Metabolic Functions Research Articles

L-Theanine Metabolism in Tea Plants: Biological Functions and Stress Tolerance Mechanisms

L-theanine, a unique non-protein amino acid predominantly found in tea plants (Camellia sinensis), plays a pivotal role in plant responses to abiotic stress and significantly influences tea quality. In this review, the metabolism and transport mechanisms of L-theanine are comprehensively discussed, highlighting its spatial distribution in tea plants, where it is most abundant in young leaves and less so in roots, stems, and older leaves. The biosynthesis of L-theanine occurs through the enzymatic conversion of glutamate and ethylamine, catalyzed by theanine synthase, primarily in the roots, from where it is transported to aerial parts of the plant for further catabolism. Environmental factors such as temperature, light, drought, elevated CO2, nutrient unavailability, and heavy metals significantly affect theanine biosynthesis and hydrolysis, with plant hormones and transcription factors playing crucial regulatory roles. Furthermore, it has been demonstrated that applying L-theanine exogenously improves other crops’ resistance to a range of abiotic stresses, suggesting its potential utility in improving crop resilience amid climate change. This review aims to elucidate the physiological mechanisms and biological functions of L-theanine metabolism under stress conditions, providing a theoretical foundation for enhancing tea quality and stress resistance in tea cultivation.

The crucial role of vascular tissues and COE2-mediated retrograde signaling in mitigating cadmium stress in Arabidopsisthaliana

Cadmium is a heavy metal that significantly harms plant growth and development by impairing enzyme activity and photosynthesis, leading to chloroplast damage. In this study, we discovered that genes specifically expressed in vascular tissues regulate the plant’s response to heavy metals by scRNA-seq. The overexpression of vascular-specific genes such as AHP1, DOF2.4, NHL1, CDF4, and ATARFB1A increased tolerance to cadmium stress by maining the chloroplast functions. In addition, we found that two chloroplast proteins PSBO1 and J3 are involved in regulating the function of chloroplasts, starch metabolism, and leaf vein development in response to cadmium stress. Further analysis revealed that COE2-mediated retrograde signaling protects chloroplast structure and function by regulating the expression of J3 and PsbO1, and managing the quality control of damaged chloroplasts via FC1 and PUB4. These findings provide insights into the mechanisms plants use to counteract the detrimental effects of cadmium stress.

Quality of whole blood stored in room temperature for up to 5 days.

Non-refrigerated whole blood can be used for bleeding emergencies when cold-stored whole blood is unavailable. Storage time in room temperature is usually limited to 24 h although there is little evidence supporting this practice. We studied the quality of whole blood stored in room temperature for 5 days to investigate the effects of prolonged storage time. Non-leukoreduced whole blood in CPDA-1 from 10 group O or A RhD positive male donors was stored in +22°C for 120 h. Samples were taken daily to assess blood cultures, blood count and metabolic parameters. Platelet function and blood coagulation were evaluated with multiple electrode aggregometry, viscoelastic tests (sonorheometry and rotational thromboelastometry), thrombin generation assay and measurements of individual clotting factors. Blood cell counts remained stable during storage. Metabolic changes were similar to those previously reported in cold-stored blood products. Most coagulation factor levels, including FVIII, decreased during storage but remained within physiological range. Thrombin generation remained mostly intact during storage. In viscoelastic tests, clotting times prolonged, but clot strength remained stable. Platelet function in multiple electrode aggregometry impaired along with storage. No bacterial growth was detected in any sample. Whole blood stored in room temperature for 5 days seems bacteriologically safe and retains most of its metabolic and hemostatic function. These results suggest that whole blood stored in room temperature may be usable for longer than the currently recommended 24 h.

Dose-Dependent Effects of Short-Chain Fatty Acids on 3T3-L1 Adipocyte Adipokine Secretion and Metabolic Function

Background: Short-chain fatty acids (SCFAs) produced from microbial fermentation of non-digestible carbohydrates and protein have been shown to modulate adipocyte adipokine secretion and metabolic function, which has implications for mitigating dysfunction in obese adipose tissue; however, the individual effects of different SCFAs and the optimal concentration required is unknown. The purpose of this study was to dose-dependently determine the effects of individual SCFAs on adipocyte adipokine secretion and metabolic function. Methods: We recapitulated the obese adipocyte inflammatory conditions using mature 3T3-L1 adipocytes and a physiological concentration of lipopolysaccharide (LPS) ± individual SCFAs, namely acetate, propionate, and butyrate, in a dose-dependent manner (0.25 mM, 0.5 mM, and 1 mM) for 24 h. Results: SCFAs dose-dependently affected inflammatory adipokine secretion, wherein at 1 mM, all three SCFAs reduced the secretion of leptin, IL-6 and IL-1β, but only propionate and butyrate reduced MCP-1/CCL2 and MIP-1α/CCL3 compared to control (p < 0.05). Interestingly, 1 mM acetate increased RANTES/CCL5 secretion versus control, whereas propionate and butyrate decreased RANTES/CCL5 secretion, and only 1 mM propionate reduced MCP-3/CCL7 secretion (p < 0.05). At the lower 0.5 mM concentration, both propionate and butyrate reduced IL-6 and IL-1β secretion compared to control (p < 0.05), and there was no difference in adipokine secretion between groups at the 0.25 mM SCFA concentration (p > 0.05). Intracellular protein expression in the ratio of phosphorylated–to–total STAT3 was reduced by all SCFAs at 1 mM and by propionate and butyrate at 0.5 mM versus control (p < 0.05). The ratio fo phosphorylated–to–total NFκB p65 expression was reduced by propionate and butyrate at 1 mM and by butyrate alone at 0.5 mM compared to control (p < 0.05). Basal (no insulin stimulation) and insulin-stimulated glucose uptake did not differ between control and any 1 mM SCFA treatment conditions (p > 0.05). Conclusions: Individual SCFAs exert different dose-dependent effects on LPS-stimulated adipocyte function.

Hypothalamic Estrogen Receptor α Is Essential for Female Marmoset Sexual Behavior Without Protecting From Obesity.

Estrogen receptor α (ERα) in the ventromedial (VMN) and arcuate (ARC) nuclei of female rodent mediobasal hypothalami (MBHs) provides a crucial molecular gateway facilitating estradiol (E2) regulation of sexual behavior, reproductive neuroendocrinology, and metabolic function. In female nonhuman primates (NHPs) and women, however, its hypothalamic counterpart remains unknown. We hypothesized that knockdown (KD) of ERα expression in the hypothalamic VMN and ARC of female marmosets would diminish sexual receptivity, while simultaneously disrupting gonadotropic and metabolic homeostasis. We ovariectomized (OVX) adult female marmosets of comparable age and weight, immediately replaced E2 at midcycle levels, and approximately 1 month later assigned monkeys to diet-induced obesity (DIO) within group (1) control, receiving scrambled short hairpin RNA (shRNA), or (2) ERαKD, receiving selective ERα gene silencing shRNA. Magnetic resonance imaging-guided neural surgery enabled hypothalamic infusion of viral vector shRNA and subsequent brain immunohistochemistry enabled observer-validated, NIS-elements computer software quantification of ERα knockdown. ERα expression was significantly diminished in the VMN and ARC, but not the preoptic area (POA), of ERαKD females coincident with elimination of timely female sexual responses, more than 80% loss of female receptivity, modestly elevated gonadotropin levels, hyperglycemia, and diminished calorie consumption. Density and intensity of ERα-expressing cells in the VMN correlated positively with female sexual receptivity and calorie consumption, negatively with timeliness of female sexual responses, and in the ARC, correlated negatively with calorie consumption. ERα activation in the female NHP MBH is critically important for female sexual behavior and modestly contributes to gonadotropic and metabolic control.

Bamboozle: A Bioinformatic Tool for Identification and Quantification of Intraspecific Barcodes.

Evolutionary changes in populations of microbes, such as microalgae, cannot be traced using conventional metabarcoding loci as they lack intraspecific resolution. Consequently, selection and competition processes among strains of the same species cannot be resolved without elaborate isolation, culturing, and genotyping efforts. Bamboozle, a new bioinformatic tool introduced here, scans the entire genome of a species and identifies allele-rich barcodes that enable direct identification of different genetic strains from a population using amplicon sequencing of a single DNA sample. We demonstrate its usefulness by identifying hypervariable barcoding loci (< 500 bp) from genomic data in two microalgal species, the diploid diatom Skeletonema marinoi and the haploid chlorophyte Chlamydomonas reinhardtii. Across the two genomes, four and twenty-two loci, respectively, were identified that could in silico resolve all analysed genotypes. All of the identified loci are within protein-coding genes with various metabolic functions. Single nucleotide polymorphisms (SNPs) provided the most reliable genetic markers, and among 54 strains of S. marinoi, three 500 bp loci contained, on average, 46 SNPs, 103 strain-specific alleles, and displayed 100% heterozygosity. This high level of heterozygosity was identified as a novel opportunity to improve strain quantification and detect false positive artefacts during denoising of amplicon sequences. Finally, we illustrate how metabarcoding of a single genetic locus can be used to track abundances of S. marinoi strains in an artificial selection experiment. As future genomic datasets become available and DNA sequencing technologies develop, Bamboozle has flexible user settings enabling optimal barcodes to be designed for other species and applications.

Lactobacillus rhamnosus GG induces STING-dependent IL-10 in intestinal monocytes and alleviates inflammatory colitis in mice.

Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-κB (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10-based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade-associated colitis. Our findings highlight the importance of STING signaling in IL-10-dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.

Effects of aerobic vs combined aerobic and resistance exercise training on maternal glucose metabolism, sympathetic nervous system control and cardiovascular hemodynamics in women with overweight/obesity during pregnancy.

This study aimed to identify the effects of acute aerobic exercise combined with resistance exercise on maternal glucose metabolism and sympathetic nervous system-regulated cardiovascular function in overweight or obese pregnancies. We conducted a randomized controlled trial of aerobic exercise combined with resistance training (aerobic + resistance; n = 25) compared with aerobic exercise (aerobic, n = 21) beginning at 16 wk and continuing until 36 wk of gestation in overweight or obese pregnant women. At preintervention and postintervention assessments, the glycometabolism, muscle sympathetic nervous system activity (MSNA) and cardiovascular parameters were measured and analyzed, containing fasting blood glucose (FBG), fasting blood insulin (FBI), 2 h glucose, glycosylated hemoglobin (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), MSNA bursts/min, MSNA bursts/100 heartbeats, resting heart rate (HR); diastolic blood pressure (DBP), mean arterial pressure (MAP), systolic blood pressure (SBP), cardiac index (CI), cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR) and total peripheral resistance index (TPRI). Compared to aerobic group, the overweight or obese pregnant women in aerobic + resistance group showed lower FBG, FBI, 2 h glucose, HbA1c and HOMA-IR (p < 0.05). Moreover, both MSNA bursts/min and MSNA burst/100 heartbeats level were reduced in aerobic + resistance group compared to aerobic group (p < 0.0001). Finally, the resting HR, DBP, SBP, MAP, CI, CO and TPRI were significantly decreased in aerobic + resistance group compared to aerobic group (p < 0.05). In summary, aerobic exercise combined with resistance training was associated with improved glycometabolism, MSNA and cardiovascular function in overweight or obese pregnant women compared to aerobic exercise alone.

Borrow Strength to Exert: Low-Crystallinity Prussian Blue for Reduction Overload Enhanced Photothermal Therapy.

The strategy "Borrow strength to exert" in Sun Tzu's Art of War refers to borrowing external forces to withstand the enemy. Inspired by this, applying this thought to cancer treatment can achieve a more efficient therapeutic effect. Therefore, a fulcrum to borrow the force is vital and significant. Compared with normal cells, tumor cells are more sensitive to redox stress owing to their abnormal redox metabolism. Herein, a regulatory protocol based on chloroauric acid (HAuCl4) is proposed to prepare small-size and low-crystallinity Prussian blue nanoparticles (LcPB NPs). Notably, LcPB NPs possess higher superoxide dismutase (SOD)-like enzyme activity to induce reduction overload and destroy metabolic processes and organelle functions, which leverages the redox status defect in tumors as the fulcrum. Due to the down-regulation of heat shock proteins (HSPs) mediated by redox imbalance, the inherent photothermal therapy (PTT) mode of LcPB NPs effectively inhibits tumor growth and disrupts calcium homeostasis. Additionally, LcPB NPs can improve the anticancer effect by inhibiting symbiotic bacteria. Meanwhile, their magnetic and optical response performance empowers magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for tumor diagnosis. Therefore, this work executing the strategy "Borrowing strength to exert" by disturbing the redox balance represents a new antineoplastic paradigm.

Transcriptome Analysis Revealed the Regulatory Mechanism of DIMBOA Affecting Early Somatic Embryogenesis in Dimocarpus longan Lour.

Dimocarpus longan Lour. is an evergreen tree of the genus Longan in the Sapindaceae family, native to tropical and subtropical regions. Longan embryonic development is closely related to fruit set and fruit quality. An in-depth study of the mechanism of longan embryonic development could therefore contribute to the development of the longan industry. DIMBOA is the principal compound representing benzoxazinoids (BXs), and is closely linked to auxin biosynthesis and signal transduction. Auxin is one of the crucial hormones for inducing somatic embryogenesis (SE) in plants. Previous research has shown that DIMBOA promotes morphogenesis in the early somatic embryogenesis of longan, but the specific regulatory mechanism has not yet been clarified. To elucidate the molecular mechanism by which DIMBOA affects early somatic embryogenesis in longan, we chose longan embryogenic cultures grown under 0 mg/L DIMBOA as the control group (the check, CK), and longan embryogenic cultures grown under 0.1 mg/L DIMBOA as the treatment group (D) to be analyzed by transcriptomic sequencing. A total of 478 differentially expressed genes (DEGs) are detected in check vs. D, of which 193 are upregulated and 285 are downregulated. These DEGs are significantly enriched in the biosynthetic and metabolic functions of various substances such as vitamin B6 (VB6) biosynthesis, phenylpropanoid pathways, and carbohydrate metabolism. DIMBOA affects SE processes in longan via TFs, including MYB, ZF, bHLH, LBD, NAC, WRKY, etc. After DIMBOA treatment, the expression of most of the key genes for IAA synthesis was significantly downregulated, VB6 content was significantly reduced, and H2O2 content was significantly increased. Therefore, it is suggested that DIMBOA directly or indirectly affects the H2O2 content through the VB6 metabolic pathway, thereby regulating the endogenous IAA level to modulate the early SE morphogenesis of longan.

Carnitine O-Acetyltransferase as a Central Player in Lipid and Branched-Chain Amino Acid Metabolism, Epigenetics, Cell Plasticity, and Organelle Function

Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups between acetyl-CoA and carnitine. This enzymatic activity ensures the optimal functioning of mitochondrial carbon flux by preventing acetyl-CoA accumulation, buffering metabolic flexibility, and regulating the balance between fatty acid and glucose oxidation. CRAT’s interplay with the mitochondrial carnitine shuttle, involving carnitine palmitoyltransferases (CPT1 and CPT2) and the carnitine carrier (SLC25A20), underscores its critical role in energy metabolism. Emerging evidence highlights the structural and functional diversity of CRAT and structurally related acetyltransferases across cellular compartments, illustrating their coordinated role in lipid metabolism, amino acid catabolism, and mitochondrial bioenergetics. Moreover, the structural insights into CRAT have paved the way for understanding its regulation and identifying potential modulators with therapeutic applications for diseases such as diabetes, mitochondrial disorders, and cancer. This review examines CRAT’s structural and functional aspects, its relationships with carnitine shuttle members and other carnitine acyltransferases, and its broader role in metabolic health and disease. The potential for targeting CRAT and its associated pathways offers promising avenues for therapeutic interventions aimed at restoring metabolic equilibrium and addressing metabolic dysfunction in disease states.

Bacterial community composition and metabolic characteristics of three representative Marine areas in northern China

Bacteria are essential components of ecosystems, participating in nutrient cycling and biogeochemical processes, and playing a crucial role in maintaining the stability of marine ecosystems. However, the biogeographic distribution patterns of bacterial diversity and metabolic functions in the estuarine and coastal areas of northern China remain unclear. Here, we used metagenomic sequencing to investigate the bacterial community composition and metabolic functions in sediments from the adjacent waters of the Yellow River Estuary, the Yellow Sea Cold Water Mass, and the adjacent waters of the Yangtze River Estuary. Among the 9164 species that were found, the most dominant microbial communities are Pseudomonadota, Actinomycetota, Bacteroidota, and Bacillota, but there are significant differences in the species composition in these three typical habitats. Amino acid metabolism and carbohydrate metabolic pathways were highly enriched. Glycoside hydrolases (GHs) predominate in carbon metabolism across all samples. In nitrogen metabolic pathway, genes related to organic degradation and synthesis are more abundant in the Yellow River Estuary than the other two habitats. In sulfur metabolic pathway, genes involved in assimilatory sulfate reduction are significantly enriched. Assimilatory sulfate reduction might be crucial for sulfur metabolism in coastal regions, with a full assimilatory nitrate reduction pathway found in Desulfobacterota. This research offers insights into the compositional diversity, metabolic functions, and biogeographic distribution patterns of bacterial communities in sediments from typical marine areas of northern China.

CHANGES IN MUSCLE OXYGENATION &amp; MOTOR UNIT ACTIVATION IN RESISTANCE EXERCISE IN OBESE WOMEN

https://youtu.be/-g6-C7YD-cg BACKGROUND The study of motor unit activation during exercise provides information on the function of the neuromuscular system and changes in muscle oxygenation for metabolic functions during exercise. The aim of this study was to examine the changes in muscle oxygenation and motor unit activation during resistance exercise and the correlation between these changes in normoweight and obese women. METHODS/ DESIGN A total of 25 women participated who were divided, based on body fat percentage (BF), into normoweight (BF: 25.4±3.41, age: 20.7±0.89 years, n=13) and obese (BF: 40.47±6.07, age: 20.5±0.97 years, n=12) and performed in the single leg extension exercise 3 sets of 10 repetitions at 60% of 1RM with a 3′ rest between sets. During the performance of the exercise, electromyographic (EMG) activity of the vastus lateralis muscle was recorded and through decomposition of the EMG signal, the amplitude of the motor unit action potential (MUAP), the firing rate (FR) was determined. Also, the change in oxygenation of the vastus lateralis muscle was recorded by near-infrared spectroscopy (NIRS) and the slope of the change in oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin during the performance of the sets was calculated. RESULTS There was a significant increase (p&amp;lt;0.05) in EMGrms activity and FR of the motor units during the performance of the sets with no difference (p&amp;lt;0.05) in the change between the two groups. The slope of increase in HHb and decrease in O2Hb was higher (p&amp;lt;0.05) in normoweight women. There was no significant correlation between the rate of change of the EMGrms signal (r = 0.08-0.30) and FR (r = 0.04-0.28) with the rate of change of O2Hb and HHb in each set either in the whole sample or in each group separately. COΝCLUSIONS In conclusion, normoweight and obese women show similar changes in neuromuscular activation during resistance exercise but different metabolic function with greater deoxygenation in normoweight women. The lack of correlation between the change in neuromuscular activation and muscle oxygenation is likely due to the increased use of anaerobic energy production mechanisms during the performance of this exercise program.

Serum choline, leptin and interleukin-6 levels in fibromyalgia syndrome-induced pain: a case–control study

BackgroundFibromyalgia Syndrome (FMS) predominantly affects middle-aged women, characterized by musculoskeletal pain, fatigue, and cognitive issues. Choline, an endogenous molecule, may influence FMS due to its analgesic and anti-inflammatory properties. This study compared choline, leptin, and interleukin-6 (IL-6) levels in FMS patients and controls and examining their association with pain severity.MethodsVolunteers with FMS were clinically diagnosed at a Physical Medicine and Rehabilitation Department. The control group included pain-free volunteers. Pain severity was gauged using a numeric scale, dietary choline intake through a questionnaire. Serum choline, leptin and (interleukin)IL-6 levels were measured from fasting blood samples of volunteers with enzyme-linked immunosorbent assays (ELISA).ResultsAll FMS patients (n = 38) and healthy volunteers (n = 38) were female. Pain score in patients with FMS was 7.6 ± 0.2. Dietary choline intake was lower in patients with FMS than the controls (p = 0.036). Serum choline and leptin levels were lower in the FMS group compared to control (p = 0.03). Serum IL-6 levels were higher in the FMS group than in the control (p < 0.001). There was weak positive correlation between IL-6 levels and pain scores and there were no correlation between leptin levels and pain scores in FMS.ConclusionsThis research highlights FMS's complex nature, involving neurochemical, immunological, and nutritional factors. It suggests the significance of choline's anti-inflammatory effect, leptin's metabolic function, and IL-6's role in FMS pathology. The results suggest that reduced dietary choline might influence serum choline, leptin, and IL-6 levels, potentially impacting FMS-related pain. This points to the potential of supplementary choline intake in FMS management.Trial registrationNot applicable (Non-interventional study).

NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer's disease progression.

Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer's disease (AD) via the release of IL-1β and ASC specks. However, whether NLRP3 is involved in pathways beyond this remained unknown. Here, we found that Aβ deposition invivo directly triggered NLRP3 activation in APP/PS1 mice, which model many features of AD. Loss of NLRP3 increased glutamine- and glutamate-related metabolism and increased expression of microglial Slc1a3, which was associated with enhanced mitochondrial and metabolic activity. The generation of α-ketoglutarate during this process impacted cellular function, including increased clearance of Aβ peptides as well as epigenetic and gene transcription changes. This pathway was conserved between murine and human cells. Critically, we could mimic this effect pharmacologically using NLRP3-specific inhibitors, but only with chronic NLRP3 inhibition. Together, these data demonstrate an additional role for NLRP3, where it can modulate mitochondrial and metabolic function, with important downstream consequences for the progression of AD.

Solute carrier family 2 members (SLC2A) as potential targets for the treatment of head and neck squamous cell carcinoma patients

ObjectiveSolute carrier family 2 (SLC2A) members have drawn interest in cancer research due to their crucial function in glucose metabolism. To understand their role in Head and Neck Squamous Cell Carcinoma (HNSCC), we have comprehensively analyzed the gene expression of SLC2A family members in HNSCC patients. MethodRNAseq data of 520 HNSCC patients and 46 normals was downloaded from The Cancer Genome Atlas (TCGA) and analyzed using various statistical methods in R. ResultComparison of gene expression between normal and tumor samples showed significantly higher expression of SLC2A1, 4, 6, and 9 in tumor samples compared to normal. Further analysis revealed that both HPV(−)ve and HPV(+)ve samples showed significantly higher expression of SLC2A1 as compared to normal, though the difference was more pronounced in the case of HPV(−)ve. In contrast, SLC2A9 showed a highly significant difference between HPV(−)ve and normal but not between HPV(+)ve and normal. Furthermore, SLC2A genes showed significant variation among the basal (BA), classical (CL), and mesenchymal (MS) expression groups of HNSCC patients. SLC2A1 and 9 were significantly overexpressed in the BA group as compared to the other two groups, suggesting that these two genes can be utilized for the targeted therapy of HPV(−)ve HNSCC patients of the BA group. ConclusionOur results suggest that the biology of SLC2A family members is complex and, they may be playing different roles in different genomic backgrounds. More studies on SLC2A family members are needed to utilize them for targeted therapy or as diagnostic biomarkers.

Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice.

Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and cognitive function in the APP/PS1 transgenic mouse (Tg) model of familial AD. Next, we profiled extracellular vesicles (EVs) and examined whether they may play a role in the protective effects of VET via intranasal administration of EVs, purified from the blood of sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show that VET reduced resting energy expenditure (REE) and improved cognition in APP/PS1 Tg mice. Administration of eEV, but not sEV, also reduced REE, but had no effect on cognition. Taken together, these data show that exercise is effective intervention to improve symptoms of AD in APP/PS1Tg mice. In addition, eEVs mediate some of these effects, implicating EVs in the treatment of age-related neurodegenerative diseases.

Exploring the mechanism and crosstalk between IL-6 and IL- 1β on M2 macrophages under metabolic stress conditions.

Macrophages are highly variable immune cells that are important in controlling inflammation and maintaining tissue balance. The ability to polarize into two major types-M1, promoting inflammation, and M2, resolving inflammation and contributing to tissue repair-determines their specific roles in health and disease. M2 macrophages are particularly important for reducing inflammation and promoting tissue regeneration, but their function is shaped mainly by surrounding cells. This is evident in obesity, diabetes, and chronic inflammation. Although many cytokines regulate macrophage polarization, interleukin-6 (IL-6) and interleukin-1β (IL-1β) are major players, but their effects on M2 macrophage behavior under metabolic stress remain unclear. This study describes the intricacies within M2 macrophages concerning IL-6 and IL-1β signaling when under metabolic stress. Though, more frequently than not, IL-6 is labelled as pro-inflammatory, it can also behave as an anti-inflammatory mediator. On the other hand, IL-1β is the main pro-inflammatory agent, particularly in metabolic disorders. The relationship between these cytokines and the macrophages is mediated through important pathways such as JAK/STAT and NFκB, which get perturbed by metabolic stress. Therefore, metabolic stress also alters the functional parameters of macrophages, including alterations in mitochondrial metabolism, glycolytic and oxidative metabolism. Phosphorylation alters the kinetics involved in energy consumption and affects their polarization and their function. However, it has been suggested that IL-6 and IL-1β may work in concert or competition when inducing M2 polarization and, importantly, implicate cytokine release, phagocytic activity, and tissue repair processes. In this review, we discuss the recent literature on the participation of IL-6 and IL-1β cytokines in macrophage polarization and how metabolic stress changes cytokine functions and synergistic relations. A better understanding of these cytokines would serve as an important step toward exploring alternative antiviral strategies directed against metabolic disturbance and, hence, approve further endeavors.

Intranasal Insulin Diminishes Postoperative Delirium and Elevated Osteocalcin and Brain Derived Neurotrophic Factor in Older Patients Undergoing Joint Replacement: A Randomized, Double-Blind, Placebo-Controlled Trial.

Brain energy metabolism disorders, including glucose utilization disorders and abnormal insulin sensitivity, are linked to the pathogenesis of postoperative delirium. Intranasal insulin has shown significant benefits in improving glucose metabolism, insulin sensitivity and cognitive function. However, its impact on postoperative delirium and insulin sensitivity biomarkers remains unknown. This randomized, double-blind, placebo-controlled trial was to evaluate whether intranasal insulin reduces the incidence and severity of postoperative delirium (POD) in older patients undergoing joint replacement, and its effect on insulin sensitivity-related biomarkers. 212 older patients (≥65 years) were randomly assigned to receive either 40 IU of intranasal insulin (n=106) or a placebo (n=106) for 8 days. The primary objective was to determine the incidence and severity of POD within 5 days after surgery, estimated using the Confusion Assessment Method (CAM) and the Delirium Rating Scale (DRS)-98. The secondary objective was insulin sensitivity, which was assessed using the homeostasis model Assessment of Insulin Resistance (HOMA-IR) and biomarkers, including total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC), and brain-derived neurotrophic factor (BDNF). Compared to placebo, intranasal insulin significantly reduced the incidence of delirium within 5 days after surgery (8 [8.33%] vs 23 [23.23%], P = 0.004, odds ratio [OR] = 3.33 [95% CI 1.41-7.88]) and the severity of delirium (P<0.001). Intranasal insulin elevated the levels of tOC, ucOC, and BDNF in the CSF on D0 (all P<0.001) and tOC levels in the plasma on D0, D1 and D3 (all P<0.001). It elevated ucOC levels in the plasma of the insulin group on D0 but not on D1 and D3 (all P<0.001). Intranasal insulin administration reduced the HOMA-IR on D3 (P=0.002). Intranasal insulin notably reduced the incidence and severity of POD in older patients undergoing joint replacement, which may be related to the elevation in osteocalcin and BDNF levels. Chinese Clinical Trial Registry (ChiCTR2300068073).

Metabolic and microbial functionality during the fermentation of traditional Amaranth stems: Insights from metagenomics, flavoromics, and metabolomics

Metabolic and microbial functionality during the fermentation of traditional Amaranth stems: Insights from metagenomics, flavoromics, and metabolomics