Neuroregeneration Improved by Sodium-D,L-Beta-Hydroxybutyrate in Primary Neuronal Cultures.

Ketone bodies are considered alternative fuels for the brain when glucose availability is limited. To determine the neuroregenerative potential of D,L-sodium-beta-hydroxybutyrate (D/L-BHB), Sprague Dawley rat primary cortical neurons were exposed to simulated central nervous system injury using a scratch assay. The neuronal cell migration, cell density and degree of regeneration in the damaged areas (gaps) in the absence (control) and presence of BHB (2 mM) were documented with automated live-cell imaging by the CytoSMART system over 24 h, which was followed by immunocytochemistry, labeling synapsin-I and ß3-tubulin. The cell density was significantly higher in the gaps with BHB treatment after 24 h compared to the control. In the control, only 1.5% of the measured gap areas became narrower over 24 h, while in the BHB-treated samples 49.23% of the measured gap areas became narrower over 24 h. In the control, the gap expanded by 63.81% post-injury, while the gap size decreased by 10.83% in response to BHB treatment, compared to the baseline. The cell density increased by 97.27% and the gap size was reduced by 74.64% in response to BHB, compared to the control. The distance travelled and velocity of migrating cells were significantly higher with BHB treatment, while more synapsin-I and ß3-tubulin were found in the BHB-treated samples after 24 h, compared to the control. The results demonstrate that D/L-BHB enhanced neuronal migration and molecular processes associated with neural regeneration and axonogenesis. These results may have clinical therapeutic applications in the future for nervous system injuries, such as for stroke, concussion and TBI patients.

Characterization of ß-Hydroxybutyrate as a Cell Autonomous Fuel for Active Excitatory and Inhibitory Neurons: ß-Hydroxybutyrate as a Fuel for Active Neurons.

The ketogenic diet is an effective treatment for drug-resistant epilepsy, but the therapeutic mechanisms are poorly understood. Although ketones are able to fuel the brain, it is not known whether ketones are directly metabolized by neurons on a time scale sufficiently rapid to fuel the bioenergetic demands of sustained synaptic transmission. Here, we show that nerve terminals can use the ketone ß-hydroxybutyrate in a cell- autonomous fashion to support neurotransmission in both excitatory and inhibitory nerve terminals and that this flexibility relies on Ca2+ dependent upregulation of mitochondrial metabolism. Using a genetically encoded ATP sensor, we show that inhibitory axons fueled by ketones sustain much higher ATP levels under steady state conditions than excitatory axons, but that the kinetics of ATP production following activity are slower when using ketones as fuel compared to lactate/pyruvate for both excitatory and inhibitory neurons.

ß-hydroxybutyrate alleviates neurological deficits by restoring glymphatic and inflammation after subarachnoid hemorrhage in mice.

BACKGROUND: Both glymphatic system dysfunction and inflammatory response aggravate neurological dysfunction after subarachnoid hemorrhage (SAH). Studies have shown that ß-hydroxybutyrate (BHB) may mitigate painful diabetic neuropathy (PDN) by upregulating SNTA1 expression and reinstating AQP4 polarity. However, the potential of BHB to ameliorate glymphatic system function and inflammatory response in SAH mice remains uncertain. METHODS: The SAH models were constructed by injection of arterial blood into cisterna Magana. Three groups of C57 mice were randomly assigned: Sham, SAH, and BHB. All mice were subjected to neurological function assessment, western blot, immunofluorescence double staining, and RNA-seq. Glymphatic system function was examined with tracer and immunofluorescence double staining, and the differential genes were examined with RNA-seq. In addition, the expression of related inflammation was detected. RESULTS: Compared with the SAH group, BHB reinstated AQP4 polarization by upregulating SNTA1 protein to enhance the glymphatic system. According to RNA-seq, the different genes were primarily connected to microglia activation, astrocytes, and inflammation. Western blot and immunofluorescence further confirmed that the related inflammatory protein expression levels were upregulated. BHB attenuated neuroinflammation after SAH. Ultimately, it can mitigate the neurological deficits in SAH mice. CONCLUSION: The study reveals a novel mechanism that BHB treatment mitigates neurologic impairment in SAH mice. We propose that BHB may play a neuroprotective effect by enhancing glymphatic system function and attenuating neuroinflammatory subarachnoid hemorrhage.

Point-of-care ß-hydroxybutyrate measurement predicts adequate glucose metabolism suppression in cardiac FDG-PET/CT.

AIMS: The aims of our study were to evaluate whether point-of-care ß-hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac [18F]-fluoro-2-deoxy-d-glucose-positron emission tomography with computerized tomography (FDG-PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging. METHODS AND RESULTS: We recruited 193 patients with any clinical indication for whole body [18F]-FDG-PET/CT. BHB level was measured with a point-of-care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point-of-care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography were measured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut-off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319). CONCLUSIONS: BHB level measured with a point-of-care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed.

Ketone bodies as chemical signals for the immune system.

Ketone bodies are short-chain fatty acids produced by the liver during periods of limited glucose availability, such as during fasting or low carbohydrate feeding. Recent studies have highlighted important nonmetabolic functions of the most abundant ketone body, ß-hydroxybutyrate (BHB). Notably, many of these functions, including limiting specific sources of inflammation, histone deacetylase inhibition, NFκB inhibition, and GPCR stimulation, are particularly important to consider in immune cells. Likewise, dietary manipulations like caloric restriction or ketogenic diet feeding have been associated with lowered inflammation, improved health outcomes, and improved host defense against infection. However, the underlying mechanisms of the broad benefits of ketosis remain incompletely understood. In this Perspective, we contextualize the current state of the field of nonmetabolic functions of ketone bodies specifically in the immune system and speculate on the molecular explanations and broader physiological significance.

Effect of postpartum drenching on plasma parameters of cows at a large-scale dairy farm.

The aim of the present study was to explore the influence of postpartum drenching with a feed additive on the plasma concentration of biochemical parameters while factoring in prepartum rumination times (RT). One hundred and sixty-one cows were fitted with a Ruminact© HR-Tag approximately 5 days before calving. Drenching and control groups were established based on calving dates. Animals in the drenched group were treated three times (Day 1/day of calving/, Day 2, and Day 3 postpartum) using a feed additive containing calcium propionate, magnesium sulphate, yeast, potassium chloride and sodium chloride mixed in approximately 25 L of lukewarm tap water. Blood samples were collected on Days 1, 2, 3, 7 and 12. Cows with below the average RT were categorised as "low rumination" and those above it as "high rumination" animals. Drenching decreased the plasma concentrations of total protein, urea and creatinine and increased the levels of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and chloride. Low rumination time prepartum resulted in higher concentrations of beta-hydroxybutyrate, total protein and activities of alkaline phosphatase and GGT, while it decreased the activity of ALT and the concentrations of calcium, magnesium, sodium and potassium. The day of lactation had an effect on all parameters except for potassium.

Effect of Acute and Chronic Ingestion of Exogenous Ketone Supplements on Blood Pressure: A Systematic Review and Meta-Analysis.

Exogenous ketone supplements have been suggested to have potential cardiovascular benefits, but their overall effect on blood pressure is unclear. Our objective was to perform a systematic review and meta-analysis on the effects of exogenous ketone supplements on blood pressure (BP) and concomitant changes in resting heart rate (HR). Five databases were searched on January 27th, 2023, for randomized and non-randomized studies. A random-effects model meta-analysis was performed including all studies jointly and separately for acute and chronic ingestion of ketone supplements. Out of 4012 studies identified in the search, 4 acute and 6 chronic studies with n = 187 participants were included. Pooled results (n = 10) showed no change in systolic (SMD [95% CI]= -0.14 [-0.40; 0.11]; I2= 30%; p = 0.17) or diastolic BP (-0.12 [-0.30; 0.05]; I2= 0%; p = 0.69), with a potential tendency observed toward increased resting heart rate (0.17 [-0.14; 0.47]; I2= 40%; p = 0.10). Similar results for systolic and diastolic BP were observed when assessing separately the effect of acute and chronic ingestion of ketone supplements (p ≥ 0.33). Supplement dosage was found to modulate the increase in resting heart rate (0.019 ± 0.006; p = 0.013; R2=100%), suggesting that higher supplement doses lead to a higher resting heart rate. Based on currently available data, acute or prolonged ingestion of ketone supplements does not seem to modulate BP. However, a tendency for HR to increase after acute ingestion was observed, particularly with higher doses. Higher quality studies with appropriate standardized measurements are needed to confirm these results.

BDH1-mediated LRRC31 regulation dependent on histone lysine ß-hydroxybutyrylation to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the most common form of lung cancer, with a consistently low 5-year survival rate. Therefore, we aim to identify key genes involved in LUAD progression to pave the way for targeted therapies in the future. BDH1 plays a critical role in the conversion between acetoacetate and ß-hydroxybutyrate. The presence of ß-hydroxybutyrate is essential for initiating lysine ß-hydroxybutyrylation (Kbhb) modifications. Histone Kbhb at the H3K9 site is attributed to transcriptional activation. We unveiled that ß-hydroxybutyrate dehydrogenase 1 (BDH1) is not only conspicuously overexpressed in LUAD, but it also modulates the overall intracellular Kbhb modification levels. The RNA sequencing analysis revealed leucine-rich repeat-containing protein 31 (LRRC31) as a downstream target gene regulated by BDH1. Ecologically expressed BDH1 hinders the accumulation of H3K9bhb in the transcription start site of LRRC31, consequently repressing the transcriptional expression of LRRC31. Furthermore, we identified potential BDH1 inhibitors, namely pimozide and crizotinib, which exhibit a synergistic inhibitory effect on the proliferation of LUAD cells exhibiting high expression of BDH1. In summary, this study elucidates the molecular mechanism by which BDH1 mediates LUAD progression through the H3K9bhb/LRRC31 axis and proposes a therapeutic strategy targeting BDH1-high-expressing LUAD, providing a fresh perspective for LUAD treatment.

A ketogenic diet reduces age-induced chronic neuroinflammation in mice Running title: ketogenic diet and brain inflammaging.

Beta-hydroxybutyrate (BHB) is a ketone body synthesized during fasting or strenuous exercise. Our previous study demonstrated that a cyclic ketogenic diet (KD), which induces BHB levels similar to fasting every other week, reduces midlife mortality and improves memory in aging mice. BHB actively regulates gene expression and inflammatory activation through non-energetic signaling pathways. Neither of these activities has been well-characterized in the brain and they may represent mechanisms by which BHB affects brain function during aging. First, we analyzed hepatic gene expression in an aging KD-treated mouse cohort using bulk RNA-seq. In addition to the downregulation of TOR pathway activity, cyclic KD reduces inflammatory gene expression in the liver. We observed via flow cytometry that KD also modulates age-related systemic T cell functions. Next, we investigated whether BHB affects brain cells transcriptionally in vitro. Gene expression analysis in primary human brain cells (microglia, astrocytes, neurons) using RNA-seq shows that BHB causes a mild level of inflammation in all three cell types. However, BHB inhibits the more pronounced LPS-induced inflammatory gene activation in microglia. Furthermore, we confirmed that BHB similarly reduces LPS-induced inflammation in primary mouse microglia and bone marrow-derived macrophages (BMDMs). BHB is recognized as an inhibitor of histone deacetylase (HDAC), an inhibitor of NLRP3 inflammasome, and an agonist of the GPCR Hcar2. Nevertheless, in microglia, BHB's anti-inflammatory effects are independent of these known mechanisms. Finally, we examined the brain gene expression of 12-month-old male mice fed with one-week and one-year cyclic KD. While a one-week KD increases inflammatory signaling, a one-year cyclic KD reduces neuroinflammation induced by aging. In summary, our findings demonstrate that BHB mitigates the microglial response to inflammatory stimuli, like LPS, possibly leading to decreased chronic inflammation in the brain after long-term KD treatment in aging mice.

Ketone Bodies Rescue Mitochondrial Dysfunction Via Epigenetic Remodeling.

Ischemic cardiac disease is a major cause of mortality worldwide. However, the exact molecular processes underlying this disorder are not fully known. This study includes a comprehensive and coordinated set of in vivo and in vitro experiments using human cardiac specimens from patients with postischemic heart failure (HF) and healthy control subjects, a murine model of HF, and cellular systems. These approaches identified for the first time a specific pattern of maladaptive chromatin remodeling, namely a double methylation of histone 3 at lysine 27 and a single methylation at lysine 36 (H3_K27me2K36me1) consistently induced by ischemic injury in all these settings: human HF; murine HF; and in vitro models. Mechanistically, this work demonstrates that this histone modification mediates the ischemia-induced transcriptional repression of PPARG coactivator 1α (PGC1α), master regulator of mitochondrial function and biogenesis. Intriguingly, both the augmented H3_K27me2K36me1 and the mitochondrial dysfunction ensued by PGC1α down-regulation were significantly attenuated by the treatment with ß-hydroxybutyrate, the most abundant ketone body in humans, revealing a novel pathway coupling metabolism to gene expression. Taken together, these findings establish maladaptive chromatin remodeling as a key mechanism in postischemic heart injury, functionally modulated by ketone bodies.

Infusions of beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, produce antidepressant-like effects on learned helplessness rats through BDNF-TrkB signaling and AMPA receptor activation, and strengthen learning ability.

Beta-hydroxybutyrate (BHB), an endogenous NLRP3 inflammasome inhibitor, has been shown to be associated with the pathophysiology of depression in rodents. However its active mechanism has not been revealed. Herein, we probed both the pathways and brain regions involved in BHB's antidepressant-like effects in a learned helplessness (LH) rat model of depression. A single bilateral infusion of BHB into the cerebral ventricles induced the antidepressant-like effects on the LH rats. The antidepressant-like effects of BHB were blocked by the TrkB inhibitor ANA-12 and the AMPA receptor antagonist NBQX, indicating that the antidepressant-like effects of BHB involve BDNF-TrkB signaling and AMPA receptor activation. Further, infusions of BHB into the prelimbic and infralimbic portions of medial prefrontal cortex, the dentate gyrus of hippocampus, and the basolateral region of amygdala produced the antidepressant-like effects on LH rats. However, infusions of BHB into the central region of amygdala, the CA3 region of hippocampus, and the shell and core regions of nucleus accumbens had no effect. Finally, a single bilateral infusion of BHB into the cerebral ventricles of naive rats strengthened learning ability on repeated active avoidance test where saline-infused animals failed to increase avoidance responses.

Biased allosteric activation of ketone body receptor HCAR2 suppresses inflammation.

Hydroxycarboxylic acid receptor 2 (HCAR2), modulated by endogenous ketone body ß-hydroxybutyrate and exogenous niacin, is a promising therapeutic target for inflammation-related diseases. HCAR2 mediates distinct pathophysiological events by activating Gi/o protein or ß-arrestin effectors. Here, we characterize compound 9n as a Gi-biased allosteric modulator (BAM) of HCAR2 and exhibit anti-inflammatory efficacy in RAW264.7 macrophages via a specific HCAR2-Gi pathway. Furthermore, four structures of HCAR2-Gi complex bound to orthosteric agonists (niacin or monomethyl fumarate), compound 9n, and niacin together with compound 9n simultaneously reveal a common orthosteric site and a unique allosteric site. Combined with functional studies, we decipher the action framework of biased allosteric modulation of compound 9n on the orthosteric site. Moreover, co-administration of compound 9n with orthosteric agonists could enhance anti-inflammatory effects in the mouse model of colitis. Together, our study provides insight to understand the molecular pharmacology of the BAM and facilitates exploring the therapeutic potential of the BAM with orthosteric drugs.

An open-label, acute clinical trial in adults to assess ketone levels, gastrointestinal tolerability, and sleepiness following consumption of (R)-1,3-butanediol (Avela™).

Introduction: A study was undertaken to determine the acute effects of a beverage made with Avela™ (R)-1,3-butanediol, on blood beta-hydroxybutyrate (BHB) levels (using the Keto-Mojo monitor), gastrointestinal (GI) tolerability (using the modified visual analogue scale GI Symptoms Tool), and sleepiness (using the Stanford Sleepiness Scale). Methods: Following a 12-h overnight fast, 26 healthy adults consumed one beverage containing 11.5 g of (R)-1,3-butanediol at each of 0, 30, and 60 min, culminating in a total intake of 34.5 g of (R)-1,3-butanediol. Blood BHB levels, GI tolerability, and sleepiness were assessed at baseline (0 min), and at 30, 60, 90, 120, 180, 240, and 300 min. At 240 min, a protein bar was consumed. Results: The mean (±SD) BHB fasting baseline level, maximal concentration, time at maximal concentration, and incremental area under the curve over 300 min were 0.23 ± 0.21 mmol/L, 2.10 ± 0.97 mmol/L, 133.85 ± 57.07 min, and 376.73 ± 156.76 mmol/L*min, respectively. BHB levels at each time point were significantly increased relative to baseline. In females, BHB Tmax was significantly greater (p = 0.046), and BHB iAUC0-300 min nearly significantly greater (p = 0.06) than in males. Discussion: The beverage formulated with Avela™ had no impact on sleepiness and was generally well-tolerated, with no or mild GI symptoms reported in most participants. Mild headaches were reported as an adverse event by five participants and judged possibly related to the study product in two of the participants.

A systematic review and meta-regression of exogenous ketone infusion rates and resulting ketosis-A tool for clinicians and researchers.

Introduction: Ketone bodies such as beta-hydroxybutyrate (BHB) have pleiotropic functional benefits as fuel and signaling metabolites and may have multiple clinical applications. An alternative to inducing ketosis by dietary modification is intravenous delivery of exogenous sources of ketones. It is unknown whether there is a strong relationship between BHB infusion rate and blood BHB concentrations in the published literature; this information is vital for clinical studies investigating therapeutic effects of ketosis. This systematic review aimed to aggregate available data and address this gap. Methods: The PubMed and EMBASE databases were searched, and data were extracted from 23 manuscripts where BHB was infused and maximum and/or steady state BHB levels assessed. Infusion rate was adjusted when racemic BHB was infused but only D-BHB was measured. Results: Using a random effects meta-regression, strong linear relationships between BHB infusion rate and maximal (y = 0.060 + 0.870x, R 2 = 87.2%, p < 0.0001) and steady state (y = -0.022 + 0.849x, R 2 = 86.9%, p < 0.0001) blood BHB concentrations were found. Sensitivity analysis found this relationship was stronger when studies in non-healthy populations were excluded (y = 0.059 + 0.831x, R 2 = 96.3%, p < 0.0001). Conclusion: There is a strong relationship between BHB infusion rate and blood BHB concentrations; the regressions described here can be used by clinicians or researchers to determine ketone delivery required for a target blood concentration.

A randomized, open-label, parallel pilot study investigating metabolic product kinetics of the novel ketone ester, bis-hexanoyl (R)-1,3-butanediol, over one week of ingestion in healthy adults.

Introduction: Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester that, when consumed, is hydrolyzed into hexanoic acid (HEX) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Methods: We undertook a randomized, parallel, open-label study in healthy adults (n = 33) to elucidate blood BHB, HEX and BDO concentrations for 8 h following consumption of three different serving sizes (SS) of BH-BD (12.5, 25 and 50 g/day) before (Day 0) and after 7 days of daily BH-BD consumption (Day 7). Results: Maximal concentration and area under the curve of all metabolites increased proportionally to SS and were greatest for BHB followed by BDO then HEX on both Day 0 and 7. Metabolite half-life tended to decrease with increasing SS for BHB and HEX. Time to peak concentration increased with increasing SS for BHB and BDO on both days. In vitro incubation of BH-BD in human plasma demonstrated BH-BD undergoes rapid spontaneous hydrolysis. Conclusion: These results demonstrate that orally ingested BH-BD is hydrolyzed into products that appear in the plasma and undergo conversion to BHB in a SS dependent manner, and that metabolism of BH-BD neither becomes saturated at serving sizes up to 50 g nor displays consistent adaptation after 7 days of daily consumption.

Low Glucose plus ß-Hydroxybutyrate Induces an Enhanced Inflammatory Response in Yak Alveolar Macrophages via Activating the GPR109A/NF-κB Signaling Pathway.

Yaks are often subject to long-term starvation and a high prevalence of respiratory diseases and mortality in the withered season, yet the mechanisms that cause this remain unclear. Research has demonstrated that ß-hydroxybutyrate (BHB) plays a significant role in regulating the immune system. Hence, we hypothesize that the low glucose and high BHB condition induced by severe starvation might have an effect on the pro-inflammatory response of the alveolar macrophages (AMs) in yaks. To validate our hypothesis, we isolated and identified primary AMs from freshly slaughtered yaks and cultured them in a medium with 5.5 mM of glucose or 2.8 mM of glucose plus 1-4 mM of BHB. Utilizing a real-time quantitative polymerase chain reaction (RT-qPCR), immunoblot assay, and enzyme-linked immunosorbent assay (ELISA), we evaluated the gene and protein expression levels of GPR109A (G-protein-coupled receptor 109A), NF-κB p65, p38, and PPARγ and the concentrations of pro-inflammatory cytokines interleukin (IL)-1ß and IL-6 and tumor necrosis factor (TNF)-α in the supernatant. The results demonstrated that AMs exposed to low glucose plus BHB had significantly higher levels of IL-1ß, IL-6, and TNF-α (p < 0.05) and higher activity of the GPR109A/NF-κB signaling pathway. A pretreatment of either pertussis toxin (PTX, inhibitor of GPR109A) or pyrrolidinedithiocarbamic (PDTC, inhibitor of NF-κB p65) was effective in preventing the elevated secretion of pro-inflammatory cytokines induced by low glucose plus BHB (p < 0.05). These results indicated that the low glucose plus BHB condition would induce an enhanced pro-inflammatory response through the activation of the GPR109A/NF-κB signaling pathway in primary yak AMs, which is probably the reason why yaks experience a higher rate of respiratory diseases and mortality. This study will offer new insight into the prevention and treatment of bovine respiratory diseases.

Magnetic Dendritic Polymer Nanospheres for High-Performance Separation of Histidine-Rich Proteins.

Magnetic nanospheres are becoming a promising platform for a wide range of applications in pharmacy, life science, and immunodiagnostics due to their high surface area, ease of synthesis and manipulation, fast separation, good biocompatibility, and recyclable performance. In this work, an innovative and efficient method is developed by in situ reducing and growing Ni(OH)2 for the preparation of dendritic mesoporous nanocomposites of silica@Fe3O4/tannic acid@nickel hydroxide (dSiO2@Fe3O4/TA@Ni(OH)2). The flower-like nanospheres have good magnetic response, large surface area, and high histidine-rich protein (His-protein) purification performance. The dSiO2@Fe3O4/TA@Ni(OH)2 nanospheres were synthesized on the basis of a φ(NaSal/CTAB) of 1/1 and a mass of ferrous chloride tetrahydrate of 0.3 g, resulting in a saturation magnetization value of 48.21 emu/g, which means it can be collected within ∼1 min using a magnetic stand. Also, the BET test showed that the surface area is 92.47 m2/g and the pore size is ∼3.9 nm for dSiO2@Fe3O4/TA@Ni(OH)2 nanocomposites. Notably, the nickel hydroxide with unique flower-like structural features enables the combination of a large number of Ni2+ ions and His-proteins for high performance. The isolation and purification experiments of the synthesized dSiO2@Fe3O4/TA@Ni(OH)2 were performed by separating His-proteins from a matrix composed of bovine hemoglobin (BHb), bovine serum albumin (BSA), and lysozyme (LYZ). The result showed that the nanospheres have a high combination capacity of ∼1880 mg/g in a rapid equilibrium time of 20 min, which was selective for the adsorption of BHb. In addition, the stability and recyclability of BHb are 80% after seven cycles. Furthermore, the nanospheres were also used to isolate His-proteins from fetal bovine serum, proving its utility. Therefore, the strategy of separating and purifying His-proteins using dSiO2@Fe3O4/TA@Ni(OH)2 nanospheres is promising for practical applications.

Exploring the role of ketone bodies in the diagnosis and treatment of psychiatric disorders.

In recent times, advances in the field of metabolomics have shed greater light on the role of metabolic disturbances in neuropsychiatric conditions. The following review explores the role of ketone bodies and ketosis in both the diagnosis and treatment of three major psychiatric disorders: major depressive disorder, anxiety disorders, and schizophrenia. Distinction is made between the potential therapeutic effects of the ketogenic diet and exogenous ketone preparations, as exogenous ketones in particular offer a standardized, reproducible manner for inducing ketosis. Compelling associations between symptoms of mental distress and dysregulation in central nervous system ketone metabolism have been demonstrated in preclinical studies with putative neuroprotective effects of ketone bodies being elucidated, including effects on inflammasomes and the promotion of neurogenesis in the central nervous system. Despite emerging pre-clinical data, clinical research on ketone body effectiveness as a treatment option for psychiatric disorders remains lacking. This gap in understanding warrants further investigating, especially considering that safe and acceptable ways of inducing ketosis are readily available.

Predicting Pregnancy Outcome in Dairy Cows: The Role of IGF-1 and Progesterone.

The purpose of this study was to determine the link between insulin-like growth factor 1 (IGF-1), progesterone (PROG), non-esterified fatty acids (NEFAs), ß-hydroxybutyrate (BHB), and glucose (GLU) and pregnancy probability after the first artificial insemination (AI) and during the first 100 days in milk (DIM), during the critical transition period. We determined levels of serum IGF-1, PROG, NEFA, BHB, and GLU in Holstein dairy cows via ELISA, using blood samples collected 7 days before parturition (DAP) until 21 days postparturition (DPP). The group was split into cows diagnosed pregnant at 100 DIM (PREG) and those that did not conceive at 100 and 150 DIM (NPREG). Serum IGF-1 and PROG median levels at 7 DAP were significantly higher in PREG vs. NPREG (p = 0.029), the only statistically significant differences across the subgroups. At 7 DAP, IGF-1 levels within the initial group showed a strong negative correlation with PROG (r = -0.693; p = 0.006), while for the PREG subgroup, the IGF-1 levels exhibited a very strong positive correlation with GLU (r = 0.860; p = 0.011) and NEFA (r = 0.872; p = 0.013). IGF-1 and PROG levels detected at 7 DAP may be useful to predict pregnancy at 100 DIM. The positive correlation of NEFA and GLU levels during the transition period demonstrates that the initial group is not in NEB; thus, the NEFA level was not a decisive factor for reproduction success.