Asperuloside Suppresses the Development of Depression through Wnt3α/GSK-3ß Signal Pathway in Rats.

Depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Traditional Chinese medicine monomer has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. The aim of this study was to investigate the antidepressant-like effects of asperuloside (ASP) and its mechanism. The depression-like behaviors of chronic unpredictable mild stress (CUMS)-exposed rats were evaluated by behavioral tests. At the same time, the behaviors of rats treated with different concentrations of ASP (10, 20, 40 mg/kg) were also evaluated. RNA sequencing was performed to screen for dysregulated genes following ASP treatment. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to state the enriched pathways. Protein expression was detected by Western blotting. With the increase of ASP concentration (over 20 mg/kg), the depression-like behaviors of the rats were alleviated, which was manifested as the increase of the number of entries in the central zone, decrease of immobility time, and the increase of swimming time, sucrose preference, and body weight. ASP activated the Wnt3α/glycogen synthase kinase 3ß (GSK-3ß)/ß-catenin signaling pathway in vivo. Knockdown of ß-catenin reversed the effects of ASP on regulating depression-like behaviors. ASP alleviates depression-like behaviors by activating the Wnt3α/GSK-3ß/ß-catenin signaling pathway, indicating that ASP may be a potential therapeutic drug for treatment of depression.

Significance of early diagnosis and treatment of adult late-onset Pompe disease on the effectiveness of enzyme replacement therapy in improving muscle strength and respiratory function: a case report.

BACKGROUND: Pompe disease, a rare autosomal recessive disorder, is caused by mutations in the acid α-glucosidase gene. Pompe disease is a congenital metabolic disorder that affects all organs, particularly the striated muscle and nerve cells. Diagnosis is typically confirmed through enzyme assays that reveal reduced acid α-glucosidase activity. Enzyme replacement therapy utilizing human α-glucosidase is an available treatment option. Timely diagnosis and treatment in the early stages of the disease significantly impact the effectiveness of enzyme replacement therapy in enhancing patient condition. Here, we present a case of a patient with Pompe disease diagnosed 20 years after the onset of clinical symptoms. CASE PRESENTATION: A 38-year-old Iranian Baloch woman referred to our rheumatology clinic with progressive muscle weakness presents with a complex medical history. On mechanical ventilation for 12 years, she has endured fatigue and limb weakness since the age of 16, exacerbated following an abortion at 19. Despite undergoing corticosteroid and azathioprine therapies, the suspected diagnosis of inflammatory myopathy did not yield improvement. Hospitalization at 23 due to respiratory failure post-pregnancy led to her continued reliance on a ventilator. A dried blood spot test indicated reduced GAA enzyme activity, confirming a diagnosis of Pompe disease through genetic testing. Treatment with myozyme for 2 years demonstrated limited efficacy, as the patient experienced improved breathing but no significant overall improvement in limb-girdle muscular weakness. This case underscores the challenges and complexities involved in diagnosing and managing rare neuromuscular disorders like Pompe disease. CONCLUSION: Early intervention with enzyme replacement therapy plays a crucial role in halting further muscle loss and disease progression in Pompe disease patients. It is important to note that treatment during advanced stages of the disease may not yield substantial benefits. Nevertheless, enzyme instability and denaturation due to temperature and neutral pH levels, along with limited delivery to disease-relevant tissues, can pose challenges in treatment. However, timely diagnosis of Pompe disease is paramount for its effective management and improved outcomes.

Unusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report.

BACKGROUND: Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life. CASE PRESENTATION: In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene. CONCLUSION: This case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease.

MRI of GlycoNOE in the human liver using GraspNOE-Dixon.

PURPOSE: The objective of this study was to develop a new MRI technique for non-invasive, free-breathing imaging of glycogen in the human liver using the nuclear Overhauser effect (NOE). METHODS: The proposed method, called GraspNOE-Dixon, uses a novel MRI sequence that combines steady-state saturation-transfer preparation with multi-echo golden-angle radial stack-of-stars sampling. Multi-echo acquisition enables fat/water-separated imaging for quantification of water-specific NOE. Image reconstruction is performed using the improved golden-angle radial sparse parallel imaging (GRASP-Pro) technique to exploit spatiotemporal correlations in dynamic images. To evaluate the proposed technique, imaging experiments were first performed on glycogen phantoms, followed by in vivo studies involving healthy volunteers and patients with fatty liver disease. In addition, a comparative assessment of signal changes before and after a 12-h fasting period was performed. RESULTS: Evaluation experiments on glycogen phantoms showed a robust linear correlation between the NOE signal and glycogen concentration. In vivo experiments demonstrated motion-robust NOE-weighted images, with potential for further acceleration. In subjects with varying liver fat content, the fat/water separation approach resulted in distortion-free Z-spectra, enabling the quantification of glycogen NOE. An approximately one-third reduction in the NOE signal was observed following a 12-h fasting period, consistent with a decrease in glycogen level. CONCLUSION: This study introduces a clinically feasible imaging technique, GraspNOE-Dixon, for free-breathing volumetric multi-echo imaging of hepatic glycogen at 3 T. The motion robust imaging technique developed here may also have applications in other body areas beyond liver imaging.

Continuous glucose monitoring in patients with inherited metabolic disorders at risk for Hypoglycemia and Nutritional implications.

Managing Inherited Metabolic Disorders (IMDs) at risk for hypoglycemia, such as Glycogen Storage Diseases (GSDs), Hereditary Fructose Metabolism Disorders (HFMDs) and Congenital Hyperinsulinism (CH), poses challenges in dietary treatments and blood glucose monitoring. The effectiveness of Continuous Glucose Monitoring (CGM) remains a subject of ongoing debate, with IMD guidelines maintaining caution. Therefore, a systematic evaluation is needed to understand the potential benefits of CGM during dietary interventions. A systematic literature review was conducted in PubMed according to the PICOS model and PRISMA recommendations on studies published from January 01, 2003, up to October 15, 2023 (PROSPERO CRD42024497744). The risk of bias was assessed using NIH Quality Assessment Tools. Twenty-four studies in GSDs (n = 13), CH (n = 10), and HFMDs (n = 1) were analyzed. In GSDs, Real-time CGM (Rt-CGM) was associated with metabolic benefits during nutritional interventions, proving to be an accurate system for hypoglycemia detection although with some concerns about reliability. Rt-CGM in CH, primarily involving children, also showed potential benefits for glycemic control and metabolic stability with acceptable accuracy, although its use during dietary changes was limited. Few experiences on Flash Glucose Monitoring (FGM) were reported, with some concerns about reliability. Overall, the studies analyzed presented different designs, and their quality was predominantly fair or poor. Heterogeneity and limited consensus on reliability and glycemic targets underscore the need for prospective studies and future recommendations for the use of CGM in optimizing nutritional status and providing personalized dietary education in individuals with IMDs prone to hypoglycemia.

Pharmacological upregulation of macrophage-derived itaconic acid by pubescenoside C attenuated myocardial ischemia-reperfusion injury.

INTRODUCTION: Myocardial ischemia-reperfusion injury (MIRI) remains a prevalent clinical challenge globally, lacking an ideal therapeutic strategy. Macrophages play a pivotal role in MIRI pathophysiology, exhibiting dynamic inflammatory and resolutive functions. Macrophage polarization and metabolism are intricately linked to MIRI, presenting potential therapeutic targets. Pubescenoside C (PBC) from Ilex pubescens showed significantly anti-inflammatory effects, however, the effect of PBC on MIRI is unknown. OBJECTIVES: This study aimed to assess the cardioprotective effects of PBC against MIRI and elucidate the underlying mechanisms. METHODS: Sprague-Dawley rats, H9c2 and RAW264.7 macrophages were used to establish the in vitro and in vivo models of MIRI. TTC/Evans blue staining, immunohistochemical staining, metabonomics analysis, chemical probe, surface plasmon resonance (SPR), co-immunoprecipitation (CO-IP) assays were used for pharmacodynamic and mechanism study. RESULTS: PBC administration effectively reduced myocardial infarct size, decreased ST-segment elevation, and lowered CK-MB levels, concurrently promoting macrophage M2 polarization in MIRI. Furthermore, PBC-treated macrophages and their conditioned culture medium attenuated the apoptosis of H9c2 cells induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Metabonomics analysis revealed that PBC increased the production of itaconic acid (ITA) and malic acid (MA) in macrophages, which conferred protection against OGD/R injury in H9c2 cells. Mechanistic investigations indicated that ITA exerted its effects by covalently modifying pyruvate kinase M2 (PKM2) at Cys474, Cys424, and Lys151, thereby facilitating PKM2's mitochondrial translocation and enhancing the PKM2/Bcl2 interaction, subsequently leading to decreased degradation of Bcl2. SPR assays further revealed that PBC bound to HSP90, facilitating the interaction between HSP90 and GSK3ß and resulting in the inactivation of GSK3ß activity and upregulation of key metabolic enzymes for ITA and MA production (Acod1 and Mdh2). CONCLUSION: PBC alleviates MIRI-induced cardiomyocyte apoptosis by modulating the HSP90/ITA/PKM2 axis. Furthermore, pharmacological upregulation of ITA emerges as a promising therapeutic approach for MIRI, hinting at PBC's potential as a candidate drug for MIRI therapy.

Exogenous Lactate Treatment Immediately after Exercise Promotes Glycogen Recovery in Type-II Muscle in Mice.

Recent studies suggest that lactate intake has a positive effect on glycogen recovery after exercise. However, it is important to verify the effect of lactate supplementation alone and the timing of glycogen recovery. Therefore, in this study, we aimed to examine the effect of lactate supplementation immediately after exercise on glycogen recovery in mice liver and skeletal muscle at 1, 3, and 5 h after exercise. Mice were randomly divided into the sedentary, exercise-only, lactate, and saline-treated groups. mRNA expression and activation of glycogen synthesis and lactate transport-related factors in the liver and skeletal muscle were assessed using real-time polymerase chain reaction. Skeletal muscle glycogen concentration showed an increasing trend in the lactate group compared with that in the control group at 3 and 5 h after post-supplementation. Additionally, exogenous lactate supplementation significantly increased the expression of core glycogen synthesis enzymes, lactate transporters, and pyruvate dehydrogenase E1 alpha 1 in the skeletal muscles. Conversely, glycogen synthesis, lactate transport, and glycogen oxidation to acetyl-CoA were not significantly affected in the liver by exogenous lactate supplementation. Overall, these results suggest that post-exercise lactate supplement enables glycogen synthesis and recovery in skeletal muscles.

Neurological glycogen storage diseases and emerging therapeutics.

Glycogen storage diseases (GSDs) comprise a group of inherited metabolic disorders characterized by defects in glycogen metabolism, leading to abnormal glycogen accumulation in multiple tissues, most notably affecting the liver, skeletal muscle, and heart. Recent findings have uncovered the importance of glycogen metabolism in the brain, sustaining a myriad of physiological functions and linking its perturbation to central nervous system (CNS) pathology. This link resulted in classification of neurological-GSDs (n-GSDs), a group of diseases with shared deficits in neurological glycogen metabolism. The n-GSD patients exhibit a spectrum of clinical presentations with common etiology while requiring tailored therapeutic approaches from the traditional GSDs. Recent research has elucidated the genetic and biochemical mechanisms and pathophysiological basis underlying different n-GSDs. Further, the last decade has witnessed some promising developments in novel therapeutic approaches, including enzyme replacement therapy (ERT), substrate reduction therapy (SRT), small molecule drugs, and gene therapy targeting key aspects of glycogen metabolism in specific n-GSDs. This preclinical progress has generated noticeable success in potentially modifying disease course and improving clinical outcomes in patients. Herein, we provide an overview of current perspectives on n-GSDs, emphasizing recent advances in understanding their molecular basis, therapeutic developments, underscore key challenges and the need to deepen our understanding of n-GSDs pathogenesis to develop better therapeutic strategies that could offer improved treatment and sustainable benefits to the patients.

A New Strategy for Adult T-Cell Leukemia Treatment Targeting Glycogen Synthase Kinase-3ß.

OBJECTIVES: The role of glycogen synthase kinase (GSK)-3ß in adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type 1 (HTLV-1) is paradoxical and enigmatic. Here, we investigated the role of GSK-3ß and its potential as a therapeutic target for ATL. METHODS: Cell proliferation/survival, cell cycle, apoptosis, and reactive oxygen species (ROS) generation were examined using the WST-8 assay, flow cytometry, and Hoechst 33342 staining, respectively. Expression of GSK-3ß and cell cycle/death-related proteins, and survival signals was analyzed using RT-PCR, immunofluorescence staining, and immunoblotting. RESULTS: HTLV-1-infected T-cell lines showed nuclear accumulation of GSK-3ß. GSK-3ß knockdown and its inhibition with 9-ING-41 and LY2090314 suppressed cell proliferation/survival. 9-ING-41 induced G2/M arrest by enhancing the expression of γH2AX, p53, p21, and p27, and suppressing the expression of CDK1, cyclin A/B, and c-Myc. It induced caspase-mediated apoptosis by decreasing the expression of Bcl-xL, Mcl-1, XIAP, c-IAP1/2, and survivin, and increasing the expression of Bak and Bax. 9-ING-41 also induced ferroptosis and necroptosis, promoted JNK phosphorylation, and suppressed IKKγ and JunB expression. It inhibited the phosphorylation of IκBα, Akt, and STAT3/5, induced ROS production, and reduced glycolysis-derived lactate levels. CONCLUSION: GSK-3ß functions as an oncogene in ATL and could be a potential therapeutic target.

Association Between Type 2 Diabetes Mellitus and Alzheimer's Disease: Common Molecular Mechanism and Therapeutic Targets.

Diabetes mellitus (DM) and Alzheimer's disease (AD) rates are rising, mirroring the global trend of an aging population. Numerous epidemiological studies have shown that those with Type 2 diabetes (T2DM) have an increased risk of developing dementia. These degenerative and progressive diseases share some risk factors. To a large extent, the amyloid cascade is responsible for AD development. Neurofibrillary tangles induce neurodegeneration and brain atrophy; this chain reaction begins with hyperphosphorylation of tau proteins caused by progressive amyloid beta (Aß) accumulation. In addition to these processes, it seems that alterations in brain glucose metabolism and insulin signalling lead to cell death and reduced synaptic plasticity in AD, before the onset of symptoms, which may be years away. Due to the substantial evidence linking insulin resistance in the brain with AD, researchers have coined the name "Type 3 diabetes" to characterize the condition. We still know little about the processes involved, even though current animal models have helped illuminate the links between T2DM and AD. This brief overview discusses insulin and IGF-1 signalling disorders and the primary molecular pathways that may connect them. The presence of GSK-3ß in AD is intriguing. These proteins' association with T2DM and pancreatic ß-cell failure suggests they might be therapeutic targets for both disorders.

[Onset of Glycogen Storage Disease Type â « in Two Brothers in the Neonatal Period].

Glycogen storage diseases (GSDs) are a group of autosomal recessive disorders of glucose metabolism.GSDs are caused by congenital deficiency of enzymes in glycogen synthesis or decomposition,which results in glycogen accumulation in organs.According to the types of enzyme deficiency,GSDs can be classified into more than ten types,among which GSD Ⅻ is a super-rare type of GSD.Two brothers with a 5-year age difference presented severe neonatal asphyxia,myasthenia,myocardial damage,anemia,and mental retardation,being GSD Ⅻ homozygous cases with neonatal onset.The results of gene detection showed that nucleotide and amino acid alterations (c.619G>A,p.E207K) of the ALDOA gene existed in the two brothers,being homozygous,and the genotypes in the parents were heterozygous.This article summarized the clinical features,diagnosis,and treatment of GSD Ⅻ,providing reference for exploring the etiology and treatment of severe asphyxia,myasthenia,anemia,and multiple organ damage in neonates after birth.

Glycogen metabolism and structure: A review.

Glycogen is a glucose polymer that plays a crucial role in glucose homeostasis by functioning as a short-term energy storage reservoir in animals and bacteria. Abnormalities in its metabolism and structure can cause several problems, including diabetes, glycogen storage diseases (GSDs) and muscular disorders. Defects in the enzymes involved in glycogen synthesis or breakdown, resulting in either excessive accumulation or insufficient availability of glycogen in cells seem to account for the most common pathogenesis. This review discusses glycogen metabolism and structure, including molecular architecture, branching dynamics, and the role of associated components within the granules. The review also discusses GSD type XV and Lafora disease, illustrating the broader implications of aberrant glycogen metabolism and structure. These conditions also impart information on important regulatory mechanisms of glycogen, which hint at potential therapeutic targets. Knowledge gaps and potential future research directions are identified.

Neuroprotection of isoorientin against microglia activation induced by lipopolysaccharide via regulating GSK3ß, NF-κb and Nrf2/HO-1 pathways.

Background: Isoorientin (ISO), a flavone C-glycoside, is a glycogen synthase kinase 3ß (GSK3ß) substrate-competitive inhibitor. ISO has potential in treatment of Alzheimer's disease (AD). An excessive activation of GSK3ß can lead to neuroinflammation causing neuronal damage. Microglia cells, as resident immune cells of the central nervous system, mediate neuroinflammation. Here, we studied the effects of ISO on microglial activation to alleviate neuroinflammation.Methods: Effects of ISO were observed upon the stimulation of mouse microglia BV2 or SIM-A9 cells by lipopolysaccharide (LPS). Lithium chloride (LiCl) was the positive control as a GSK3ß inhibitor. The release of TNF-α and NO were analyzed by ELISA and Griess assays, while expressions of COX-2, Iba-1, BDNF, GSK3ß, NF-κB p65, IκB, Nrf2 and HO-1 were detected by Western blotting. In the co-culture model of SIM-A9 cells and differentiated SH-SY5Y human neuroblastoma cells, effects of ISO on microglia-mediated neuronal damage were evaluated with the MTS assay.Results: ISO significantly inhibited the production of TNF-α (p < 0.01), NO (p < 0.001) and the expression of COX-2 (p < 0.01) and Iba-1 (p < 0.05) induced by LPS, and increased BDNF. The cell viability of SH-SY5Y was inhibited by LPS in the co-culture, which was prevented by ISO pretreatment. ISO increased the expression of p-GSK3ß (Ser9), IκB and HO-1 in the cytoplasm, decreased NF-κB p65 and increased Nrf2 in the nucleus compared with the LPS group.Conclusion: ISO attenuated the activation of microglia through regulating the GSK3ß, NF-κB and Nrf2/HO-1 signaling pathways to exert neuroprotection.

Continuous glucose monitoring metrics in people with liver glycogen storage disease and idiopathic ketotic hypoglycemia: A single-center, retrospective, observational study.

BACKGROUND: Cohort data on continuous glucose monitoring (CGM) metrics are scarce for liver glycogen storage diseases (GSDs) and idiopathic ketotic hypoglycemia (IKH). The aim of this study was to retrospectively describe CGM metrics for people with liver GSDs and IKH. PATIENTS AND METHODS: CGM metrics (descriptive, glycemic variation and glycemic control parameters) were calculated for 47 liver GSD and 14 IKH patients, categorized in cohorts by disease subtype, age and treatment status, and compared to published age-matched CGM metrics from healthy individuals. Glycemic control was assessed as time-in-range (TIR; ≥3.9 - ≤7.8 and ≥3.9 - ≤10.0 mmol/L), time-below-range (TBR; <3.0 mmol/L and ≥3.0 - ≤3.9 mmol/L), and time-above-range (TAR; >7.8 and >10.0 mmol/L). RESULTS: Despite all patients receiving dietary treatment, GSD cohorts displayed significantly different CGM metrics compared to healthy individuals. Decreased TIR together with increased TAR were noted in GSD I, GSD III, and GSD XI (Fanconi-Bickel syndrome) cohorts (all p < 0.05). In addition, all GSD I cohorts showed increased TBR (all p < 0.05). In GSD IV an increased TBR (p < 0.05) and decreased TAR were noted (p < 0.05). In GSD IX only increased TAR was observed (p < 0.05). IKH patient cohorts, both with and without treatment, presented CGM metrics similar to healthy individuals. CONCLUSION: Despite dietary treatment, most liver GSD cohorts do not achieve CGM metrics comparable to healthy individuals. International recommendations on the use of CGM and clinical targets for CGM metrics in liver GSD patients are warranted, both for patient care and clinical trials.

Identification of AS1842856 as a novel small-molecule GSK3α/ß inhibitor against Tauopathy by accelerating GSK3α/ß exocytosis.

Glycogen synthase kinase-3α/ß (GSK3α/ß) is a critical kinase for Tau hyperphosphorylation which contributes to neurodegeneration. Despite the termination of clinical trials for GSK3α/ß inhibitors in Alzheimer's disease (AD) treatment, there is a pressing need for novel therapeutic strategies targeting GSK3α/ß. Here, we identified the compound AS1842856 (AS), a specific forkhead box protein O1 (FOXO1) inhibitor, reduced intracellular GSK3α/ß content in a FOXO1-independent manner. Specifically, AS directly bound to GSK3α/ß, promoting its translocation to the multivesicular bodies (MVBs) and accelerating exocytosis, ultimately decreasing intracellular GSK3α/ß content. Expectedly, AS treatment effectively suppressed Tau hyperphosphorylation in cells exposed to okadaic acid or expressing the TauP301S mutant. Furthermore, AS was visualized to penetrate the blood-brain barrier (BBB) using an imaging mass microscope. Long-term treatment of AS enhanced cognitive function in P301S transgenic mice by mitigating Tau hyperphosphorylation through downregulation of GSK3α/ß expression in the brain. Altogether, AS represents a novel small-molecule GSK3α/ß inhibitor that facilitates GSK3α/ß exocytosis, holding promise as a therapeutic agent for GSK3α/ß hyperactivation-associated disorders.

Neuromuscular junction dysfunction in a mouse model of Lafora disease.

Lafora disease (LD), a fatal neurodegenerative disorder, is caused by mutations in the EPM2A gene coding laforin phosphatase or NHLRC1 gene coding malin ubiquitin ligase. The LD symptoms include epileptic seizures, ataxia, dementia, and cognitive decline. Studies on LD have primarily concentrated on the pathophysiology in the brain. A few studies have reported motor symptoms, muscle weakness and muscle atrophy. Intriguingly, skeletal muscles are known to accumulate Lafora polyglucosan bodies. Using Laforin-deficient mice, an established model for LD, we demonstrate that LD pathology correlated with structural and functional impairments in the neuromuscular junction (NMJ). Specifically, we find impairment in the NMJ transmission, which coincides with altered expression of NMJ-associated genes and reduced motor endplate area, fragmented junctions and loss of fully innervated junctions at NMJ. We also observe a reduction of alpha motor neurons in the lumbar spinal cord, with significant presynaptic morphological alterations. Disorganized myofibrillar patterns, slight z-line streaming, and muscle atrophy are also evident in LD animals. In summary, our study offers novel insight into the neuropathic and myopathic alterations leading to motor deficits in LD.

Valorization of Baltic Sea farmed blue mussels: Chemical profiling and prebiotic potential for nutraceutical and functional food development.

The severe eutrophication of the Baltic Sea requires mussel (Mytilus spp.) farming to remove nutrients, but farming in a low salinity environment results in smaller mussels that require value enhancement to be economically viable. This study evaluates the biomass valorisation of smaller Baltic mussels, focusing on the extraction of oil, protein and glycogen. It analyses the amino acid profiles, oil and fatty acid contents and glycogen levels of the mussels, as well as their prebiotic properties on beneficial gut bacteria. In addition, the study improves the extraction of bioactive compounds through enzymatic hydrolysis. Results indicate significant seasonal differences, with summer mussels having higher meat and lower ash content, and a rich content of essential fatty acids, particularly omega-3, and amino acids, underscoring the mussels' sustainability as a food source. The enzymatically treated biomass exhibited notable prebiotic activity, proposing health-promoting benefits. The study underscores the valorization of Baltic mussel biomass, highlighting its role in health, nutrition, and environmental sustainability.

Protective effect of lycopene against celecoxib induced fat deposition and glycogen reduction in liver cells.

Objective: Oxidative stress develops because of a shift in the prooxidant-antioxidant balance toward the former, because of disturbances in redox signaling and control. Celecoxib (Cb), a selective COX-2 inhibitor, is a drug that effectively decreases pain and inflammation. However, Cb causes oxidative injury to hepatic tissues via enhanced lipid peroxidation, thus resulting in excessive production of reactive oxygen species. Consequently, frequent or long-term Cb use may lead to hepatic, renal, and other noticeable adverse effects. Lycopene (lyco), a potent antioxidant naturally occurring in pigmented fruits and vegetables, actively eradicates singlet oxygen and other free radicals, thereby protecting cells against destruction of the plasma membrane by free radicals. Methods: We hypothesized that lyco might protect rat liver cells against Cb-induced oxidative stress, thus reducing fatty infiltration and glycogen depletion. Rats were randomized into three groups (with ten rats each) receiving control (group A, saline only), Cb (group B, 50 mg/kg, orally), or Cb + lyco (group C, 50 mg/kg, orally) for 30 days. Subsequently, liver tissues were examined, and the average liver weight and histological changes in fat and glycogen content were determined. Results: Lyco mitigated hepatocyte damage in Cb-treated rats, reducing fat accumulation and glycogen loss, probably through its antioxidant properties. Concomitant lyco and Cb intake prevented hepatotoxic adverse effects due to oxidative injury, as well as non-alcoholic fatty liver disease (NAFLD), a key component of metabolic syndrome. Moreover, the binding orientation of lyco in the binding site of COX-2 enzyme revealed that the docked complex had noteworthy binding strength. Conclusion: In conclusion, our study revealed lyco's protective effects against Cb-induced hepatic damage by reducing fat and glycogen depletion.

No Effects of Carbohydrate Ingestion on Muscle Metabolism or Performance During Short-Duration High-Intensity Intermittent Exercise.

Carbohydrates are critical for high-intensity exercise performance. However, the effects of carbohydrate supplementation on muscle metabolism and performance during short-duration high-intensity intermittent exercise remain inadequately explored. Our aim was to address this aspect in a randomized, counterbalanced, double-blinded crossover design. Eleven moderately-to-well-trained males performed high-intensity intermittent cycling receiving carbohydrate (CHO, ~55 g/h) or placebo (PLA) fluid supplementation. Three exercise periods (EX1-EX3) were completed comprising 10 × 45 s at ~105% Wmax interspersed with 135 s rest between bouts and ~20 min between periods. Repeated sprint ability (5 × 6 s sprints with 24 s recovery) was assessed at baseline and after each period. Thigh muscle biopsies were obtained at baseline and before and after EX3 to determine whole-muscle and fiber-type-specific glycogen depletion. No differences were found in muscle glycogen degradation at the whole-muscle (p = 0.683) or fiber-type-specific level (p = 0.763-0.854) with similar post-exercise whole-muscle glycogen concentrations (146 ± 20 and 122 ± 15 mmol·kg-1 dw in CHO and PLA, respectively). Repeated sprint ability declined by ~9% after EX3 with no between-condition differences (p = 0.971) and no overall differences in ratings of perceived exertion (p = 0.550). This was despite distinctions in blood glucose concentrations throughout exercise, reaching post-exercise levels of 5.3 ± 0.2 and 4.1 ± 0.2 mmol·L-1 (p < 0.001) in CHO and PLA, respectively, accompanied by fivefold higher plasma insulin levels in CHO (p < 0.001). In conclusion, we observed no effects of carbohydrate ingestion on net muscle glycogen breakdown or sprint performance during short-duration high-intensity intermittent exercise despite elevated blood glucose and insulin levels. These results therefore question the efficacy of carbohydrate supplementation strategies in high-intensity intermittent sports.

In Vivo Glucose Transporter-2 Regulation of Dorsomedial Versus Ventrolateral VMN Astrocyte Metabolic Sensor and Glycogen Metabolic Enzyme Gene Expression in Female Rat.

Astrocyte glycogenolysis shapes ventromedial hypothalamic nucleus (VMN) regulation of glucostasis in vivo. Glucose transporter-2 (GLUT2), a plasma membrane glucose sensor, controls hypothalamic primary astrocyte culture glycogen metabolism in vitro. In vivo gene silencing tools and single-cell laser-catapult-microdissection/multiplex qPCR techniques were used here to examine whether GLUT2 governs dorsomedial (VMNdm) and/or ventrolateral (VMNvl) VMN astrocyte metabolic sensor and glycogen metabolic enzyme gene profiles. GLUT2 gene knockdown diminished astrocyte GLUT2 mRNA in both VMN divisions. Hypoglycemia caused GLUT2 siRNA-reversible up-regulation of this gene profile in the VMNdm, but down-regulated VMNvl astrocyte GLUT2 transcription. GLUT2 augmented baseline VMNdm and VMNvl astrocyte glucokinase (GCK) gene expression, but increased (VMNdm) or reduced (VMNvl) GCK transcription during hypoglycemia. GLUT2 imposed opposite control, namely stimulation versus inhibition of VMNdm or VMNvl astrocyte 5'-AMP-activated protein kinase-alpha 1 and -alpha 2 gene expression, respectively. GLUT2 stimulated astrocyte glycogen synthase (GS) gene expression in each VMN division. GLUT2 inhibited transcription of the AMP-sensitive glycogen phosphorylase (GP) isoform GP-brain type (GPbb) in each site, yet diminished (VMNdm) or augmented (VMNvl) astrocyte GP-muscle type (GPmm) mRNA. GLUT2 enhanced VMNdm and VMNvl glycogen accumulation during euglycemia, and curbed hypoglycemia-associated VMNdm glycogen depletion. Results show that VMN astrocytes exhibit opposite, division-specific GLUT2 transcriptional responsiveness to hypoglycemia. Data document divergent GLUT2 control of GCK, AMPK catalytic subunit, and GPmm gene profiles in VMNdm versus VMNvl astrocytes. Ongoing studies seek to determine how differential GLUT2 regulation of glucose and energy sensor function and glycogenolysis in each VMN location may affect local neuron responses to hypoglycemia.