bims-kimdis Biomed News
on Ketones, inflammation and mitochondria in disease
Issue of 2025–05–25
nineteen papers selected by
Matías Javier Monsalves Álvarez, Universidad Andrés Bello



  1. Nutr Res. 2025 Apr 22. pii: S0271-5317(25)00062-4. [Epub ahead of print]139 16-49
      Ketogenesis and the PI3K/AKT/mTOR pathway are linked to metabolic imbalance and disease progression. While ketone metabolism and mTOR inhibition are mechanistically connected, their functional relationship across disease models remains unclear. Although ketogenesis can be induced by ketone ingestion, ketogenic diet, or fasting, their individual effects on this pathway require further clarification. This study systematically reviews the relationship between ketogenesis and PI3K/AKT/mTOR signaling, following PRISMA guidelines across 3 databases. Eligible studies that met the selection criteria were evaluated using the risk of bias tools. In most studies involving the ketogenic diet or ketone bodies, suppression of the signaling pathway may lead to positive outcomes in terms of survival rate, lifespan, improved metabolic homeostasis, enhanced neurovascular function and suppressed progression of tumors. By contrast, β-hydroxybutyrate supplementation is associated with the up-regulation of AKT and downstream markers. It may exert an anabolic activity by activating the mTOR signaling pathway in muscle atrophy models and is associated with muscle recovery. Although fasting increases p-AKT expression, this may not necessarily indicate activation of the downstream mTOR signaling cascade, as it could result from an insulin response or regulatory feedback mechanisms. Regulation of the mTOR signaling by ketogenesis may be tissue-specific. Inhibition of PI3K/AKT/mTOR in ketogenesis-induced circumstances may justify the importance of a ketogenic-based diet regimen in combating metabolic diseases. However, future studies should consider standardizing factors such as the duration of fasting, timing, composition of the ketogenic diet and target tissues as these factors may affect study outcomes.
    Keywords:  Ketogenesis; Ketogenic diet; Ketone bodies; PI3K/AKT/mTOR
    DOI:  https://doi.org/10.1016/j.nutres.2025.04.010
  2. J Adv Res. 2025 May 19. pii: S2090-1232(25)00353-4. [Epub ahead of print]
       BACKGROUND: Thoracic aortic aneurysm (TAA) is a serious condition characterized by dilation of the thoracic aorta, often leading to aortic dissection or rupture. Current treatments involve surgical and pharmacological interventions and do not effectively address the underlying molecular mechanisms. This study explores the effects of ketogenic diet (KD) on TAA, focusing on histone deacetylase 1 (HDAC1) and vascular smooth muscle cells (VSMCs) function.
    METHODS: A β-aminopropionitrile monofumarate (BAPN)-induced TAA mouse model was used. Mice were divided into groups receiving either a standard diet or KD. Additionally, β-hydroxybutyrate (BHB), a KD-derived ketone body, and parthenolide or ITSA-1 were administered. The study measured survival rates, aortic dilation, elastin degradation, VSMC contractile markers, mitochondrial function, and oxidative stress levels.
    RESULTS: KD significantly improved survival rates and reduced aortic dilation and elastin degradation in the TAA mouse model. BHB also mitigated TAA development, demonstrating similar protective effects. KD and BHB were particularly effective in preserving mitochondrial function and maintaining VSMC contractile phenotype by restoring contractile marker expression. Additionally, KD and BHB significantly reduced oxidative stress levels. The addition of HDAC1 inhibitor parthenolide or HDAC agonist ITSA-1 further evaluated the protective effects of BHB against vascular damage.
    CONCLUSION: Our study reveals the important roles of KD and BHB in regulating HDAC1, preserving mitochondrial function, maintaining VSMC phenotype, and reducing oxidative stress in TAA. Our findings demonstrate KD and BHB as promising therapeutic strategies for treating TAA by targeting specific molecular pathways involved in its progression. This study highlights the significance and innovation of lifestyle interventions, such as KD, in mitigating TAA by addressing its underlying molecular mechanisms.
    Keywords:  Histone deacetylase 1; Ketogenic diet; Thoracic aortic aneurysm; Vascular Remodeling; β-hydroxybutyrate
    DOI:  https://doi.org/10.1016/j.jare.2025.05.035
  3. Eur J Endocrinol. 2025 May 20. pii: lvaf106. [Epub ahead of print]
       BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder linked to insulin resistance and elevated androgens. While ketogenic diets reduce androgen and glucose levels in women with PCOS, the direct role of β-hydroxybutyrate (BHB) remains unclear. This study aimed to determine whether BHB supplementation acutely lowers circulating androgen and glucose levels in women with PCOS.
    METHODS: A randomized, placebo-controlled crossover trial was conducted involving 20 women diagnosed with PCOS. Participants underwent fasting blood sampling on two occasions. They were randomly assigned to receive either a ketone supplement or a taste-matched placebo. Each intervention was administered over 10 hours, with one dose administered the evening before and another two hours prior to blood collection.
    RESULTS: Following BHB supplementation, blood D-β-hydroxybutyrate (D-BHB) levels reached 2.4±1.2 mM, compared to 0.1±0.1 mM in the control group (p<0.001). Androgen concentrations were generally lower with BHB supplementation, with mean reductions in testosterone (-13%, CI 95%: -27 to 1, p=0.067), free testosterone (-21%, 95% CI: -43 to 1%, p=0.057), androstenedione (-14%, CI 95%: -29 to 0, p=0.050), and 11-ketotestosterone (-21%, CI 95%: -38 to -4, p=0.020) compared to control. Fasting plasma glucose levels were 4.6±0.7 mM after BHB supplementation, versus 5.1±0.4 mM in the placebo group (mean -10%, CI 95%: -5 to -15%, p<0.001).
    CONCLUSION: Ketone supplementation acutely lowers androgen and glucose levels in women with PCOS. These findings highlight the potential for ketone-based therapies as a novel treatment for PCOS and suggest the need for long-term clinical trials to further explore these effects.
    Keywords:  3-hydroxybutyrate; PCOS; androgens; glucose; ketones; metabolism
    DOI:  https://doi.org/10.1093/ejendo/lvaf106
  4. Circ Res. 2025 May 23. 136(11): 1407-1432
      Physical exercise is critical for preventing and managing chronic conditions, such as cardiovascular disease, type 2 diabetes, hypertension, and sarcopenia. Regular physical activity significantly reduces cardiovascular and all-cause mortality. Exercise also enhances metabolic health by promoting muscle growth, mitochondrial biogenesis, and improved nutrient storage while preventing age-related muscle dysfunction. Key metabolic benefits include increased glucose uptake, enhanced fat oxidation, and the release of exercise-induced molecules called myokines, which mediate interorgan communication and improve overall metabolic function. These myokines and other exercise-induced signaling molecules hold promise as therapeutic targets for aging and obesity-related conditions.
    Keywords:  cardiovascular diseases; epinephrine; hypertension; muscle, skeletal; sarcopenia
    DOI:  https://doi.org/10.1161/CIRCRESAHA.124.325614
  5. Clin Nutr. 2025 Apr 30. pii: S0261-5614(25)00116-5. [Epub ahead of print]50 92-103
       BACKGROUND & AIMS: Time-restricted eating (TRE) is a type of intermittent fasting, requiring individuals to limit their eating timeframe to specific hours in the day, while maintaining a fasting period greater than 12 h. Fat oxidation (FOx) is a critical determinant in the pathophysiology of metabolic diseases, with impaired FOx contributing to conditions such as insulin resistance and obesity, whereas enhanced FOx is associated with improved metabolic health. However, the impact of the 16:8 TRE model on FOx remains largely unexplored. The aim of this study was to determine the effect of a 6-week TRE on resting and exercise substrate oxidation, body composition, and blood markers related to metabolic health.
    METHODS: Thirty-three healthy, young males (age: 27.5 ± 6 years, body mass: 76.5 ± 8.4 kg, maximal oxygen uptake [V˙O2max]: 43.9 ± 6.6 mL·kg-1·min-1) were assigned to either TRE (n = 16) or control group (n = 17), with efforts to match baseline characteristics, including V˙O2max and body composition. The TRE group followed a 16:8 program for 6 weeks, while controls maintained their existing dietary habits. Body composition, blood glucose, insulin, blood lipids, resting substrate oxidation, and FOx during cycling at 40 % V˙O2max were assessed before and after the 6-week period. Data were analyzed using both intention-to-treat (ITT) and per-protocol approaches.
    RESULTS: Thirty-three participants were included in the ITT analysis, while 31 participants were included in the per-protocol analysis. Compared to baseline, results showed a significant difference (p < 0.05) between TRE and control groups in body mass (TRE versus control) (Δ = -2.8 kg versus Δ = 0.7 kg), fat mass (Δ = -1.4 kg versus Δ = 0.4 kg), percent body fat (-1.7 % versus 0.4 %), lean mass (Δ = -1.4 kg versus Δ = 0.3 kg), and visceral adipose tissue mass (Δ = -39.7 g versus Δ = 46.4 g). There was a significant difference between TRE and control groups in resting respiratory exchange ratio (RER, Δ = -0.02 versus Δ = 0.02; p = 0.016), FOx (Δ = 0.33 mg·kg FFM-1·min-1versus Δ = -0.37 mg·kg FFM-1·min-1; p = 0.007), and carbohydrate oxidation (Δ = -0.39 mg·kg FFM-1·min-1versus Δ = 0.45 mg·kg FFM-1·min-1; p = 0.037) after the 6-week period. Exercise substrate oxidation and fasting blood glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein cholesterol did not significantly change over time in either group (p > 0.05).
    CONCLUSIONS: In summary, a 6-week TRE significantly reduces body mass, fat mass, and resting RER as well as increases resting FOx in young, healthy males. However, it does not affect blood markers related to cardiometabolic health or exercise substrate oxidation. This trial was registered at https://clinicaltrials.gov/study/NCT06498102asNCT06498102.
    Keywords:  Body composition; Cardiometabolic health; Intermittent fasting; Lipid oxidation
    DOI:  https://doi.org/10.1016/j.clnu.2025.04.022
  6. Pflugers Arch. 2025 May 19.
      Cardiac diastolic dysfunction is a hallmark of diabetic cardiomyopathy (DCM), particularly in postmenopausal women where estrogen deficiency exacerbates cardiac remodeling. This study investigated the roles of NLRP3 inflammasome activation and cardiac mast cell (CMC) behavior in diabetic ovariectomized (OVX) rat models. Female Wistar rats were divided into five groups: sham-operated, OVX, diabetic (Sham-DM), OVX-diabetic (OVX-DM), and OVX-DM treated with the NLRP3 inhibitor MCC950. Diabetes was induced using a high-calorie quick fat diet (13.8% crude fat, 24.35% crude protein, 25% sucrose; 406.80 kcal/100 g) followed by a single intraperitoneal injection of streptozotocin (30 mg/kg). MCC950 (10 mg/kg BW, intraperitoneally) was administered daily for 4 weeks. Echocardiography revealed significant diastolic dysfunction in OVX-DM rats, with increased left ventricular internal diameter (LVIDd) and reduced mitral valve E/A ratio, while MCC950 treatment partially restored diastolic function (p < 0.05). Masson's trichrome staining showed increased myocardial fibrosis in OVX-DM rats (2.59 ± 0.20%) compared to Sham-DM (1.94 ± 0.16%, p < 0.05), which was reduced with MCC950 treatment (0.88 ± 0.13%, p < 0.05). Western blot analysis demonstrated elevated expression of NLRP3, cleaved caspase-1, IL-1β, and GSDMD-N in OVX-DM hearts. MCC950 significantly reduced cleaved caspase-1, IL-1β, and GSDMD-N expression without altering NLRP3 protein levels. Additionally, mast cell degranulation was markedly increased in OVX-DM rats (62.14%) compared to controls (P < 0.05) and was attenuated by MCC950 (31.06%, P < 0.05). These findings suggest that NLRP3 inflammasome activation under conditions of estrogen deficiency and diabetes contributes to myocardial pyroptosis and mast cell degranulation, driving cardiac remodeling in postmenopausal DCM. Targeting NLRP3 pathways may provide an effective therapeutic strategy to mitigate diastolic dysfunction, fibrosis, and inflammation in diabetic hearts.
    Keywords:  Cardiac inflammation; Cardiac mast cell; Diabetic heart disease; NLRP3 inflammasome; Postmenopausal
    DOI:  https://doi.org/10.1007/s00424-025-03092-6
  7. Curr Opin Clin Nutr Metab Care. 2025 May 05.
       AIM OF THE REVIEW: Weight loss is a primary goal in the treatment of obesity, but its effect on body composition - particularly fat-free mass (FFM) and skeletal muscle mass (SM) - is of increasing concern. This review examines the effects of antiobesity medications, particularly glucagon-like peptide-1 receptor analogs (GLP-1 RA), on body composition, the risk of sarcopenia, and strategies to preserve muscle mass during pharmacological weight loss.
    RECENT FINDINGS: Studies have shown that while GLP-1 RA are effective in reducing fat mass, up to 40% of the total weight loss can come from FFM. However, it is important to distinguish between FFM and SM, as FFM includes nonmuscle components. Resistance training and adequate protein intake can mitigate muscle loss, but the evidence for their efficacy in the context of GLP-1 RA therapy is mixed. If these measures are insufficient to prevent and maintain muscle mass, the use of some nutrients, such as branched chain amino acids, creatine, leucine, omega-3 fatty acids and vitamin D, may be beneficial. Newer pharmacological approaches, such as bimagrumab, a human monoclonal antibody that acts by binding to the activin type II receptor II (ActRII), and other activin or myostatin inhibitors, show promise in preserving muscle mass while promoting fat loss.
    SUMMARY: GLP-1 RA therapy for obesity should include resistance training, optimal protein intake and, if needed, specific nutrients and possibly pharmacological interventions to preserve muscle mass. Further research is needed to assess the long-term effects of GLP-1 RA on muscle health and to refine strategies to prevent sarcopenia in patients undergoing pharmacological weight loss.
    Keywords:  body composition; glucagon-like peptide-1 receptor agonists; sarcopenia; weight loss
    DOI:  https://doi.org/10.1097/MCO.0000000000001130
  8. Biochem Biophys Res Commun. 2025 May 17. pii: S0006-291X(25)00717-X. [Epub ahead of print]771 152003
      Duchenne muscular dystrophy (DMD) is a genetic disease, with no curative therapy, and is associated with mitochondrial dysfunction in skeletal muscle. Thus, mitochondrial treatment is a potential therapy for DMD. However, few studies have reported on such treatments because of the difficulty of drug delivery to mitochondria. Here, we used MITO-Porter to deliver coenzyme Q10 to the mitochondria of primary skeletal muscle cells isolated from DMD model rats. Our results show the therapeutic potential of mitochondrial activation for DMD.
    Keywords:  Coenzyme Q(10); Decreased mitochondrial respiratory capacity; Drug delivery system; Duchenne muscular dystrophy; Nanoparticle; Skeletal muscle cell
    DOI:  https://doi.org/10.1016/j.bbrc.2025.152003
  9. Acta Physiol (Oxf). 2025 Jun;241(6): e70056
      
    Keywords:  bioenergetics; brown adipose tissue; disease; ectothermic; endothermic; mitochondria; sarcopenia; ucp1
    DOI:  https://doi.org/10.1111/apha.70056
  10. Diabetologia. 2025 May 21.
       AIMS/HYPOTHESIS: Previous studies reporting lower skeletal muscle mitochondrial function in type 1 diabetes did not account for cardiorespiratory fitness, a key confounder when assessing mitochondrial function. We hypothesised that, compared with healthy individuals, muscle mitochondrial phenotypic differences would be abolished in individuals with type 1 diabetes when matched for age, sex, BMI and maximal oxygen uptake ( V˙O2max ).
    METHODS: Seventeen individuals with type 1 diabetes and seventeen healthy control individuals matched for age, sex, BMI and V˙O2max participated and underwent a muscle biopsy from the vastus lateralis. Mitochondrial respiration was assessed by high-resolution respirometry, and mitochondrial density and morphology were assessed by transmission electron microscopy.
    RESULTS: V˙O2max (individuals with type 1 diabetes 40±10 kg-1 min-1; control individuals 41±8 ml kg-1 min-1; p=0.51) and mitochondrial oxidative phosphorylation capacity (individuals with type 1 diabetes 101±35 [pmol O2] s-1 mg-1; control individuals 99±23 [pmol O2] s-1 mg-1, p=0.82) did not differ between groups. Both intermyofibrillar (individuals with type 1 diabetes 6.07±2.16%; control individuals 6.01±1.11%; p=0.92) and subsarcolemmal (individuals with type 1 diabetes 18.70±8.16%; control individuals 19.29±7.36%; p=0.83) mitochondrial densities were not different between groups. Mitochondrial respiration normalised by density did not differ between groups. However, individuals with type 1 diabetes and higher HbA1c displayed lower rates of mitochondrial respiration than those with lower HbA1c, whereas those with higher BMI displayed lower mitochondrial densities than those with lower BMI.
    CONCLUSIONS/INTERPRETATION: Collectively, our study demonstrates that when matched for age, sex, BMI and V˙O2max , maximal muscle mitochondrial respiration and morphology in people with type 1 diabetes are not impaired. These findings highlight the importance of habitual exercise, optimal glucose management and a healthy BMI in maintaining mitochondrial health in individuals with type 1 diabetes.
    Keywords:  Maximal oxygen uptake; Mitochondrial density; Mitochondrial respiration; Muscle bioenergetics; Muscle mitochondria; Skeletal muscle; Type 1 diabetes
    DOI:  https://doi.org/10.1007/s00125-025-06451-1
  11. J Nutr Biochem. 2025 May 15. pii: S0955-2863(25)00125-1. [Epub ahead of print] 109962
      Butyrate is a four-carbon short-chain fatty acid produced from microbial fermentation of dietary fibers present at high millimolar concentrations in the colonic lumen. However, in an intact epithelium, macrophages residing in the lamina propria are exposed to only micromolar butyrate concentrations. Current studies show anti-inflammatory properties of butyrate and suggest that it might have therapeutic applications in inflammatory bowel disease and colonic cancer. We now show that the effect of butyrate on human macrophages is strongly concentration dependent: 0.1 mM butyrate suppresses LPS-induced production of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. Experiments with siRNA knockdown and small molecule inhibitors suggest that this is mediated by a mechanism involving PPAR-γ signaling, whereas we observed no or only a minor effect of histone acetylation. In contrast, 10 mM butyrate promotes macrophage cell death, does not inhibit LPS-induced production of TNF-α, and promotes production of IL-1β, while production of anti-inflammatory IL-10 is reduced in a mechanism involving G protein-coupled receptors, the lipid transporter CD36, and the kinase SRC. We propose that butyrate is a signaling molecule for intestinal integrity, since intestinal disruption exposes macrophages to high butyrate concentrations.
    Keywords:  Butyrate; cytokines; inflammation; macrophage; short-chain fatty acid
    DOI:  https://doi.org/10.1016/j.jnutbio.2025.109962
  12. Curr Opin Clin Nutr Metab Care. 2025 May 21.
       PURPOSE OF REVIEW: To critically evaluate the latest evidence on the weight-loss effects of chrono-nutrition, culminating in identification of remaining gaps in the literature and future recommendations.
    RECENT FINDINGS: There appear to be six articles on this topic published over the past 2 years that have ostensibly examined the weight-loss effects of chrono-nutrition strategies relative to comparator conditions involving standard eating patterns in which meal timing is not manipulated. Some of those studies have concluded that TRE may be superior to standard energy restriction for weight-loss but the data presented do not consistently support that inference.
    SUMMARY: Chrono-nutrition strategies remain a popular dietary approach to weight-loss and yet there is a paucity of primary data showing that these strategies are more effective than any other means of eliciting a negative energy balance but without altering daily eating patterns.
    Keywords:  alternate-day fasting; body weight loss; chrono-nutrition; intermittent fasting; time-restricted eating
    DOI:  https://doi.org/10.1097/MCO.0000000000001135
  13. J Appl Physiol (1985). 2025 May 22.
      Age-related skeletal muscle atrophy is a muscle group-specific process. Therefore, we were interested in understanding exercise-induced hypertrophy across different muscles in older individuals. This review provides a comprehensive summary of the available information on muscle-specific hypertrophy responses to exercise training with aging (≥60y). In total, 6018 peer-reviewed publications were reviewed for inclusion (e.g., supervised resistance (RE) or aerobic (AE) exercise training; MRI, CT, or ultrasound determined muscle size), resulting in 1417 individuals from 68 studies (RE: n=1254; AE: n=163). Data were divided across age (60-69y, 70-79y, 80-89y, ≥90y) and duration (≤9, 10-14, 15-19, 20-24, ≥25wks), with the majority coming from the sexa- and septuagenarians (n=1335, 94%) and 10-14wks of training (n=806, 57%). The number of muscle groups (RE: 7, AE: 8) and subcomponent muscles (RE: 10, AE: 16) were a low representation of the whole-body musculature, with 79% of the data (n=1113) coming from the quadriceps. The 10-14wk responses showed a range of unique muscle-specific hypertrophy and atrophy (RE: 60-69y: 2-14% across six muscles; 70-79y: 1-12% across nine muscles; AE: 70-79y: -6% to +9% across 22 muscles). The large quadriceps-only resistance exercise training dataset (60-79 yrs) showed that no additional hypertrophy was observed with increased training repetitions (i.e., dose), and that men and women elicited an equivalent hypertrophic training response. The optimal exercise training mode(s) and dose(s) for all of the skeletal muscles of sexa-, septa-, octo-, and nonagenarian women and men is far from being elucidated based on the current scientific literature.
    Keywords:  aging; exercise; sarcopenia; skeletal muscle
    DOI:  https://doi.org/10.1152/japplphysiol.00892.2024
  14. Arch Gerontol Geriatr. 2025 May 08. pii: S0167-4943(25)00147-5. [Epub ahead of print]136 105890
       OBJECTIVE: Arterial stiffness (AS) is regarded as an independent predictor of cardiovascular events and all-cause mortality, and it is significantly associated with global mortality rates. Physical activity (PA) plays a positive role in reducing AS and improving cardiovascular health. The aim of this study is to compare the differences between high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) in their effects on reducing AS.
    METHODS: We conducted a comprehensive search of the PubMed, Cochrane, Embase, Web of Science, and EBSCO electronic databases, covering the period from their inception to January 10, 2025. We used a fixed-effect model to compare the changes in pulse wave velocity (PWV) before and after intervention between the HIIT group and the MICT group. Data were reported using the weighted mean difference (WMD) and 95 % confidence interval (95 % CI).
    RESULTS: This study included 619 participants from 22 studies. Compared to MICT, HIIT demonstrated a more significant reduction in PWV (-0.10 m/s [95 % CI:0.16 to -0.03], P = 0.005). Additionally, we found that HIIT was superior in reducing CF-PWV (-0.10 m/s [95 % CI:0.17 to -0.02], P = 0.01).
    CONCLUSION: HIIT is more effective than MICT in improving PWV and promoting arterial health in adults.
    Keywords:  Arterial stiffness; High-intensity interval exercise; Moderate-intensity continuous training; Pulse wave velocity
    DOI:  https://doi.org/10.1016/j.archger.2025.105890
  15. J Biol Chem. 2025 May 15. pii: S0021-9258(25)02089-7. [Epub ahead of print] 110239
      Histone proteolysis is sometimes described as an extreme post-translational modification (PTM), as it removes both a stretch of histone sequence and any PTMs that were previously added to it. Such an acute and significant loss of information could trigger many different downstream effects, making it attractive as a mechanism for rapid gene silencing or activation. Yet protease activity is challenging to study and is often treated like background noise that is best kept as low as possible. As both histones and protease activity are highly abundant in most cells, evidence of proteolysis of histone tails - a.k.a. histone clipping - has often been dismissed as nonspecific noise. Yet over the past decades there have been several studies that suggest this activity should not be ignored, as it may represent a rare but relevant process that plays important roles in cell biology. Here I review the key studies that both support this argument and raise additional questions about the mechanisms and functions of histone clipping.
    DOI:  https://doi.org/10.1016/j.jbc.2025.110239
  16. Cureus. 2025 Apr;17(4): e82585
      Amyotrophic lateral sclerosis (ALS) is often complicated by severe malnutrition, increasing the risk of metabolic disturbances. Non-diabetic ketoacidosis (NDKA) is a rare but serious complication, typically related to prolonged fasting or catabolic states. A 62-year-old female patient with ALS and hypothyroidism presented with pneumonia and tetraplegia. Her body mass index (BMI) was 17 kg/m². Laboratory findings showed a high anion gap (AG) metabolic acidosis (pH 7.23, bicarbonate 13 mmol/L, partial pressure of carbon dioxide (pCO₂) 28 mmHg) without hyperlactatemia, but with significant ketonemia (5 mmol/L), severe hypophosphatemia, and signs of systemic inflammation. Upon admission, she received an intravenous infusion of 4.2% sodium bicarbonate. The simplified strong ion difference (SID) was preserved, excluding dilutional or hyperchloremic causes. Stewart's physicochemical approach, supported by a Gamblegram, revealed an acidosis due to unmeasured fixed acids, specifically ketone bodies. In light of this, bicarbonate therapy was discontinued, and nutritional correction with glucose hydration led to rapid clinical and biochemical improvement. This case illustrates the diagnostic and therapeutic value of Stewart's model in complex acid-base disturbances and underscores the need for early nutritional assessment in ALS patients. To our knowledge, this is the first reported case of NDKA in ALS, highlighting a rare but clinically relevant metabolic complication.
    Keywords:  acid-base disorders; amyotrophic lateral sclerosis; keto acidosis; protein energy malnutrition (pem); stewart approach
    DOI:  https://doi.org/10.7759/cureus.82585
  17. J Biochem Mol Toxicol. 2025 Jun;39(6): e70289
      Silver nanoparticles (AgNPs) are extensively mass-produced and widely utilized across diverse fields owing to their potent bactericidal properties. Nevertheless, prior research regarding the distribution of AgNPs In Vivo has revealed that they can penetrate into and accumulate in brain tissue, potentially leading to neurotoxicity. In the current study, we initially delved into the impacts of different dosages of AgNPs (10-250 mg/kg body weight) on behavioral cognitive function. After 28 days of oral ingestion of AgNPs, we observed impaired learning and memory performance in the high-dose-treated group of mice. Moreover, we evaluated the alterations in molecules associated with endoplasmic reticulum (ER) stress and the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, conducting a preliminary exploration of the neurotoxic mechanisms of AgNPs. The results demonstrated that subacute oral exposure to AgNPs might disrupt cognitive function via the ER stress and NLRP3 inflammasome activation pathways. Our data highlight the neurotoxic effects of AgNPs and the significant role played by NLRP3 inflammasome activation in neurological deficits.
    Keywords:  NOD‐like receptor protein 3 inflammasome; neurological lesion; pro‐inflammatory cascade; silver nanoparticles; unfolded protein response
    DOI:  https://doi.org/10.1002/jbt.70289