-Kidney-Metabolic (CKM) syndrome, as defined by the American Heart Association (AHA), describes a set of interrelated metabolic risk factors and their effects on the kidneys and cardiovascular system. This syndrome emphasizes the complexity of managing patients with combined conditions and identifies several knowledge gaps, including disease mechanisms, clinical phenotype variability, and the impact of social determinants of health. The Chronic Cardiovascular-Kidney Disorder (CCKD) framework proposes a shift from the term "syndrome" to "disorder," focusing on concurrent cardiovascular and kidney problems regardless of their sequence. Key messages • The CCKD concept calls for simplification and conceptual clarity, arguing that understanding the bidirectional acceleration of disease progression between heart and kidney dysfunction can lead to more effective treatment strategies. • Both CKM and CCKD share common pathophysiological mechanisms and risk factors, including hypertension, diabetes, obesity, and dyslipidemia. Managing these conditions requires a comprehensive approach that addresses the underlying risk factors and pathophysiological mechanisms. • Future directions include embracing precision medicine, public health strategies, interdisciplinary care models, and ongoing research and innovation. Both frameworks underscore the need for comprehensive, interdisciplinary care models and innovative treatment strategies to address the complex interplay between cardiovascular and kidney diseases.

Immunomodulatory effects of HYCO-3, a dual action CO-releaser/Nrf2 activator.

HYCOs are hybrid molecules consisting of activators of the transcription factor Nrf2 conjugated to carbon monoxide (CO)-releasing moieties. These "dual action" compounds have been designed to mimic the activity of heme oxygenase-1 (HO-1), a stress inducible cytoprotective enzyme that degrades heme to CO which expression is regulated by Nrf2. HYCOs have recently shown efficacy in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, the mechanism(s) of action of HYCOs still remain to be fully investigated. Here, we assessed the effects of HYCO-3, a prototype of these hybrids, on myeloid-derived cells, microglial cells and T lymphocytes obtained from EAE-immunized mice. HYCO-3 exerted immunomodulatory effects on all the examined cell populations by inhibiting the generation of pro-inflammatory cytokines and nitric oxide, and downregulating antigen-presenting capacity of these cells. The observed effects support the view that HYCOs are promising candidates to be developed for the treatment of autoimmune and chronic inflammatory disorders.

Harnessing the therapeutic potential of exercise in extracellular vesicle-based therapy in metabolic disease associated cardiovascular complications.

Cardiovascular disease (CVD) is a leading cause of mortality, affecting ∼18 million individuals each year. Obesity and type 2 diabetes mellitus in particular, both chronic metabolic disorders, are risk factors for CVD. The salutary effects of physical activity in preventing and ameliorating CVD have long been acknowledged, as it improves glucose and lipid homeostasis, alongside attenuating oxidative damage, increasing mitochondrial function, and ultimately improving cardiac function. Exercise serves as a catalyst for the secretion of extracellular vesicles (EVs), facilitating inter-tissue communication, by which tissues can deliver important signals from one tissue to another. In recent years, an increasing number of studies have focused on the cargo encapsulated within exercise-derived EVs, as well as the orchestration of inter-tissue crosstalk aimed at modulating metabolism and tissue function in CVDs. The precise mechanisms underpinning the cardioprotective properties of exercise-derived EVs, however, remains only partially elucidated. This review explores novel EV based therapeutic options in CVD and, in particular, EVs derived from models of exercise to alter metabolism and enhance cardiovascular outcomes.

Inhalation Exposure to Cross-linked Polyacrylic Acid Induces Pulmonary Disorders.

Organic polymers, widely used in food, daily necessities, and medicines, include cross-linked polyacrylic acid (CL-PAA), which has been reported to induce severe lung disease. While previous studies mainly used intratracheal instillation, our research focused on inhalation exposure to corroborate these findings. We conducted 5-day (short-term) and 13-week (subchronic) inhalation exposure studies with CL-PAA. In the short-term study, male F344 rats inhaled CL-PAA at 0.2, 2.0, or 20mg/m³ for 6hours/day over 5 days. Rats were dissected 3 days and 1 month post-exposure. In the subchronic study, rats inhaled CL-PAA at 0.2 or 2.0mg/m³ for 6hours/day, 5 days/week for 13 weeks, with dissections from 3 days to 6 months post-exposure. To investigate the mechanism of pulmonary disorders, an additional short-term study with 20mg/m³ CL-PAA included intraperitoneal injections of the antioxidant N-acetylcysteine (NAC) (200mg/kg) with dissection the day after exposure. Short-term exposure led to concentration-dependent increases in neutrophil influx, cytokine-induced neutrophil chemoattractant (CINC), total protein, lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Histopathology showed concentration-dependent neutrophil infiltration. Subchronic exposure caused persistent increases in BALF total protein and lung HO-1, with ongoing neutrophil infiltration and fibrosis. NAC administration reduced neutrophils, total protein, LDH, and CINC in BALF, and HO-1 in lung tissue, improving histopathological findings. Inhalation of CL-PAA caused concentration-dependent lung inflammation and persistent fibrosis. The no observed adverse effect level (NOAEL) for chronic pulmonary disorders was 0.2mg/m³. Oxidative stress linked to CL-PAA-induced inflammation was mitigated by NAC administration.

Volumetric Analysis of Motor Cortex and Basal Ganglia in Pediatric Celiac Disease Patients Using volBrain: Implications for Neurological Dysfunction-Preliminary Results

Background/Objectives: Celiac disease (CD) is a common immune-mediated, chronic systemic disorder that is treated with a strict, life-long gluten-free diet (GFD). In addition to gastrointestinal manifestations, CD also presents with a variety of extraintestinal symptoms, including significant neurological and neuropsychiatric symptoms. Among these neurological manifestations, motor dysfunctions are particularly notable. The aim of this study is to investigate the potential volumetric differences in brain structures, particularly the motor cortex and basal ganglia, between pediatric CD patients and healthy controls using the volBrain software AssemblyNet version 1.0. Methods: This prospective study included pediatric patients with CD who complained of neurological symptoms and were scheduled for brain magnetic resonance imaging (MRI). All children had been previously diagnosed with CD and their adherence to GFD was evaluated using the Biagi score. Brain MRIs were performed on all included patients to obtain volumetry at the onset of the disease. For volumetric and segmentation data, the volBrain software was used. Results: In total, 12 pediatric patients with CD were included, with a median duration of a GFD of 5.3 years at the time of the MRI examination. There were no statistically significant differences between patients compliant with the GFD and those non-compliant in terms of age or duration of GFD. Volumetric analysis revealed deviations in all patients analyzed, which involved either a decrease or increase in the volume of the structures studied. Conclusion: Despite the limited number of patients in this study, the initial findings support previously described neurological manifestations in patients with CD. Newly developed MRI tools have the potential to enable a more detailed analysis of disease progression and its impact on the motor cortex.

Periplaneta americana L. extract exerts neuroprotective effects by inhibiting endoplasmic reticulum stress via AKT-dependent pathway in experimental models of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder that currently has no curable strategies. More and more evidence suggests that endoplasmic reticulum (ER) stress plays an essential role in PD pathogenesis. Periplaneta americana L. (P. americana) is a traditional Chinese medicine with diverse therapeutic properties. This study aims to investigate the neuroprotective effect and underlying mechanism of P. americana in in vitro and in vivo PD models. The exposure of SH-SY5Y cells to 1-methyl-4-phenyl-pyridinium (MPP+) was used as the in vitro PD model. MTT assay, Hoechst staining, Calcein AM-PI staining and flow cytometry were performed to measure the cell viability and apoptosis. DCFH-DA and JC-1 assay were used to measure the intracellular ROS and mitochondrial membrane potential (Δψm), respectively. Western-blot and immunostaining were conducted to detect the expression of key molecules related with ER stress. For the in vivo PD model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro-pyridine (MPTP), the motor function of mice was assessed by behavioral tests, the level of TH was examined by western-blot and immunostaining, the expression of key molecules related with ER stress was measured by western-blot. Periplaneta americana ethanol extract (PAE) concentration-dependently inhibited MPP+-induced cell loss and increased cell viability. PAE also remarkably attenuated ROS accumulation, the decline of Δψm as well as the excessive ER stress. The neuroprotective effects of PAE could be blocked by ROS inducer trimethylamine N-Oxide or ER stress activator tunicaymycin, while the antioxidant N-Acetyl-L-cysteine or ER stress inhibitor sodium 4-phenylbutyrate mimicked the effects of PAE. Furthermore, we found that PAE could activate AKT/GSK3β/β-catenin pathway. The effect of PAE on ROS production, Δψm and ER stress was blocked by AKT inhibitor MK-2206. In in vivo model, PAE significantly improved motor function, prevented dopaminergic neuronal loss and attenuated ER stress in substantia nigra and striatum of MPTP-treated mice. Similarly, the effects of PAE on MPTP-treated mice were also abolished by MK-2206. Our results suggest that P. americana exerts neuroprotective effects through inhibiting ER stress via AKT-dependent pathway. Periplaneta americana may represent a promising therapeutic agent for PD treatment and is worthy of further being exploited.

The Anti-Elixir Triad: Non-Synced Circadian Rhythm, Gut Dysbiosis and Telomeric Damage.

Aging is an inevitable life process which is accelerated by lifestyle and environmental factors. It is an irreversible accretion of molecular and cellular damage associated with changes in the body composition and deterioration in physiological functions. Each cell (other than stem cells), reaches the limit of its ability to replicate, known as cellular or replicative senescence and consequently, the organs lose their physiological functions resulting in overall impairment. Other factors that promote aging include smoking, alcohol, UV rays, sleep habits, food, stress, sedentary life style and genetic abnormalities. These stress factors, can alter our endogenous clock (the circadian rhythm) and the microbial commensals. As a result of effect of these stressors, the microorganisms that generally support human physiological processes become baleful. The disturbance of natural physiology instigates many age-related pathologies, such as cardiovascular diseases, chronic obstructive pulmonary disorder, cerebrovascular diseases, opportunistic infections, high blood pressure, cancer, diabetes, kidney diseases, dementia, and Alzheimer's disease. The present review covers the three most essential processes of the circadian clock; the circadian gene mechanism and regulation, the mitotic clock (which plays a vital role in the telomere's attrition) and gut microbiota and their metabolome that drive aging and lead to age-related pathologies. In conclusion, maintaining a synchronized circadian rhythm, a healthy gut microbiome and telomere integrity is essential for mitigating the effects of aging and promoting longevity. The interplay among these factors underscores the importance of lifestyle choices in enhancing overall health and lifespan.

The Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Liraglutide Regulates Sirtuin-1-Mediated Neutrophil Extracellular Traps to Improve Diabetes-Induced Bone Metabolism Imbalance

Background: Diabetes mellitus (DM) is a chronic metabolic disorder that disrupts normal bone remodeling. Objectives: This study aimed to investigate how the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LIR) addresses bone metabolism imbalances induced by type-II diabetes. Methods: Type-II diabetic rat models were established through a single intraperitoneal injection of streptozotocin (STZ). Blood glucose levels were measured using a blood glucose meter, and insulin levels were assessed using an assay kit. Bone formation markers [alkaline phosphatase (ALP), osteocalcin (OCN), and procollagen I N-terminal propeptide (PINP)] and bone resorption markers [tartrate-resistant acid phosphatase (TRACP) and CTX-1] were monitored using assay kits. Bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro under high-fat and high-glucose (HFHS) conditions to mimic diabetic bone metabolism dysregulation. Neutrophil extracellular traps (NETs) formation was examined through immunofluorescent staining and Western blot analysis. Results: Liraglutide was found to reduce STZ-induced NETs formation, as indicated by decreased expression of cit-H3 by 36.90% - 53.57%, myeloperoxidase (MPO) by 55.81% - 65.12%, NE by 53.95% - 65.17%, and PAD4 by 46.81% - 63.83%, alongside increased Sirtuin-1 (SIRT1) expression in femur tissue (70.71% - 91.19%). In vitro, LIR enhanced osteogenesis and inhibited apoptosis, effects that were partially reversed by SIRT1 knockdown. Additionally, SIRT1 knockdown partially restored LIR-induced reductions in oxidative stress, inflammation, and NETs formation. Conclusions: LIR mitigates diabetes-induced bone metabolism imbalance by inhibiting NETs formation through SIRT1 mediation.